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Conserved domains on  [gi|1034558029|ref|XP_016856607|]
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neuron-specific calcium-binding protein hippocalcin isoform X1 [Homo sapiens]

Protein Classification

EF-hand domain-containing protein( domain architecture ID 11473824)

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

Gene Ontology:  GO:0005509
PubMed:  2479149

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
41-175 7.25e-19

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


:

Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 78.68  E-value: 7.25e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  41 GILNVDEFKKIYANFFpygdaskfaEHVFRTFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREE 120
Cdd:COG5126    20 GVLERDDFEALFRRLW---------ATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADE 90
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034558029 121 mleivqaiYKMVSSVMKMPEDEstpekrTEKIFRQMDTNNDGKLSLEEFIRGAKS 175
Cdd:COG5126    91 --------FRRLLTALGVSEEE------ADELFARLDTDGDGKISFEEFVAAVRD 131
 
Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
41-175 7.25e-19

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 78.68  E-value: 7.25e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  41 GILNVDEFKKIYANFFpygdaskfaEHVFRTFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREE 120
Cdd:COG5126    20 GVLERDDFEALFRRLW---------ATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADE 90
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034558029 121 mleivqaiYKMVSSVMKMPEDEstpekrTEKIFRQMDTNNDGKLSLEEFIRGAKS 175
Cdd:COG5126    91 --------FRRLLTALGVSEEE------ADELFARLDTDGDGKISFEEFVAAVRD 131
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
100-174 7.57e-17

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: 71.04  E-value: 7.57e-17
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034558029 100 KLMWAFSMYDLDGNGYISREEMLEIVQAIYkmvssvmkmpedESTPEKRTEKIFRQMDTNNDGKLSLEEFIRGAK 174
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLG------------EGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
98-174 1.52e-12

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 59.96  E-value: 1.52e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034558029  98 EQKLMWAFSMYDLDGNGYISREEMLEIVQAIYkmvssvmkmpEDESTPEKRTEKIFRQMDTNNDGKLSLEEFIRGAK 174
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLE----------EGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
63-178 3.15e-11

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 60.08  E-value: 3.15e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  63 KFAEHVFRTFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREEMleivqaiykmvSSVMKMP--- 139
Cdd:NF041410   27 QFQKQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDEL-----------AAAAPPPppp 95
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1034558029 140 EDESTPEKRTEKIFRQMDTNNDGKLSLEEFIRGAKSDPS 178
Cdd:NF041410   96 PDQAPSTELADDLLSALDTDGDGSISSDELSAGLTSAGS 134
PTZ00184 PTZ00184
calmodulin; Provisional
73-171 6.02e-11

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 57.85  E-value: 6.02e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  73 DTNSDGTIDFREFIIALSVTSR-GRLEQKLMWAFSMYDLDGNGYISREEMLEIvqaiykMVSSVMKMPEDEstpekrTEK 151
Cdd:PTZ00184   57 DADGNGTIDFPEFLTLMARKMKdTDSEEEIKEAFKVFDRDGNGFISAAELRHV------MTNLGEKLTDEE------VDE 124
                          90       100
                  ....*....|....*....|
gi 1034558029 152 IFRQMDTNNDGKLSLEEFIR 171
Cdd:PTZ00184  125 MIREADVDGDGQINYEEFVK 144
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
100-128 1.58e-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: 40.44  E-value: 1.58e-05
                           10        20
                   ....*....|....*....|....*....
gi 1034558029  100 KLMWAFSMYDLDGNGYISREEMLEIVQAI 128
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
41-175 7.25e-19

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 78.68  E-value: 7.25e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  41 GILNVDEFKKIYANFFpygdaskfaEHVFRTFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREE 120
Cdd:COG5126    20 GVLERDDFEALFRRLW---------ATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADE 90
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034558029 121 mleivqaiYKMVSSVMKMPEDEstpekrTEKIFRQMDTNNDGKLSLEEFIRGAKS 175
Cdd:COG5126    91 --------FRRLLTALGVSEEE------ADELFARLDTDGDGKISFEEFVAAVRD 131
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
100-174 7.57e-17

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: 71.04  E-value: 7.57e-17
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034558029 100 KLMWAFSMYDLDGNGYISREEMLEIVQAIYkmvssvmkmpedESTPEKRTEKIFRQMDTNNDGKLSLEEFIRGAK 174
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLG------------EGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
65-126 2.58e-16

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: 69.50  E-value: 2.58e-16
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034558029  65 AEHVFRTFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREEMLEIVQ 126
Cdd:cd00051     2 LREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
98-174 1.52e-12

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 59.96  E-value: 1.52e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034558029  98 EQKLMWAFSMYDLDGNGYISREEMLEIVQAIYkmvssvmkmpEDESTPEKRTEKIFRQMDTNNDGKLSLEEFIRGAK 174
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLE----------EGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
21-129 4.32e-12

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 60.58  E-value: 4.32e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  21 EFSELELQEWYKGFLKDCP--TGILNVDEFKKIYANFFPYGDAsKFAEHVFRTFDTNSDGTIDFREFIIALSV--TSRGR 96
Cdd:COG5126    26 DFEALFRRLWATLFSEADTdgDGRISREEFVAGMESLFEATVE-PFARAAFDLLDTDGDGKISADEFRRLLTAlgVSEEE 104
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1034558029  97 LEQklmwAFSMYDLDGNGYISREEMLEIVQAIY 129
Cdd:COG5126   105 ADE----LFARLDTDGDGKISFEEFVAAVRDYY 133
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
63-178 3.15e-11

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 60.08  E-value: 3.15e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  63 KFAEHVFRTFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREEMleivqaiykmvSSVMKMP--- 139
Cdd:NF041410   27 QFQKQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDEL-----------AAAAPPPppp 95
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1034558029 140 EDESTPEKRTEKIFRQMDTNNDGKLSLEEFIRGAKSDPS 178
Cdd:NF041410   96 PDQAPSTELADDLLSALDTDGDGSISSDELSAGLTSAGS 134
PTZ00184 PTZ00184
calmodulin; Provisional
73-171 6.02e-11

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 57.85  E-value: 6.02e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  73 DTNSDGTIDFREFIIALSVTSR-GRLEQKLMWAFSMYDLDGNGYISREEMLEIvqaiykMVSSVMKMPEDEstpekrTEK 151
Cdd:PTZ00184   57 DADGNGTIDFPEFLTLMARKMKdTDSEEEIKEAFKVFDRDGNGFISAAELRHV------MTNLGEKLTDEE------VDE 124
                          90       100
                  ....*....|....*....|
gi 1034558029 152 IFRQMDTNNDGKLSLEEFIR 171
Cdd:PTZ00184  125 MIREADVDGDGQINYEEFVK 144
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
98-171 4.51e-10

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 55.18  E-value: 4.51e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  98 EQKLMWAFSMYDLDGNGYISREEMLEIVQAIYKMVSSVM------KMPEDE----------STPEKRTEKIFRQMDTNND 161
Cdd:COG5126     4 RRKLDRRFDLLDADGDGVLERDDFEALFRRLWATLFSEAdtdgdgRISREEfvagmeslfeATVEPFARAAFDLLDTDGD 83
                          90
                  ....*....|
gi 1034558029 162 GKLSLEEFIR 171
Cdd:COG5126    84 GKISADEFRR 93
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
41-170 1.59e-07

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: 50.01  E-value: 1.59e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  41 GILNVDEFKKIYAnffPYGDASKFA---EHVFRTFDTNSDGTIDFREFI--IALSVTSRGRLEQKLMWAFSmYDLDGNGY 115
Cdd:cd16227   137 GKLDKTEFSAFQH---PEEYPHMHPvliEQTLRDKDKDNDGFISFQEFLgdRAGHEDKEWLLVEKDRFDED-YDKDGDGK 212
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034558029 116 ISREEMLEIVqaiykmvssvmkMPEDESTPEKRTEKIFRQMDTNNDGKLSLEEFI 170
Cdd:cd16227   213 LDGEEILSWL------------VPDNEEIAEEEVDHLFASADDDHDDRLSFDEIL 255
EF-hand_7 pfam13499
EF-hand domain pair;
68-126 1.17e-06

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 44.17  E-value: 1.17e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034558029  68 VFRTFDTNSDGTIDFREFIIALSVTSRGR--LEQKLMWAFSMYDLDGNGYISREEMLEIVQ 126
Cdd:pfam13499   7 AFKLLDSDGDGYLDVEELKKLLRKLEEGEplSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
26-171 2.24e-06

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: 45.67  E-value: 2.24e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  26 ELQEWYKGFLKDCpTGILNVDEFKKIYAN---FFPYGDASKFaehvFRTFDTNSDGTIDFREFIialsvtsrgRLEQKLM 102
Cdd:cd16185     1 ELRQWFRAVDRDR-SGSIDVNELQKALAGgglLFSLATAEKL----IRMFDRDGNGTIDFEEFA---------ALHQFLS 66
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034558029 103 ---WAFSMYDLDGNGYISREEMLEIVQAI-YKMVSSVMKmpedestpekrteKIFRQMDTNNDGKLSLEEFIR 171
Cdd:cd16185    67 nmqNGFEQRDTSRSGRLDANEVHEALAASgFQLDPPAFQ-------------ALFRKFDPDRGGSLGFDDYIE 126
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
72-171 5.14e-06

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: 45.42  E-value: 5.14e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  72 FDTNSDGTIDFRE----------FIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREEMleivQAIYKMVSSVMKMPED 141
Cdd:cd15902    53 YDENEDGKIEIRElanilpteenFLLLFRREQPLISSVEFMKIWRKYDTDGSGFIEAKEL----KGFLKDLLLKNKKHVS 128
                          90       100       110
                  ....*....|....*....|....*....|
gi 1034558029 142 ESTPEKRTEKIFRQMDTNNDGKLSLEEFIR 171
Cdd:cd15902   129 PPKLDEYTKLILKEFDANKDGKLELDEMAK 158
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
17-168 1.03e-05

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: 44.71  E-value: 1.03e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  17 RENTEFSELELQEWYKGFLKDCpTGILNVDEFKKIYANFFPYGDASK---------FAEHVFRTFDTNSDGTIDFRE--- 84
Cdd:cd16179    87 RDNPLDSSVEFMKVWREYDKDN-SGYIEADELKNFLKHLLKEAKRDNdvsedklieYTDTILQLFDRNKDGKLQLSEmar 165
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  85 -------FIIALSVTSRGRLEQK-LMWAFSMYDLDGNGYISREEM-------LEIVQAIYkmvssvmkmpeDESTPEKRT 149
Cdd:cd16179   166 llpvkenFLCRPIFKGAGKLTREdIDRVFALYDRDNNGTIENEELtgflkdlLELVQEDY-----------DEQDLEEFK 234
                         170
                  ....*....|....*....
gi 1034558029 150 EKIFRQMDTNNDGKLSLEE 168
Cdd:cd16179   235 EIILRGWDFNNDGKISRKE 253
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
100-128 1.58e-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: 40.44  E-value: 1.58e-05
                           10        20
                   ....*....|....*....|....*....
gi 1034558029  100 KLMWAFSMYDLDGNGYISREEMLEIVQAI 128
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
40-170 1.58e-05

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: 43.29  E-value: 1.58e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  40 TGILNVDEFKKIYanffpygdasKFAE---HVFRTFDTNSDGTIDFREFIIALsvTSRG-RL-EQKLMWAFSMYDLDGNG 114
Cdd:cd16180    51 SGTINFDEFVGLW----------KYIQdwrRLFRRFDRDRSGSIDFNELQNAL--SSFGyRLsPQFVQLLVRKFDRRRRG 118
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034558029 115 YISREEMLEIvqaiykmVSSVMKMpedestpekrTEKiFRQMDTNNDGK--LSLEEFI 170
Cdd:cd16180   119 SISFDDFVEA-------CVTLKRL----------TDA-FRKYDTNRTGYatISYEDFL 158
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
105-170 1.80e-05

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: 41.05  E-value: 1.80e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034558029 105 FSMYDLDGNGYISREEMLEIvqaiykMVSSvmKMPEDEstpekrTEKIFRQMDTNNDGKLSLEEFI 170
Cdd:cd00052     5 FRSLDPDGDGLISGDEARPF------LGKS--GLPRSV------LAQIWDLADTDKDGKLDKEEFA 56
calgranulins cd05030
Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 ...
43-87 2.00e-05

Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 family of EF-hand calcium-modulated proteins, including S100A8, S100A9, and S100A12 . Note that the S-100 hierarchy, to which this Calgranulin group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. These proteins are expressed mainly in granulocytes, and are involved in inflammation, allergy, and neuritogenesis, as well as in host-parasite response. Calgranulins are modulated not only by calcium, but also by other metals such as zinc and copper. Structural data suggested that calgranulins may exist in multiple structural forms, homodimers, as well as hetero-oligomers. For example, the S100A8/S100A9 complex called calprotectin plays important roles in the regulation of inflammatory processes, wound repair, and regulating zinc-dependent enzymes as well as microbial growth.


Pssm-ID: 240156 [Multi-domain]  Cd Length: 88  Bit Score: 41.56  E-value: 2.00e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1034558029  43 LNVDEFKKIY----ANFFPYGDASKFAEHVFRTFDTNSDGTIDFREFII 87
Cdd:cd05030    27 LYKKEFKQLVekelPNFLKKEKNQKAIDKIFEDLDTNQDGQLSFEEFLV 75
EFh_HEF_CR cd16177
EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is ...
63-171 2.21e-05

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: 43.71  E-value: 2.21e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  63 KFAEHV---FRTFDTNSDGTIDFREFIIALSVTSRGRL--------EQKLMWAFSMYDLDGNGYISREEMLEIVQAIYKM 131
Cdd:cd16177    43 NFGEKMkefMQKYDKNADGRIEMAELAQILPTEENFLLcfrqhvgsSSEFMEAWRKYDTDRSGYIEANELKGFLSDLLKK 122
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1034558029 132 VSSvmkmPEDESTPEKRTEKIFRQMDTNNDGKLSLEEFIR 171
Cdd:cd16177   123 ANR----PYDEKKLQEYTQTILRMFDLNGDGKLGLSEMAR 158
EFh_HEF_CB cd16176
EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or ...
72-171 2.39e-05

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: 43.67  E-value: 2.39e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  72 FDTNSDGTIDFREFIIALSVTS------RGRLE--QKLMWAFSMYDLDGNGYISREEMLEIVQAIYKMVssvmKMPEDES 143
Cdd:cd16176    50 YGQSTDGKIGIVELAQILPTEEnfllffRQQLKssEEFMQTWRKYDADHSGFIEADELKSFLKDLLKKA----NKPFDES 125
                          90       100
                  ....*....|....*....|....*...
gi 1034558029 144 TPEKRTEKIFRQMDTNNDGKLSLEEFIR 171
Cdd:cd16176   126 KLEEYTHTMLKMFDSNNDGKLGLTEMAR 153
EFh_DMD_DYTN_DTN cd15901
EF-hand-like motif found in the dystrophin/dystrobrevin/dystrotelin family; The dystrophin ...
71-133 3.74e-05

EF-hand-like motif found in the dystrophin/dystrobrevin/dystrotelin family; The dystrophin/dystrobrevin/dystrotelin family has been characterized by a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. Dystrophin is the founder member of this family. It is a sub-membrane cytoskeletal protein associated with the inner surface membrane. Dystrophin and its close paralog utrophin have a large N-terminal extension of actin-binding CH domains, up to 24 spectrin repeats, and a WW domain. Its further paralog, dystrophin-related protein 2 (DRP-2), retains only two of the spectrin repeats. Dystrophin, utrophin or DRP2 can form the core of a membrane-bound complex consisting of dystroglycan, sarcoglycans and syntrophins, known as the dystrophin-glycoprotein complex (DGC) that plays an important role in brain development and disease, as well as in the prevention of muscle damage. Dystrobrevins, including alpha- and beta-dystrobrevin, lack the large N-terminal extension found in dystrophin, but alpha-dystrobrevin has a characteristic C-terminal extension. Dystrobrevins are part of the DGC. They physically associate with members of the dystrophin family and with the syntrophins through their homologous C-terminal coiled coil motifs. In contrast, dystrotelins lack both the large N-terminal extension found in dystrophin and the obvious syntrophin-binding sites (SBSs). Dystrotelins are not critical for mammalian development. They may be involved in other forms of cytokinesis. Moreover, dystrotelin is unable to heterodimerize with members of the dystrophin or dystrobrevin families, or to homodimerize.


Pssm-ID: 319999  Cd Length: 163  Bit Score: 42.26  E-value: 3.74e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034558029  71 TFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDlDGNGYISREEMLEIVQAIYKMVS 133
Cdd:cd15901    62 LYDRNRTGCIRLLSVKIALITLCAASLLDKYRYLFGQLA-DSSGFISRERLTQFLQDLLQIPD 123
PTZ00183 PTZ00183
centrin; Provisional
69-174 4.75e-05

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 41.98  E-value: 4.75e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  69 FRTFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREEMLEIVQAiykmvssvmKMPEDEstPEKR 148
Cdd:PTZ00183   23 FDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTK---------KLGERD--PREE 91
                          90       100
                  ....*....|....*....|....*.
gi 1034558029 149 TEKIFRQMDTNNDGKLSLEEFIRGAK 174
Cdd:PTZ00183   92 ILKAFRLFDDDKTGKISLKNLKRVAK 117
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
73-168 5.24e-05

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: 5.24e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  73 DTNSDGTIDFREFIIALsVTSRGRLEQkLMW------AFSMY-DLDGNGYISREEMLEIVqaiykmvssvmkMPEDESTP 145
Cdd:cd16226   166 DKNKDGFISLEEYIGDM-YRDDDEEED-PDWvksereQFKEFrDKNKDGKMDREEVKDWI------------LPEDYDHA 231
                          90       100
                  ....*....|....*....|...
gi 1034558029 146 EKRTEKIFRQMDTNNDGKLSLEE 168
Cdd:cd16226   232 EAEAKHLIYEADDDKDGKLTKEE 254
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
105-192 6.65e-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: 42.34  E-value: 6.65e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029 105 FSMYDLDGNGYISREEMLEIVQAIYKmvSSVMKMPEDESTPEKRTEkIFRQMDTNNDGKLSLEEFIRGAKSDPSIVRLLQ 184
Cdd:cd15902     5 WMHFDADGNGYIEGKELDSFLRELLK--ALNGKDKTDDEVAEKKKE-FMEKYDENEDGKIEIRELANILPTEENFLLLFR 81

                  ....*...
gi 1034558029 185 CDPSSASQ 192
Cdd:cd15902    82 REQPLISS 89
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
100-171 7.14e-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: 41.11  E-value: 7.14e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034558029 100 KLMWAFSMYDLDGNGYISREEMLEIVQAIykmvssvmkmpeDESTPEKRTEKIFRQMDTNNDGKLSLEEFIR 171
Cdd:cd15898     1 WLRRQWIKADKDGDGKLSLKEIKKLLKRL------------NIRVSEKELKKLFKEVDTNGDGTLTFDEFEE 60
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
26-171 7.87e-05

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: 41.36  E-value: 7.87e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  26 ELQEWYKGFLKDCpTGILNVDEFKKIYANffpyGDASKFAEHV----FRTFDTNSDGTIDFREFIialsvtsrgRLEQKL 101
Cdd:cd16180     1 ELRRIFQAVDRDR-SGRISAKELQRALSN----GDWTPFSIETvrlmINMFDRDRSGTINFDEFV---------GLWKYI 66
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034558029 102 M-W--AFSMYDLDGNGYISREEMLEIVQAI-YKMVSSVmkmpedestpekrTEKIFRQMDTNNDGKLSLEEFIR 171
Cdd:cd16180    67 QdWrrLFRRFDRDRSGSIDFNELQNALSSFgYRLSPQF-------------VQLLVRKFDRRRRGSISFDDFVE 127
PTZ00183 PTZ00183
centrin; Provisional
18-177 1.02e-04

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 40.83  E-value: 1.02e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  18 ENTEFSELELQEWYKGF-LKDCP-TGILNVDEFKkiyANFFPYGDASKfAEHVFRTF---DTNSDGTIDFREFIIALSVT 92
Cdd:PTZ00183    7 ERPGLTEDQKKEIREAFdLFDTDgSGTIDPKELK---VAMRSLGFEPK-KEEIKQMIadvDKDGSGKIDFEEFLDIMTKK 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  93 SRGR-LEQKLMWAFSMYDLDGNGYISreemleivqaiYKMVSSVMKMPEDESTPEKRTEKIFRQmDTNNDGKLSLEEFIR 171
Cdd:PTZ00183   83 LGERdPREEILKAFRLFDDDKTGKIS-----------LKNLKRVAKELGETITDEELQEMIDEA-DRNGDGEISEEEFYR 150

                  ....*.
gi 1034558029 172 GAKSDP 177
Cdd:PTZ00183  151 IMKKTN 156
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
68-169 1.66e-04

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: 41.03  E-value: 1.66e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  68 VFRTFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREEMLEIVQAIYKMVSSVMKMPEDESTPEK 147
Cdd:cd16226    40 IVDKIDKNGDGFVTEEELKDWIKYVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKATYGFLDDEEEDDDLHESYKKMIR 119
                          90       100
                  ....*....|....*....|..
gi 1034558029 148 RTEKIFRQMDTNNDGKLSLEEF 169
Cdd:cd16226   120 RDERRWKAADQDGDGKLTKEEF 141
EFh_SPARC_SMOC cd16234
EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding ...
98-169 1.94e-04

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein SMOC-1, SMOC-2, and similar proteins; SMOC proteins corresponds to a group matricellular proteins that are involved in direct or indirect modulation of growth factor signaling pathways and play diverse roles in physiological processes involving extensive tissue remodeling, migration, proliferation, and angiogenesis. They may mediate intercellular signaling and cell type-specific differentiation during gonad and reproductive tract development. SMOC-1 is localized in basement membranes. Its mutations have been found to be associated with individuals with Warrdenburg Anopthalmia Syndrome. SMOC-2 is ubiquitously expressed and is involved in angiogenesis and the regulation of cell cycle progression. It enhances the angiogenic effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). It has also been implicated in generalized vitiligo. SMOC proteins consist of a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain conserved only in SMOC proteins, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.


Pssm-ID: 320013  Cd Length: 104  Bit Score: 39.19  E-value: 1.94e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034558029  98 EQKLMWAFSMYDLDGNGYISREEmleiVQAIYKMVSSVMKmpedestPEKRTEKIFRQMDTNNDGKLSLEEF 169
Cdd:cd16234    38 EQVLDWKFSQLDKNKNGVLERKE----WKPFKRLLKKAVK-------PKKCARKFPKYCDVNKDKKISLTEW 98
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
12-168 2.30e-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: 40.80  E-value: 2.30e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  12 MLQDLRENTEFSELELQEWYKGFLKDcPTGILNVDEFKKIYANFF----PYGDASKFAEHV---FRTFDTNSDGTIDFRE 84
Cdd:cd15902    77 LLLFRREQPLISSVEFMKIWRKYDTD-GSGFIEAKELKGFLKDLLlknkKHVSPPKLDEYTkliLKEFDANKDGKLELDE 155
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  85 FIIALSVTSRGRLEQKLMW-----------AFSMYDLDGNGYISREEMLEIVQAIYKMVSSVMKMPEDestpEKRTEKIF 153
Cdd:cd15902   156 MAKLLPVQENFLLKFQILGamdltkedfekVFEHYDKDNNGVIEGNELDALLKDLLEKNKADIDKPDL----ENFRDAIL 231
                         170
                  ....*....|....*
gi 1034558029 154 RQMDTNNDGKLSLEE 168
Cdd:cd15902   232 RACDKNKDGKIQKTE 246
EFh_CREC_cab45 cd16225
EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also ...
96-169 2.84e-04

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: 40.36  E-value: 2.84e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034558029  96 RLEQKLMWAFSMYDLDGNGYISREEMLE-IVQaiykmvssvmKMPEDESTPEKRTEKIFRQMDTNNDGKLSLEEF 169
Cdd:cd16225    31 KKRKKLKEIFKKVDVNTDGFLSAEELEDwIME----------KTQEHFQEAVEENEQIFKAVDTDKDGNVSWEEY 95
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
60-171 3.63e-04

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: 40.09  E-value: 3.63e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  60 DASKFAEHVFRTFDTNSDGTIDFRE----------FIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREEMLEIVQAIY 129
Cdd:cd16179    46 ALEELKEEFMEAYDENQDGRIDIRElaqllpteenFLLLFRRDNPLDSSVEFMKVWREYDKDNSGYIEADELKNFLKHLL 125
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1034558029 130 KmvssvMKMPEDESTPEK---RTEKIFRQMDTNNDGKLSLEEFIR 171
Cdd:cd16179   126 K-----EAKRDNDVSEDKlieYTDTILQLFDRNKDGKLQLSEMAR 165
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
104-171 3.72e-04

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: 39.13  E-value: 3.72e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034558029 104 AFSMYDLDGNGYISREEMLEIVQAIYKMVSSVMKmpedeSTPEKRTEKIFRQMDT---------NNDGKLSLEEFIR 171
Cdd:cd15900     5 AFKMFDLDGDGELDKEEFNKVQSIIRSQTSVGQR-----HRDHTNGESTKLGMNStlaryffgkDGKQKLSIEKFLE 76
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
100-128 6.03e-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: 35.84  E-value: 6.03e-04
                          10        20
                  ....*....|....*....|....*....
gi 1034558029 100 KLMWAFSMYDLDGNGYISREEMLEIVQAI 128
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
41-171 6.39e-04

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: 38.42  E-value: 6.39e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  41 GILNVDEFKKIYANFFPYGDaSKFAEHVFRTFDTNSDGTIDFREFIIAL-SVTSRGRLEQklmwAFSMYDLDGNGYISRE 119
Cdd:cd15898    15 GKLSLKEIKKLLKRLNIRVS-EKELKKLFKEVDTNGDGTLTFDEFEELYkSLTERPELEP----IFKKYAGTNRDYMTLE 89
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034558029 120 EMLEIVQAIykmvssvmkmpEDESTPEKRTEKIFRQMDTN-NDGKLSLEEFIR 171
Cdd:cd15898    90 EFIRFLREE-----------QGENVSEEECEELIEKYEPErENRQLSFEGFTN 131
EF-hand_6 pfam13405
EF-hand domain;
100-128 8.01e-04

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 35.62  E-value: 8.01e-04
                          10        20
                  ....*....|....*....|....*....
gi 1034558029 100 KLMWAFSMYDLDGNGYISREEMLEIVQAI 128
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSL 29
EFh_SPARC_EC cd00252
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
89-170 9.32e-04

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC)-like proteins; The SPARC protein family represents a diverse group of proteins that share a follistatin-like (FS) domain and an extracellular calcium-binding (EC) domain with two EF-hand motifs. It includes SPARC (for secreted protein acidic and rich in cysteine, also termed osteonectin/ON, or basement-membrane protein 40/BM-40), SPARC-like protein 1 (for secreted protein, acidic and rich in cysteines-like 1/ SPARCL1, also termed high endothelial venule protein/Hevi, or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2), testicans 1, 2, and 3 (also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycans, or SPOCK), secreted modular calcium-binding protein SMOC-1 (also termed SPARC-related modular calcium-binding protein 1) and SMOC-2 (also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2/SMAP-2), follistatin-related protein 1 (FRP-1, also termed follistatin-like protein 1/fstl-1, TSC-36/Flik, TGF-beta inducible protein). The SPARC proteins have been implicated in modulating cell interaction with the extracellular milieu, including regulation of extracellular matrix assembly and deposition, counter-adhesion, effects on extracellular protease activity, and modulation of growth factor/cytokine signaling pathways, as well as in development and disease.


Pssm-ID: 320009  Cd Length: 107  Bit Score: 37.35  E-value: 9.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  89 LSVTSRGRLEQklmWAFSMYDLDGNGYISREEMLEIVQaiykmvssvMKMPedestPEKRTEKIFRQMDTNNDGKLSLEE 168
Cdd:cd00252    38 LSGTMRKEIAQ---WEFDNLDNNKDGKLDKRELAPFRA---------PLMP-----LEHCARGFFESCDLNKDKKISLQE 100

                  ..
gi 1034558029 169 FI 170
Cdd:cd00252   101 WL 102
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
70-168 9.50e-04

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: 38.96  E-value: 9.50e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  70 RTFDTNSDGTIDFREFIIALSVTSRGrlEQKLMWAFS-------MYDLDGNGYISREEMLEIVqaiykmvssvmkMPEDE 142
Cdd:cd15899   167 EDLDKNGDGFISLEEFISDPYSADEN--EEEPEWVKVekerfveLRDKDKDGKLDGEELLSWV------------DPSNQ 232
                          90       100
                  ....*....|....*....|....*.
gi 1034558029 143 STPEKRTEKIFRQMDTNNDGKLSLEE 168
Cdd:cd15899   233 EIALEEAKHLIAESDENKDGKLSPEE 258
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
21-125 1.04e-03

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: 38.00  E-value: 1.04e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  21 EFSEL--ELQEW---YKGFLKDcPTGILNVDEFKKIYANFfPYGDASKFAEHVFRTFDTNSDGTIDFREFIIALSVTsrg 95
Cdd:cd16183    58 EFAALwkYITDWqncFRSFDRD-NSGNIDKNELKQALTSF-GYRLSDQFYDILVRKFDRQGRGTIAFDDFIQCCVVL--- 132
                          90       100       110
                  ....*....|....*....|....*....|..
gi 1034558029  96 rleQKLMWAFSMYDLDGNGYI--SREEMLEIV 125
Cdd:cd16183   133 ---QTLTDSFRRYDTDQDGWIqiSYEQFLEMV 161
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
69-171 1.07e-03

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: 37.98  E-value: 1.07e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  69 FRTFDTNSDGTIDFREF-----IIA---------LSVTSRGRLEQKLMWAFSMY--DLDGNGYISREEMLEIVQAIYKMV 132
Cdd:cd15900     6 FKMFDLDGDGELDKEEFnkvqsIIRsqtsvgqrhRDHTNGESTKLGMNSTLARYffGKDGKQKLSIEKFLEFQENLQEEI 85
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034558029 133 SSV---MKM------PEDESTpEKR--------------TEKIFRQMDTNNDGKLSLEEFIR 171
Cdd:cd15900    86 DDVdtaLTFyhlagaSIDRKT-FKRaakvvagvelsdhvVDVVFTIFDEDGDGILSHKEFIS 146
S-100 cd00213
S-100: S-100 domain, which represents the largest family within the superfamily of proteins ...
111-171 1.42e-03

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: 36.31  E-value: 1.42e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034558029 111 DGNGY-ISREEMLEIVQaiyKMVSSVMKMPEDESTpekrTEKIFRQMDTNNDGKLSLEEFIR 171
Cdd:cd00213    21 EGDKDtLSKKELKELLE---TELPNFLKNQKDPEA----VDKIMKDLDVNKDGKVDFQEFLV 75
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
65-177 1.66e-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: 38.19  E-value: 1.66e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  65 AEHVFRTFDTNSDGTIDFREFIIAL------------SVTSRGRLEQKLMWA----FSMYDLDGNGYISREEMLeivqai 128
Cdd:cd15899    73 SKEQFRAVDPDEDGHVSWDEYKNDTygsvgddeenvaDNIKEDEEYKKLLLKdkkrFEAADQDGDLILTLEEFL------ 146
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034558029 129 ykmvssVMKMPED-ESTPEKRTEKIFRQMDTNNDGKLSLEEFIRGAKSDP 177
Cdd:cd15899   147 ------AFLHPEEsPYMLDFVIKETLEDLDKNGDGFISLEEFISDPYSAD 190
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
150-175 1.80e-03

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: 34.68  E-value: 1.80e-03
                          10        20
                  ....*....|....*....|....*.
gi 1034558029 150 EKIFRQMDTNNDGKLSLEEFIRGAKS 175
Cdd:pfam00036   3 KEIFRLFDKDGDGKIDFEEFKELLKK 28
EF-hand_5 pfam13202
EF hand;
150-171 1.98e-03

EF hand;


Pssm-ID: 433035 [Multi-domain]  Cd Length: 25  Bit Score: 34.22  E-value: 1.98e-03
                          10        20
                  ....*....|....*....|..
gi 1034558029 150 EKIFRQMDTNNDGKLSLEEFIR 171
Cdd:pfam13202   2 KDTFRQIDLNGDGKISKEELRR 23
EF-hand_8 pfam13833
EF-hand domain pair;
39-89 2.35e-03

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 34.98  E-value: 2.35e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034558029  39 PTGILNVDEFKKIYANFFPYGDASKFAEHVFRTFDTNSDGTIDFREFIIAL 89
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLL 51
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
150-175 2.75e-03

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: 33.89  E-value: 2.75e-03
                           10        20
                   ....*....|....*....|....*.
gi 1034558029  150 EKIFRQMDTNNDGKLSLEEFIRGAKS 175
Cdd:smart00054   3 KEAFRLFDKDGDGKIDFEEFKDLLKA 28
EFh_calglandulin_like cd16252
EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The ...
91-169 3.80e-03

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: 35.58  E-value: 3.80e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  91 VTSRGRLEQKLMWAFSMYDLDGNGYISREEMLEIVQAIykmVSSVMKMP-EDEstpekRTEKIFRQMDTNNDGKLSLEEF 169
Cdd:cd16252    29 FQTSEQQEEAIRKAFQMLDKDKSGFIEWNEIKYILSTV---PSSMPVAPlSDE-----EAEAMIQAADTDGDGRIDFQEF 100
EF-hand_8 pfam13833
EF-hand domain pair;
112-170 3.87e-03

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 34.21  E-value: 3.87e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034558029 112 GNGYISREEMLEIvqaiykmvSSVMKMPEdesTPEKRTEKIFRQMDTNNDGKLSLEEFI 170
Cdd:pfam13833   1 EKGVITREELKRA--------LALLGLKD---LSEDEVDILFREFDTDGDGYISFDEFC 48
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
69-176 4.50e-03

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: 36.91  E-value: 4.50e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  69 FRTFDTNSDGTIDFREFIIA---------LSVTSRGRLEQKLMWA-----FSMYDLDGNGYISREEMLEIVQaiykmvss 134
Cdd:cd16227    78 FEEADEDGDGKVTWEEYLADsfgyddednEEMIKDSTEDDLKLLEddkemFEAADLNKDGKLDKTEFSAFQH-------- 149
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1034558029 135 vmkmPED-ESTPEKRTEKIFRQMDTNNDGKLSLEEFIRGAKSD 176
Cdd:cd16227   150 ----PEEyPHMHPVLIEQTLRDKDKDNDGFISFQEFLGDRAGH 188
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
141-168 4.55e-03

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: 36.79  E-value: 4.55e-03
                          10        20        30
                  ....*....|....*....|....*....|.
gi 1034558029 141 DESTPE---KRTEKIFRQMDTNNDGKLSLEE 168
Cdd:cd16226    26 DQLTPEeskERLGIIVDKIDKNGDGFVTEEE 56
EFh_HEF_CB cd16176
EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or ...
14-121 5.31e-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: 36.74  E-value: 5.31e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  14 QDLRENTEFseleLQEWYKgFLKDcPTGILNVDEFKKIYANFF-----PYgDASKFAEH---VFRTFDTNSDGTIDFREF 85
Cdd:cd16176    79 QQLKSSEEF----MQTWRK-YDAD-HSGFIEADELKSFLKDLLkkankPF-DESKLEEYthtMLKMFDSNNDGKLGLTEM 151
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1034558029  86 IIALSVTSRGRLE--------QKLMWAFSMYDLDGNGYISREEM 121
Cdd:cd16176   152 ARLLPVQENFLLKfqgvkmcgKEFNKIFELYDQDGNGYIDENEL 195
S-100 cd00213
S-100: S-100 domain, which represents the largest family within the superfamily of proteins ...
36-89 5.62e-03

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: 34.77  E-value: 5.62e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034558029  36 KDCPTGILNVDEFKKI----YANFFPYGDASKFAEHVFRTFDTNSDGTIDFREFIIAL 89
Cdd:cd00213    20 KEGDKDTLSKKELKELleteLPNFLKNQKDPEAVDKIMKDLDVNKDGKVDFQEFLVLI 77
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
26-170 5.82e-03

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: 36.09  E-value: 5.82e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  26 ELQEWYKGFLKDcPTGILNVDEFKKIYANffpyGDASKFAEH----VFRTFDTNSDGTIDFREFiialsvTSRGRLEQKL 101
Cdd:cd16184     1 EVQQWFQAVDRD-RSGKISAKELQQALVN----GNWSHFNDEtcrlMIGMFDKDKSGTIDIYEF------QALWNYIQQW 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029 102 MWAFSMYDLDGNGYISREEMleiVQAIYKM--------VSSVM---------KMPEDE----STPEKRTEKIFRQMDTNN 160
Cdd:cd16184    70 KQVFQQFDRDRSGSIDENEL---HQALSQMgyrlspqfVQFLVskydprarrSLTLDQfiqvCVQLQSLTDAFRQRDTQM 146
                         170
                  ....*....|..
gi 1034558029 161 DG--KLSLEEFI 170
Cdd:cd16184   147 TGtiTISYEDFL 158
EF-hand_7 pfam13499
EF-hand domain pair;
40-90 6.03e-03

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 34.15  E-value: 6.03e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034558029  40 TGILNVDEFKKIYANFFPYGDASK-FAEHVFRTFDTNSDGTIDFREFIIALS 90
Cdd:pfam13499  16 DGYLDVEELKKLLRKLEEGEPLSDeEVEELFKEFDLDKDGRISFEEFLELYS 67
EF-hand_6 pfam13405
EF-hand domain;
150-175 6.52e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 32.92  E-value: 6.52e-03
                          10        20
                  ....*....|....*....|....*.
gi 1034558029 150 EKIFRQMDTNNDGKLSLEEFIRGAKS 175
Cdd:pfam13405   3 REAFKLFDKDGDGKISLEELRKALRS 28
EFh_PEF_Group_II_CAPN_like cd16182
Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family ...
71-172 7.16e-03

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: 35.66  E-value: 7.16e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  71 TFDTNSDGTIDFREFIIALSvtsrgRLeQKLMWAFSMYDLDGNGYISREEMLEIVQAI-YKMVSSVM------------K 137
Cdd:cd16182    50 LMDTNGSGRLDLEEFKTLWS-----DL-KKWQAIFKKFDTDRSGTLSSYELRKALESAgFHLSNKVLqalvlryadstgR 123
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1034558029 138 MPEDE----STPEKRTEKIFRQMDTNNDGK--LSLEEFIRG 172
Cdd:cd16182   124 ITFEDfvscLVRLKTAFETFSALDKKNEGVipLTLEEWLLL 164
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
68-90 7.67e-03

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: 32.74  E-value: 7.67e-03
                           10        20
                   ....*....|....*....|...
gi 1034558029   68 VFRTFDTNSDGTIDFREFIIALS 90
Cdd:smart00054   5 AFRLFDKDGDGKIDFEEFKDLLK 27
calgranulins cd05030
Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 ...
146-170 7.88e-03

Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 family of EF-hand calcium-modulated proteins, including S100A8, S100A9, and S100A12 . Note that the S-100 hierarchy, to which this Calgranulin group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. These proteins are expressed mainly in granulocytes, and are involved in inflammation, allergy, and neuritogenesis, as well as in host-parasite response. Calgranulins are modulated not only by calcium, but also by other metals such as zinc and copper. Structural data suggested that calgranulins may exist in multiple structural forms, homodimers, as well as hetero-oligomers. For example, the S100A8/S100A9 complex called calprotectin plays important roles in the regulation of inflammatory processes, wound repair, and regulating zinc-dependent enzymes as well as microbial growth.


Pssm-ID: 240156 [Multi-domain]  Cd Length: 88  Bit Score: 34.25  E-value: 7.88e-03
                          10        20
                  ....*....|....*....|....*
gi 1034558029 146 EKRTEKIFRQMDTNNDGKLSLEEFI 170
Cdd:cd05030    50 QKAIDKIFEDLDTNQDGQLSFEEFL 74
EFh_CREC_RCN2 cd16224
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed ...
104-171 8.19e-03

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: 35.87  E-value: 8.19e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034558029 104 AFSMYDLDGNGYISREEMLeivqAIYKMVSSVMKMPEDESTPEKRTEKIFrqmDTNNDGKLSLEEFIR 171
Cdd:cd16224   166 ALEEHDKDGDGFISLEEFL----GDYRKDPTANEDPEWIIVEKDRFVNDY---DKDNDGKLDPQELLP 226
EFh_CREC_RCN2 cd16224
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed ...
62-168 8.35e-03

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: 35.87  E-value: 8.35e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034558029  62 SKFA-EHVFRTFDTNSDGTIDFREFIIALsvTSRGRLEQKLMWAF-------SMYDLDGNGYISREEMLEIVqaiykmvs 133
Cdd:cd16224   159 TEFViQEALEEHDKDGDGFISLEEFLGDY--RKDPTANEDPEWIIvekdrfvNDYDKDNDGKLDPQELLPWV-------- 228
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1034558029 134 svmkMPEDESTPEKRTEKIFRQMDTNNDGKLSLEE 168
Cdd:cd16224   229 ----VPNNYGIAQEEALHLIDEMDLNGDGRLSEEE 259
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
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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