Wikipedia

PTPN6

Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the PTPN6 gene.[5]

PTPN6
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPTPN6, HCP, HCPH, HPTP1C, PTP-1C, SH-PTP1, SHP-1, SHP-1L, SHP1, protein tyrosine phosphatase, non-receptor type 6, protein tyrosine phosphatase non-receptor type 6
External IDsOMIM: 176883; MGI: 96055; HomoloGene: 56589; GeneCards: PTPN6; OMA:PTPN6 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5777

15170

Ensembl

ENSG00000111679

ENSMUSG00000004266

UniProt

P29350

P29351

RefSeq (mRNA)

NM_002831
NM_080548
NM_080549

NM_001077705
NM_013545

RefSeq (protein)

NP_002822
NP_536858
NP_536859

NP_001071173
NP_038573

Location (UCSC)Chr 12: 6.95 – 6.96 MbChr 6: 124.7 – 124.72 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling, (e.g., the LYN-CD22-SHP-1 pathway). Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported.[6]

Expression

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SHP-1 gene has two promoters: P-1, active in epithelial cells, and P-2, active in hemopoietic cells. In addition the expression of SHP-1 is low in epithelial cells and high in hemopoietic cells. SHP-1 level in epithelial cells increases and in hematopoietic cells decreases in cancer.[7]

Interactions

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PTPN6 has been shown to interact with:

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000111679 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000004266 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  6. ^ "Entrez Gene: PTPN6 protein tyrosine phosphatase, non-receptor type 6".
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  9. ^ Kozlowski M, Larose L, Lee F, Le DM, Rottapel R, Siminovitch KA (April 1998). "SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain". Mol. Cell. Biol. 18 (4): 2089–99. doi:10.1128/mcb.18.4.2089. PMC 121439. PMID 9528781.
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  17. ^ Hua CT, Gamble JR, Vadas MA, Jackson DE (October 1998). "Recruitment and activation of SHP-1 protein-tyrosine phosphatase by human platelet endothelial cell adhesion molecule-1 (PECAM-1). Identification of immunoreceptor tyrosine-based inhibitory motif-like binding motifs and substrates". J. Biol. Chem. 273 (43): 28332–40. doi:10.1074/jbc.273.43.28332. PMID 9774457.
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  19. ^ Tomic S, Greiser U, Lammers R, Kharitonenkov A, Imyanitov E, Ullrich A, Böhmer FD (September 1995). "Association of SH2 domain protein tyrosine phosphatases with the epidermal growth factor receptor in human tumor cells. Phosphatidic acid activates receptor dephosphorylation by PTP1C". J. Biol. Chem. 270 (36): 21277–84. doi:10.1074/jbc.270.36.21277. PMID 7673163.
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  21. ^ Klingmüller U, Lorenz U, Cantley LC, Neel BG, Lodish HF (March 1995). "Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals". Cell. 80 (5): 729–38. doi:10.1016/0092-8674(95)90351-8. PMID 7889566. S2CID 16866005.
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  23. ^ a b c Ganju RK, Brubaker SA, Chernock RD, Avraham S, Groopman JE (June 2000). "Beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk". J. Biol. Chem. 275 (23): 17263–8. doi:10.1074/jbc.M000689200. PMID 10747947.
  24. ^ Kon-Kozlowski M, Pani G, Pawson T, Siminovitch KA (February 1996). "The tyrosine phosphatase PTP1C associates with Vav, Grb2, and mSos1 in hematopoietic cells". J. Biol. Chem. 271 (7): 3856–62. doi:10.1074/jbc.271.7.3856. PMID 8632004.
  25. ^ Saci A, Liu WQ, Vidal M, Garbay C, Rendu F, Bachelot-Loza C (May 2002). "Differential effect of the inhibition of Grb2-SH3 interactions in platelet activation induced by thrombin and by Fc receptor engagement". Biochem. J. 363 (Pt 3): 717–25. doi:10.1042/0264-6021:3630717. PMC 1222524. PMID 11964172.
  26. ^ Eklund EA, Goldenberg I, Lu Y, Andrejic J, Kakar R (September 2002). "SHP1 protein-tyrosine phosphatase regulates HoxA10 DNA binding and transcriptional repression activity in undifferentiated myeloid cells". J. Biol. Chem. 277 (39): 36878–88. doi:10.1074/jbc.M203917200. PMID 12145285.
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  36. ^ Wang LL, Blasioli J, Plas DR, Thomas ML, Yokoyama WM (February 1999). "Specificity of the SH2 domains of SHP-1 in the interaction with the immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B". J. Immunol. 162 (3): 1318–23. doi:10.4049/jimmunol.162.3.1318. PMID 9973385.
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  42. ^ Yoshida K, Kufe D (December 2001). "Negative regulation of the SHPTP1 protein tyrosine phosphatase by protein kinase C delta in response to DNA damage". Mol. Pharmacol. 60 (6): 1431–8. doi:10.1124/mol.60.6.1431. PMID 11723252.
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  44. ^ Keilhack H, Müller M, Böhmer SA, Frank C, Weidner KM, Birchmeier W, Ligensa T, Berndt A, Kosmehl H, Günther B, Müller T, Birchmeier C, Böhmer FD (January 2001). "Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1". J. Cell Biol. 152 (2): 325–34. doi:10.1083/jcb.152.2.325. PMC 2199605. PMID 11266449.
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  46. ^ Dustin LB, Plas DR, Wong J, Hu YT, Soto C, Chan AC, Thomas ML (March 1999). "Expression of dominant-negative src-homology domain 2-containing protein tyrosine phosphatase-1 results in increased Syk tyrosine kinase activity and B cell activation". J. Immunol. 162 (5): 2717–24. doi:10.4049/jimmunol.162.5.2717. PMID 10072516.
  47. ^ Yetter A, Uddin S, Krolewski JJ, Jiao H, Yi T, Platanias LC (August 1995). "Association of the interferon-dependent tyrosine kinase Tyk-2 with the hematopoietic cell phosphatase". J. Biol. Chem. 270 (31): 18179–82. doi:10.1074/jbc.270.31.18179. PMID 7629131.
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