ID PTN6_RAT Reviewed; 613 AA. AC P81718; DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 24-JAN-2024, entry version 153. DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 6; DE EC=3.1.3.48; DE AltName: Full=Protein-tyrosine phosphatase SHP-1; GN Name=Ptpn6; Synonyms=Ptph6; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA]. RA Aoki N., Yamaguchi-Aoki Y., Ullrich A.; RT "The rat SH2-containing protein-tyrosine phosphatase SHP-1 is a positive RT regulator of NGF-induced neuronal differentiation of PC12 cells."; RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, AND INTERACTION WITH RP MTUS1. RX PubMed=17068200; DOI=10.1210/me.2006-0005; RA Li J.-M., Mogi M., Tsukuda K., Tomochika H., Iwanami J., Min L.-J., RA Nahmias C., Iwai M., Horiuchi M.; RT "Angiotensin II-induced neural differentiation via angiotensin II type 2 RT (AT2) receptor-MMS2 cascade involving interaction between AT2 receptor- RT interacting protein and Src homology 2 domain-containing protein-tyrosine RT phosphatase 1."; RL Mol. Endocrinol. 21:499-511(2007). RN [3] RP INTERACTION WITH KLRI1 AND KLRI2. RX PubMed=18713988; DOI=10.4049/jimmunol.181.5.3177; RA Saether P.C., Westgaard I.H., Hoelsbrekken S.E., Benjamin J., Lanier L.L., RA Fossum S., Dissen E.; RT "KLRE/I1 and KLRE/I2: a novel pair of heterodimeric receptors that RT inversely regulate NK cell cytotoxicity."; RL J. Immunol. 181:3177-3182(2008). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Modulates signaling by tyrosine phosphorylated cell surface CC receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may CC interact with other cellular components to modulate its own phosphatase CC activity against interacting substrates. Together with MTUS1, induces CC UBE2V2 expression upon angiotensin II stimulation. Plays a key role in CC hematopoiesis. {ECO:0000269|PubMed:17068200}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620; EC=3.1.3.48; CC Evidence={ECO:0000250|UniProtKB:P29351, ECO:0000255|PROSITE- CC ProRule:PRU10044}; CC -!- SUBUNIT: Monomer. Interacts with MTUS1 (PubMed:17068200). Interacts CC with MILR1 (tyrosine-phosphorylated) (By similarity). Interacts with CC KIT (By similarity). Interacts with SIRPA/PTPNS1 (By similarity). CC Interacts with FCRL2 and FCRL4 (By similarity). Interacts with CD84 (By CC similarity). Interacts with CD300LF (By similarity). Interacts with CC CDK2 (By similarity). Interacts with KIR2DL1; the interaction is CC enhanced by ARRB2 (By similarity). Interacts (via SH2 1 domain) with CC ROS1; the interaction is direct and promotes ROS1 dephosphorylation (By CC similarity). Interacts with EGFR; inhibits EGFR-dependent activation of CC MAPK/ERK (By similarity). Interacts with LYN (By similarity). Interacts CC with the tyrosine phosphorylated form of PDPK1 (By similarity). CC Interacts with CEACAM1 (via cytoplasmic domain); this interaction CC depends on the monomer/dimer equilibrium and is phosphorylation- CC dependent (By similarity). Interacts with MPIG6B (via ITIM motif) (By CC similarity). Interacts with KLRI1 and KLRI2 (PubMed:18713988). CC Interacts with moesin/MSN. Interacts with CLEC12B (via ITIM motif). CC {ECO:0000250|UniProtKB:P29350, ECO:0000250|UniProtKB:P29351, CC ECO:0000269|PubMed:17068200, ECO:0000269|PubMed:18713988}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17068200}. Nucleus CC {ECO:0000269|PubMed:17068200}. Note=In neurons, translocates into the CC nucleus after treatment with angiotensin II. Shuttles between the CC cytoplasm and nucleus via its association with PDPK (By similarity). CC {ECO:0000250}. CC -!- DEVELOPMENTAL STAGE: Highly expressed in embryonic cerebral cortex CC between day 18 and up to birth. Expression levels decrease after birth CC (at protein level). {ECO:0000269|PubMed:17068200}. CC -!- DOMAIN: The N-terminal SH2 domain functions as an auto-inhibitory CC domain, blocking the catalytic domain in the ligand-free close CC conformation. {ECO:0000250}. CC -!- PTM: Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT CC increases tyrosine phosphorylation (By similarity). Phosphorylation at CC Tyr-566 enhances phosphatase activity (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non- CC receptor class 2 subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U77038; AAD00262.1; -; mRNA. DR RefSeq; NP_446360.1; NM_053908.1. DR AlphaFoldDB; P81718; -. DR SMR; P81718; -. DR BioGRID; 250571; 3. DR DIP; DIP-47802N; -. DR IntAct; P81718; 5. DR STRING; 10116.ENSRNOP00000059867; -. DR iPTMnet; P81718; -. DR PhosphoSitePlus; P81718; -. DR jPOST; P81718; -. DR PaxDb; 10116-ENSRNOP00000059867; -. DR GeneID; 116689; -. DR KEGG; rno:116689; -. DR UCSC; RGD:620660; rat. DR AGR; RGD:620660; -. DR CTD; 5777; -. DR RGD; 620660; Ptpn6. DR eggNOG; KOG0790; Eukaryota. DR InParanoid; P81718; -. DR OrthoDB; 2911650at2759; -. DR PhylomeDB; P81718; -. DR Reactome; R-RNO-114604; GPVI-mediated activation cascade. DR Reactome; R-RNO-1433559; Regulation of KIT signaling. DR Reactome; R-RNO-201556; Signaling by ALK. DR Reactome; R-RNO-210990; PECAM1 interactions. DR Reactome; R-RNO-388841; Costimulation by the CD28 family. DR Reactome; R-RNO-389948; PD-1 signaling. DR Reactome; R-RNO-432142; Platelet sensitization by LDL. DR Reactome; R-RNO-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling. DR Reactome; R-RNO-5690714; CD22 mediated BCR regulation. DR Reactome; R-RNO-6798695; Neutrophil degranulation. DR Reactome; R-RNO-877300; Interferon gamma signaling. DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling. DR Reactome; R-RNO-912694; Regulation of IFNA/IFNB signaling. DR Reactome; R-RNO-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR PRO; PR:P81718; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0042105; C:alpha-beta T cell receptor complex; ISO:RGD. DR GO; GO:0097440; C:apical dendrite; IDA:RGD. DR GO; GO:0005911; C:cell-cell junction; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0032991; C:protein-containing complex; ISO:RGD. DR GO; GO:0050839; F:cell adhesion molecule binding; ISO:RGD. DR GO; GO:0005126; F:cytokine receptor binding; IPI:RGD. DR GO; GO:0046703; F:natural killer cell lectin-like receptor binding; IPI:RGD. DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IBA:GO_Central. DR GO; GO:0140031; F:phosphorylation-dependent protein binding; ISO:RGD. DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD. DR GO; GO:0019901; F:protein kinase binding; ISO:RGD. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISO:RGD. DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD. DR GO; GO:0017124; F:SH3 domain binding; ISO:RGD. DR GO; GO:0005001; F:transmembrane receptor protein tyrosine phosphatase activity; ISS:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; ISO:RGD. DR GO; GO:0030154; P:cell differentiation; ISS:UniProtKB. DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; IEP:RGD. DR GO; GO:1905867; P:epididymis development; ISO:RGD. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISO:RGD. DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD. DR GO; GO:0000165; P:MAPK cascade; ISO:RGD. DR GO; GO:0035855; P:megakaryocyte development; ISO:RGD. DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central. DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISO:RGD. DR GO; GO:0002924; P:negative regulation of humoral immune response mediated by circulating immunoglobulin; ISO:RGD. DR GO; GO:0106015; P:negative regulation of inflammatory response to wounding; ISO:RGD. DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:RGD. DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:RGD. DR GO; GO:0033007; P:negative regulation of mast cell activation involved in immune response; ISO:RGD. DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISO:RGD. DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD. DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISO:RGD. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:RGD. DR GO; GO:0070527; P:platelet aggregation; ISO:RGD. DR GO; GO:0030220; P:platelet formation; ISO:RGD. DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISO:RGD. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD. DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB. DR GO; GO:0045577; P:regulation of B cell differentiation; ISO:RGD. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:RGD. DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; ISO:RGD. DR GO; GO:0048678; P:response to axon injury; IEP:RGD. DR GO; GO:0042098; P:T cell proliferation; ISO:RGD. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD. DR CDD; cd14606; PTPc-N6; 1. DR CDD; cd09931; SH2_C-SH2_SHP_like; 1. DR CDD; cd10340; SH2_N-SH2_SHP_like; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR Gene3D; 3.30.505.10; SH2 domain; 2. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR000242; PTP_cat. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR003595; Tyr_Pase_cat. DR InterPro; IPR000387; Tyr_Pase_dom. DR InterPro; IPR012152; Tyr_Pase_non-rcpt_typ-6/11. DR PANTHER; PTHR46257; TYROSINE-PROTEIN PHOSPHATASE CORKSCREW; 1. DR PANTHER; PTHR46257:SF4; TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 6; 1. DR Pfam; PF00017; SH2; 2. DR Pfam; PF00102; Y_phosphatase; 1. DR PIRSF; PIRSF000929; Tyr-Ptase_nr_6; 1. DR PRINTS; PR00700; PRTYPHPHTASE. DR PRINTS; PR00401; SH2DOMAIN. DR SMART; SM00194; PTPc; 1. DR SMART; SM00404; PTPc_motif; 1. DR SMART; SM00252; SH2; 2. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF55550; SH2 domain; 2. DR PROSITE; PS50001; SH2; 2. DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1. DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1. PE 1: Evidence at protein level; KW Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protein phosphatase; KW Reference proteome; Repeat; SH2 domain. FT CHAIN 1..613 FT /note="Tyrosine-protein phosphatase non-receptor type 6" FT /id="PRO_0000094760" FT DOMAIN 6..102 FT /note="SH2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191, FT ECO:0000305" FT DOMAIN 112..215 FT /note="SH2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191, FT ECO:0000305" FT DOMAIN 246..517 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 549..598 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 556..594 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 455 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160, FT ECO:0000255|PROSITE-ProRule:PRU10044" FT BINDING 421 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 455..461 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 502 FT /ligand="substrate" FT /evidence="ECO:0000250" FT MOD_RES 12 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 59 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P29351" FT MOD_RES 66 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P29350" FT MOD_RES 379 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P29351" FT MOD_RES 538 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P29351" FT MOD_RES 566 FT /note="Phosphotyrosine; by LYN" FT /evidence="ECO:0000250|UniProtKB:P29350" SQ SEQUENCE 613 AA; 69578 MW; 29364B22E8F45C87 CRC64; MLSRGWFHRD LSGPDAETLL KGRGVPGSFL ARPSRKNQGD FSLSVRVDDQ VTHIRIQNSG DFYDLYGGEK FATSTELVEY YTQQQGILQD RDGTIIHLKY PLNCSDPTSE RWYHGHMSGG QAESLLQAKG EPWTFLVRES LSQPGDFVLS VLNDQPKAAP GSPLRVTHIK VMCEGGRYTV GGSETFDSLT DLVEHFKKTG IEEASGAFVY LRQPYYATRV NAADIENRVL ELNKKQESED TAKAGFWEEF ESLQKQEAKN LHQRLEGQRP ENKSKNRYKN ILPFDHSRVI LQGRDSNIPG SDYINANYVK NQLLGPDENS KTYIASQGCL DATVNDFWQM AWQENTRVIV MTTREVEKGR NKCVPYWPEV GTQRVYGLYS VTNCKEHDTA EYKLRTLQIS PLDNGDLVRE IWHYQYLSWP DHGVPSEPGG VLSFLDQINQ RQESLPHAGP IIVHCSAGIG RTGTIIVIDM LMESVSTKGL DCDIDIQKTI QMVRAQRSGM VQTEAQYKFI YVAIAQFIET TKKKLEIIQS QRGQESEYGN ITYPPALRSA HAKASRTSSK HKEEVYENVH SKNKKEEKVK KQRSADKEKN KGSLKRNISL TPCRGLRWAD RDL //