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Conserved domains on  [gi|1050115333|ref|NP_001316850|]
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calmodulin-3 isoform 2 [Homo sapiens]

Protein Classification

EF-hand domain-containing protein( domain architecture ID 1000080)

EF-hand (EFh) domain-containing protein may be involved in binding intracellular calcium and in calcium signal transduction

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTZ00184 super family cl33172
calmodulin; Provisional
1-113 8.22e-69

calmodulin; Provisional


The actual alignment was detected with superfamily member PTZ00184:

Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 203.07  E-value: 8.22e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   1 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK 80
Cdd:PTZ00184   37 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDTDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEK 116
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1050115333  81 LTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:PTZ00184  117 LTDEEVDEMIREADVDGDGQINYEEFVKMMMSK 149
 
Name Accession Description Interval E-value
PTZ00184 PTZ00184
calmodulin; Provisional
1-113 8.22e-69

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 203.07  E-value: 8.22e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   1 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK 80
Cdd:PTZ00184   37 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDTDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEK 116
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1050115333  81 LTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:PTZ00184  117 LTDEEVDEMIREADVDGDGQINYEEFVKMMMSK 149
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
1-113 1.04e-43

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 227455 [Multi-domain]  Cd Length: 160  Bit Score: 139.75  E-value: 1.04e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   1 MRSLGQNPTEAELQDMINEVDAdGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK 80
Cdd:COG5126    46 LRSLGFNPSEAEINKLFEEIDA-GNETVDFPEFLTVMSVKLKRGDKEEELREAFKLFDKDHDGYISIGELRRVLKSLGER 124
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1050115333  81 LTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:COG5126   125 LSDEEVEKLLKEYDEDGDGEIDYEEFKKLIKDS 157
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
49-111 9.03e-24

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 86.06  E-value: 9.03e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1050115333  49 EIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMT 111
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
47-111 2.50e-18

EF-hand domain pair;


Pssm-ID: 433258 [Multi-domain]  Cd Length: 67  Bit Score: 72.29  E-value: 2.50e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050115333  47 EEEIREAFRVFDKDGNGYISAAELRHVMTNL--GEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMT 111
Cdd:pfam13499   1 EEKLKEAFKLLDKDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
85-113 1.49e-06

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 41.21  E-value: 1.49e-06
                           10        20
                   ....*....|....*....|....*....
gi 1050115333   85 EVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
PTZ00184 PTZ00184
calmodulin; Provisional
1-113 8.22e-69

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 203.07  E-value: 8.22e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   1 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK 80
Cdd:PTZ00184   37 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDTDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEK 116
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1050115333  81 LTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:PTZ00184  117 LTDEEVDEMIREADVDGDGQINYEEFVKMMMSK 149
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
1-113 1.04e-43

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 227455 [Multi-domain]  Cd Length: 160  Bit Score: 139.75  E-value: 1.04e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   1 MRSLGQNPTEAELQDMINEVDAdGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK 80
Cdd:COG5126    46 LRSLGFNPSEAEINKLFEEIDA-GNETVDFPEFLTVMSVKLKRGDKEEELREAFKLFDKDHDGYISIGELRRVLKSLGER 124
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1050115333  81 LTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:COG5126   125 LSDEEVEKLLKEYDEDGDGEIDYEEFKKLIKDS 157
PTZ00183 PTZ00183
centrin; Provisional
1-113 1.54e-34

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 116.33  E-value: 1.54e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   1 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK 80
Cdd:PTZ00183   43 MRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKLGERDPREEILKAFRLFDDDKTGKISLKNLKRVAKELGET 122
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1050115333  81 LTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:PTZ00183  123 ITDEELQEMIDEADRNGDGEISEEEFYRIMKKT 155
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
49-111 9.03e-24

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 86.06  E-value: 9.03e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1050115333  49 EIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMT 111
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
47-111 2.50e-18

EF-hand domain pair;


Pssm-ID: 433258 [Multi-domain]  Cd Length: 67  Bit Score: 72.29  E-value: 2.50e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050115333  47 EEEIREAFRVFDKDGNGYISAAELRHVMTNL--GEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMT 111
Cdd:pfam13499   1 EEKLKEAFKLLDKDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EFh_calglandulin_like cd16252
EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The ...
26-111 3.46e-16

EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The family corresponds to a group of uncharacterized calglandulin-like proteins. Although their biological function remain unclear, they show high sequence similarity with human calglandulin-like protein GAGLP, which is an ortholog of calglandulin from the venom glands of Bothrops insularis snake. Both GAGLP and calglandulin are putative Ca2+-binding proteins with four EF-hand motifs. However, members in this family contain only three EF-hand motifs. In this point, they may belong to the parvalbumin-like EF-hand family, which is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix).


Pssm-ID: 319995 [Multi-domain]  Cd Length: 106  Bit Score: 67.94  E-value: 3.46e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  26 GTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK-----LTDEEVDEMIREADIDGDGQ 100
Cdd:cd16252    15 GSFNYSKFFEYMQKFQTSEQQEEAIRKAFQMLDKDKSGFIEWNEIKYILSTVPSSmpvapLSDEEAEAMIQAADTDGDGR 94
                          90
                  ....*....|.
gi 1050115333 101 VNYEEFVQMMT 111
Cdd:cd16252    95 IDFQEFSDMVK 105
PTZ00183 PTZ00183
centrin; Provisional
45-113 1.03e-14

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 65.48  E-value: 1.03e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1050115333  45 DSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:PTZ00183   14 DQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKK 82
EFh_parvalbumin_like cd16251
EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes ...
26-112 2.53e-14

EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes alpha- and beta-parvalbumins, and a group of uncharacterized calglandulin-like proteins. Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI


Pssm-ID: 319994 [Multi-domain]  Cd Length: 101  Bit Score: 63.32  E-value: 2.53e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  26 GTIDFPEFLTMMARKMKdtdSEEEIREAFRVFDKDGNGYISAAELRHVMTNL---GEKLTDEEVDEMIREADIDGDGQVN 102
Cdd:cd16251    15 GSFNYKKFFEHVGLKQK---SEDQIKKVFQILDKDKSGFIEEEELKYILKGFsiaGRDLTDEETKALLAAGDTDGDGKIG 91
                          90
                  ....*....|
gi 1050115333 103 YEEFVQMMTA 112
Cdd:cd16251    92 VEEFATLVAG 101
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
16-111 3.05e-12

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 59.08  E-value: 3.05e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  16 MINEVDADGNGTIDFPEFltmmarkmKDTDSE-EEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREAD 94
Cdd:cd16180    42 MINMFDRDRSGTINFDEF--------VGLWKYiQDWRRLFRRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFD 113
                          90
                  ....*....|....*..
gi 1050115333  95 IDGDGQVNYEEFVQMMT 111
Cdd:cd16180   114 RRRRGSISFDDFVEACV 130
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
12-75 1.58e-11

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 54.86  E-value: 1.58e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1050115333  12 ELQDMINEVDADGNGTIDFPEFLTMMaRKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMT 75
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAAL-KSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
7-108 1.61e-11

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination.


Pssm-ID: 320058 [Multi-domain]  Cd Length: 165  Bit Score: 57.26  E-value: 1.61e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   7 NPTEAELqdMINEVDADGNGTIDFPEFLTMMarkmkdtDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEV 86
Cdd:cd16183    35 NPETVRL--MIGMFDRDNSGTINFQEFAALW-------KYITDWQNCFRSFDRDNSGNIDKNELKQALTSFGYRLSDQFY 105
                          90       100
                  ....*....|....*....|..
gi 1050115333  87 DEMIREADIDGDGQVNYEEFVQ 108
Cdd:cd16183   106 DILVRKFDRQGRGTIAFDDFIQ 127
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
49-109 8.64e-11

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 55.30  E-value: 8.64e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050115333  49 EIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQM 109
Cdd:cd16185     1 ELRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDRDGNGTIDFEEFAAL 61
EFh_parvalbumin_beta cd16255
EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed ...
46-112 1.27e-10

EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed Oncomodulin-1 (OM), is a small calcium-binding protein that is expressed in hepatomas, as well as in the blastocyst and the cytotrophoblasts of the placenta. It is also found to be expressed in the cochlear outer hair cells of the organ of Corti and frequently expressed in neoplasms. Mammalian beta-parvalbumin is secreted by activated macrophages and neutrophils. It may function as a tissue-specific Ca2+-dependent regulatory protein, and may also serve as a specialized cytosolic Ca2+ buffer. Beta-parvalbumin acts as a potent growth-promoting signal between the innate immune system and neurons in vivo. It has high and specific affinity for its receptor on retinal ganglion cells (RGC) and functions as the principal mediator of optic nerve regeneration. It exerts its effects in a cyclic adenosine monophosphate (cAMP)-dependent manner and can further elevate intracellular cAMP levels. Moreover, beta-parvalbumin is associated with efferent function and outer hair cell electromotility, and can identify different hair cell types in the mammalian inner ear. Beta-parvalbumin is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. The EF site displays a high-affinity for Ca2+/Mg2+, and the CD site is a low-affinity Ca2+-specific site. In addition, beta-parvalbumin is distinguished from other parvalbumins by its unusually low isoelectric point (pI = 3.1) and sequence eccentricities (e.g., Y57-L58-D59 instead of F57-I58-E59).


Pssm-ID: 319998 [Multi-domain]  Cd Length: 101  Bit Score: 53.58  E-value: 1.27e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  46 SEEEIREAFRVFDKDGNGYISAAELRHVMTNL---GEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTA 112
Cdd:cd16255    32 SADDVKKVFEIIDQDKSGFIEEEELKLFLQNFssgARELTDAETKAFLKAGDSDGDGKIGVEEFQALVKA 101
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
13-107 8.17e-10

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 53.98  E-value: 8.17e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  13 LQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEI---REAFR-VFDKDGNGYISAAELRHVMTNLGEKLTDEEVDE 88
Cdd:cd15899   162 IKETLEDLDKNGDGFISLEEFISDPYSADENEEEPEWVkveKERFVeLRDKDKDGKLDGEELLSWVDPSNQEIALEEAKH 241
                          90
                  ....*....|....*....
gi 1050115333  89 MIREADIDGDGQVNYEEFV 107
Cdd:cd15899   242 LIAESDENKDGKLSPEEIL 260
EFh_PEF_Group_II_CAPN_like cd16182
Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family ...
16-108 1.49e-09

Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family belongs to the second group of penta-EF hand (PEF) proteins. It includes classical (also called conventional or typical) calpain (referring to a calcium-dependent papain-like enzymes, EC 3.4.22.17) large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14) and two calpain small subunits (CAPNS1 and CAPNS2), which are largely confined to animals (metazoans). These PEF-containing are nonlysosomal intracellular calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates in response to calcium signalling. The classical mu- and m-calpains are heterodimers consisting of homologous but a distinct (large) L-subunit/chain (CAPN1 or CAPN2) and a common (small) S-subunit/chain (CAPNS1 or CAPNS2). These L-subunits (CAPN1 and CAPN2) and S-subunit CAPNS1 are ubiquitously found in all tissues. Other calpains likely consist of an isolated L-subunit/chain alone. Many of them, such as CAPNS2, CAPN3 (in skeletal muscle, or lens), CAPN8 (in stomach), CAPN9 (in digestive tracts), CAPN11 (in testis), CAPN12 (in follicles), are tissue-specific and have specific functions in distinct organs. The L-subunits of similar structure (called CALPA and B) also have been found in Drosophila melanogaster. The S-subunit seems to have a chaperone-like function for proper folding of the L-subunit. The catalytic L-subunits contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The S-subunits only have the PEF domain following an N-terminal Gly-rich hydrophobic domain. The calpains undergo a rearrangement of the protein backbone upon Ca2+-binding.


Pssm-ID: 320057 [Multi-domain]  Cd Length: 167  Bit Score: 52.23  E-value: 1.49e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  16 MINEVDADGNGTIDFPEFLTMMARKmkdtdseEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLtDEEVDEMIREADI 95
Cdd:cd16182    47 LIALMDTNGSGRLDLEEFKTLWSDL-------KKWQAIFKKFDTDRSGTLSSYELRKALESAGFHL-SNKVLQALVLRYA 118
                          90
                  ....*....|...
gi 1050115333  96 DGDGQVNYEEFVQ 108
Cdd:cd16182   119 DSTGRITFEDFVS 131
EF-hand_8 pfam13833
EF-hand domain pair;
61-111 2.40e-09

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 49.24  E-value: 2.40e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1050115333  61 GNGYISAAELRHVMTNLGEK-LTDEEVDEMIREADIDGDGQVNYEEFVQMMT 111
Cdd:pfam13833   1 EKGVITREELKRALALLGLKdLSEDEVDILFREFDTDGDGYISFDEFCVLLE 52
EFh_parvalbumin_alpha cd16254
EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2 ...
26-110 3.93e-09

EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2+/Mg2+-binding protein expressed mainly in fast-twitch skeletal myofibrils, where it may act as a soluble relaxing factor facilitating the Ca2+-mediated relaxation phase. It is also expressed in rapidly firing neurons, particularly GABA-ergic neurons, and thus may confer protection against Ca2+ toxicity. The major role of alpha-parvalbumin is metal buffering and transport of Ca2+. It binds different metal cations, and exhibits very high affinity for Ca2+ and physiologically significant affinity for Mg2+. Alpha-parvalbumin is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Both metal ion-binding sites in alpha-parvalbumin are high-affinity sites. Additionally, in contrast to beta-parvalbumin, alpha-parvalbumin is less acidic and has an additional residue in the C-terminal helix.


Pssm-ID: 319997 [Multi-domain]  Cd Length: 101  Bit Score: 49.82  E-value: 3.93e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  26 GTIDFPEFLTMMARKMKdtdSEEEIREAFRVFDKDGNGYISAAELRHVMTNL---GEKLTDEEVDEMIREADIDGDGQVN 102
Cdd:cd16254    15 DSFDYKKFFEMVGLKKK---SADDVKKVFHILDKDKSGFIEEDELKFVLKGFspdGRDLSDKETKALLAAGDKDGDGKIG 91

                  ....*...
gi 1050115333 103 YEEFVQMM 110
Cdd:cd16254    92 IDEFATLV 99
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
1-38 5.43e-09

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 48.31  E-value: 5.43e-09
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1050115333   1 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMA 38
Cdd:cd00051    26 LKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
1-110 5.58e-09

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 50.36  E-value: 5.58e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   1 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMkdtdSEEEIREAFRVFDKDGNGYISAAELRHVMTN-LGE 79
Cdd:cd15898    26 LKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLT----ERPELEPIFKKYAGTNRDYMTLEEFIRFLREeQGE 101
                          90       100       110
                  ....*....|....*....|....*....|..
gi 1050115333  80 KLTDEEVDEMIREADIDG-DGQVNYEEFVQMM 110
Cdd:cd15898   102 NVSEEECEELIEKYEPEReNRQLSFEGFTNFL 133
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
14-109 8.25e-09

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 50.29  E-value: 8.25e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  14 QDMINEVDADGNGTIDFPEFLTMMARKMKdtdseeeIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREA 93
Cdd:cd16185    39 EKLIRMFDRDGNGTIDFEEFAALHQFLSN-------MQNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKF 111
                          90
                  ....*....|....*.
gi 1050115333  94 DIDGDGQVNYEEFVQM 109
Cdd:cd16185   112 DPDRGGSLGFDDYIEL 127
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
3-110 9.99e-09

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 50.81  E-value: 9.99e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   3 SLGQNPTEAELQDMINEV----DADGNGTIDFPEFLTMMA---------RKMKDTDSEEEIREAFRVFDKDGNGYISAAE 69
Cdd:cd15902    32 LNGKDKTDDEVAEKKKEFmekyDENEDGKIEIRELANILPteenflllfRREQPLISSVEFMKIWRKYDTDGSGFIEAKE 111
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1050115333  70 LRHVMTNLGEKL--------TDEEVDEMIREADIDGDGQVNYEEFVQMM 110
Cdd:cd15902   112 LKGFLKDLLLKNkkhvsppkLDEYTKLILKEFDANKDGKLELDEMAKLL 160
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
13-108 1.92e-08

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 48.82  E-value: 1.92e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  13 LQDMINEVDADGNGTIDFPEFLTMMaRKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKltdEEVDEMIRE 92
Cdd:cd15898     2 LRRQWIKADKDGDGKLSLKEIKKLL-KRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTER---PELEPIFKK 77
                          90
                  ....*....|....*.
gi 1050115333  93 ADIDGDGQVNYEEFVQ 108
Cdd:cd15898    78 YAGTNRDYMTLEEFIR 93
ELC_N cd22949
N-terminal domain of Myosin essential light chain ELC; ELC is part of the apicomplexan ...
46-113 2.01e-08

N-terminal domain of Myosin essential light chain ELC; ELC is part of the apicomplexan membrane-associated protein complex called the glideosome, which is essential for parasite motility. The glideosome is composed of six proteins: myosin A (MyoA), essential light chain ELC, myosin light chain MLC1 (also called MTIP), and the glideosome-associated proteins GAP40, GAP45, and GAP50. MyoA is a Class XIV myosin implicated in gliding motility, as well as host cell and tissue invasion by parasites. ELC binds to the MyoA neck region adjacent to the MLC1-binding site, and both myosin light chains co-located to the glideosome. Although ELCs bind to a conserved MyoA sequence, P. falciparum ELC adopts a distinct structure in the free and MyoA-bound state. Therefore ELCs enhance MyoA performance by inducing alpha helical structure formation in MyoA and thus stiffening its lever arm. It has been shown that disruption of MyoA, MLC1, or ELC have dramatic effects on parasite motility but do not affect parasite shape or replication. The ELC N-terminal domain is part of the EF-hand calcium binding motif superfamily. Calcium binding has no effect on the structure of ELCs.


Pssm-ID: 439385 [Multi-domain]  Cd Length: 66  Bit Score: 46.96  E-value: 2.01e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1050115333  46 SEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMireadidgDGQVNYEEFVQMMTAK 113
Cdd:cd22949     1 MEEKFREAFILFDRDGDGELTMYEAVLAMRSCGIPLTNDEKDAL--------PASMNWDQFENWAKKK 60
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
49-108 2.06e-08

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 49.06  E-value: 2.06e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050115333  49 EIREAFRVFDKDGNGYISAAELRHVMTN-LGEKLTDEEVDEMIREADIDGDGQVNYEEFVQ 108
Cdd:cd16180     1 ELRRIFQAVDRDRSGRISAKELQRALSNgDWTPFSIETVRLMINMFDRDRSGTINFDEFVG 61
EFh_PEF_Group_II_sorcin_like cd16181
Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The ...
16-107 3.51e-08

Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The family corresponds to the second group of penta-EF hand (PEF) proteins that includes sorcin, grancalcin, and similar proteins. Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. It contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH. Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It can strongly interact with sorcin to form a heterodimer and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. In contrast with sorcin, GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320056 [Multi-domain]  Cd Length: 165  Bit Score: 48.52  E-value: 3.51e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  16 MINEVDADGNGTIDFPEFLTMMArkmkdtdSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADI 95
Cdd:cd16181    45 MIAMLDRDHSGKMGFNEFKELWA-------ALNQWKTTFMQYDRDRSGTVEPQELQQAIRSFGYNLSPQALNVIVKRYSK 117
                          90
                  ....*....|..
gi 1050115333  96 dgDGQVNYEEFV 107
Cdd:cd16181   118 --NGRITFDDFV 127
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
10-107 4.80e-08

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 49.24  E-value: 4.80e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  10 EAELQDMINEVDADGNGTIDFPEFLTMMArkmKDTDSEEEIREAFRV---FDKDGNGYISAAELRHVMTNLGEKLTDEEV 86
Cdd:cd16227   158 PVLIEQTLRDKDKDNDGFISFQEFLGDRA---GHEDKEWLLVEKDRFdedYDKDGDGKLDGEEILSWLVPDNEEIAEEEV 234
                          90       100
                  ....*....|....*....|.
gi 1050115333  87 DEMIREADIDGDGQVNYEEFV 107
Cdd:cd16227   235 DHLFASADDDHDDRLSFDEIL 255
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
52-107 7.66e-08

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 45.67  E-value: 7.66e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1050115333  52 EAFRVFDKDGNGYISAAELRHVMTNLGekLTDEEVDEMIREADIDGDGQVNYEEFV 107
Cdd:cd00052     3 QIFRSLDPDGDGLISGDEARPFLGKSG--LPRSVLAQIWDLADTDKDGKLDKEEFA 56
EF-hand_6 pfam13405
EF-hand domain;
49-78 1.02e-07

EF-hand domain;


Pssm-ID: 433181 [Multi-domain]  Cd Length: 30  Bit Score: 44.48  E-value: 1.02e-07
                          10        20        30
                  ....*....|....*....|....*....|
gi 1050115333  49 EIREAFRVFDKDGNGYISAAELRHVMTNLG 78
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
50-108 1.20e-07

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.


Pssm-ID: 320032 [Multi-domain]  Cd Length: 140  Bit Score: 46.84  E-value: 1.20e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1050115333  50 IREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQ 108
Cdd:cd16202     2 LKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQ 60
EFh_parvalbumins cd16253
EF-hand, calcium binding motif, found in parvalbumins; Parvalbumins are small, acidic, ...
26-112 1.74e-07

EF-hand, calcium binding motif, found in parvalbumins; Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI


Pssm-ID: 319996 [Multi-domain]  Cd Length: 101  Bit Score: 45.63  E-value: 1.74e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  26 GTIDFPEFLTMMARKMKdtdSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK---LTDEEVDEMIREADIDGDGQVN 102
Cdd:cd16253    15 DSFDHKAFFKAVGLSKK---SPADIKKVFNILDQDKSGFIEEEELKLFLKNFSDGarvLSDKETKNFLAAGDSDGDGKIG 91
                          90
                  ....*....|
gi 1050115333 103 YEEFVQMMTA 112
Cdd:cd16253    92 VDEFKSMVKA 101
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
16-108 1.22e-06

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.


Pssm-ID: 320054 [Multi-domain]  Cd Length: 165  Bit Score: 44.34  E-value: 1.22e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  16 MINEVDADGNGTIDFPEFlTMMARKMKDtdseeeIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADi 95
Cdd:cd15897    45 MIAMMDRDHSGKLNFSEF-KGLWNYIKA------WQEIFRTYDTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYD- 116
                          90
                  ....*....|...
gi 1050115333  96 DGDGQVNYEEFVQ 108
Cdd:cd15897   117 RGRGNIDFDDFIQ 129
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
17-105 1.44e-06

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 44.88  E-value: 1.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  17 INEVDADGNGTIDFPEFLTMMARK---MKDTDSEEEIREAFRVF-DKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIRE 92
Cdd:cd16226   162 LEDIDKNKDGFISLEEYIGDMYRDddeEEDPDWVKSEREQFKEFrDKNKDGKMDREEVKDWILPEDYDHAEAEAKHLIYE 241
                          90
                  ....*....|...
gi 1050115333  93 ADIDGDGQVNYEE 105
Cdd:cd16226   242 ADDDKDGKLTKEE 254
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
16-108 1.47e-06

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.


Pssm-ID: 320059 [Multi-domain]  Cd Length: 165  Bit Score: 44.18  E-value: 1.47e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  16 MINEVDADGNGTIDFPEFltmmarkmkdtdSE-----EEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMI 90
Cdd:cd16184    42 MIGMFDKDKSGTIDIYEF------------QAlwnyiQQWKQVFQQFDRDRSGSIDENELHQALSQMGYRLSPQFVQFLV 109
                          90
                  ....*....|....*...
gi 1050115333  91 READIDGDGQVNYEEFVQ 108
Cdd:cd16184   110 SKYDPRARRSLTLDQFIQ 127
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
85-113 1.49e-06

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 41.21  E-value: 1.49e-06
                           10        20
                   ....*....|....*....|....*....
gi 1050115333   85 EVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_PEF_CAPN13_14 cd16195
Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and ...
16-110 2.96e-06

Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and similar proteins; CAPN13, also termed calcium-activated neutral proteinase 13 (CANP 13), a 63.6 kDa calpain large subunit that exhibits a restricted tissue distribution with low levels of expression detected only in human testis and lung. In calpain family, CAPN13 is most closely related to calpain-14 (CAPN14). CAPN14, also termed calcium-activated neutral proteinase 14 (CANP 14), is a 76.7 kDa calpain large subunit that is most highly expressed in the oesophagus. Its expression and calpain activity can be induced by IL-13. Both CAPN13 and CAPN14 contain a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320070 [Multi-domain]  Cd Length: 168  Bit Score: 43.35  E-value: 2.96e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  16 MINEVDADGNGTIDFPEFLTM--MARKMKDTdseeeireaFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEM-IRE 92
Cdd:cd16195    48 MVALMDLSVNGRLSLEEFSRLwkKLRKYKDI---------FQKADVSKSGFLSLSELRNAIQAAGIRVSDDLLNLMaLRY 118
                          90
                  ....*....|....*...
gi 1050115333  93 AdiDGDGQVNYEEFVQMM 110
Cdd:cd16195   119 G--DSSGRISFESFICLM 134
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
49-77 3.56e-06

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 40.44  E-value: 3.56e-06
                           10        20
                   ....*....|....*....|....*....
gi 1050115333   49 EIREAFRVFDKDGNGYISAAELRHVMTNL 77
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EF-hand_7 pfam13499
EF-hand domain pair;
10-75 3.58e-06

EF-hand domain pair;


Pssm-ID: 433258 [Multi-domain]  Cd Length: 67  Bit Score: 41.09  E-value: 3.58e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050115333  10 EAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTD-SEEEIREAFRVFDKDGNGYISAAELRHVMT 75
Cdd:pfam13499   1 EEKLKEAFKLLDKDGDGYLDVEELKKLLRKLEEGEPlSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
85-112 5.26e-06

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 40.08  E-value: 5.26e-06
                          10        20
                  ....*....|....*....|....*...
gi 1050115333  85 EVDEMIREADIDGDGQVNYEEFVQMMTA 112
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKK 28
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
49-77 5.44e-06

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 40.08  E-value: 5.44e-06
                          10        20
                  ....*....|....*....|....*....
gi 1050115333  49 EIREAFRVFDKDGNGYISAAELRHVMTNL 77
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29
PLN02964 PLN02964
phosphatidylserine decarboxylase
47-110 8.06e-06

phosphatidylserine decarboxylase


Pssm-ID: 215520 [Multi-domain]  Cd Length: 644  Bit Score: 42.92  E-value: 8.06e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050115333  47 EEEIREAFRVF---DKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMM 110
Cdd:PLN02964  175 ETERSFARRILaivDYDEDGQLSFSEFSDLIKAFGNLVAANKKEELFKAADLNGDGVVTIDELAALL 241
EFh_PEF_CalpA_B cd16196
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), ...
16-111 8.24e-06

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins; The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.


Pssm-ID: 320071 [Multi-domain]  Cd Length: 167  Bit Score: 42.19  E-value: 8.24e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  16 MINEVDADGNGTIDFPEF--LTMMARKMKDtdseeeireAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMI-RE 92
Cdd:cd16196    46 MVAMMDVDRSGKLGFEEFkkLWEDLRSWKR---------VFKLFDTDGSGSFSSFELRNALNSAGFRLSNATLNALVlRY 116
                          90
                  ....*....|....*....
gi 1050115333  93 AdiDGDGQVNYEEFVQMMT 111
Cdd:cd16196   117 S--NKDGRISFDDFIMCAV 133
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
43-110 9.62e-06

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 40.72  E-value: 9.62e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1050115333   43 DTDSEEEIreaFRVFDKDGNGYISAAELRHVMTNLGekLTDEEVDEMIREADIDGDGQVNYEEFVQMM 110
Cdd:smart00027   8 DKAKYEQI---FRSLDKNQDGTVTGAQAKPILLKSG--LPQTLLAKIWNLADIDNDGELDKDEFALAM 70
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
13-106 9.70e-06

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 42.57  E-value: 9.70e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  13 LQDMINEVDADGNGTIDFPEfLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVD----- 87
Cdd:cd16226    37 LGIIVDKIDKNGDGFVTEEE-LKDWIKYVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKATYGFLDDEEEDDDLhesyk 115
                          90       100
                  ....*....|....*....|....*.
gi 1050115333  88 EMIR-------EADIDGDGQVNYEEF 106
Cdd:cd16226   116 KMIRrderrwkAADQDGDGKLTKEEF 141
EFh_CREC_RCN2 cd16224
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed ...
9-110 9.71e-06

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed calcium-binding protein ERC-55, or E6-binding protein (E6BP), or TCBP-49, is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. It is associated with tumorigenesis, in particular with transformation of cells of the cervix induced by human papillomavirus (HPV), through binding to human papillomavirus (HPV) E6 oncogenic protein. It specifically interacts with vitamin D receptor among nuclear receptors. RCN2 contains an N-terminal signal sequence followed by six copies of the EF-hand Ca2+-binding motif, and a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320022 [Multi-domain]  Cd Length: 268  Bit Score: 42.42  E-value: 9.71e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   9 TEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEE-EIREAFRV---FDKDGNGYISAAE-LRHVMTNlGEKLTD 83
Cdd:cd16224   159 TEFVIQEALEEHDKDGDGFISLEEFLGDYRKDPTANEDPEwIIVEKDRFvndYDKDNDGKLDPQElLPWVVPN-NYGIAQ 237
                          90       100
                  ....*....|....*....|....*..
gi 1050115333  84 EEVDEMIREADIDGDGQVNYEEFVQMM 110
Cdd:cd16224   238 EEALHLIDEMDLNGDGRLSEEEILENQ 264
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
50-110 2.32e-05

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 40.73  E-value: 2.32e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050115333  50 IREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMM 110
Cdd:cd15898     2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELY 62
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
12-40 2.36e-05

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 38.13  E-value: 2.36e-05
                           10        20
                   ....*....|....*....|....*....
gi 1050115333   12 ELQDMINEVDADGNGTIDFPEFLTMMARK 40
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
9-113 2.48e-05

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 41.57  E-value: 2.48e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   9 TEAELQDMINEVDADGNGTIDFPE----------FLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLG 78
Cdd:cd15902   132 LDEYTKLILKEFDANKDGKLELDEmakllpvqenFLLKFQILGAMDLTKEDFEKVFEHYDKDNNGVIEGNELDALLKDLL 211
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1050115333  79 EK------LTDEE--VDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:cd15902   212 EKnkadidKPDLEnfRDAILRACDKNKDGKIQKTELALFLSAK 254
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
23-110 4.80e-05

EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, MICU3, and similar proteins; This family includes mitochondrial calcium uptake protein MICU1 and its two additional paralogs, MICU2 and MICU3. MICU1 localizes to the inner mitochondrial membrane (IMM). It functions as a gatekeeper of the mitochondrial calcium uniporter (MCU) and regulates MCU-mediated mitochondrial Ca2+ uptake, which is essential for maintaining mitochondrial homoeostasis. MICU1 and MICU2 are physically associated within the uniporter complex and are co-expressed across all tissues. They may play non-redundant roles in the regulation of the mitochondrial calcium uniporter. At present, the precise molecular function of MICU2 and MICU3 remain unclear. MICU2 may play possible roles in Ca2+ sensing and regulation of MCU, calcium buffering with a secondary impact on transport or assembly and stabilization of MCU. MICU3 likely has a role in mitochondrial calcium handling. All members in this family contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


Pssm-ID: 320080 [Multi-domain]  Cd Length: 152  Bit Score: 39.90  E-value: 4.80e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  23 DGNGTIDFPEFLTMMARKMKDTDseeEIREAFRvFDKDGNGYISAAELRHVM-TNLGEKLTDEEVDEMIREADIDGDGQV 101
Cdd:cd15900    64 DGKQKLSIEKFLEFQENLQEEID---DVDTALT-FYHLAGASIDRKTFKRAAkVVAGVELSDHVVDVVFTIFDEDGDGIL 139

                  ....*....
gi 1050115333 102 NYEEFVQMM 110
Cdd:cd15900   140 SHKEFISVM 148
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
50-108 4.99e-05

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 320035 [Multi-domain]  Cd Length: 141  Bit Score: 39.67  E-value: 4.99e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  50 IREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADID-GDGQVNYEEFVQ 108
Cdd:cd16205     2 LKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDdNQGTLDFEEFCA 61
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
54-106 7.29e-05

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination.


Pssm-ID: 320058 [Multi-domain]  Cd Length: 165  Bit Score: 39.55  E-value: 7.29e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1050115333  54 FRVFDKDGNGYISAAELRHVMTNlG--EKLTDEEVDEMIREADIDGDGQVNYEEF 106
Cdd:cd16183     6 FQRVDKDRSGQISATELQQALSN-GtwTPFNPETVRLMIGMFDRDNSGTINFQEF 59
EFh_PI-PLCeta1 cd16220
EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...
50-113 8.36e-05

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, or phospholipase C-eta-1 (PLC-eta-1), or phospholipase C-like protein 3 (PLC-L3), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the zona incerta and in the spinal cord. PI-PLC-eta1 may perform a fundamental role in the brain. It may also act in synergy with other PLC subtypes. For instance, it is activated via intracellular Ca2+ mobilization and then plays a role in the amplification of GPCR (G-protein-coupled receptor)-mediated PLC-beta signals. In addition, its activity can be stimulated by ionomycin. PI-PLC-eta1 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320050 [Multi-domain]  Cd Length: 141  Bit Score: 39.24  E-value: 8.36e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1050115333  50 IREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGD-GQVNYEEFV---QMMTAK 113
Cdd:cd16220     2 VKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENqGTLTFEEFCvfyKMMSLR 69
S-100 cd00213
S-100: S-100 domain, which represents the largest family within the superfamily of proteins ...
58-110 9.23e-05

S-100: S-100 domain, which represents the largest family within the superfamily of proteins carrying the Ca-binding EF-hand motif. Note that this S-100 hierarchy contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100 proteins are expressed exclusively in vertebrates, and are implicated in intracellular and extracellular regulatory activities. Intracellularly, S100 proteins act as Ca-signaling or Ca-buffering proteins. The most unusual characteristic of certain S100 proteins is their occurrence in extracellular space, where they act in a cytokine-like manner through RAGE, the receptor for advanced glycation products. Structural data suggest that many S100 members exist within cells as homo- or heterodimers and even oligomers; oligomerization contributes to their functional diversification. Upon binding calcium, most S100 proteins change conformation to a more open structure exposing a hydrophobic cleft. This hydrophobic surface represents the interaction site of S100 proteins with their target proteins. There is experimental evidence showing that many S100 proteins have multiple binding partners with diverse mode of interaction with different targets. In addition to S100 proteins (such as S100A1,-3,-4,-6,-7,-10,-11,and -13), this group includes the ''fused'' gene family, a group of calcium binding S100-related proteins. The ''fused'' gene family includes multifunctional epidermal differentiation proteins - profilaggrin, trichohyalin, repetin, hornerin, and cornulin; functionally these proteins are associated with keratin intermediate filaments and partially crosslinked to the cell envelope. These ''fused'' gene proteins contain N-terminal sequence with two Ca-binding EF-hands motif, which may be associated with calcium signaling in epidermal cells and autoprocessing in a calcium-dependent manner. In contrast to S100 proteins, "fused" gene family proteins contain an extraordinary high number of almost perfect peptide repeats with regular array of polar and charged residues similar to many known cell envelope proteins.


Pssm-ID: 238131 [Multi-domain]  Cd Length: 88  Bit Score: 38.24  E-value: 9.23e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1050115333  58 DKDGNGY-ISAAELRHVMTN-----LGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMM 110
Cdd:cd00213    19 GKEGDKDtLSKKELKELLETelpnfLKNQKDPEAVDKIMKDLDVNKDGKVDFQEFLVLI 77
EFh_HEF_SCGN cd16178
EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand ...
32-105 9.25e-05

EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a calcium sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. It also serves as a calcium buffer in neurons. Thus, SCGN may be linked to the pathogenesis of neurological diseases such as Alzheimer's, and also acts as a serum marker of neuronal damage, or as a tumor biomarker. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. All six EF hand motifs of SCGN in some eukaryotes, including D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, could potentially bind six calcium ions. In contrast, SCGNs from higher eukaryotes have at least one non-functional EF-hand motif due to the mutation(s) or deletions. For instance, the EF1 loop does not coordinate calcium ion due to the key residue asparagine replaced by lysine in SCGNs of many mammalian species. Moreover, the EF2 loop seems to be competent for calcium-binding in most mammalian SCGNs except for human and chimpanzee orthologs.


Pssm-ID: 320078 [Multi-domain]  Cd Length: 257  Bit Score: 39.69  E-value: 9.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  32 EFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNL----GEKLTDEEVDE----MIREADIDGDGQVNY 103
Cdd:cd16178    76 ENFLLFFRREEPLDSSVEFMRIWRKYDADSSGYISAAELKNFLRDLflqhKKVITEDKLDEytdtMMKIFDKNKDGRLDL 155

                  ..
gi 1050115333 104 EE 105
Cdd:cd16178   156 ND 157
EF-hand_7 pfam13499
EF-hand domain pair;
3-37 1.07e-04

EF-hand domain pair;


Pssm-ID: 433258 [Multi-domain]  Cd Length: 67  Bit Score: 37.62  E-value: 1.07e-04
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1050115333   3 SLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMM 37
Cdd:pfam13499  32 EEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
51-113 1.40e-04

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 38.76  E-value: 1.40e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050115333  51 REAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGD-GQVNYEEFV---QMMTAK 113
Cdd:cd16221     3 KQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNqGTLGFEEFCafyKMMSTR 69
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
12-39 1.44e-04

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 36.22  E-value: 1.44e-04
                          10        20
                  ....*....|....*....|....*...
gi 1050115333  12 ELQDMINEVDADGNGTIDFPEFLTMMAR 39
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKK 28
EF-hand_11 pfam08976
EF-hand domain; This domain is found predominantly in DJ binding proteins.
36-113 2.55e-04

EF-hand domain; This domain is found predominantly in DJ binding proteins.


Pssm-ID: 401068  Cd Length: 105  Bit Score: 37.39  E-value: 2.55e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1050115333  36 MMARKMKDTDSE-EEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:pfam08976   7 ILARLHKAVASHyHAITQEFENFDTLKSNTISRDEFRAICNRHIQILTDEQFDRLWNELPVNAKGRLKYPDFLSKFSIE 85
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
52-110 2.60e-04

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 38.49  E-value: 2.60e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1050115333  52 EAFRVFDKDGNGYISAAEL----RHVMTNL-GEKLTDEEVDEMIRE----ADIDGDGQVNYEEFVQMM 110
Cdd:cd15902     3 EVWMHFDADGNGYIEGKELdsflRELLKALnGKDKTDDEVAEKKKEfmekYDENEDGKIEIRELANIL 70
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
2-113 2.68e-04

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that ScPlc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like SCPlc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 320037 [Multi-domain]  Cd Length: 142  Bit Score: 37.61  E-value: 2.68e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   2 RSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARkMKDtdsEEEIREAFRVFDKDGNGYISAAELRHVMTNL-GEK 80
Cdd:cd16207    29 RRLHINCSESYLRELFDKADTDKKGYLNFEEFQEFVKL-LKR---RKDIKAIFKQLTKPGSDGLTLEEFLKFLRDVqKED 104
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1050115333  81 LTDEEVDEM----IREADIDGDGQVNYEEFVQMMTAK 113
Cdd:cd16207   105 VDRETWEKIfekfARRIDDSDSLTMTLEGFTSFLLSS 141
EFh_PEF_sorcin cd16187
Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2 ...
16-107 3.63e-04

Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. The up-regulation of sorcin is correlated with a number of cancer types, including colorectal, gastric and breast cancer. It may represent a therapeutic target for reversing tumor multidrug resistance (MDR). Sorcin participates in the regulation of calcium homeostasis in cells and is necessary for the activation of mitosis and cytokinesis. It enhances metastasis and promotes epithelial-to-mesenchymal transition of colorectal cancer. Moreover, sorcin has been implicated in the regulation of intracellular Ca2+ cycling and cardiac excitation-contraction coupling. It displays the anti-apoptotic properties via the modulation of mitochondrial Ca2+ handling in cardiac myocytes. It can target and activate the sarcolemmal Na+/Ca2+ exchanger (NCX1) in cardiac muscle. Meanwhile, sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit. It also associates with calcium/calmodulin-dependent protein kinase IIdeltaC (CaMKIIdelta(C)) and further modulates ryanodine receptor (RyR) function in cardiac myocytes. Furthermore, sorcin may act as a Ca2+ sensor for glucose-induced nuclear translocation and the activation of carbohydrate-responsive element-binding protein (ChREBP)-dependent genes. As a mitochondrial chaperone TRAP1 interactor, sorcin involves in mitochondrial metabolism through the TRAP1 pathway. In addition, sorcin may regulate the inhibition of type I interferon response in cells through interacting with foot-and-mouth disease virus (FMDV) VP1. Sorcin contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH.


Pssm-ID: 320062 [Multi-domain]  Cd Length: 165  Bit Score: 37.58  E-value: 3.63e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  16 MINEVDADGNGTIDFPEFLTMMArkmkdtdSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADI 95
Cdd:cd16187    45 MISMLDRDMSGTMGFNEFKELWA-------VLNGWRQHFISFDSDRSGTVDPQELQKALTTMGFRLSPQAVNSIAKRYST 117
                          90
                  ....*....|..
gi 1050115333  96 dgDGQVNYEEFV 107
Cdd:cd16187   118 --NGKITFDDYI 127
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
1-43 3.79e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 227455 [Multi-domain]  Cd Length: 160  Bit Score: 37.67  E-value: 3.79e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1050115333   1 MRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKD 43
Cdd:COG5126   118 LKSLGERLSDEEVEKLLKEYDEDGDGEIDYEEFKKLIKDSPTI 160
EF-hand_5 pfam13202
EF hand;
50-74 7.10e-04

EF hand;


Pssm-ID: 433035 [Multi-domain]  Cd Length: 25  Bit Score: 34.22  E-value: 7.10e-04
                          10        20
                  ....*....|....*....|....*
gi 1050115333  50 IREAFRVFDKDGNGYISAAELRHVM 74
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRRLL 25
EF-hand_8 pfam13833
EF-hand domain pair;
1-39 7.22e-04

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 34.98  E-value: 7.22e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1050115333   1 MRSLG-QNPTEAELQDMINEVDADGNGTIDFPEFLTMMAR 39
Cdd:pfam13833  14 LALLGlKDLSEDEVDILFREFDTDGDGYISFDEFCVLLER 53
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
54-106 9.15e-04

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.


Pssm-ID: 320059 [Multi-domain]  Cd Length: 165  Bit Score: 36.47  E-value: 9.15e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1050115333  54 FRVFDKDGNGYISAAELRHVMTNL-GEKLTDEEVDEMIREADIDGDGQVNYEEF 106
Cdd:cd16184     6 FQAVDRDRSGKISAKELQQALVNGnWSHFNDETCRLMIGMFDKDKSGTIDIYEF 59
EF-hand_8 pfam13833
EF-hand domain pair;
24-77 1.44e-03

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 34.21  E-value: 1.44e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1050115333  24 GNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNL 77
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54
EFhand_Ca_insen pfam08726
Ca2+ insensitive EF hand; EF hands are helix-loop-helix binding motifs involved in the ...
43-110 1.51e-03

Ca2+ insensitive EF hand; EF hands are helix-loop-helix binding motifs involved in the regulation of many cellular processes. EF hands usually bind to Ca2+ ions which causes a major conformational change that allows the protein to interact with its designated targets. This domain corresponds to an EF hand which has partially or entirely lost its calcium-binding properties. The calcium insensitive EF hand is still able to mediate protein-protein recognition.


Pssm-ID: 430177  Cd Length: 69  Bit Score: 34.60  E-value: 1.51e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050115333  43 DTDSEEEIREAFRVFdKDGNGYISAAELRHvmtNLGEKLTDEEVDEMIREADIDGD---GQVNYEEFVQMM 110
Cdd:pfam08726   1 DTDTAEQVEASFRAL-AGGKPYVTEEDLRR---ELTPDQAEYCIARMPPYSGPDGDsvpGAYDYVSFSEAL 67
EF-hand_4 pfam12763
Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin ...
47-110 1.53e-03

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.


Pssm-ID: 289529  Cd Length: 104  Bit Score: 35.04  E-value: 1.53e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1050115333  47 EEEIREAFRVFD--KDGNGYISAAELRHVMTNlgEKLTDEEVDEMIREADIDGDGQVNYEEFVQMM 110
Cdd:pfam12763   6 EWEIKKYWEIFSglKPENNKLTGDQVSPVLKN--SRLPDDQLAKIWDLADIDSDGKLDFEEFCIAM 69
EFh_CREC_RCN3 cd16230
EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand ...
4-110 1.73e-03

EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand calcium-binding protein RLP49, is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal His-Asp-Glu-Leu (HDEL) tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320028 [Multi-domain]  Cd Length: 268  Bit Score: 36.11  E-value: 1.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   4 LGQNPTEAELQDMINEVD--ADGNGTIDFPEFLTMMARKMKDTdSEEEIREAFRVFDKDGNGYISAAELRHVMTNL---G 78
Cdd:cd16230    28 LSPEESQARLGRIVDRMDraGDGDGWVSLAELRAWIAHTQQRH-IRDSVSAAWQTYDTDRDGRVGWEELRNATYGHyepG 106
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1050115333  79 EKLTDEEVDEMIRE-----------ADIDGDGQVNYEEFVQMM 110
Cdd:cd16230   107 EEFHDVEDAETYKKmlarderrfrvADQDGDSMATREELTAFL 149
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
4-106 2.45e-03

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 35.88  E-value: 2.45e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   4 LGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTdSEEEIREAFRVFDKDGNGYISAAELRHVMtnLGEKLTD 83
Cdd:cd15899    28 LTPEESKRRLGVIVSKMDVDKDGFISAKELHSWILESFKRH-AMEESKEQFRAVDPDEDGHVSWDEYKNDT--YGSVGDD 104
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1050115333  84 EEVD------------------EMIREADIDGDGQVNYEEF 106
Cdd:cd15899   105 EENVadnikedeeykklllkdkKRFEAADQDGDLILTLEEF 145
EFh_PEF_CAPN1 cd16198
Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1); CAPN1, also termed ...
16-107 2.59e-03

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1); CAPN1, also termed calpain-1 80-kDa catalytic subunit, or calpain-1 large subunit, or micromolar-calpain (muCANP), or calcium-activated neutral proteinase 1 (CANP 1), or cell proliferation-inducing gene 30 protein, is a ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine protease that contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The catalytic subunit CAPN1 in complex with a regulatory subunit encoded by CAPNS1 forms a mu-calpain heterodimer. CAPN1 plays a central role in postmortem proteolysis and meat tenderization processes, as well as in regulation of proliferation and survival of skeletal satellite cells. It also acts as a novel regulator in IgE-mediated mast cell activation and could serve as a potential therapeutic target for the management of allergic inflammation. Moreover, CAPN1 is involved in neutrophil motility and functions as a potential target for intervention in inflammatory disease. It also facilitates age-associated aortic wall calcification and fibrosis through the regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells, and thus plays a role in hypertension and atherosclerosis. The proteolytic cleavage of beta-amyloid precursor protein and tau protein by CAPN1 may be involved in plaque formation. Furthermore, CAPN1 is activated in the brains of individuals with Alzheimer's disease. It is involved in the maintenance of a proliferative neural stem cell pool. The activation and macrophage inflammation of CAPN1 in hypercholesterolemic nephropathy is promoted by nicotinic acetylcholine receptor alpha1 (nAChRalpha1). In addition, CAPN1 displays a functional role in hemostasis, as well as in sickle cell disease.


Pssm-ID: 320073 [Multi-domain]  Cd Length: 169  Bit Score: 35.55  E-value: 2.59e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  16 MINEVDADGNGTIDFPEFLTMMARkmkdtdseeeIRE---AFRVFDKDGNGYISAAELRHVMTNLGEKLTDeEVDEMIRE 92
Cdd:cd16198    48 MVNLMDKDGNGKLGLVEFNILWNK----------IRNyltIFRKFDLDKSGSMSAYEMRLALESAGFKLNN-RLHQVIVA 116
                          90
                  ....*....|....*
gi 1050115333  93 ADIDGDGQVNYEEFV 107
Cdd:cd16198   117 RYADPNLAIDFDNFV 131
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
49-106 4.27e-03

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.


Pssm-ID: 320054 [Multi-domain]  Cd Length: 165  Bit Score: 34.71  E-value: 4.27e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1050115333  49 EIREAFRVFDKDgNGYISAAELRHVMTNLGEKLTD-----EEVDEMIREADIDGDGQVNYEEF 106
Cdd:cd15897     1 QLRNVFQAVAGD-DGEISATELQQALSNVGWTHFDlgfslETCRSMIAMMDRDHSGKLNFSEF 62
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
9-113 4.76e-03

EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and similar proteins; CBN, the product of the cbn gene, is a Drosophila homolog to vertebrate neuronal six EF-hand calcium binding proteins. It is expressed through most of ontogenesis with a selective distribution in the nervous system and in a few small adult thoracic muscles. Its precise biological role remains unclear. CBN contains six EF-hand motifs, but some of them may not bind calcium ions due to the lack of key residues.


Pssm-ID: 320079 [Multi-domain]  Cd Length: 261  Bit Score: 35.08  E-value: 4.76e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   9 TEAELQDMINEV----DADGNGTIDFPE----------FLTMMARKMKdTDSEEEIREAFRVFDKDGNGYISAAELRHVM 74
Cdd:cd16179    43 SETALEELKEEFmeayDENQDGRIDIRElaqllpteenFLLLFRRDNP-LDSSVEFMKVWREYDKDNSGYIEADELKNFL 121
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1050115333  75 TNL-----------GEKLTdEEVDEMIREADIDGDGQVNYEEFVQMMTAK 113
Cdd:cd16179   122 KHLlkeakrdndvsEDKLI-EYTDTILQLFDRNKDGKLQLSEMARLLPVK 170
EFh_PEF_CAPN1_like cd16189
Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1), m-type calpain (CAPN2) ...
14-107 5.10e-03

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1), m-type calpain (CAPN2), and similar proteins; The family includes mu-type calpain (CAPN1) and m-type calpain (CAPN2), both of which are ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine proteases that contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The catalytic subunit CAPN1 or CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms a mu- or m-calpain heterodimer, respectively.


Pssm-ID: 320064 [Multi-domain]  Cd Length: 168  Bit Score: 34.64  E-value: 5.10e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  14 QDMINEVDADGNGTIDFPEFLTMMARKMKdtdseeeIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDeEVDEMIREA 93
Cdd:cd16189    46 RNMVNLLDKDGSGKLGLVEFQILWTKIQK-------YLKIYKKFDTDGSGTMSSYEMRLALEEAGFKLNN-QLHQVLVAR 117
                          90
                  ....*....|....
gi 1050115333  94 DIDGDGQVNYEEFV 107
Cdd:cd16189   118 YADQELTIDFDNFV 131
EFh_CREC_cab45 cd16225
EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also ...
14-105 5.64e-03

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.


Pssm-ID: 320023 [Multi-domain]  Cd Length: 278  Bit Score: 34.58  E-value: 5.64e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  14 QDMINEVDADGNGTIDFPEFLTMMAR------KMKDTDSEEEIREAFR-VFDKDGNGYISAAELRHVMTNLGEKLTDEEV 86
Cdd:cd16225   171 KEILHDLDQDGDEKLTLDEFVSLPPGtveeqqAEDDDEWKKERKKEFEeVIDLNHDGKVTKEELEEYMDPRNERHALNEA 250
                          90
                  ....*....|....*....
gi 1050115333  87 DEMIREADIDGDGQVNYEE 105
Cdd:cd16225   251 KQLIAVADENKDGKLSLEE 269
EFh_PEF_CAPN8 cd16191
Penta-EF hand, calcium binding motifs, found in calpain-8 (CAPN8); CAPN8, also termed new ...
14-110 7.70e-03

Penta-EF hand, calcium binding motifs, found in calpain-8 (CAPN8); CAPN8, also termed new calpain 2 (nCL-2), or stomach-specific M-type calpain, is a calpain large subunit predominantly expressed in the stomach. It appears to be involved in membrane trafficking in the gastric surface mucus cells (pit cells), via its location at the Golgi and interaction with the beta-subunit of coatomer complex (beta-COP) of vesicles derived from the Golgi. Moreover, CAPN8, together with CAPN9, forms an active protease complex, G-calpain, in which both proteins are essential for stability and activity. The G-Calpain has been implicated in gastric mucosal defense. CAPN8 exists as both a monomer and homo-oligomer, but not as a heterodimer with the conventional calpain regulatory subunit (30K). The monomer and homodimer forms predominate. CAPN8 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320066 [Multi-domain]  Cd Length: 168  Bit Score: 33.99  E-value: 7.70e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  14 QDMINEVDADGNGTIDFPEFLTMMARKMKdtdseeeIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDeEVDEMIREA 93
Cdd:cd16191    46 REMISLLDTDGTGTLGLVEFRILWMKIQK-------YLAIYKKVDSDRSGTIDAHEMRNALQEAGFTLNN-KIQQSIVQR 117
                          90
                  ....*....|....*..
gi 1050115333  94 DIDGDGQVNYEEFVQMM 110
Cdd:cd16191   118 YASNKLTINFDGFIACM 134
EFh_CREC_RCN3 cd16230
EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand ...
21-106 8.13e-03

EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand calcium-binding protein RLP49, is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal His-Asp-Glu-Leu (HDEL) tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320028 [Multi-domain]  Cd Length: 268  Bit Score: 34.18  E-value: 8.13e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  21 DADGNGTIDFPEFL-TMMARKMKDTDSEEEIREAFRVFDK-----DGNGYISAAELRHVMTNLGEKLTDEEVDEMIREAD 94
Cdd:cd16230     4 DAHGNFQYDHEAFLgREVAKEFDQLSPEESQARLGRIVDRmdragDGDGWVSLAELRAWIAHTQQRHIRDSVSAAWQTYD 83
                          90
                  ....*....|..
gi 1050115333  95 IDGDGQVNYEEF 106
Cdd:cd16230    84 TDRDGRVGWEEL 95
EFh_HEF_CB cd16176
EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or ...
33-110 8.94e-03

EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or D-28K, or avian-type vitamin D-dependent calcium-binding protein, is a unique intracellular calcium binding protein that functions as both a calcium sensor and buffer in eukaryotic cells, which undergoes a conformational change upon calcium binding and protects cells against insults of high intracellular calcium concentration. CB is highly expressed in brain and sensory neurons. It plays essential roles in neural functioning, altering synaptic interactions in the hippocampus, modulating calcium channel activity, calcium transients, and intrinsic neuronal firing activity. It prevents a neuronal death, as well as maintains and controls calcium homeostasis. CB also modulates the activity of proteins participating in the development of neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and bipolar disorder. Moreover, CB interacts with Ran-binding protein M, a protein known to involve in microtubule function. It also interacts with alkaline phosphatase and myo-inositol monophosphatase, as well as caspase 3, an enzyme that plays an important role in the regulation of apoptosis. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions with high affinity.


Pssm-ID: 320076 [Multi-domain]  Cd Length: 243  Bit Score: 34.04  E-value: 8.94e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333  33 FLTMMARKMKdtdSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLT--------DEEVDEMIREADIDGDGQVNYE 104
Cdd:cd16176    73 FLLFFRQQLK---SSEEFMQTWRKYDADHSGFIEADELKSFLKDLLKKANkpfdesklEEYTHTMLKMFDSNNDGKLGLT 149

                  ....*.
gi 1050115333 105 EFVQMM 110
Cdd:cd16176   150 EMARLL 155
EFh_HEF_CR cd16177
EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is ...
2-110 9.21e-03

EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t specific neurons of the central and peripheral nervous system. It possibly functions as a calcium buffer, calcium sensor, and apoptosis regulator, which may be implicated in many biological processes, including cell proliferation, differentiation, and cell death. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. CR I-II consists of EF-hand motifs 1 and 2, and CR III-VI consists of EF-hand motifs 3-6. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. Thus, CR has two pairs of cooperative binding sites (I-II and III-IV), which display high affinity calcium-binding sites, and one independent calcium ion-binding site (V), which displays lower affinity binding.


Pssm-ID: 320077 [Multi-domain]  Cd Length: 248  Bit Score: 34.08  E-value: 9.21e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050115333   2 RSLGQNPTEAELQDMINEV----DADGNGTIDFPEFLTMMARK-------MKDTDSEEEIREAFRVFDKDGNGYISAAEL 70
Cdd:cd16177    33 RGAGVDSKSANFGEKMKEFmqkyDKNADGRIEMAELAQILPTEenfllcfRQHVGSSSEFMEAWRKYDTDRSGYIEANEL 112
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1050115333  71 RHVMTNL--------GEKLTDEEVDEMIREADIDGDGQVNYEEFVQMM 110
Cdd:cd16177   113 KGFLSDLlkkanrpyDEKKLQEYTQTILRMFDLNGDGKLGLSEMARLL 160
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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