Conserved Protein Domain Family
EFh_SPARC_TICN

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cd16232: EFh_SPARC_TICN 
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.
Statistics
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PSSM-Id: 320011
View PSSM: cd16232
Aligned: 14 rows
Threshold Bit Score: 148.287
Threshold Setting Gi: 560126870
Created: 18-Nov-2014
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
Feature 1:putative Ca binding site [ion binding site]
Evidence:
  • Comment:Based on the structure evidence how the first EF-hand motif in Homo sapiens SPARC (1SRA) binds Ca2+ ion.
  • Comment:Unlike other members in SPARC family, the substitution of a ligating Asp residue 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+ with low affinity.
  • Citation:PMID 8119487
  • Citation:PMID 9323035

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                            #   #      #
Q92563       199 CTGQDLADLGDRLRDWFQLLHENSKqngsassvagp---------asgldkslgasCKDSIGWMFSKLDTSADLFLDQTE 269 human
XP_005092964 197 CTTSEFSQMRTRMMGWFHLLHGQDHlakkqagnikhfhkhvsvkkelrehdgnrceCFKSAMWQFNQMDKNGDDHLNEFE 276 California sea ...
KFM76800     175 CNENELKAMGDRLLDWFSVVMADHRrgqsrrrsf-------------rlshtqlpdCKPEVSWMFQHLDTDGDLKLSLQE 241 Stegodyphus mim...
KFD67620     154 CTEKQLVTIEDLLVRWFTSLRMQSTnaeavsl------------------pkhhirCQPDVGWMFAQLDGNHDGHLEHDE 215 pig whipworm
ERG80519     115 CGEQELHRIGGRLLQWFIEMHKVSGadvevss------------------qkrdveCRPDVAWMFEQWDGNNDGELSVKE 176 pig roundworm
CDJ88497      85 CSHAELISMGGRLLQWFSDMHRIHTgrektl-------------------pahkiaCRNDVAWMFEQWDGDNDGLLSKDE 145 barber pole worm
CCD68035      40 CTRSELMRMGGRLVKWFKDVHAQESgadhtl-------------------klhsvpCRVEVGWMFNQWDGNQDGKLSKAE 100 Caenorhabditis ...
EEN60739     113 CSTEELEDMGNRLLEWFKVLRKNEEkekpdtn------------------knvqicYEPAVGWMFSKLDVNFDLFLSKKE 174 Florida lancelet
NP_001262857 428 CKPQQLTAIGNRLLDWFSVIMADSKkrrqhsqk---------------skahfppaCKTEAKWMFGHLDLNNDGQLSLQE 492 fruit fly
Q9BQ16       201 CSDLEFREVANRLRDWFKALHESGSqnkktktllrpe--------rsrfdtsilpiCKDSLGWMFNRLDTNYDLLLDQSE 272 human
Feature 1                                                   
Q92563       270 LAAINLDKYEVCIRPFFNSC--DTYKDGRVSTAEWCFCFWREK 310 human
XP_005092964 277 MSVMEENSMEPCMRPYLTSC--DRNADGKLSSDEWCCCFANVV 317 California sea hare
KFM76800     242 LYDLENDDQEHCLRPYLLDC--DVERDLVLSPYEWCSCFDKSQ 282 Stegodyphus mimosarum
KFD67620     216 LYTLDHEKYKNCIHHFLDQC--DLNQDAQLSLDEWCDCFEWAG 256 pig whipworm
ERG80519     177 LAPLESDANEKCLKAFIDRCdtDPGNDDVITLEEWCDCFAWAD 219 pig roundworm
CDJ88497     146 LMPLEGNGRESCLAQFIDMCd-DMVVDGQISVDEWCDCFSFAD 187 barber pole worm
CCD68035     101 LRPIERGGNEACVEEFIDMCd-DMVVDGSISVDEWCDCFTFSD 142 Caenorhabditis elegans
EEN60739     175 LSLIEYDEYEHCITPFIDRC--DRIKDGILSANEWCSCFEEAS 215 Florida lancelet
NP_001262857 493 MYDLEHDQNERCIKPFIDTC--DLDTDSSINTREWCRCFEKTD 533 fruit fly
Q9BQ16       273 LRSIYLDKNEQCTKAFFNSC--DTYKDSLISNNEWCYCFQRQQ 313 human

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