ID PTN6_MOUSE Reviewed; 595 AA. AC P29351; O35128; Q63872; Q63873; Q63874; Q921G3; Q9QVA6; Q9QVA7; Q9QVA8; AC Q9R0V6; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 11-JUL-2002, sequence version 2. DT 02-SEP-2026, entry version 239. DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 6; DE EC=3.1.3.48 {ECO:0000269|PubMed:33990399}; DE AltName: Full=70Z-SHP; DE AltName: Full=Hematopoietic cell protein-tyrosine phosphatase; DE AltName: Full=PTPTY-42; DE AltName: Full=Protein-tyrosine phosphatase 1C; DE Short=PTP-1C; DE AltName: Full=SH-PTP1; DE Short=SHP-1; GN Name=Ptpn6; Synonyms=Hcp, Hcph, Ptp1C; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=DBA/2J; RX PubMed=1732748; DOI=10.1128/mcb.12.2.836-846.1992; RA Yi T., Cleveland J.L., Ihle J.N.; RT "Protein tyrosine phosphatase containing SH2 domains: characterization, RT preferential expression in hematopoietic cells, and localization to human RT chromosome 12p12-p13."; RL Mol. Cell. Biol. 12:836-846(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1373816; DOI=10.1128/mcb.12.5.2396-2405.1992; RA Matthews R.J., Bowne D.B., Flores E., Thomas M.L.; RT "Characterization of hematopoietic intracellular protein tyrosine RT phosphatases: description of a phosphatase containing an SH2 domain and RT another enriched in proline-, glutamic acid-, serine-, and threonine-rich RT sequences."; RL Mol. Cell. Biol. 12:2396-2405(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS MOTHEATEN AND VIABLE MOTHEATEN. RC STRAIN=C57BL/6J; TISSUE=Bone marrow; RX PubMed=8324828; DOI=10.1016/0092-8674(93)90369-2; RA Schultz L.D., Schweitzer P.A., Rajan T.V., Yi T., Ihle J.N., Matthews R.J., RA Thomas M.L., Beier D.R.; RT "Mutations at the murine motheaten locus are within the hematopoietic cell RT protein-tyrosine phosphatase (Hcph) gene."; RL Cell 73:1445-1454(1993). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3). RX PubMed=9445485; RA Ansari-Lari M.A., Oeltjen J.C., Schwartz S., Zhang Z., Muzny D.M., Lu J., RA Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., Gibbs R.A.; RT "Comparative sequence analysis of a gene-rich cluster at human chromosome RT 12p13 and its syntenic region in mouse chromosome 6."; RL Genome Res. 8:29-40(1998). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), AND SUBUNIT. RC STRAIN=C3H/HeJ; TISSUE=Adrenal gland; RX PubMed=10419485; DOI=10.1074/jbc.274.31.21725; RA Martin A., Tsui H.W., Shulman M.J., Isenman D., Tsui F.W.; RT "Murine SHP-1 splice variants with altered Src homology 2 (SH2) domains. RT Implications for the SH2-mediated intramolecular regulation of SHP-1."; RL J. Biol. Chem. 274:21725-21734(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 54-68; 128-135; 137-151; 242-252; 278-285; 293-308 AND RP 373-382, AND PHOSPHORYLATION. RX PubMed=1385421; DOI=10.1016/s0021-9258(18)35855-1; RA Yeung Y.-G., Berg K.L., Pixley F.J., Angeletti R.H., Stanley E.R.; RT "Protein tyrosine phosphatase-1C is rapidly phosphorylated in tyrosine in RT macrophages in response to colony stimulating factor-1."; RL J. Biol. Chem. 267:23447-23450(1992). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 342-451, AND TISSUE SPECIFICITY. RC STRAIN=BALB/cJ; TISSUE=Myeloid leukemia cell; RX PubMed=1932742; DOI=10.1182/blood.v78.9.2222.2222; RA Yi T., Cleveland J.L., Ihle J.N.; RT "Identification of novel protein tyrosine phosphatases of hematopoietic RT cells by polymerase chain reaction amplification."; RL Blood 78:2222-2228(1991). RN [9] RP INTERACTION WITH SIRPA. RX PubMed=9712903; DOI=10.1074/jbc.273.35.22719; RA Veillette A., Thibaudeau E., Latour S.; RT "High expression of inhibitory receptor SHPS-1 and its association with RT protein tyrosine phosphatase SHP-1 in macrophages."; RL J. Biol. Chem. 273:22719-22728(1998). RN [10] RP INTERACTION WITH KIT, FUNCTION IN MODULATING KIT SIGNALING, AND RP PHOSPHORYLATION. RX PubMed=9528781; DOI=10.1128/mcb.18.4.2089; RA Kozlowski M., Larose L., Lee F., Le D.M., Rottapel R., Siminovitch K.A.; RT "SHP-1 binds and negatively modulates the c-Kit receptor by interaction RT with tyrosine 569 in the c-Kit juxtamembrane domain."; RL Mol. Cell. Biol. 18:2089-2099(1998). RN [11] RP INTERACTION WITH CEACAM1. RX PubMed=9867848; DOI=10.1074/jbc.274.1.335; RA Huber M., Izzi L., Grondin P., Houde C., Kunath T., Veillette A., RA Beauchemin N.; RT "The carboxyl-terminal region of biliary glycoprotein controls its tyrosine RT phosphorylation and association with protein-tyrosine phosphatases SHP-1 RT and SHP-2 in epithelial cells."; RL J. Biol. Chem. 274:335-344(1999). RN [12] RP FUNCTION, AND INTERACTION WITH LILRB4A. RX PubMed=10026201; DOI=10.1074/jbc.274.9.5791; RA Lu-Kuo J.M., Joyal D.M., Austen K.F., Katz H.R.; RT "gp49B1 inhibits IgE-initiated mast cell activation through both RT immunoreceptor tyrosine-based inhibitory motifs, recruitment of src RT homology 2 domain-containing phosphatase-1, and suppression of early and RT late calcium mobilization."; RL J. Biol. Chem. 274:5791-5796(1999). RN [13] RP INTERACTION WITH LILRB4A, AND MUTAGENESIS OF 30-ARG--ARG-33 AND ARG-136. RX PubMed=9973385; DOI=10.4049/jimmunol.162.3.1318; RA Wang L.L., Blasioli J., Plas D.R., Thomas M.L., Yokoyama W.M.; RT "Specificity of the SH2 domains of SHP-1 in the interaction with the RT immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B."; RL J. Immunol. 162:1318-1323(1999). RN [14] RP INTERACTION WITH PIRB. RX PubMed=10327049; DOI=10.1038/sj.onc.1202552; RA Maeda A., Scharenberg A.M., Tsukada S., Bolen J.B., Kinet J.P., RA Kurosaki T.; RT "Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced RT activation of Syk and Btk by SHP-1."; RL Oncogene 18:2291-2297(1999). RN [15] RP INTERACTION WITH CD300LF. RC STRAIN=C57BL/6J; RX PubMed=14662855; DOI=10.4049/jimmunol.171.12.6541; RA Chung D.-H., Humphrey M.B., Nakamura M.C., Ginzinger D.G., Seaman W.E., RA Daws M.R.; RT "CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit RT osteoclast formation."; RL J. Immunol. 171:6541-6548(2003). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-377 AND TYR-536, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Mast cell; RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864; RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., RA Kawakami T., Salomon A.R.; RT "Quantitative time-resolved phosphoproteomic analysis of mast cell RT signaling."; RL J. Immunol. 179:5864-5876(2007). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [18] RP MUTAGENESIS OF ILE-482. RX PubMed=19419305; DOI=10.1359/jbmr.090417; RA Babij P., Roudier M., Graves T., Han C.Y., Chhoa M., Li C.M., Juan T., RA Morony S., Grisanti M., Li X., Yu L., Dwyer D., Lloyd D.J., Bass M.B., RA Richards W.G., Ebeling C., Amato J., Carlson G.; RT "New variants in the Enpp1 and Ptpn6 genes cause low BMD, crystal-related RT arthropathy, and vascular calcification."; RL J. Bone Miner. Res. 24:1552-1564(2009). RN [19] RP INTERACTION WITH CEACAM1. RX PubMed=19948503; DOI=10.1083/jcb.200904150; RA Mueller M.M., Klaile E., Vorontsova O., Singer B.B., Obrink B.; RT "Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and RT recruitment of SHP-2 and c-Src."; RL J. Cell Biol. 187:569-581(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-57, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [21] RP INTERACTION WITH MILR1. RX PubMed=20526344; DOI=10.1038/ni.1886; RA Hitomi K., Tahara-Hanaoka S., Someya S., Fujiki A., Tada H., Sugiyama T., RA Shibayama S., Shibuya K., Shibuya A.; RT "An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E- RT mediated immediate hypersensitivity reactions."; RL Nat. Immunol. 11:601-607(2010). RN [22] RP INTERACTION WITH MPIG6B. RX PubMed=23112346; DOI=10.1126/scisignal.2002936; RA Mazharian A., Wang Y.J., Mori J., Bem D., Finney B., Heising S., Gissen P., RA White J.G., Berndt M.C., Gardiner E.E., Nieswandt B., Douglas M.R., RA Campbell R.D., Watson S.P., Senis Y.A.; RT "Mice lacking the ITIM-containing receptor G6b-B exhibit RT macrothrombocytopenia and aberrant platelet function."; RL Sci. Signal. 5:RA78-RA78(2012). RN [23] RP INTERACTION WITH MOESIN/MSN. RX PubMed=29247647; DOI=10.1016/j.bbrc.2017.12.061; RA Gomez C.P., Descoteaux A.; RT "Moesin and myosin IIA modulate phagolysosomal biogenesis in macrophages."; RL Biochem. Biophys. Res. Commun. 495:1964-1971(2018). RN [24] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=33990399; DOI=10.4049/jimmunol.2100109; RA Alborzian Deh Sheikh A., Akatsu C., Abdu-Allah H.H.M., Suganuma Y., RA Imamura A., Ando H., Takematsu H., Ishida H., Tsubata T.; RT "The Protein Tyrosine Phosphatase SHP-1 (PTPN6) but Not CD45 (PTPRC) Is RT Essential for the Ligand-Mediated Regulation of CD22 in BCR-Ligated B RT Cells."; RL J. Immunol. 206:2544-2551(2021). CC -!- FUNCTION: Tyrosine phosphatase enzyme that plays important roles in CC controlling immune signaling pathways and fundamental physiological CC processes such as hematopoiesis. Dephosphorylates and negatively CC regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR CC and FGFR, thereby modulating their signaling activities CC (PubMed:9528781). When recruited to immunoreceptor tyrosine-based CC inhibitory motif (ITIM)-containing receptors such as immunoglobulin- CC like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CC CD22, CLEC12A and other receptors involved in immune regulation, CC initiates their dephosphorylation and subsequently inhibits downstream CC signaling events (PubMed:10026201, PubMed:33990399). Modulates the CC signaling of several cytokine receptors including IL-4 receptor. CC Additionally, targets multiple cytoplasmic signaling molecules CC including STING1, LCK or STAT1 among others involved in diverse CC cellular processes including modulation of T-cell activation or cGAS- CC STING signaling. Within the nucleus, negatively regulates the activity CC of some transcription factors such as NFAT5 via direct CC dephosphorylation. Also acts as a key transcriptional regulator of CC hepatic gluconeogenesis by controlling recruitment of RNA polymerase II CC to the PCK1 promoter together with STAT5A. CC {ECO:0000250|UniProtKB:P29350, ECO:0000269|PubMed:10026201, CC ECO:0000269|PubMed:33990399, ECO:0000269|PubMed:9528781}. CC -!- CATALYTIC ACTIVITY: CC Reaction=O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10044, ECO:0000269|PubMed:33990399}; CC -!- SUBUNIT: Monomer. Interacts with PIRB; when PIRB is phosphorylated by CC LYN at 'Tyr-794' and 'Tyr-824' (PubMed:10327049). Interacts with MTUS1 CC (By similarity). Interacts with MILR1 (tyrosine-phosphorylated) CC (PubMed:20526344). Interacts with KIT (PubMed:9528781). Interacts with CC SIRPA/PTPNS1 (PubMed:9712903). Interacts with LILRB1 and LILRB2. CC Interacts with LILRB4. Interacts with FCRL2 and FCRL4. Interacts with CC FCRL3 and FCRL6 (tyrosine phosphorylated form). Interacts with CD84. CC Interacts with CD300LF (PubMed:14662855). Interacts with CDK2. CC Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts CC (via SH2 1 domain) with ROS1; the interaction is direct and promotes CC ROS1 dephosphorylation. Interacts with EGFR; inhibits EGFR-dependent CC activation of MAPK/ERK. Interacts with the tyrosine phosphorylated form CC of PDPK1 (By similarity). Interacts with CEACAM1 (via cytoplasmic CC domain); this interaction depends on the monomer/dimer equilibrium and CC is phosphorylation-dependent (PubMed:19948503, PubMed:9867848). CC Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts CC with KLRI1 and KLRI2 (By similarity). Interacts with moesin/MSN. CC Interacts with Lilrb4a (when tyrosine phosphorylated); the interaction CC enhances Lilrb4a-mediated inhibition of mast cell activation CC (PubMed:10026201, PubMed:9973385). Interacts with CLEC12B (via ITIM CC motif). Interacts with polymerase II components POLR2C and POLR2J; CC these interactions recruit RNA polymerase II to the PCK1 promoter. CC Interacts with TNFRSF10A; this interaction enables the inhibition of T- CC cell receptor signaling via LCK (By similarity). CC {ECO:0000250|UniProtKB:P29350, ECO:0000250|UniProtKB:P81718, CC ECO:0000269|PubMed:10026201, ECO:0000269|PubMed:10327049, CC ECO:0000269|PubMed:19948503, ECO:0000269|PubMed:20526344, CC ECO:0000269|PubMed:23112346, ECO:0000269|PubMed:29247647, CC ECO:0000269|PubMed:9528781, ECO:0000269|PubMed:9712903, CC ECO:0000269|PubMed:9867848, ECO:0000269|PubMed:9973385}. CC -!- INTERACTION: CC P29351; Q91YS8: Camk1; NbExp=3; IntAct=EBI-2620699, EBI-911352; CC P29351; P35329: Cd22; NbExp=5; IntAct=EBI-2620699, EBI-300059; CC P29351; Q9Z1S8: Gab2; NbExp=2; IntAct=EBI-2620699, EBI-641738; CC P29351; P42225: Stat1; NbExp=2; IntAct=EBI-2620699, EBI-647118; CC P29351; B7UM99: tir; Xeno; NbExp=2; IntAct=EBI-2620699, EBI-2504426; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}. Note=In CC neurons, translocates into the nucleus after treatment with angiotensin CC II. Shuttles between the cytoplasm and nucleus via its association with CC PDPK1 (By similarity). {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P29351-1; Sequence=Displayed; CC Name=2; CC IsoId=P29351-2; Sequence=VSP_005131; CC Name=3; CC IsoId=P29351-3; Sequence=VSP_005132, VSP_005133; CC -!- TISSUE SPECIFICITY: Expressed predominantly in hematopoietic cells. CC {ECO:0000269|PubMed:1932742}. 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 (PubMed:1385421, PubMed:9528781). CC Phosphorylation at Tyr-564 by LYN enhances phosphatase activity. CC Phosphorylation at Thr-394 by TAOK3 leads to polyubiquitination and CC subsequent proteasomal degradation (By similarity). CC {ECO:0000250|UniProtKB:P29350, ECO:0000269|PubMed:1385421, CC ECO:0000269|PubMed:9528781}. CC -!- PTM: Ubiquitinated after phosphorylation by TAOK3. Ubiquitinated by a CC cooperation between ITCH and WWP2 via 'Lys-27'-mediated polyubiquitin CC chains resulting in the reduction of its association with LCK. CC {ECO:0000250|UniProtKB:P29350}. CC -!- DISEASE: Note=Defects in Ptpn6 are the cause of the motheaten (me) or CC viable motheaten (mev) phenotypes. Mice homozygous for the recessive CC allelic mutations develop severe defects in hematopoiesis. 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; M68902; AAA37796.1; -; mRNA. DR EMBL; M90389; AAA40007.1; -; mRNA. DR EMBL; S63763; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; S63764; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; S63803; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC002397; AAC36009.1; -; Genomic_DNA. DR EMBL; AC002397; AAC36008.1; -; Genomic_DNA. DR EMBL; U65955; AAD00152.1; -; Genomic_DNA. DR EMBL; U65952; AAD00152.1; JOINED; Genomic_DNA. DR EMBL; U65953; AAD00152.1; JOINED; Genomic_DNA. DR EMBL; U65954; AAD00152.1; JOINED; Genomic_DNA. DR EMBL; U65955; AAD00151.1; -; Genomic_DNA. DR EMBL; U65951; AAD00151.1; JOINED; Genomic_DNA. DR EMBL; U65952; AAD00151.1; JOINED; Genomic_DNA. DR EMBL; U65953; AAD00151.1; JOINED; Genomic_DNA. DR EMBL; U65954; AAD00151.1; JOINED; Genomic_DNA. DR EMBL; BC012660; AAH12660.1; -; mRNA. DR CCDS; CCDS39628.1; -. [P29351-1] DR CCDS; CCDS51908.1; -. [P29351-2] DR PIR; A44390; A44390. DR RefSeq; NP_001071173.1; NM_001077705.2. [P29351-2] DR RefSeq; NP_038573.2; NM_013545.3. [P29351-1] DR AlphaFoldDB; P29351; -. DR SMR; P29351; -. DR BioGRID; 200256; 23. DR CORUM; P29351; -. DR DIP; DIP-41455N; -. DR ELM; P29351; -. DR FunCoup; P29351; 1999. DR IntAct; P29351; 15. DR MINT; P29351; -. DR STRING; 10090.ENSMUSP00000004377; -. DR CarbonylDB; P29351; -. DR GlyGen; P29351; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site). DR iPTMnet; P29351; -. DR PhosphoSitePlus; P29351; -. DR SwissPalm; P29351; -. DR jPOST; P29351; -. DR PaxDb; 10090-ENSMUSP00000004377; -. DR PeptideAtlas; P29351; -. DR ProteomicsDB; 301880; -. [P29351-1] DR ProteomicsDB; 301881; -. [P29351-2] DR ProteomicsDB; 301882; -. [P29351-3] DR Antibodypedia; 728; 1064 antibodies from 51 providers. DR DNASU; 15170; -. DR Ensembl; ENSMUST00000004377.15; ENSMUSP00000004377.9; ENSMUSG00000004266.16. [P29351-2] DR Ensembl; ENSMUST00000112484.10; ENSMUSP00000108103.4; ENSMUSG00000004266.16. [P29351-1] DR Ensembl; ENSMUST00000171549.9; ENSMUSP00000129124.3; ENSMUSG00000004266.16. [P29351-2] DR Ensembl; ENSMUST00000174265.2; ENSMUSP00000133991.2; ENSMUSG00000004266.16. [P29351-3] DR GeneID; 15170; -. DR KEGG; mmu:15170; -. DR UCSC; uc009drk.2; mouse. [P29351-1] DR AGR; MGI:96055; -. DR CTD; 5777; -. DR MGI; MGI:96055; Ptpn6. DR VEuPathDB; HostDB:ENSMUSG00000004266; -. DR eggNOG; KOG0790; Eukaryota. DR GeneTree; ENSGT00940000159480; -. DR HOGENOM; CLU_001645_9_10_1; -. DR InParanoid; P29351; -. DR OMA; VKIMCEN; -. DR OrthoDB; 8815311at2759; -. DR PhylomeDB; P29351; -. DR Reactome; R-MMU-114604; GPVI-mediated activation cascade. DR Reactome; R-MMU-1433559; Regulation of KIT signaling. DR Reactome; R-MMU-201556; Signaling by ALK. DR Reactome; R-MMU-210990; PECAM1 interactions. DR Reactome; R-MMU-389948; Co-inhibition by PD-1. DR Reactome; R-MMU-432142; Platelet sensitization by LDL. DR Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling. DR Reactome; R-MMU-5690714; CD22 mediated BCR regulation. DR Reactome; R-MMU-6798695; Neutrophil degranulation. DR Reactome; R-MMU-877300; Interferon gamma signaling. DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling. DR Reactome; R-MMU-912694; Regulation of IFNA/IFNB signaling. DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR Reactome; R-MMU-9927353; Co-inhibition by BTLA. DR BioGRID-ORCS; 15170; 2 hits in 81 CRISPR screens. DR PRO; PR:P29351; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; P29351; protein. DR Bgee; ENSMUSG00000004266; Expressed in granulocyte and 172 other cell types or tissues. DR ExpressionAtlas; P29351; baseline and differential. DR GO; GO:0042105; C:alpha-beta T cell receptor complex; IDA:MGI. DR GO; GO:0097440; C:apical dendrite; ISO:GO_Central. DR GO; GO:0005911; C:cell-cell junction; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:UniProt. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005730; C:nucleolus; ISO:GO_Central. DR GO; GO:0005654; C:nucleoplasm; ISO:GO_Central. DR GO; GO:0005634; C:nucleus; ISO:GO_Central. DR GO; GO:0005886; C:plasma membrane; ISO:GO_Central. DR GO; GO:0032991; C:protein-containing complex; ISO:GO_Central. DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:UniProtKB. DR GO; GO:0005126; F:cytokine receptor binding; ISO:GO_Central. DR GO; GO:0046703; F:natural killer cell lectin-like receptor binding; ISO:GO_Central. 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:GO_Central. DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:MGI. DR GO; GO:0019901; F:protein kinase binding; ISO:GO_Central. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:ARUK-UCL. DR GO; GO:0042169; F:SH2 domain binding; IDA:MGI. DR GO; GO:0017124; F:SH3 domain binding; IDA:MGI. DR GO; GO:0005001; F:transmembrane receptor protein tyrosine phosphatase activity; ISS:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; IMP:MGI. DR GO; GO:0160162; P:CD27 signaling pathway; ISO:GO_Central. DR GO; GO:0030154; P:cell differentiation; ISS:UniProtKB. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:MGI. DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; ISO:GO_Central. DR GO; GO:1905867; P:epididymis development; IMP:UniProtKB. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:MGI. DR GO; GO:0090594; P:inflammatory response to wounding; ISO:GO_Central. DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI. DR GO; GO:0035855; P:megakaryocyte development; IMP:MGI. DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central. DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IMP:MGI. DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:GO_Central. DR GO; GO:0050859; P:negative regulation of B cell receptor signaling pathway; ISO:GO_Central. DR GO; GO:0002924; P:negative regulation of humoral immune response mediated by circulating immunoglobulin; IMP:MGI. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:GO_Central. DR GO; GO:0106015; P:negative regulation of inflammatory response to wounding; IDA:UniProt. DR GO; GO:0045824; P:negative regulation of innate immune response; ISO:GO_Central. DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IGI:ARUK-UCL. DR GO; GO:0031665; P:negative regulation of lipopolysaccharide-mediated signaling pathway; IGI:ARUK-UCL. DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:MGI. DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:MGI. DR GO; GO:0033007; P:negative regulation of mast cell activation involved in immune response; IDA:UniProtKB. DR GO; GO:1902564; P:negative regulation of neutrophil activation; ISO:GO_Central. DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:MGI. DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI. DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IMP:MGI. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IGI:ARUK-UCL. DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; ISO:GO_Central. DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISO:GO_Central. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:GO_Central. DR GO; GO:0070527; P:platelet aggregation; IMP:MGI. DR GO; GO:0030220; P:platelet formation; IGI:MGI. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:GO_Central. DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IMP:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:GO_Central. DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISO:GO_Central. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:GO_Central. DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI. DR GO; GO:0045577; P:regulation of B cell differentiation; IMP:MGI. 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:GO_Central. DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IGI:MGI. DR GO; GO:0042110; P:T cell activation; ISO:GO_Central. 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 FunFam; 3.30.505.10:FF:000012; Tyrosine-protein phosphatase non-receptor type; 1. DR FunFam; 3.30.505.10:FF:000018; Tyrosine-protein phosphatase non-receptor type; 1. DR FunFam; 3.90.190.10:FF:000018; Tyrosine-protein phosphatase non-receptor type; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR Gene3D; 3.30.505.10; SH2 domain; 2. DR InterPro; IPR052123; Non-rcpt_Tyr_Phosphatase. 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 Alternative splicing; Cytoplasm; Direct protein sequencing; KW Disease variant; Hydrolase; Isopeptide bond; Nucleus; Phosphoprotein; KW Protein phosphatase; Reference proteome; Repeat; SH2 domain; KW Ubl conjugation. FT CHAIN 1..595 FT /note="Tyrosine-protein phosphatase non-receptor type 6" FT /id="PRO_0000094759" FT DOMAIN 4..100 FT /note="SH2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 110..213 FT /note="SH2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 244..515 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 536..595 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 558..589 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 453 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160, FT ECO:0000255|PROSITE-ProRule:PRU10044" FT BINDING 419 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 453..459 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 500 FT /ligand="substrate" FT /evidence="ECO:0000250" FT MOD_RES 10 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P81718" FT MOD_RES 57 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 64 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P29350" FT MOD_RES 377 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:17947660" FT MOD_RES 394 FT /note="Phosphothreonine; by TAOK3" FT /evidence="ECO:0000250|UniProtKB:P29350" FT MOD_RES 536 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:17947660" FT MOD_RES 564 FT /note="Phosphotyrosine; by LYN" FT /evidence="ECO:0000250|UniProtKB:P29350" FT CROSSLNK 308 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29350" FT VAR_SEQ 1..39 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_005132" FT VAR_SEQ 1..3 FT /note="MVR -> MLSRG (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_005131" FT VAR_SEQ 40..44 FT /note="SLSVR -> MLSRG (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_005133" FT VARIANT 77..99 FT /note="EYYTQQQGILQDRDGTIIHLKYP -> VPRPHIWRAGGVTAAGQGRALD FT (in motheaten (me))" FT VARIANT 100..595 FT /note="Missing (in motheaten (me))" FT MUTAGEN 30..33 FT /note="RPSR->KPSE: Slight reduction in binding to FT phosphorylated Lilrb4a." FT /evidence="ECO:0000269|PubMed:9973385" FT MUTAGEN 136 FT /note="R->K: Abolishes binding to phosphorylated Lilrb4a." FT /evidence="ECO:0000269|PubMed:9973385" FT MUTAGEN 482 FT /note="I->F: Mice display a low bone mass density and are FT associated with osteopenia and elevated inflammatory FT cytokines." FT /evidence="ECO:0000269|PubMed:19419305" FT CONFLICT 240 FT /note="A -> R (in Ref. 1; AAA37796)" FT /evidence="ECO:0000305" FT CONFLICT 572 FT /note="K -> Q (in Ref. 1; AAA37796)" FT /evidence="ECO:0000305" FT CONFLICT 586 FT /note="E -> D (in Ref. 6; AAH12660)" FT /evidence="ECO:0000305" SQ SEQUENCE 595 AA; 67559 MW; CF17300D032638D2 CRC64; MVRWFHRDLS GPDAETLLKG RGVPGSFLAR PSRKNQGDFS LSVRVDDQVT HIRIQNSGDF YDLYGGEKFA TLTELVEYYT QQQGILQDRD GTIIHLKYPL NCSDPTSERW YHGHISGGQA ESLLQAKGEP WTFLVRESLS QPGDFVLSVL NDQPKAGPGS PLRVTHIKVM CEGGRYTVGG SETFDSLTDL VEHFKKTGIE EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA KAGFWEEFES LQKQEVKNLH QRLEGQRPEN KSKNRYKNIL PFDHSRVILQ GRDSNIPGSD YINANYVKNQ LLGPDENSKT YIASQGCLDA TVNDFWQMAW QENTRVIVMT TREVEKGRNK CVPYWPEVGT QRVYGLYSVT NSREHDTAEY KLRTLQISPL DNGDLVREIW HYQYLSWPDH GVPSEPGGVL SFLDQINQRQ ESLPHAGPII VHCSAGIGRT GTIIVIDMLM ESISTKGLDC DIDIQKTIQM VRAQRSGMVQ TEAQYKFIYV AIAQFIETTK KKLEIIQSQK GQESEYGNIT YPPAVRSAHA KASRTSSKHK EEVYENVHSK SKKEEKVKKQ RSADKEKNKG SLKRK //