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Conserved domains on  [gi|975096486|ref|XP_015263167|]
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Protein Classification

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List of domain hits

Name Accession Description Interval E-value
EFh_SPARC_TICN2 cd16238
EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also ...
344-455 7.24e-80

EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (Spock2), is an extracellular heparan sulphate proteoglycan expressed in brain, lung, and testis. It inhibits neurite extension from cultured primary cerebellar neurons and may play regulatory roles in the development of the central nervous system. It also participates in diverse steps of neurogenesis. Moreover, TICN2 may contribute to ECM remodeling by regulating function(s) of other testican family members, which possess membrane-type matrix metalloproteinases (MT-MMPs) inhibitory function. Furthermore, TICN2 corresponding gene SPOCK2 acts as a susceptibility gene for bronchopulmonary dysplasia. TICN2 contains an N-terminal signal peptide, a testican-specific domain followed by a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, a thyroglobulin-like domain (TY), and a C-terminal region with two putative glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr292 in the +Y position of EF-hand 2 in TICN2 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


:

Pssm-ID: 320017  Cd Length: 112  Bit Score: 246.00  E-value: 7.24e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 344 CTGQDLADLGDRLRDWFQLLHENAKQNSSGSTGASPVNVLDKSLVASCKDSIGWMFSKLDTNGDLFLDQTELAAINLDKY 423
Cdd:cd16238    1 CTGQDLADLGDRLRDWFQLLHENSKQNGSGSPPASPASALDRSLVASCKDSIGWMFSKLDTSGDLFLDQAELAAINLDKY 80
                         90       100       110
                 ....*....|....*....|....*....|..
gi 975096486 424 EICIRPFFNSCDTYKDGRVSTAEWCFCFWREK 455
Cdd:cd16238   81 EVCIRPFFNSCDTYRDGRVSTAEWCFCFWREK 112
RNase_HI_RT_DIRS1 cd09275
DIRS1 family of RNase HI in long-term repeat retroelements; Ribonuclease H (RNase H) enzymes ...
39-144 9.34e-32

DIRS1 family of RNase HI in long-term repeat retroelements; Ribonuclease H (RNase H) enzymes are divided into two major families, Type 1 and Type 2, based on amino acid sequence similarities and biochemical properties. RNase H is an endonuclease that cleaves the RNA strand of an RNA/DNA hybrid in a sequence non-specific manner in the presence of divalent cations. RNase H is widely present in various organisms, including bacteria, archaea and eukaryotes. RNase HI has also been observed as adjunct domains to the reverse transcriptase gene in retroviruses, in long-term repeat (LTR)-bearing retrotransposons and non-LTR retrotransposons. RNase HI in LTR retrotransposons perform degradation of the original RNA template, generation of a polypurine tract (the primer for plus-strand DNA synthesis), and final removal of RNA primers from newly synthesized minus and plus strands. The catalytic residues for RNase H enzymatic activity, three aspartatic acids and one glutamic acid residue (DEDD), are unvaried across all RNase H domains. Phylogenetic patterns of RNase HI of LTR retroelements is classified into five major families, Ty3/Gypsy, Ty1/Copia, Bel/Pao, DIRS1 and the vertebrate retroviruses. The structural features of DIRS1-group elements are different from typical LTR elements. RNase H inhibitors have been explored as an anti-HIV drug target because RNase H inactivation inhibits reverse transcription.


:

Pssm-ID: 260007  Cd Length: 120  Bit Score: 118.54  E-value: 9.34e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486  39 CGHLIAQGKWSPQQASHSINWLELRAVSLALRASHQHMQDQHLLVRTDNMSTKAHINRQGGTRSKSLFKESRILLQWAEQ 118
Cdd:cd09275   15 LLNSRAHGPWSADERNKHINLLELKAVLLALQHFAAELKNRKILIRTDNTTAVAYINKQGGTSSPPLLALARQILLWCEQ 94
                         90       100
                 ....*....|....*....|....*.
gi 975096486 119 YTLSLRAEHLRGLSNQQADWLSRENL 144
Cdd:cd09275   95 RNIWLRASHIPGVLNTEADRLSRLGL 120
TY cd00191
Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 ...
457-521 4.41e-23

Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases


:

Pssm-ID: 238114  Cd Length: 66  Bit Score: 92.53  E-value: 4.41e-23
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 975096486 457 PCLVELERIQIQEAAKKKPGVFIPSCDEDGYYRKMQCDPGSGECWCVDHLGMELTGTRMHGT-PDC 521
Cdd:cd00191    1 PCERERASALESLAGPKLSGLYVPQCDEDGNYEPVQCHGSTGYCWCVDPDGEEIPGTRTRGGpPNC 66
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
292-325 1.70e-10

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.


:

Pssm-ID: 197624  Cd Length: 46  Bit Score: 56.15  E-value: 1.70e-10
                           10        20        30
                   ....*....|....*....|....*....|....
gi 975096486   292 VCGSDGHTYSSVCKLEQQACLTSKQLTVKCEGQC 325
Cdd:smart00280  13 VCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46
 
Name Accession Description Interval E-value
EFh_SPARC_TICN2 cd16238
EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also ...
344-455 7.24e-80

EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (Spock2), is an extracellular heparan sulphate proteoglycan expressed in brain, lung, and testis. It inhibits neurite extension from cultured primary cerebellar neurons and may play regulatory roles in the development of the central nervous system. It also participates in diverse steps of neurogenesis. Moreover, TICN2 may contribute to ECM remodeling by regulating function(s) of other testican family members, which possess membrane-type matrix metalloproteinases (MT-MMPs) inhibitory function. Furthermore, TICN2 corresponding gene SPOCK2 acts as a susceptibility gene for bronchopulmonary dysplasia. TICN2 contains an N-terminal signal peptide, a testican-specific domain followed by a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, a thyroglobulin-like domain (TY), and a C-terminal region with two putative glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr292 in the +Y position of EF-hand 2 in TICN2 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


Pssm-ID: 320017  Cd Length: 112  Bit Score: 246.00  E-value: 7.24e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 344 CTGQDLADLGDRLRDWFQLLHENAKQNSSGSTGASPVNVLDKSLVASCKDSIGWMFSKLDTNGDLFLDQTELAAINLDKY 423
Cdd:cd16238    1 CTGQDLADLGDRLRDWFQLLHENSKQNGSGSPPASPASALDRSLVASCKDSIGWMFSKLDTSGDLFLDQAELAAINLDKY 80
                         90       100       110
                 ....*....|....*....|....*....|..
gi 975096486 424 EICIRPFFNSCDTYKDGRVSTAEWCFCFWREK 455
Cdd:cd16238   81 EVCIRPFFNSCDTYRDGRVSTAEWCFCFWREK 112
SPARC_Ca_bdg pfam10591
Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of ...
342-448 1.61e-39

Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of Secreted Protein Acidic and Rich in Cysteine is responsible for the anti-spreading activity of human urothelial cells. It is rich in alpha-helices. This extracellular calcium-binding domain contains two EF-hands that each coordinates one Ca2+ ion, forming a helix-loop-helix structure that not only drives the conformation of the protein but is also necessary for biological activity. The anti-spreading activity was dependent on the coordination of Ca2+ by a Glu residue at the Z position of EF-hand 2.


Pssm-ID: 313749  Cd Length: 110  Bit Score: 139.76  E-value: 1.61e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486  342 ETCTGQDLADLGDRLRDWFQLLHENAKQNSSGSTGASP-VNVLDKSLVASCKDSIGWMFSKLDTNGDLFLDQTELAAIN- 419
Cdd:pfam10591   1 PCCTDQELAEFPRRLRDWLKNLHESLKRRREQKDHYVElEKRKEQSPYPMCKEPLGWMFHRLDTNDDLLLDQEELAPIRa 80
                          90       100       110
                  ....*....|....*....|....*....|
gi 975096486  420 -LDKYEICIRPFFNSCDTYKDGRVSTAEWC 448
Cdd:pfam10591  81 pLVPMEHCIKPFFESCDANKDGLISLEEWC 110
RNase_HI_RT_DIRS1 cd09275
DIRS1 family of RNase HI in long-term repeat retroelements; Ribonuclease H (RNase H) enzymes ...
39-144 9.34e-32

DIRS1 family of RNase HI in long-term repeat retroelements; Ribonuclease H (RNase H) enzymes are divided into two major families, Type 1 and Type 2, based on amino acid sequence similarities and biochemical properties. RNase H is an endonuclease that cleaves the RNA strand of an RNA/DNA hybrid in a sequence non-specific manner in the presence of divalent cations. RNase H is widely present in various organisms, including bacteria, archaea and eukaryotes. RNase HI has also been observed as adjunct domains to the reverse transcriptase gene in retroviruses, in long-term repeat (LTR)-bearing retrotransposons and non-LTR retrotransposons. RNase HI in LTR retrotransposons perform degradation of the original RNA template, generation of a polypurine tract (the primer for plus-strand DNA synthesis), and final removal of RNA primers from newly synthesized minus and plus strands. The catalytic residues for RNase H enzymatic activity, three aspartatic acids and one glutamic acid residue (DEDD), are unvaried across all RNase H domains. Phylogenetic patterns of RNase HI of LTR retroelements is classified into five major families, Ty3/Gypsy, Ty1/Copia, Bel/Pao, DIRS1 and the vertebrate retroviruses. The structural features of DIRS1-group elements are different from typical LTR elements. RNase H inhibitors have been explored as an anti-HIV drug target because RNase H inactivation inhibits reverse transcription.


Pssm-ID: 260007  Cd Length: 120  Bit Score: 118.54  E-value: 9.34e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486  39 CGHLIAQGKWSPQQASHSINWLELRAVSLALRASHQHMQDQHLLVRTDNMSTKAHINRQGGTRSKSLFKESRILLQWAEQ 118
Cdd:cd09275   15 LLNSRAHGPWSADERNKHINLLELKAVLLALQHFAAELKNRKILIRTDNTTAVAYINKQGGTSSPPLLALARQILLWCEQ 94
                         90       100
                 ....*....|....*....|....*.
gi 975096486 119 YTLSLRAEHLRGLSNQQADWLSRENL 144
Cdd:cd09275   95 RNIWLRASHIPGVLNTEADRLSRLGL 120
TY cd00191
Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 ...
457-521 4.41e-23

Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases


Pssm-ID: 238114  Cd Length: 66  Bit Score: 92.53  E-value: 4.41e-23
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 975096486 457 PCLVELERIQIQEAAKKKPGVFIPSCDEDGYYRKMQCDPGSGECWCVDHLGMELTGTRMHGT-PDC 521
Cdd:cd00191    1 PCERERASALESLAGPKLSGLYVPQCDEDGNYEPVQCHGSTGYCWCVDPDGEEIPGTRTRGGpPNC 66
Thyroglobulin_1 pfam00086
Thyroglobulin type-1 repeat; Thyroglobulin type 1 repeats are thought to be involved in the ...
458-521 3.67e-22

Thyroglobulin type-1 repeat; Thyroglobulin type 1 repeats are thought to be involved in the control of proteolytic degradation. The domain usually contains six conserved cysteines. These form three disulphide bridges. Cysteines 1 pairs with 2, 3 with 4 and 5 with 6.


Pssm-ID: 333828  Cd Length: 66  Bit Score: 89.66  E-value: 3.67e-22
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 975096486  458 CLVELERIQIQEAAKKKP-GVFIPSCDEDGYYRKMQCDPGSGECWCVDHLGMELTGTR-MHGTPDC 521
Cdd:pfam00086   1 CQRERARALEQLAGGRPAsGLYIPQCDEDGFYKPVQCHGSTGYCWCVDPEGKEIPGTRtRGGDPNC 66
TY smart00211
Thyroglobulin type I repeats; The N-terminal region of human thyroglobulin contains 11 type-1 ...
479-523 2.94e-16

Thyroglobulin type I repeats; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases and binding partners of heparin.


Pssm-ID: 214561  Cd Length: 46  Bit Score: 72.41  E-value: 2.94e-16
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 975096486   479 IPSCDEDGYYRKMQCDPGSGECWCVDHLGMELTGTRMHGT-PDCDD 523
Cdd:smart00211   1 IPQCDEDGNYEPVQCDGSSGQCWCVDATGREIPGTRTEGGdPDCPS 46
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
292-325 1.70e-10

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.


Pssm-ID: 197624  Cd Length: 46  Bit Score: 56.15  E-value: 1.70e-10
                           10        20        30
                   ....*....|....*....|....*....|....
gi 975096486   292 VCGSDGHTYSSVCKLEQQACLTSKQLTVKCEGQC 325
Cdd:smart00280  13 VCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46
Kazal_2 pfam07648
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
281-325 4.13e-10

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.


Pssm-ID: 336754  Cd Length: 49  Bit Score: 55.17  E-value: 4.13e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 975096486  281 CKPCHMTQLASVCGSDGHTYSSVCKLEQQACLTSKQL--TVKCEGQC 325
Cdd:pfam07648   3 CCQCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVghKVKYDGSC 49
KAZAL_FS cd00104
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
292-325 1.17e-09

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.


Pssm-ID: 238052  Cd Length: 41  Bit Score: 53.43  E-value: 1.17e-09
                         10        20        30
                 ....*....|....*....|....*....|....
gi 975096486 292 VCGSDGHTYSSVCKLEQQACLTSKQLTVKCEGQC 325
Cdd:cd00104    8 VCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41
 
Name Accession Description Interval E-value
EFh_SPARC_TICN2 cd16238
EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also ...
344-455 7.24e-80

EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (Spock2), is an extracellular heparan sulphate proteoglycan expressed in brain, lung, and testis. It inhibits neurite extension from cultured primary cerebellar neurons and may play regulatory roles in the development of the central nervous system. It also participates in diverse steps of neurogenesis. Moreover, TICN2 may contribute to ECM remodeling by regulating function(s) of other testican family members, which possess membrane-type matrix metalloproteinases (MT-MMPs) inhibitory function. Furthermore, TICN2 corresponding gene SPOCK2 acts as a susceptibility gene for bronchopulmonary dysplasia. TICN2 contains an N-terminal signal peptide, a testican-specific domain followed by a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, a thyroglobulin-like domain (TY), and a C-terminal region with two putative glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr292 in the +Y position of EF-hand 2 in TICN2 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


Pssm-ID: 320017  Cd Length: 112  Bit Score: 246.00  E-value: 7.24e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 344 CTGQDLADLGDRLRDWFQLLHENAKQNSSGSTGASPVNVLDKSLVASCKDSIGWMFSKLDTNGDLFLDQTELAAINLDKY 423
Cdd:cd16238    1 CTGQDLADLGDRLRDWFQLLHENSKQNGSGSPPASPASALDRSLVASCKDSIGWMFSKLDTSGDLFLDQAELAAINLDKY 80
                         90       100       110
                 ....*....|....*....|....*....|..
gi 975096486 424 EICIRPFFNSCDTYKDGRVSTAEWCFCFWREK 455
Cdd:cd16238   81 EVCIRPFFNSCDTYRDGRVSTAEWCFCFWREK 112
EFh_SPARC_TICN cd16232
EF-hand, extracellular calcium-binding (EC) motif, found in testicans; Testicans are nervous ...
344-455 1.20e-50

EF-hand, extracellular calcium-binding (EC) motif, found in testicans; Testicans are nervous system-expressed proteoglycans that play important roles in the regulation of protease activity, as well as in the determination of age at menarche. Testican-1 (TICN1, also termed protein SPOCK) is a secreted chimeric proteoglycan that is highly expressed in brain and carries both chondroitin and heparan sulfate glycosaminoglycan side chains. It has been implicated in autoimmune disease. It also acts as a regulator of bone morphogenetic protein (BMP) signaling and show critical functions in the nervous system. Testican-2 (TICN2, also termed protein SPOCK2) is an extracellular heparan sulphate proteoglycan highly expressed in brain. It may play regulatory roles in the development of the central nervous system. It also participates in diverse steps of neurogenesis. TICN1, but not TICN2, inhibits cathepsin L. TICN1 also inhibits attachment and neurite outgrowth in cultures of N2A neuroblastoma cells, While TICN2 is able to inhibit neurite outgrowth from primary cerebellar cells. Testicans contain an N-terminal signal peptide, a testican-specific domain followed by a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, a thyroglobulin-like domain (TY), and a C-terminal region with two putative glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr orTyr in the +Y position of EF hand 2 in testican-2 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ with low affinity. The substitution of a ligating Asp residue by Phe or Tyr in the +Y position of EF-hand 2 in testicans could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


Pssm-ID: 320011  Cd Length: 108  Bit Score: 169.47  E-value: 1.20e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 344 CTGQDLADLGDRLRDWFQLLHENAKQNSSgstgASPVNVLDKSLVASCKDSIGWMFSKLDTNGDLFLDQTELAAINLDKY 423
Cdd:cd16232    1 CTESELSEMGDRLLDWFSVLHEQSNKAKK----TSSSKRFDKSHLPECKPSVGWMFNQLDTNNDLHLSQSELYDLELDKY 76
                         90       100       110
                 ....*....|....*....|....*....|..
gi 975096486 424 EICIRPFFNSCDTYKDGRVSTAEWCFCFWREK 455
Cdd:cd16232   77 EPCIKPFLDSCDRNKDGKISSDEWCDCFQRAD 108
EFh_SPARC_TICN1 cd16237
EF-hand, extracellular calcium-binding (EC) motif, found in testican-1 (TICN1); TICN1, also ...
344-456 2.06e-41

EF-hand, extracellular calcium-binding (EC) motif, found in testican-1 (TICN1); TICN1, also termed protein SPOCK, or SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 1 (Spock1), is a secreted chimeric proteoglycan that is highly expressed in brain and carries both chondroitin and heparan sulfate glycosaminoglycan side chains. It promotes resistance against Pseudomonas aeruginosa-induced keratitis through regulation of matrix metalloproteinase (MMP)-2 expression and activation. It also acts as a potential cancer prognostic marker that promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/Akt pathway. Moreover, TICN1 corresponding gene SPOCK1 is a novel transforming growth factor-beta target gene that regulates lung cancer cell epithelial-mesenchymal transition. It is also up-regulated by chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like (CHD1L), and promotes human hepatocellular carcinoma (HCC) cell invasiveness and metastasis. Furthermore, TICN1 inhibits the lysosomal cysteine protease cathepsin L in intracellular vesicles and in the extracellular milieu. TICN1 contains an N-terminal signal sequence known to direct nascent polypeptides to the extracellular space, an unique region to the testicans, a follistatin (FS)-like domain generally involving five disulfide bridges, an extracellular calcium-binding (EC) domain including a pair of EF hands, and a thyroglobulin type-1 (TY) domain followed by a C-terminal acidic region with high density of negatively charged amino acids. The substitution of a ligating Asp residue by Phe291 in the +Y position of EF-hand 2 in TICN1 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


Pssm-ID: 320016  Cd Length: 112  Bit Score: 144.80  E-value: 2.06e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 344 CTGQDLADLGDRLRDWFQLLHENAKQNSSGSTGASPVNVLDKSLVASCKDSIGWMFSKLDTNGDLFLDQTELAAINLDKY 423
Cdd:cd16237    1 CTDKELRNLASRLKDWFGALHEDANRVIKPTSSFTAQGRFDTSILPICKDSLGWMFNKLDMNYDLLLDPSEISAIYLDKY 80
                         90       100       110
                 ....*....|....*....|....*....|...
gi 975096486 424 EICIRPFFNSCDTYKDGRVSTAEWCFCFwrEKP 456
Cdd:cd16237   81 EPCMKPLFNSCDSFKDGKLSNNEWCYCF--QKP 111
EFh_SPARC_TICN3 cd16239
EF-hand, extracellular calcium-binding (EC) motif, found in testican-3 (TICN3); TICN3, also ...
344-455 1.18e-39

EF-hand, extracellular calcium-binding (EC) motif, found in testican-3 (TICN3); TICN3, also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 3 (Spock3), is a brain-specific heparan sulfate proteoglycan that shows a widespread distribution within the extracellular matrix of the brain. It plays an important role in the formation or maintenance of major neuronal structures in the brain. It also functions as a novel regulator to reduce the activity of matrix metalloproteinase (MMP) in adult T-cell leukemia (ATL). It suppresses membrane-type 1 MMP-mediated MMP-2 activation and tumor invasion. Moreover, TICN3 corresponding gene SPOCK3 acts as a risk gene for adult attention-deficit/hyperactivity disorder (ADHD) and personality disorders. TICN3 contains an N-terminal signal peptide, a testican-specific domain followed by the follistatin-like (FS) and extracellular calcium-binding (EC) domains characteristic of the BM-40 family. Towards the C-terminus they contain a thyroglobulin-like domain (TY) and a novel sequence (domain V), which includes two potential glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr295 in the +Y position of EF-hand 2 in testican-3 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


Pssm-ID: 320018  Cd Length: 113  Bit Score: 140.15  E-value: 1.18e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 344 CTGQDLADLGDRLRDWFQLLHENAKQNSSGSTGASPVNV-LDKSLVASCKDSIGWMFSKLDTNGDLFLDQTELAAINLDK 422
Cdd:cd16239    1 CSDLEFREVANRLRDWFKALHESGSQNKKTKIVRRPERSrFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELGSIYLDK 80
                         90       100       110
                 ....*....|....*....|....*....|...
gi 975096486 423 YEICIRPFFNSCDTYKDGRVSTAEWCFCFWREK 455
Cdd:cd16239   81 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQRQQ 113
SPARC_Ca_bdg pfam10591
Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of ...
342-448 1.61e-39

Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of Secreted Protein Acidic and Rich in Cysteine is responsible for the anti-spreading activity of human urothelial cells. It is rich in alpha-helices. This extracellular calcium-binding domain contains two EF-hands that each coordinates one Ca2+ ion, forming a helix-loop-helix structure that not only drives the conformation of the protein but is also necessary for biological activity. The anti-spreading activity was dependent on the coordination of Ca2+ by a Glu residue at the Z position of EF-hand 2.


Pssm-ID: 313749  Cd Length: 110  Bit Score: 139.76  E-value: 1.61e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486  342 ETCTGQDLADLGDRLRDWFQLLHENAKQNSSGSTGASP-VNVLDKSLVASCKDSIGWMFSKLDTNGDLFLDQTELAAIN- 419
Cdd:pfam10591   1 PCCTDQELAEFPRRLRDWLKNLHESLKRRREQKDHYVElEKRKEQSPYPMCKEPLGWMFHRLDTNDDLLLDQEELAPIRa 80
                          90       100       110
                  ....*....|....*....|....*....|
gi 975096486  420 -LDKYEICIRPFFNSCDTYKDGRVSTAEWC 448
Cdd:pfam10591  81 pLVPMEHCIKPFFESCDANKDGLISLEEWC 110
EFh_SPARC_EC cd00252
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
344-453 1.49e-36

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: 131.34  E-value: 1.49e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 344 CTGQDLADLGDRLRDWFQLLHENAKQNSSGSTGAspvnvLDKSLVASCKDSIGWMFSKLDTNGDLFLDQTELAAINLD-- 421
Cdd:cd00252    1 CPGSELMQFPDRLLDWLLLLKEQDENRSYDNNKR-----GHDLSGTMRKEIAQWEFDNLDNNKDGKLDKRELAPFRAPlm 75
                         90       100       110
                 ....*....|....*....|....*....|..
gi 975096486 422 KYEICIRPFFNSCDTYKDGRVSTAEWCFCFWR 453
Cdd:cd00252   76 PLEHCARGFFESCDLNKDKKISLQEWLGCFGV 107
RNase_HI_RT_DIRS1 cd09275
DIRS1 family of RNase HI in long-term repeat retroelements; Ribonuclease H (RNase H) enzymes ...
39-144 9.34e-32

DIRS1 family of RNase HI in long-term repeat retroelements; Ribonuclease H (RNase H) enzymes are divided into two major families, Type 1 and Type 2, based on amino acid sequence similarities and biochemical properties. RNase H is an endonuclease that cleaves the RNA strand of an RNA/DNA hybrid in a sequence non-specific manner in the presence of divalent cations. RNase H is widely present in various organisms, including bacteria, archaea and eukaryotes. RNase HI has also been observed as adjunct domains to the reverse transcriptase gene in retroviruses, in long-term repeat (LTR)-bearing retrotransposons and non-LTR retrotransposons. RNase HI in LTR retrotransposons perform degradation of the original RNA template, generation of a polypurine tract (the primer for plus-strand DNA synthesis), and final removal of RNA primers from newly synthesized minus and plus strands. The catalytic residues for RNase H enzymatic activity, three aspartatic acids and one glutamic acid residue (DEDD), are unvaried across all RNase H domains. Phylogenetic patterns of RNase HI of LTR retroelements is classified into five major families, Ty3/Gypsy, Ty1/Copia, Bel/Pao, DIRS1 and the vertebrate retroviruses. The structural features of DIRS1-group elements are different from typical LTR elements. RNase H inhibitors have been explored as an anti-HIV drug target because RNase H inactivation inhibits reverse transcription.


Pssm-ID: 260007  Cd Length: 120  Bit Score: 118.54  E-value: 9.34e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486  39 CGHLIAQGKWSPQQASHSINWLELRAVSLALRASHQHMQDQHLLVRTDNMSTKAHINRQGGTRSKSLFKESRILLQWAEQ 118
Cdd:cd09275   15 LLNSRAHGPWSADERNKHINLLELKAVLLALQHFAAELKNRKILIRTDNTTAVAYINKQGGTSSPPLLALARQILLWCEQ 94
                         90       100
                 ....*....|....*....|....*.
gi 975096486 119 YTLSLRAEHLRGLSNQQADWLSRENL 144
Cdd:cd09275   95 RNIWLRASHIPGVLNTEADRLSRLGL 120
TY cd00191
Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 ...
457-521 4.41e-23

Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases


Pssm-ID: 238114  Cd Length: 66  Bit Score: 92.53  E-value: 4.41e-23
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 975096486 457 PCLVELERIQIQEAAKKKPGVFIPSCDEDGYYRKMQCDPGSGECWCVDHLGMELTGTRMHGT-PDC 521
Cdd:cd00191    1 PCERERASALESLAGPKLSGLYVPQCDEDGNYEPVQCHGSTGYCWCVDPDGEEIPGTRTRGGpPNC 66
Thyroglobulin_1 pfam00086
Thyroglobulin type-1 repeat; Thyroglobulin type 1 repeats are thought to be involved in the ...
458-521 3.67e-22

Thyroglobulin type-1 repeat; Thyroglobulin type 1 repeats are thought to be involved in the control of proteolytic degradation. The domain usually contains six conserved cysteines. These form three disulphide bridges. Cysteines 1 pairs with 2, 3 with 4 and 5 with 6.


Pssm-ID: 333828  Cd Length: 66  Bit Score: 89.66  E-value: 3.67e-22
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 975096486  458 CLVELERIQIQEAAKKKP-GVFIPSCDEDGYYRKMQCDPGSGECWCVDHLGMELTGTR-MHGTPDC 521
Cdd:pfam00086   1 CQRERARALEQLAGGRPAsGLYIPQCDEDGFYKPVQCHGSTGYCWCVDPEGKEIPGTRtRGGDPNC 66
TY smart00211
Thyroglobulin type I repeats; The N-terminal region of human thyroglobulin contains 11 type-1 ...
479-523 2.94e-16

Thyroglobulin type I repeats; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases and binding partners of heparin.


Pssm-ID: 214561  Cd Length: 46  Bit Score: 72.41  E-value: 2.94e-16
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 975096486   479 IPSCDEDGYYRKMQCDPGSGECWCVDHLGMELTGTRMHGT-PDCDD 523
Cdd:smart00211   1 IPQCDEDGNYEPVQCDGSSGQCWCVDATGREIPGTRTEGGdPDCPS 46
EFh_SPARC_like cd16231
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
344-451 3.00e-12

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC) and similar proteins; This family includes secreted protein acidic and rich in cysteine (SPARC), secreted protein, acidic and rich in cysteine-like 1 (SPARCL1), and similar proteins. SPARC is a prototypic collagen-binding matricellular protein that is involved in extracellular matrix (ECM) assembly and fibrosis through binding both fibrillar collagen and basal lamina collagen IV. It regulates the activity of matrix metalloproteinases (MMPs), as well as the growth factor signaling mediated by cell surface receptors including vascular endothelial growth factor (VEGF) receptor, basic fibroblast growth factor (bFGF), and transforming growth factor (TGF) beta1. It also shows survival activity in tumor progression. SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an alpha-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site. SPARCL1 is the closest family member to SPARC. It shares the three primary domains contained within SPARC with an expanded N-terminal domain. SPARCL1 may function as both a tumor suppressor and as a regulator of angiogenesis. It can bind to collagens and be counter-adhesive to wild-type dermal fibroblasts, but do not influence rates of cell proliferation. Moreover, SPARCL1 can influence central nervous system (CNS) development and synaptic rearrangement.


Pssm-ID: 320010  Cd Length: 116  Bit Score: 63.14  E-value: 3.00e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 344 CTGQDLADLGDRLRDW-FQLLHENAKQNSSGStgaspvNVLDKSLVASCKDS------IGWMFSKLDTN-GDLFLDQTEL 415
Cdd:cd16231    1 CLDEELSEFPLRMRDWlKNVMVQLAERDELHE------GLTEKELEDFQKNYkmyvypVHWKFCDLDQHpHDRYLSHHEL 74
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 975096486 416 AAIN--LDKYEICIRPFFNSCDTYKDGRVSTAEWCFCF 451
Cdd:cd16231   75 APLRapLVPMEHCTTPFLETCDADNDKLISLKEWGACL 112
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
292-325 1.70e-10

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.


Pssm-ID: 197624  Cd Length: 46  Bit Score: 56.15  E-value: 1.70e-10
                           10        20        30
                   ....*....|....*....|....*....|....
gi 975096486   292 VCGSDGHTYSSVCKLEQQACLTSKQLTVKCEGQC 325
Cdd:smart00280  13 VCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46
Kazal_2 pfam07648
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
281-325 4.13e-10

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.


Pssm-ID: 336754  Cd Length: 49  Bit Score: 55.17  E-value: 4.13e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 975096486  281 CKPCHMTQLASVCGSDGHTYSSVCKLEQQACLTSKQL--TVKCEGQC 325
Cdd:pfam07648   3 CCQCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVghKVKYDGSC 49
KAZAL_FS cd00104
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
292-325 1.17e-09

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.


Pssm-ID: 238052  Cd Length: 41  Bit Score: 53.43  E-value: 1.17e-09
                         10        20        30
                 ....*....|....*....|....*....|....
gi 975096486 292 VCGSDGHTYSSVCKLEQQACLTSKQLTVKCEGQC 325
Cdd:cd00104    8 VCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41
EFh_SPARC_SPARCL1 cd16236
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein, acidic and rich ...
395-451 5.70e-08

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein, acidic and rich in cysteine-like 1 (SPARCL1); SPARCL1, also termed SPARC-like protein 1, or high endothelial venule protein (Hevin), or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2, is a diversely expressed and developmentally regulated extracellular matrix glycoprotein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. It plays a pivotal role in the corneal wound healing. SPARCL1 may function as both a tumor suppressor and as a regulator of angiogenesis. It regulates cell migration/invasion and suppresses metastasis in many cancers, including prostate cancer, colorectal cancer, gastric cancer, and breast cancer. It can bind to collagens and be counter-adhesive to wild-type dermal fibroblasts, but do not influence rates of cell proliferation. Moreover, SPARCL1 contributes to neural development and participates in remodeling events associated with neuronal degeneration following neural injury. It can influence central nervous system (CNS) development and synaptic rearrangement. SPARCL1 is the closest family member to secreted protein acidic and rich in cysteine (SPARC), but does not compensate for the absence of SPARC in the CNS. SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an alpha-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site. SPARCL1 shares the three primary domains contained within SPARC with an expanded N-terminal domain.


Pssm-ID: 320015  Cd Length: 93  Bit Score: 50.37  E-value: 5.70e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 395 IGWMFSKLDTN-GDLFLDQTELAAI--NLDKYEICIRPFFNSCDTYKDGRVSTAEWCFCF 451
Cdd:cd16236   30 VHWQFAQLDQHpSDRFLTHSELAPLraSLVPMEHCITRFFQECDADKDKLITLKEWCHCF 89
EFh_SPARC_SMOC cd16234
EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding ...
397-451 1.57e-06

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: 46.50  E-value: 1.57e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 975096486 397 WMFSKLDTNGDLFLDQTEL--------AAINLDKyeiCIRPFFNSCDTYKDGRVSTAEWCFCF 451
Cdd:cd16234   43 WKFSQLDKNKNGVLERKEWkpfkrllkKAVKPKK---CARKFPKYCDVNKDKKISLTEWLNCL 102
RNase_HI_RT_Ty3 cd09274
Ty3/Gypsy family of RNase HI in long-term repeat retroelements; Ribonuclease H (RNase H) ...
40-141 3.47e-06

Ty3/Gypsy family of RNase HI in long-term repeat retroelements; Ribonuclease H (RNase H) enzymes are divided into two major families, Type 1 and Type 2, based on amino acid sequence similarities and biochemical properties. RNase H is an endonuclease that cleaves the RNA strand of an RNA/DNA hybrid in a sequence non-specific manner in the presence of divalent cations. RNase H is widely present in various organisms, including bacteria, archaea and eukaryotes. RNase HI has also been observed as adjunct domains to the reverse transcriptase gene in retroviruses, in long-term repeat (LTR)-bearing retrotransposons and non-LTR retrotransposons. RNase HI in LTR retrotransposons perform degradation of the original RNA template, generation of a polypurine tract (the primer for plus-strand DNA synthesis), and final removal of RNA primers from newly synthesized minus and plus strands. The catalytic residues for RNase H enzymatic activity, three aspartatic acids and one glutamic acid residue (DEDD), are unvaried across all RNase H domains. Phylogenetic patterns of RNase HI of LTR retroelements is classified into five major families, Ty3/Gypsy, Ty1/Copia, Bel/Pao, DIRS1 and the vertebrate retroviruses. Ty3/Gypsy family widely distributed among the genomes of plants, fungi and animals. RNase H inhibitors have been explored as an anti-HIV drug target because RNase H inactivation inhibits reverse transcription.


Pssm-ID: 260006  Cd Length: 121  Bit Score: 45.95  E-value: 3.47e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486  40 GHLIA--QGKWSPQQASHSINWLELRAVSLALRASHQHMQDQHLLVRTDNMSTKaHINRQggtrsKSLfkeSRILLQWAE 117
Cdd:cd09274   24 ERPIAffSRKLTPAERNYSTTEKELLAIVWALKKFRHYLLGRPFTVYTDHKALK-YLLTQ-----KDL---NGRLARWLL 94
                         90       100
                 ....*....|....*....|....*..
gi 975096486 118 ---QYTLSLraEHLRGLSNQQADWLSR 141
Cdd:cd09274   95 llsEFDFEI--EYRPGKENVVADALSR 119
EFh_SPARC_SPARC cd16235
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
344-451 3.59e-05

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC); SPARC, also termed basement-membrane protein 40 (BM-40), or osteonectin (ON), is a prototypic collagen-binding matricellular protein that is essential for embryo development in invertebrates and highly expressed in bone. It participates in normal tissue remodeling as it regulates the deposition of extracellular matrix, as well as in neoplastic transformation. It is involved in extracellular matrix (ECM) assembly and fibrosis through binding both fibrillar collagen and basal lamina collagen IV. It regulates the activity of matrix metalloproteinases (MMPs), as well as the growth factor signaling mediated by cell surface receptors including vascular endothelial growth factor (VEGF) receptor, basic fibroblast growth factor (bFGF), and transforming growth factor (TGF) beta1. SPARC shows survival activity in tumor progression. It plays a role in metastatic process to the lung during melanoma progression. It can suppress prostate cancer cell growth and survival. Moreover, SPARC is a bone- associated protein that has a major role in bone development and mineralisationis. It is involved in the initiation and progression of vascular calcification and upregulated by adiponectin. Furthermore, SPARC may be one of the molecules that govern the uptake and delivery of proteins from blood to the cerebrospinal fluid (CSF) during brain development. SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an alpha-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site. Platelet-derived growth factor (PDGF) also interacts with its EC domain, but in a calcium-independent manner, whereas collagen binding is calcium-dependent.


Pssm-ID: 320014  Cd Length: 96  Bit Score: 42.69  E-value: 3.59e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486 344 CTGQDLADLGDRLRDWFQllhenakqnssgstgaspvNVLDKSLVASCKDSIGWMFSKLDTNG-DLFLDQTELAAIN--L 420
Cdd:cd16235    1 CLDSELTEFPLRMRDWLK-------------------NVLVTLYERDYIFPVHWQFGQLDQHPiDGYLSHTELAPLRapL 61
                         90       100       110
                 ....*....|....*....|....*....|.
gi 975096486 421 DKYEICIRPFFNSCDTYKDGRVSTAEWCFCF 451
Cdd:cd16235   62 IPMEHCTTRFFETCDLDNDKYIALDEWAGCF 92
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
397-448 4.28e-05

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: 41.38  E-value: 4.28e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 975096486 397 WMFSKLDTNGDLFLDQTELAAI------NLDKYEicIRPFFNSCDTYKDGRVSTAEWC 448
Cdd:cd00051    4 EAFRLFDKDGDGTISADELKAAlkslgeGLSEEE--IDEMIREVDKDGDGKIDFEEFL 59
RNase_H_like cd06222
Ribonuclease H-like superfamily, including RNase H, HI, HII, HIII, and RNase-like domain IV of ...
55-141 7.81e-05

Ribonuclease H-like superfamily, including RNase H, HI, HII, HIII, and RNase-like domain IV of spliceosomal protein Prp8; Ribonuclease H (RNase H) enzymes are divided into two major families, Type 1 and Type 2, based on amino acid sequence similarities and biochemical properties. RNase H is an endonuclease that cleaves the RNA strand of an RNA/DNA hybrid in a sequence non-specific manner in the presence of divalent cations. It is widely present in various organisms, including bacteria, archaea, and eukaryotes. Most prokaryotic and eukaryotic genomes contain multiple RNase H genes. Despite the lack of amino acid sequence homology, type 1 and type 2 RNase H share a main-chain fold and steric configurations of the four acidic active-site residues and have the same catalytic mechanism and functions in cells. RNase H is involved in DNA replication, repair and transcription. An important RNase H function is to remove Okazaki fragments during DNA replication. RNase H inhibitors have been explored as anti-HIV drug targets since RNase H inactivation inhibits reverse transcription. This model also includes the Prp8 domain IV, which adopts the RNase fold but shows low sequence homology; domain IV is implicated in key spliceosomal interactions.


Pssm-ID: 259998 [Multi-domain]  Cd Length: 121  Bit Score: 42.30  E-value: 7.81e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 975096486  55 HSINWLELRAVSLALR-ASHQHMqdQHLLVRTDNMSTKAHINRQGGTRSKSLFKESRILLQWAEQYTLSLraEHLRGLSN 133
Cdd:cd06222   38 PTALEAELLALLLALElALDLGY--LKVIIESDSKYVVDLINSGSFKWSPNILLIEDILLLLSRFWSVKI--SHVPREGN 113

                 ....*...
gi 975096486 134 QQADWLSR 141
Cdd:cd06222  114 QVADALAK 121
EF-hand_7 pfam13499
EF-hand domain pair;
392-446 1.91e-04

EF-hand domain pair;


Pssm-ID: 338778 [Multi-domain]  Cd Length: 68  Bit Score: 39.56  E-value: 1.91e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 975096486  392 KDSIGWMFSKLDTNGDLFLDQTELA---------AINLDKYEicIRPFFNSCDTYKDGRVSTAE 446
Cdd:pfam13499   1 EEKLKEAFKLLDKDGDGYLDVEELKkllrklfeeGEKLSDEE--VEELFKEFDLDKDGRISFEE 62
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.17
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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