PTPN6

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Protein tyrosine phosphatase, non-receptor type 6
Protein PTPN6 PDB 1fpr.png
PDB rendering based on 1fpr.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PTPN6 ; HCP; HCPH; HPTP1C; PTP-1C; SH-PTP1; SHP-1; SHP-1L; SHP1
External IDs OMIM176883 MGI96055 HomoloGene56589 ChEMBL: 3166 GeneCards: PTPN6 Gene
EC number 3.1.3.48
RNA expression pattern
PBB GE PTPN6 206687 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5777 15170
Ensembl ENSG00000111679 ENSMUSG00000004266
UniProt P29350 P29351
RefSeq (mRNA) NM_002831 NM_001077705
RefSeq (protein) NP_002822 NP_001071173
Location (UCSC) Chr 12:
7.06 – 7.07 Mb
Chr 6:
124.72 – 124.74 Mb
PubMed search [1] [2]

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.[1]

Function[edit]

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.[2]

Expression[edit]

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 hemopoetic cells. SHP-1 level in epithelial cells increases and in hematopoetic cells decreases in cancer.[3]

Interactions[edit]

PTPN6 has been shown to interact with:

References[edit]

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  2. ^ "Entrez Gene: PTPN6 protein tyrosine phosphatase, non-receptor type 6". 
  3. ^ Amin S, Kumar A, Nilchi L, Wright K, Kozlowski M (August 2011). "Breast cancer cells proliferation is regulated by tyrosine phosphatase SHP1 through c-jun N-terminal kinase and cooperative induction of RFX-1 and AP-4 transcription factors". Mol. Cancer Res. 9 (8): 1112–25. doi:10.1158/1541-7786.MCR-11-0097. PMID 21719561. 
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  5. ^ 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. PMC 121439. PMID 9528781. 
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  7. ^ Blasioli J, Paust S, Thomas ML (January 1999). "Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22". J. Biol. Chem. 274 (4): 2303–7. doi:10.1074/jbc.274.4.2303. PMID 9890995. 
  8. ^ Otipoby KL, Draves KE, Clark EA (November 2001). "CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1". J. Biol. Chem. 276 (47): 44315–22. doi:10.1074/jbc.M105446200. PMID 11551923. 
  9. ^ Greer SF, Justement LB (May 1999). "CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1". J. Immunol. 162 (9): 5278–86. PMID 10228003. 
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  15. ^ 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. 
  16. ^ Keilhack H, Tenev T, Nyakatura E, Godovac-Zimmermann J, Nielsen L, Seedorf K, Böhmer FD (September 1998). "Phosphotyrosine 1173 mediates binding of the protein-tyrosine phosphatase SHP-1 to the epidermal growth factor receptor and attenuation of receptor signaling". J. Biol. Chem. 273 (38): 24839–46. doi:10.1074/jbc.273.38.24839. PMID 9733788. 
  17. ^ 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. 
  18. ^ Xu MJ, Zhao R, Cao H, Zhao ZJ (May 2002). "SPAP2, an Ig family receptor containing both ITIMs and ITAMs". Biochem. Biophys. Res. Commun. 293 (3): 1037–46. doi:10.1016/S0006-291X(02)00332-7. PMID 12051764. 
  19. ^ 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. 
  20. ^ 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. 
  21. ^ 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. 
  22. ^ 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. 
  23. ^ Jiao H, Berrada K, Yang W, Tabrizi M, Platanias LC, Yi T (December 1996). "Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1". Mol. Cell. Biol. 16 (12): 6985–92. PMC 231702. PMID 8943354. 
  24. ^ Wu DW, Stark KC, Dunnington D, Dillon SB, Yi T, Jones C, Pelus LM (February 2000). "SH2-Containing protein tyrosine phosphatase-1 (SHP-1) association with Jak2 in UT-7/Epo cells". Blood Cells Mol. Dis. 26 (1): 15–24. doi:10.1006/bcmd.2000.0273. PMID 10772872. 
  25. ^ a b Mousseau DD, Banville D, L'Abbé D, Bouchard P, Shen SH (February 2000). "PILRalpha, a novel immunoreceptor tyrosine-based inhibitory motif-bearing protein, recruits SHP-1 upon tyrosine phosphorylation and is paired with the truncated counterpart PILRbeta". J. Biol. Chem. 275 (6): 4467–74. doi:10.1074/jbc.275.6.4467. PMID 10660620. 
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  27. ^ Fournier N, Chalus L, Durand I, Garcia E, Pin JJ, Churakova T, Patel S, Zlot C, Gorman D, Zurawski S, Abrams J, Bates EE, Garrone P (August 2000). "FDF03, a novel inhibitory receptor of the immunoglobulin superfamily, is expressed by human dendritic and myeloid cells". J. Immunol. 165 (3): 1197–209. doi:10.4049/jimmunol.165.3.1197. PMID 10903717. 
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  29. ^ Xu Mj, Zhao R, Zhao ZJ (June 2000). "Identification and characterization of leukocyte-associated Ig-like receptor-1 as a major anchor protein of tyrosine phosphatase SHP-1 in hematopoietic cells". J. Biol. Chem. 275 (23): 17440–6. doi:10.1074/jbc.M001313200. PMID 10764762. 
  30. ^ Fanger NA, Cosman D, Peterson L, Braddy SC, Maliszewski CR, Borges L (November 1998). "The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes". Eur. J. Immunol. 28 (11): 3423–34. doi:10.1002/(SICI)1521-4141(199811)28:11<3423::AID-IMMU3423>3.0.CO;2-2. PMID 9842885. 
  31. ^ Colonna M, Samaridis J, Cella M, Angman L, Allen RL, O'Callaghan CA, Dunbar R, Ogg GS, Cerundolo V, Rolink A (April 1998). "Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules". J. Immunol. 160 (7): 3096–100. PMID 9531263. 
  32. ^ 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. PMID 9973385. 
  33. ^ Yu CL, Jin YJ, Burakoff SJ (January 2000). "Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 regulation". J. Biol. Chem. 275 (1): 599–604. doi:10.1074/jbc.275.1.599. PMID 10617656. 
  34. ^ Chiang GG, Sefton BM (June 2001). "Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase". J. Biol. Chem. 276 (25): 23173–8. doi:10.1074/jbc.M101219200. PMID 11294838. 
  35. ^ Lorenz U, Ravichandran KS, Pei D, Walsh CT, Burakoff SJ, Neel BG (March 1994). "Lck-dependent tyrosyl phosphorylation of the phosphotyrosine phosphatase SH-PTP1 in murine T cells". Mol. Cell. Biol. 14 (3): 1824–34. PMC 358540. PMID 8114715. 
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  39. ^ Kumar S, Avraham S, Bharti A, Goyal J, Pandey P, Kharbanda S (October 1999). "Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase SHPTP1". J. Biol. Chem. 274 (43): 30657–63. doi:10.1074/jbc.274.43.30657. PMID 10521452. 
  40. ^ 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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  43. ^ 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.