protein tyrosine phosphatase 11, non-receptor type; SH2-containing protein phosphatase-2 (PTPN11, Syp, SHPTP2)
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Function
- acts downstream of various receptor & cytoplasmic protein tyrosine kinases to participate in signal transduction from the cell surface to the nucleus
- SH2 containing protein tyrosine phosphatases may act preferentially on substrates that are phosphorylated on more than one Tyr
- interaction of their SH2 domain(s) with phosphorylated Tyr(s) may position the enzyme to hydrolyze unprotected phospho-Tyr
- phosphorylation enhances phosphatase activity
- phosphorylated on Tyr-546 & Tyr-584 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 & other SH2-containing proteins
- may interact with phosphorylated IRS-1
- interacts with phosphorylated LIME1 & BCAR3
- interacts with SHB & INPP5D/SHIP1 (putative)
- interacts with PTPNS1 & CD84. interacts with phosphorylated SIT1 & MPZL1
- interacts with FCRL3, FCRL4, FCRL6 & ANKHD1
Structure
- Syp is the mammalian homolog of drosophila "corkscrew" (Csw)
- SH2 domains repress phosphatase activity
- binding of SH2 domains to phospho-Tyr containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme
- belongs to the protein-tyrosine phosphatase family non-receptor class 2 subfamily
- contains 2 SH2 domains
- contains 1 tyrosine-protein phosphatase domain
Compartment
Alternative splicing
named isoforms=3
Expression
- widely expressed in human tissues
- particularly abundant in heart, brain & skeletal muscle
Pathology
- defects in PTPN11 are associated with
More general terms
References
- ↑ Feng GS, Hui CC, Pawson T. SH2-containing phosphotyrosine phosphatase as a target of protein-tyrosine kinases. Science. 1993 Mar 12;259(5101):1607-11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8096088
- ↑ Vogel W, Lammers R, Huang J, Ullrich A. Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation. Science. 1993 Mar 12;259(5101):1611-4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7681217
- ↑ Ahmad S, Banville D, Zhao Z, Fischer EH, Shen SH. A widely expressed human protein-tyrosine phosphatase containing src homology 2 domains. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2197-201. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7681589
- ↑ Saltiel AR. The paradoxical regulation of protein phosphorylation in insulin action. FASEB J. 1994 Oct;8(13):1034-40. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7926368
- ↑ Atlas of genetics & cytogenetics in oncology haematology http://atlasgeneticsoncology.org/genes/PTPN11ID41910ch12q24.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=PTPN11
- ↑ UniProt http://www.uniprot.org/uniprot/Q06124.html
Database
- UniProt: http://www.uniprot.org/uniprot/Q06124.html
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5781
- OMIM: https://mirror.omim.org/entry/151100
- OMIM: https://mirror.omim.org/entry/163950
- OMIM: https://mirror.omim.org/entry/163955
- OMIM: https://mirror.omim.org/entry/176876
- OMIM: https://mirror.omim.org/entry/607785
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5781