Conserved Protein Domain Family
EFh_SPARC_TICN3

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cd16239: EFh_SPARC_TICN3 
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.
Statistics
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PSSM-Id: 320018
View PSSM: cd16239
Aligned: 4 rows
Threshold Bit Score: 231.446
Threshold Setting Gi: 573882182
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 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+ with low affinity.
  • Citation:PMID 8119487

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                    #   #      #        
gi 67473703  201 CSDLEFREVANRLRDWFKALHESGSqnkktktllrpersrfdtsilpiCKDSLGWMFNRLDTNYDLLLDQSELRSIYLDK 280
gi 156717308 202 CTDREFREIANRLRDWFKALHESGFqnkksktvtraersrfdtsilpiCRDSLGWMFNRLDTNYDLLLDQSELGSIYIDK 281
gi 543722778 110 CSDLEFREVANRLRDWFKALHESGIqnkktrivqrpertrfdtsilpiCKDSLGWMFNRLDTNYDLLLDQSELGSIYLDK 189
gi 573882182 174 CSDMELREVVSRLRDWFKVLHENGSqnkkvkiqrpe-rsrfdtsilpiCKDSLGWMFNRLDTNFDLLLDQSELASLYLDK 252
                         90       100       110
                 ....*....|....*....|....*....|...
Feature 1                                         
gi 67473703  281 NEQCTKAFFNSCDTYKDSLISNNEWCYCFQRQQ 313
gi 156717308 282 NEQCTKAFFNTCDTYKDSLISNNEWCYCFQRQQ 314
gi 543722778 190 NEPCTRAFFNSCDTYKDSLISNNEWCYCFQRQQ 222
gi 573882182 253 NEHCTKSFFNSCDTYRDGLISNNEWCSCFQRQQ 285

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