Tyrosine-protein phosphatase non-receptor type 11

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Basic Information
Short Name PTPN11, SHP2
UNP ID Q06124
Organism Homo sapiens
Cys Site Cys463
Family/Domain Protein-tyrosine phosphatase family,
Non-receptor class 2 subfamily
Known Ligand Ligand list
Function Type Post-translational Modification, Phosphatase

Summary

Protein Function

The Src homology-2 domain-containing phosphatase (SHP-2), a member of the ubiquitously expressed protein-tyrosine phosphatase (PTP) family, contains a cysteine residue at its active site. SHP-2 is known to localize in the cytosol and nucleus, and plays important biological functions in response to various growth factors, hormones, and cytokines. Recent studies have shown that activation of SHP-2 increases survival of various cell types, including neural progenitor cells and neurons, through activation of ERK1/2. SHP-2 is thought to promote ERK signaling by dephosphorylating negative regulators of the Ras-ERK pathway, such as PAG/Cbp, Ras-GAP, or GAP-binding sites on receptor tyrosine kinases or Sprouty proteins. Additionally, transient activation of the ERK1/2 signaling cascade has been implicated in regulating neuronal survival after stroke. (PMID: 23382182)

Cys Function & Property

Cys463 is one the active residues of PTPN11, which act as a phosphocysteine intermediate in catalytic process.

  • Hydrophobic property:
580-hydro.png
  • SASA:
Cys463: 3.3 A^2

Protein Sequence

MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA
VTHIKIQNTG DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY
PLNCADPTSE RWFHGHLSGK EAEKLLTEKG KHGSFLVRES QSHPGDFVLS
VRTGDDKGES NDGKSKVTHV MIRCQELKYD VGGGERFDSL TDLVEHYKKN
PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT DKVKQGFWEE
FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP
VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS
RVIVMTTKEV ERGKSKCVKY WPDEYALKEY GVMRVRNVKE SAAHDYTLRE
LKLSKVGQAL LQGNTERTVW QYHFRTWPDH GVPSDPGGVL DFLEEVHHKQ
ESIMDAGPVV VHCSAGIGRT GTFIVIDILI DIIREKGVDC DIDVPKTIQM
VRSQRSGMVQ TEAQYRFIYM AVQHYIETLQ RRIEEEQKSK RKGHEYTNIK
YSLADQTSGD QSPLPPCTPT PPCAEMREDS ARVYENVGLM QQQKSFR

Structural Information

  • Known structure with covalent ligand:
Unknown
  • Protein structure:
580.png

Related Pathway

Experimental Evidence

Cys-directed Mutation

Reference

  1. Shi Z Q, Sunico C R, McKercher S R, et al. S-nitrosylated SHP-2 contributes to NMDA receptor-mediated excitotoxicity in acute ischemic stroke[J]. Proceedings of the National Academy of Sciences, 2013, 110(8): 3137-3142. 23382182
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