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protein tyrosine phosphatase H (transmembrane-type protein-tyrosine phosphatase type H, stomach cancer-associated protein tyrosine phosphatase 1, SAP-1, PTPRH, SAP1)
Function:
- may contribute to contact inhibition of cell growth & motility by mediating the dephosphorylation of focal adhesion- associated substrates & thus negatively regulating integrin- promoted signaling processes
- induces apoptotosis by at least 2 distinct mechanisms:
1) inhibition of cell survival
2) signaling mediated by PI 3-kinase, Akt, & ILK & activation of a caspase-dependent proapoptotic pathway
- inhibits basal activity of LCK & its activation in response to TCR stimulation & TCR-induced activation of MAP kinase & surface expression of CD69
- inhibits TCR-induced tyrosine phosphorylation of LAT & ZAP-70
- inhibits both basal activity of DOK1 & its CD2-induced tyrosine phosphorylation
- induces dephosphorylation of p130cas, focal adhesion kinase & c-Src
- reduces migratory activity of Jurkat cells
- regulated by reversible dimerization
- dimerization reduces its catalytic activity
- interacts with LCK
protein tyrosine phosphate + H2O protein tyrosine + phosphate
Structure:
- homodimer; disulfide-linked (probable)
- extracellular domain mediates homodimerization
- one or more Cys in the extracellular domain is essential for the formation of dimers probably by forming a disulfide bond
- cytoplasmic domain mediates the interaction with LCK
- belongs to the protein-tyrosine phosphatase family receptor class 3 subfamily
- contains 8 fibronectin F3 modules
- contains 1 tyrosine-protein phosphatase domain
Compartment:
- membrane, cytoplasm
Alternative splicing: named isoforms=2
Expression:
- expressed in brain, spleen & liver > heart & stomach
Pathology:
- expressed in pancreatic cancer & colorectal cancer cells, but not in normal pancreas or colon
- expression in hepatocellular carcinoma is related to the differentiation status of the tumor & expression is inversely related to tumor aggressiveness
- induced at the early stage of hepatocellular carcinoma & is suppressed at later stages
General
glycoprotein
tyrosine phosphatase, receptor type
Properties
SIZE: entity length = 1115 aa
MW = 122 kD
COMPARTMENT: cytoplasm
cellular membrane
STATE: active state
MOTIF: signal sequence {1-27}
fibronectin type III domain or F3 module {30-117}
MOTIF: N-glycosylation site {N35}
N-glycosylation site {N83}
fibronectin type III domain or F3 module {119-206}
MOTIF: N-glycosylation site {N172}
fibronectin type III domain or F3 module {207-296}
MOTIF: N-glycosylation site {N256}
N-glycosylation site {N285}
fibronectin type III domain or F3 module {297-384}
MOTIF: N-glycosylation site {N350}
fibronectin type III domain or F3 module {386-473}
MOTIF: N-glycosylation site {N434}
N-glycosylation site {N468}
fibronectin type III domain or F3 module {475-563}
MOTIF: N-glycosylation site {N556}
fibronectin type III domain or F3 module {565-663}
MOTIF: N-glycosylation site {N642}
fibronectin type III domain or F3 module {665-749}
transmembrane domain {755-775}
Tyrosine-protein phosphatase {820-1079}
MOTIF: cysteine residue {C1020}
Database Correlations
OMIM 602510
UniProt Q9HD43
PFAM correlations
Entrez Gene 5794
Kegg hsa:5794
ENZYME 3.1.3.48
References
UniProt :accession Q9HD43