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Conserved domains on  [gi|2462597421|ref|XP_054206103|]
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testican-3 isoform X2 [Homo sapiens]

Protein Classification

testican-3( domain architecture ID 12199549)

testican-3 may participate in diverse steps of neurogenesis; it is a BM-40/SPARC/osteonectin family protein containing Kazal-type serine protease inhibitor/follistatin-like, EF-hand, and thyroglobulin type-1 repeat domains

CATH:  3.30.60.30|4.10.800.10
Gene Symbol:  SPOCK3
Gene Ontology:  GO:0005576|GO:0005509
PubMed:  23418755|10641790|22249026|19995574|12051857|28707401|2479149|8797845
SCOP:  4003413|4003524

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EFh_SPARC_TICN3 cd16239
EF-hand, extracellular calcium-binding (EC) motif, found in testican-3 (TICN3); TICN3, also ...
 201-313 3.17e-80

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: 243.00  E-value: 3.17e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFKALHESGSQNKKTKTLLRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELRSIYLDK 280
Cdd:cd16239     1 CSDLEFREVANRLRDWFKALHESGSQNKKTKIVRRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELGSIYLDK 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462597421 281 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQRQQ 313
Cdd:cd16239    81 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQRQQ 113
TY cd00191
Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 ...
 316-380 3.53e-22

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: 89.45  E-value: 3.53e-22
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462597421 316 PCQTELSNIQKRQGVKKLLGQYIPLCDEDGYYKPTQCHGSVGQCWCVDRYGNEVMGSRI-NGVADC 380
Cdd:cd00191     1 PCERERASALESLAGPKLSGLYVPQCDEDGNYEPVQCHGSTGYCWCVDPDGEEIPGTRTrGGPPNC 66
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
 140-183 2.65e-11

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


:

Pssm-ID: 197624  Cd Length: 46  Bit Score: 58.07  E-value: 2.65e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2462597421  140 KQCPVVYpSPVCGSDGHTYSFQCKLEYQACVLGKQISVKCEGHC 183
Cdd:smart00280   4 EACPREY-DPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46
 
Name Accession Description Interval E-value
EFh_SPARC_TICN3 cd16239
EF-hand, extracellular calcium-binding (EC) motif, found in testican-3 (TICN3); TICN3, also ...
 201-313 3.17e-80

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: 243.00  E-value: 3.17e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFKALHESGSQNKKTKTLLRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELRSIYLDK 280
Cdd:cd16239     1 CSDLEFREVANRLRDWFKALHESGSQNKKTKIVRRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELGSIYLDK 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462597421 281 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQRQQ 313
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 ...
 199-307 3.72e-42

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: 463162  Cd Length: 111  Bit Score: 144.41  E-value: 3.72e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 199 RACSDLEFREVANRLRDWFKALHESGSQNKKTKTLLRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELRSIY- 277
Cdd:pfam10591   1 PCCTDEELAEFPRRMRDWLKLLLEALRNRRERKDHSSTLEKRDESLLYPCCKDPLGWMFKRLDTNDDLLLDHEELAPIRa 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462597421 278 -LDKNEQCTKAFFNSCDTYKDSLISNNEWCY 307
Cdd:pfam10591  81 pLKPEEHCIKPFFESCDANKDKLISLEEWCC 111
TY cd00191
Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 ...
 316-380 3.53e-22

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: 89.45  E-value: 3.53e-22
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462597421 316 PCQTELSNIQKRQGVKKLLGQYIPLCDEDGYYKPTQCHGSVGQCWCVDRYGNEVMGSRI-NGVADC 380
Cdd:cd00191     1 PCERERASALESLAGPKLSGLYVPQCDEDGNYEPVQCHGSTGYCWCVDPDGEEIPGTRTrGGPPNC 66
Thyroglobulin_1 pfam00086
Thyroglobulin type-1 repeat; Thyroglobulin type 1 repeats are thought to be involved in the ...
 317-380 1.26e-21

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: 459665  Cd Length: 66  Bit Score: 87.74  E-value: 1.26e-21
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462597421 317 CQTELSNIQKR-QGVKKLLGQYIPLCDEDGYYKPTQCHGSVGQCWCVDRYGNEVMGSR-INGVADC 380
Cdd:pfam00086   1 CERERARALEQaASGRPASGLYIPNCDEDGFYKPVQCHGSTGYCWCVDPEGQEIPGTRtRGGDPDC 66
TY smart00211
Thyroglobulin type I repeats; The N-terminal region of human thyroglobulin contains 11 type-1 ...
 338-380 1.00e-13

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: 65.09  E-value: 1.00e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2462597421  338 IPLCDEDGYYKPTQCHGSVGQCWCVDRYGNEVMGSR-INGVADC 380
Cdd:smart00211   1 IPQCDEDGNYEPVQCDGSSGQCWCVDATGREIPGTRtEGGDPDC 44
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
 140-183 2.65e-11

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


Pssm-ID: 197624  Cd Length: 46  Bit Score: 58.07  E-value: 2.65e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2462597421  140 KQCPVVYpSPVCGSDGHTYSFQCKLEYQACVLGKQISVKCEGHC 183
Cdd:smart00280   4 EACPREY-DPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46
Kazal_2 pfam07648
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
 137-183 9.39e-11

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: 400135  Cd Length: 50  Bit Score: 56.73  E-value: 9.39e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462597421 137 STCKQCPVVYPSPVCGSDGHTYSFQCKLEYQACVLGKQIS---VKCEGHC 183
Cdd:pfam07648   1 NCNCQCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKeekVKYDGSC 50
KAZAL_FS cd00104
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
 142-183 2.31e-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 [Multi-domain]  Cd Length: 41  Bit Score: 52.66  E-value: 2.31e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2462597421 142 CPVVYpSPVCGSDGHTYSFQCKLEYQACVLGKQISVKCEGHC 183
Cdd:cd00104     1 CPKEY-DPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41
 
Name Accession Description Interval E-value
EFh_SPARC_TICN3 cd16239
EF-hand, extracellular calcium-binding (EC) motif, found in testican-3 (TICN3); TICN3, also ...
 201-313 3.17e-80

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: 243.00  E-value: 3.17e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFKALHESGSQNKKTKTLLRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELRSIYLDK 280
Cdd:cd16239     1 CSDLEFREVANRLRDWFKALHESGSQNKKTKIVRRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELGSIYLDK 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462597421 281 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQRQQ 313
Cdd:cd16239    81 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQRQQ 113
EFh_SPARC_TICN cd16232
EF-hand, extracellular calcium-binding (EC) motif, found in testicans; Testicans are nervous ...
 201-313 1.13e-53

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: 174.48  E-value: 1.13e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFKALHESGSQNKKTKTLLRpersrFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELRSIYLDK 280
Cdd:cd16232     1 CTESELSEMGDRLLDWFSVLHEQSNKAKKTSSSKR-----FDKSHLPECKPSVGWMFNQLDTNNDLHLSQSELYDLELDK 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462597421 281 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQRQQ 313
Cdd:cd16232    76 YEPCIKPFLDSCDRNKDGKISSDEWCDCFQRAD 108
EFh_SPARC_TICN1 cd16237
EF-hand, extracellular calcium-binding (EC) motif, found in testican-1 (TICN1); TICN1, also ...
 201-311 8.52e-49

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: 162.13  E-value: 8.52e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFKALHESGSQNKKTkTLLRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELRSIYLDK 280
Cdd:cd16237     1 CTDKELRNLASRLKDWFGALHEDANRVIKP-TSSFTAQGRFDTSILPICKDSLGWMFNKLDMNYDLLLDPSEISAIYLDK 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462597421 281 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQR 311
Cdd:cd16237    80 YEPCMKPLFNSCDSFKDGKLSNNEWCYCFQK 110
SPARC_Ca_bdg pfam10591
Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of ...
 199-307 3.72e-42

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: 463162  Cd Length: 111  Bit Score: 144.41  E-value: 3.72e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 199 RACSDLEFREVANRLRDWFKALHESGSQNKKTKTLLRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELRSIY- 277
Cdd:pfam10591   1 PCCTDEELAEFPRRMRDWLKLLLEALRNRRERKDHSSTLEKRDESLLYPCCKDPLGWMFKRLDTNDDLLLDHEELAPIRa 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462597421 278 -LDKNEQCTKAFFNSCDTYKDSLISNNEWCY 307
Cdd:pfam10591  81 pLKPEEHCIKPFFESCDANKDKLISLEEWCC 111
EFh_SPARC_TICN2 cd16238
EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also ...
 201-313 5.13e-36

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: 128.52  E-value: 5.13e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFKALHESGSQNKkTKTLLRPERSRFDTSILPICKDSLGWMFNRLDTNYDLLLDQSELRSIYLDK 280
Cdd:cd16238     1 CTGQDLADLGDRLRDWFQLLHENSKQNG-SGSPPASPASALDRSLVASCKDSIGWMFSKLDTSGDLFLDQAELAAINLDK 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462597421 281 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQRQQ 313
Cdd:cd16238    80 YEVCIRPFFNSCDTYRDGRVSTAEWCFCFWREK 112
TY cd00191
Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 ...
 316-380 3.53e-22

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: 89.45  E-value: 3.53e-22
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462597421 316 PCQTELSNIQKRQGVKKLLGQYIPLCDEDGYYKPTQCHGSVGQCWCVDRYGNEVMGSRI-NGVADC 380
Cdd:cd00191     1 PCERERASALESLAGPKLSGLYVPQCDEDGNYEPVQCHGSTGYCWCVDPDGEEIPGTRTrGGPPNC 66
Thyroglobulin_1 pfam00086
Thyroglobulin type-1 repeat; Thyroglobulin type 1 repeats are thought to be involved in the ...
 317-380 1.26e-21

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: 459665  Cd Length: 66  Bit Score: 87.74  E-value: 1.26e-21
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462597421 317 CQTELSNIQKR-QGVKKLLGQYIPLCDEDGYYKPTQCHGSVGQCWCVDRYGNEVMGSR-INGVADC 380
Cdd:pfam00086   1 CERERARALEQaASGRPASGLYIPNCDEDGFYKPVQCHGSTGYCWCVDPEGQEIPGTRtRGGDPDC 66
EFh_SPARC_EC cd00252
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 201-309 8.02e-21

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: 87.04  E-value: 8.02e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFKALHESGSQNKKTKTLLRPERSRFDtsilpiCKDSLGWMFNRLDTNYDLLLDQSELRSI--YL 278
Cdd:cd00252     1 CPGSELMQFPDRLLDWLLLLKEQDENRSYDNNKRGHDLSGTM------RKEIAQWEFDNLDNNKDGKLDKRELAPFraPL 74

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462597421 279 DKNEQCTKAFFNSCDTYKDSLISNNEWCYCF 309
Cdd:cd00252    75 MPLEHCARGFFESCDLNKDKKISLQEWLGCF 105
TY smart00211
Thyroglobulin type I repeats; The N-terminal region of human thyroglobulin contains 11 type-1 ...
 338-380 1.00e-13

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: 65.09  E-value: 1.00e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2462597421  338 IPLCDEDGYYKPTQCHGSVGQCWCVDRYGNEVMGSR-INGVADC 380
Cdd:smart00211   1 IPQCDEDGNYEPVQCDGSSGQCWCVDATGREIPGTRtEGGDPDC 44
EFh_SPARC_like cd16231
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 201-309 2.90e-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: 2.90e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFK-------ALHESGsqNKKTKTLLRPERSRFDTSILPICkdslgWMFNRLDTN-YDLLLDQSE 272
Cdd:cd16231     1 CLDEELSEFPLRMRDWLKnvmvqlaERDELH--EGLTEKELEDFQKNYKMYVYPVH-----WKFCDLDQHpHDRYLSHHE 73

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462597421 273 LRSIY--LDKNEQCTKAFFNSCDTYKDSLISNNEWCYCF 309
Cdd:cd16231    74 LAPLRapLVPMEHCTTPFLETCDADNDKLISLKEWGACL 112
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
 140-183 2.65e-11

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


Pssm-ID: 197624  Cd Length: 46  Bit Score: 58.07  E-value: 2.65e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2462597421  140 KQCPVVYpSPVCGSDGHTYSFQCKLEYQACVLGKQISVKCEGHC 183
Cdd:smart00280   4 EACPREY-DPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46
Kazal_2 pfam07648
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
 137-183 9.39e-11

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: 400135  Cd Length: 50  Bit Score: 56.73  E-value: 9.39e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462597421 137 STCKQCPVVYPSPVCGSDGHTYSFQCKLEYQACVLGKQIS---VKCEGHC 183
Cdd:pfam07648   1 NCNCQCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKeekVKYDGSC 50
KAZAL_FS cd00104
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
 142-183 2.31e-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 [Multi-domain]  Cd Length: 41  Bit Score: 52.66  E-value: 2.31e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2462597421 142 CPVVYpSPVCGSDGHTYSFQCKLEYQACVLGKQISVKCEGHC 183
Cdd:cd00104     1 CPKEY-DPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41
EFh_SPARC_SMOC cd16234
EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding ...
 255-309 2.46e-08

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: 51.51  E-value: 2.46e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 255 WMFNRLDTNYDLLLDQSELRSI--YLDKN---EQCTKAFFNSCDTYKDSLISNNEWCYCF 309
Cdd:cd16234    43 WKFSQLDKNKNGVLERKEWKPFkrLLKKAvkpKKCARKFPKYCDVNKDKKISLTEWLNCL 102
EFh_SPARC_SPARCL1 cd16236
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein, acidic and rich ...
 201-309 2.65e-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: 51.14  E-value: 2.65e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFKALhesgsqnkktktLLRPersrfdTSILPIckdslGWMFNRLDTN-YDLLLDQSELRSIY-- 277
Cdd:cd16236     1 CTDSEVVQFPLRMRDWLKNI------------LMQL------YYIYPV-----HWQFAQLDQHpSDRFLTHSELAPLRas 57

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462597421 278 LDKNEQCTKAFFNSCDTYKDSLISNNEWCYCF 309
Cdd:cd16236    58 LVPMEHCITRFFQECDADKDKLITLKEWCHCF 89
EFh_SPARC_SPARC cd16235
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 201-309 4.43e-06

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: 45.00  E-value: 4.43e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462597421 201 CSDLEFREVANRLRDWFKALhesgsqnkkTKTLLrpERSrfdtSILPIckdslGWMFNRLDTN-YDLLLDQSELRSIY-- 277
Cdd:cd16235     1 CLDSELTEFPLRMRDWLKNV---------LVTLY--ERD----YIFPV-----HWQFGQLDQHpIDGYLSHTELAPLRap 60

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462597421 278 LDKNEQCTKAFFNSCDTYKDSLISNNEWCYCF 309
Cdd:cd16235    61 LIPMEHCTTRFFETCDLDNDKYIALDEWAGCF 92
KAZAL_PSTI cd01327
Kazal-type pancreatic secretory trypsin inhibitors (PSTI) and related proteins, including the ...
 142-183 3.94e-03

Kazal-type pancreatic secretory trypsin inhibitors (PSTI) and related proteins, including the second domain of the ovomucoid turkey inhibitor and the C-terminal domain of the esophagus cancer-related gene-2 protein (ECRG-2), are members of the superfamily of kazal-type proteinase inhibitors and follistatin-like proteins.


Pssm-ID: 238648  Cd Length: 45  Bit Score: 34.95  E-value: 3.94e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2462597421 142 CPVVYpSPVCGSDGHTYSFQCKLEYQACVLGKQISVKCEGHC 183
Cdd:cd01327     5 CPKDY-DPVCGTDGVTYSNECLLCAENLKRQTNIRIKHDGEC 45
 
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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