PTN22_HUMAN
ID PTN22_HUMAN Reviewed; 807 AA.
AC Q9Y2R2; A0N0K6; B1ALC8; D4NZ71; E9PLD8; E9PPI1; O95063; O95064; Q6IPX8;
AC Q8WVM1;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 22;
DE EC=3.1.3.48 {ECO:0000269|PubMed:21719704};
DE AltName: Full=Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP;
DE AltName: Full=Lymphoid phosphatase;
DE Short=LyP;
DE AltName: Full=PEST-domain phosphatase;
DE Short=PEP;
GN Name=PTPN22; Synonyms=PTPN8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND INTERACTION WITH CBL.
RX PubMed=10068674;
RA Cohen S., Dadi H., Shaoul E., Sharfe N., Roifman C.M.;
RT "Cloning and characterization of a lymphoid-specific, inducible human
RT protein tyrosine phosphatase, Lyp.";
RL Blood 93:2013-2024(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND VARIANT TRP-620.
RX PubMed=21044313; DOI=10.1186/1471-2199-11-78;
RA Wang S., Dong H., Han J., Ho W.T., Fu X., Zhao Z.J.;
RT "Identification of a variant form of tyrosine phosphatase LYP.";
RL BMC Mol. Biol. 11:78-78(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT TRP-620.
RA Liu T., Zhang J., Fu G., Zhang Q., Ye M., Zhou J., Wu J., Shen Y., Yu M.,
RA Chen S., Mao M., Chen Z.;
RT "Human protein tyrosine phosphatase (70zpep) homolog.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA Nickerson D.A.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT TRP-620.
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT TRP-620.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5).
RC TISSUE=Lymph;
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 [9]
RP FUNCTION.
RX PubMed=16461343; DOI=10.1074/jbc.m600498200;
RA Wu J., Katrekar A., Honigberg L.A., Smith A.M., Conn M.T., Tang J.,
RA Jeffery D., Mortara K., Sampang J., Williams S.R., Buggy J., Clark J.M.;
RT "Identification of substrates of human protein-tyrosine phosphatase
RT PTPN22.";
RL J. Biol. Chem. 281:11002-11010(2006).
RN [10]
RP REVIEW ON FUNCTION.
RX PubMed=17729039; DOI=10.1080/08916930701464897;
RA Vang T., Miletic A.V., Bottini N., Mustelin T.;
RT "Protein tyrosine phosphatase PTPN22 in human autoimmunity.";
RL Autoimmunity 40:453-461(2007).
RN [11]
RP ALTERNATIVE SPLICING (ISOFORM 6).
RX PubMed=22427951; DOI=10.1371/journal.pone.0033067;
RA Chang H.H., Tai T.S., Lu B., Iannaccone C., Cernadas M., Weinblatt M.,
RA Shadick N., Miaw S.C., Ho I.C.;
RT "PTPN22.6, a dominant negative isoform of PTPN22 and potential biomarker of
RT rheumatoid arthritis.";
RL PLoS ONE 7:E33067-E33067(2012).
RN [12]
RP FUNCTION, AND INTERACTION WITH TRAF3.
RX PubMed=23871208; DOI=10.1016/j.immuni.2013.06.013;
RA Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z.,
RA Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H.,
RA Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C.,
RA Corbett J.A., Binstadt B.A., Mescher M.F., Ley K., Bottini N.,
RA Peterson E.J.;
RT "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-
RT driven, type 1 interferon-dependent immunity.";
RL Immunity 39:111-122(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-449, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP FUNCTION.
RX PubMed=23991106; DOI=10.1371/journal.pone.0072384;
RA Spalinger M.R., Lang S., Vavricka S.R., Fried M., Rogler G., Scharl M.;
RT "Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced
RT cytokine release and autophagy.";
RL PLoS ONE 8:E72384-E72384(2013).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-294 IN COMPLEX WITH INHIBITOR,
RP FUNCTION, PHOSPHORYLATION AT SER-35, AND MUTAGENESIS OF SER-35 AND THR-36.
RX PubMed=18056643; DOI=10.1073/pnas.0706233104;
RA Yu X., Sun J.P., He Y., Guo X., Liu S., Zhou B., Hudmon A., Zhang Z.Y.;
RT "Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific
RT tyrosine phosphatase implicated in autoimmune diseases.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:19767-19772(2007).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-302, DISULFIDE BOND, AND
RP MUTAGENESIS OF CYS-129 AND CYS-231.
RX PubMed=19371084; DOI=10.1021/bi900166y;
RA Tsai S.J., Sen U., Zhao L., Greenleaf W.B., Dasgupta J., Fiorillo E.,
RA Orru V., Bottini N., Chen X.S.;
RT "Crystal structure of the human lymphoid tyrosine phosphatase catalytic
RT domain: insights into redox regulation.";
RL Biochemistry 48:4838-4845(2009).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-302, AND FUNCTION.
RX PubMed=19167335; DOI=10.1016/j.cell.2008.11.038;
RA Barr A.J., Ugochukwu E., Lee W.H., King O.N.F., Filippakopoulos P.,
RA Alfano I., Savitsky P., Burgess-Brown N.A., Mueller S., Knapp S.;
RT "Large-scale structural analysis of the classical human protein tyrosine
RT phosphatome.";
RL Cell 136:352-363(2009).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 2-309 OF WILD TYPE AND VARIANT
RP GLN-263, VARIANT GLN-263, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF
RP VARIANT GLN-263.
RX PubMed=18981062; DOI=10.1093/hmg/ddn363;
RA Orru V., Tsai S.J., Rueda B., Fiorillo E., Stanford S.M., Dasgupta J.,
RA Hartiala J., Zhao L., Ortego-Centeno N., D'Alfonso S., Arnett F.C., Wu H.,
RA Gonzalez-Gay M.A., Tsao B.P., Pons-Estel B., Alarcon-Riquelme M.E., He Y.,
RA Zhang Z.Y., Allayee H., Chen X.S., Martin J., Bottini N., Danieli M.G.,
RA Galeazzi M., Sabbadini M.G., Migliaresi S., Sebastiani G.D.;
RT "A loss-of-function variant of PTPN22 is associated with reduced risk of
RT systemic lupus erythematosus.";
RL Hum. Mol. Genet. 18:569-579(2009).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-310 IN COMPLEX WITH SUBSTRATE.
RA Seidel R.D., Love J., Piserchio A., Cowburn D.;
RT "Lyp/PTPN22 phosphatase domain: substrate recognition and specificity for
RT Src family kinases.";
RL Submitted (DEC-2009) to the PDB data bank.
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-294 OF MUTANT SER-227 ALONE AND
RP IN COMPLEX WITH SKAP2 PEPTIDE, SUBSTRATE SPECIFICITY, AND FUNCTION.
RX PubMed=21719704; DOI=10.1074/jbc.m111.254722;
RA Yu X., Chen M., Zhang S., Yu Z.H., Sun J.P., Wang L., Liu S., Imasaki T.,
RA Takagi Y., Zhang Z.Y.;
RT "Substrate specificity of lymphoid-specific tyrosine phosphatase (Lyp) and
RT identification of Src kinase-associated protein of 55 kDa homolog (SKAP-
RT HOM) as a Lyp substrate.";
RL J. Biol. Chem. 286:30526-30534(2011).
RN [21]
RP VARIANT RA TRP-620, INTERACTION WITH CSK, AND TISSUE SPECIFICITY.
RX PubMed=15208781; DOI=10.1086/422827;
RA Begovich A.B., Carlton V.E., Honigberg L.A., Schrodi S.J.,
RA Chokkalingam A.P., Alexander H.C., Ardlie K.G., Huang Q., Smith A.M.,
RA Spoerke J.M., Conn M.T., Chang M., Chang S.Y., Saiki R.K., Catanese J.J.,
RA Leong D.U., Garcia V.E., McAllister L.B., Jeffery D.A., Lee A.T.,
RA Batliwalla F., Remmers E., Criswell L.A., Seldin M.F., Kastner D.L.,
RA Amos C.I., Sninsky J.J., Gregersen P.K.;
RT "A missense single-nucleotide polymorphism in a gene encoding a protein
RT tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis.";
RL Am. J. Hum. Genet. 75:330-337(2004).
RN [22]
RP VARIANT SLE TRP-620.
RX PubMed=15273934; DOI=10.1086/423790;
RA Kyogoku C., Langefeld C.D., Ortmann W.A., Lee A., Selby S., Carlton V.E.H.,
RA Chang M., Ramos P., Baechler E.C., Batliwalla F.M., Novitzke J.,
RA Williams A.H., Gillett C., Rodine P., Graham R.R., Ardlie K.G.,
RA Gaffney P.M., Moser K.L., Petri M., Begovich A.B., Gregersen P.K.,
RA Behrens T.W.;
RT "Genetic association of the R620W polymorphism of protein tyrosine
RT phosphatase PTPN22 with human SLE.";
RL Am. J. Hum. Genet. 75:504-507(2004).
RN [23]
RP VARIANT IDDM TRP-620, AND CHARACTERIZATION OF VARIANT IDDM TRP-620.
RX PubMed=15004560; DOI=10.1038/ng1323;
RA Bottini N., Musumeci L., Alonso A., Rahmouni S., Nika K., Rostamkhani M.,
RA MacMurray J., Meloni G.F., Lucarelli P., Pellecchia M., Eisenbarth G.S.,
RA Comings D., Mustelin T.;
RT "A functional variant of lymphoid tyrosine phosphatase is associated with
RT type I diabetes.";
RL Nat. Genet. 36:337-338(2004).
RN [24]
RP INVOLVEMENT IN GRAVES DISEASE, INVOLVEMENT IN ADDISON DISEASE, AND VARIANT
RP TRP-620.
RX PubMed=15531553; DOI=10.1210/jc.2004-1108;
RA Velaga M.R., Wilson V., Jennings C.E., Owen C.J., Herington S.,
RA Donaldson P.T., Ball S.G., James R.A., Quinton R., Perros P., Pearce S.H.;
RT "The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP)
RT gene is a major determinant of Graves' disease.";
RL J. Clin. Endocrinol. Metab. 89:5862-5865(2004).
RN [25]
RP INVOLVEMENT IN HASHIMOTO THYROIDITIS, AND VARIANT TRP-620.
RX PubMed=15719322; DOI=10.1086/429096;
RA Criswell L.A., Pfeiffer K.A., Lum R.F., Gonzales B., Novitzke J., Kern M.,
RA Moser K.L., Begovich A.B., Carlton V.E., Li W., Lee A.T., Ortmann W.,
RA Behrens T.W., Gregersen P.K.;
RT "Analysis of families in the multiple autoimmune disease genetics
RT consortium (MADGC) collection: the PTPN22 620W allele associates with
RT multiple autoimmune phenotypes.";
RL Am. J. Hum. Genet. 76:561-571(2005).
RN [26]
RP VARIANT VTLG TRP-620.
RX PubMed=16015369; DOI=10.1038/sj.gene.6364243;
RA Canton I., Akhtar S., Gavalas N.G., Gawkrodger D.J., Blomhoff A.,
RA Watson P.F., Weetman A.P., Kemp E.H.;
RT "A single-nucleotide polymorphism in the gene encoding lymphoid protein
RT tyrosine phosphatase (PTPN22) confers susceptibility to generalised
RT vitiligo.";
RL Genes Immun. 6:584-587(2005).
RN [27]
RP VARIANT TRP-620, AND CHARACTERIZATION OF VARIANT TRP-620.
RX PubMed=19265110; DOI=10.4049/jimmunol.0713370;
RA Arechiga A.F., Habib T., He Y., Zhang X., Zhang Z.Y., Funk A.,
RA Buckner J.H.;
RT "Cutting edge: the PTPN22 allelic variant associated with autoimmunity
RT impairs B cell signaling.";
RL J. Immunol. 182:3343-3347(2009).
RN [28]
RP VARIANTS GLN-263 AND TRP-620, AND CHARACTERIZATION OF VARIANTS GLN-263 AND
RP TRP-620.
RX PubMed=21287672; DOI=10.1002/ibd.21630;
RA Diaz-Gallo L.M., Espino-Paisan L., Fransen K., Gomez-Garcia M.,
RA van Sommeren S., Cardena C., Rodrigo L., Mendoza J.L., Taxonera C.,
RA Nieto A., Alcain G., Cueto I., Lopez-Nevot M.A., Bottini N., Barclay M.L.,
RA Crusius J.B., van Bodegraven A.A., Wijmenga C., Ponsioen C.Y., Gearry R.B.,
RA Roberts R.L., Weersma R.K., Urcelay E., Merriman T.R., Alizadeh B.Z.,
RA Martin J.;
RT "Differential association of two PTPN22 coding variants with Crohn's
RT disease and ulcerative colitis.";
RL Inflamm. Bowel Dis. 17:2287-2294(2011).
RN [29]
RP VARIANTS PHE-201; GLN-263 AND TRP-266, AND CHARACTERIZATION OF VARIANTS
RP PHE-201; GLN-263 AND TRP-266.
RX PubMed=22952725; DOI=10.1371/journal.pone.0043631;
RA Liu J., Chen M., Li R., Yang F., Shi X., Zhu L., Wang H.M., Yao W., Liu Q.,
RA Meng F.G., Sun J.P., Pang Q., Yu X.;
RT "Biochemical and functional studies of lymphoid-specific tyrosine
RT phosphatase (Lyp) variants S201F and R266W.";
RL PLoS ONE 7:E43631-E43631(2012).
CC -!- FUNCTION: Acts as negative regulator of T-cell receptor (TCR) signaling
CC by direct dephosphorylation of the Src family kinases LCK and FYN,
CC ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key
CC signaling molecules (PubMed:16461343, PubMed:18056643). Associates with
CC and probably dephosphorylates CBL. Dephosphorylates LCK at its
CC activating 'Tyr-394' residue (PubMed:21719704). Dephosphorylates ZAP70
CC at its activating 'Tyr-493' residue (PubMed:16461343). Dephosphorylates
CC the immune system activator SKAP2 (PubMed:21719704). Positively
CC regulates toll-like receptor (TLR)-induced type 1 interferon production
CC (PubMed:23871208). Promotes host antiviral responses mediated by type 1
CC interferon (By similarity). Regulates NOD2-induced pro-inflammatory
CC cytokine secretion and autophagy (PubMed:23991106). Dephosphorylates
CC phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also
CC called N-arachidonoylethanolamide) (By similarity).
CC {ECO:0000250|UniProtKB:P29352, ECO:0000269|PubMed:16461343,
CC ECO:0000269|PubMed:18056643, ECO:0000269|PubMed:19167335,
CC ECO:0000269|PubMed:21719704, ECO:0000269|PubMed:23871208,
CC ECO:0000269|PubMed:23991106}.
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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10044, ECO:0000269|PubMed:21719704};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine
CC phosphate = N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine +
CC phosphate; Xref=Rhea:RHEA:56532, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:131894;
CC Evidence={ECO:0000250|UniProtKB:P29352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56533;
CC Evidence={ECO:0000250|UniProtKB:P29352};
CC -!- ACTIVITY REGULATION: Down-regulated by phosphorylation.
CC -!- SUBUNIT: Interacts with CSK (PubMed:15208781). Interacts with LPXN (By
CC similarity). Interacts with CBL (PubMed:10068674). Interacts with TRAF3
CC (via MATH domain); the interaction promotes TRAF3 polyubiquitination
CC (PubMed:23871208). {ECO:0000250|UniProtKB:P29352,
CC ECO:0000269|PubMed:10068674, ECO:0000269|PubMed:15208781,
CC ECO:0000269|PubMed:18056643, ECO:0000269|PubMed:21719704,
CC ECO:0000269|PubMed:23871208, ECO:0000269|Ref.19}.
CC -!- INTERACTION:
CC Q9Y2R2; P20963: CD247; NbExp=4; IntAct=EBI-1211241, EBI-1165705;
CC Q9Y2R2; P00533: EGFR; NbExp=3; IntAct=EBI-1211241, EBI-297353;
CC Q9Y2R2; P62993: GRB2; NbExp=2; IntAct=EBI-1211241, EBI-401755;
CC Q9Y2R2; P06239: LCK; NbExp=6; IntAct=EBI-1211241, EBI-1348;
CC Q9Y2R2; O43586: PSTPIP1; NbExp=6; IntAct=EBI-1211241, EBI-1050964;
CC Q9Y2R2; O75563: SKAP2; NbExp=3; IntAct=EBI-1211241, EBI-2483161;
CC Q9Y2R2; Q13114: TRAF3; NbExp=2; IntAct=EBI-1211241, EBI-357631;
CC Q9Y2R2; P43403: ZAP70; NbExp=4; IntAct=EBI-1211241, EBI-1211276;
CC Q9Y2R2; Q3UND0: Skap2; Xeno; NbExp=2; IntAct=EBI-1211241, EBI-642769;
CC Q9Y2R2; Q60803: Traf3; Xeno; NbExp=5; IntAct=EBI-1211241, EBI-520135;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P29352}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=LyP1;
CC IsoId=Q9Y2R2-1; Sequence=Displayed;
CC Name=2; Synonyms=LyP2;
CC IsoId=Q9Y2R2-2; Sequence=VSP_005134;
CC Name=3;
CC IsoId=Q9Y2R2-3; Sequence=VSP_039728;
CC Name=4; Synonyms=LYP3;
CC IsoId=Q9Y2R2-4; Sequence=VSP_039729;
CC Name=5;
CC IsoId=Q9Y2R2-5; Sequence=VSP_039725, VSP_039726, VSP_039727;
CC Name=6; Synonyms=PTPN22.6;
CC IsoId=Q9Y2R2-6; Sequence=VSP_044428, VSP_044429;
CC -!- TISSUE SPECIFICITY: Expressed in bone marrow, B and T-cells, PBMCs,
CC natural killer cells, monocytes, dendritic cells and neutrophils
CC (PubMed:15208781). Both isoform 1 and 4 are predominantly expressed in
CC lymphoid tissues and cells. Isoform 1 is expressed in thymocytes and
CC both mature B and T-cells. {ECO:0000269|PubMed:15208781}.
CC -!- INDUCTION: By muramyl-dipeptide and lipopolysaccharide.
CC {ECO:0000269|PubMed:23991106}.
CC -!- PTM: Phosphorylation on Ser-35 by PKC/PRKCD abrogates its ability to
CC dephosphorylate and inactivate the SRC family kinases.
CC {ECO:0000269|PubMed:18056643}.
CC -!- DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic,
CC relapsing, inflammatory, and often febrile multisystemic disorder of
CC connective tissue, characterized principally by involvement of the
CC skin, joints, kidneys and serosal membranes. It is of unknown etiology,
CC but is thought to represent a failure of the regulatory mechanisms of
CC the autoimmune system. The disease is marked by a wide range of system
CC dysfunctions, an elevated erythrocyte sedimentation rate, and the
CC formation of LE cells in the blood or bone marrow.
CC {ECO:0000269|PubMed:15273934}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Diabetes mellitus, insulin-dependent (IDDM) [MIM:222100]: A
CC multifactorial disorder of glucose homeostasis that is characterized by
CC susceptibility to ketoacidosis in the absence of insulin therapy.
CC Clinical features are polydipsia, polyphagia and polyuria which result
CC from hyperglycemia-induced osmotic diuresis and secondary thirst. These
CC derangements result in long-term complications that affect the eyes,
CC kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:15004560}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory
CC disease with autoimmune features and a complex genetic component. It
CC primarily affects the joints and is characterized by inflammatory
CC changes in the synovial membranes and articular structures, widespread
CC fibrinoid degeneration of the collagen fibers in mesenchymal tissues,
CC and by atrophy and rarefaction of bony structures.
CC {ECO:0000269|PubMed:15208781}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Vitiligo (VTLG) [MIM:193200]: A pigmentary disorder of the
CC skin and mucous membranes. It is characterized by circumscribed
CC depigmented macules and patches, commonly on extensor aspects of
CC extremities, on the face or neck and in skin folds. Vitiligo is a
CC progressive disorder in which some or all of the melanocytes in the
CC affected skin are selectively destroyed. It is a multifactorial
CC disorder with a complex etiology probably including autoimmune
CC mechanisms, and is associated with an elevated risk of other autoimmune
CC diseases. {ECO:0000269|PubMed:16015369}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to intron retention. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Lacks most of the phosphatase domain and
CC functions as a dominant negative isoform of the full length PTPN22.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class 4 subfamily. {ECO:0000305}.
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DR EMBL; AF001846; AAD00904.1; -; mRNA.
DR EMBL; AF001847; AAD00905.1; -; mRNA.
DR EMBL; GU479452; ADD59979.1; -; mRNA.
DR EMBL; AF077031; AAD27764.1; -; mRNA.
DR EMBL; AK310570; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; EF064714; ABK41897.1; -; Genomic_DNA.
DR EMBL; AL137856; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56575.1; -; Genomic_DNA.
DR EMBL; CH471122; EAW56576.1; -; Genomic_DNA.
DR EMBL; BC017785; AAH17785.1; -; mRNA.
DR EMBL; BC071670; AAH71670.1; -; mRNA.
DR CCDS; CCDS863.1; -. [Q9Y2R2-1]
DR CCDS; CCDS864.2; -. [Q9Y2R2-3]
DR RefSeq; NP_001180360.1; NM_001193431.2. [Q9Y2R2-4]
DR RefSeq; NP_001295226.1; NM_001308297.1.
DR RefSeq; NP_036543.4; NM_012411.5. [Q9Y2R2-3]
DR RefSeq; NP_057051.3; NM_015967.6. [Q9Y2R2-1]
DR PDB; 2P6X; X-ray; 1.90 A; A/B=1-302.
DR PDB; 2QCJ; X-ray; 3.00 A; A/B=1-294.
DR PDB; 2QCT; X-ray; 2.80 A; A/B=1-294.
DR PDB; 3BRH; X-ray; 2.20 A; A/B=1-310.
DR PDB; 3H2X; X-ray; 2.20 A; A=1-302.
DR PDB; 3OLR; X-ray; 2.50 A; A/B/C/D=1-294.
DR PDB; 3OMH; X-ray; 2.90 A; A/B/C/D=1-294.
DR PDB; 4J51; X-ray; 2.30 A; A/B=1-303.
DR PDB; 7AAM; X-ray; 2.15 A; C=787-807.
DR PDBsum; 2P6X; -.
DR PDBsum; 2QCJ; -.
DR PDBsum; 2QCT; -.
DR PDBsum; 3BRH; -.
DR PDBsum; 3H2X; -.
DR PDBsum; 3OLR; -.
DR PDBsum; 3OMH; -.
DR PDBsum; 4J51; -.
DR PDBsum; 7AAM; -.
DR AlphaFoldDB; Q9Y2R2; -.
DR SMR; Q9Y2R2; -.
DR BioGRID; 117604; 50.
DR DIP; DIP-29953N; -.
DR IntAct; Q9Y2R2; 38.
DR MINT; Q9Y2R2; -.
DR STRING; 9606.ENSP00000352833; -.
DR BindingDB; Q9Y2R2; -.
DR ChEMBL; CHEMBL2889; -.
DR GuidetoPHARMACOLOGY; 3084; -.
DR DEPOD; PTPN22; -.
DR iPTMnet; Q9Y2R2; -.
DR PhosphoSitePlus; Q9Y2R2; -.
DR BioMuta; PTPN22; -.
DR DMDM; 20139861; -.
DR jPOST; Q9Y2R2; -.
DR MassIVE; Q9Y2R2; -.
DR MaxQB; Q9Y2R2; -.
DR PaxDb; Q9Y2R2; -.
DR PeptideAtlas; Q9Y2R2; -.
DR PRIDE; Q9Y2R2; -.
DR ProteomicsDB; 21761; -.
DR ProteomicsDB; 22726; -.
DR ProteomicsDB; 85874; -. [Q9Y2R2-1]
DR ProteomicsDB; 85875; -. [Q9Y2R2-2]
DR ProteomicsDB; 85876; -. [Q9Y2R2-3]
DR ProteomicsDB; 85877; -. [Q9Y2R2-4]
DR ProteomicsDB; 85878; -. [Q9Y2R2-5]
DR Antibodypedia; 33846; 310 antibodies from 34 providers.
DR DNASU; 26191; -.
DR Ensembl; ENST00000460620.5; ENSP00000433141.1; ENSG00000134242.16. [Q9Y2R2-5]
DR GeneID; 26191; -.
DR KEGG; hsa:26191; -.
DR UCSC; uc001edt.4; human. [Q9Y2R2-1]
DR CTD; 26191; -.
DR DisGeNET; 26191; -.
DR GeneCards; PTPN22; -.
DR HGNC; HGNC:9652; PTPN22.
DR HPA; ENSG00000134242; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; PTPN22; -.
DR MIM; 152700; phenotype.
DR MIM; 180300; phenotype.
DR MIM; 193200; phenotype.
DR MIM; 222100; phenotype.
DR MIM; 600716; gene.
DR neXtProt; NX_Q9Y2R2; -.
DR OpenTargets; ENSG00000134242; -.
DR Orphanet; 397; Giant cell arteritis.
DR Orphanet; 900; Granulomatosis with polyangiitis.
DR Orphanet; 85410; Oligoarticular juvenile idiopathic arthritis.
DR Orphanet; 85408; Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis.
DR Orphanet; 536; Systemic lupus erythematosus.
DR Orphanet; 3437; Vogt-Koyanagi-Harada disease.
DR PharmGKB; PA33995; -.
DR VEuPathDB; HostDB:ENSG00000134242; -.
DR eggNOG; KOG0789; Eukaryota.
DR GeneTree; ENSGT00940000160958; -.
DR InParanoid; Q9Y2R2; -.
DR PhylomeDB; Q9Y2R2; -.
DR TreeFam; TF351977; -.
DR BRENDA; 3.1.3.48; 2681.
DR PathwayCommons; Q9Y2R2; -.
DR Reactome; R-HSA-202427; Phosphorylation of CD3 and TCR zeta chains.
DR Reactome; R-HSA-202430; Translocation of ZAP-70 to Immunological synapse.
DR SignaLink; Q9Y2R2; -.
DR SIGNOR; Q9Y2R2; -.
DR BioGRID-ORCS; 26191; 17 hits in 1088 CRISPR screens.
DR ChiTaRS; PTPN22; human.
DR EvolutionaryTrace; Q9Y2R2; -.
DR GeneWiki; PTPN22; -.
DR GenomeRNAi; 26191; -.
DR Pharos; Q9Y2R2; Tchem.
DR PRO; PR:Q9Y2R2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y2R2; protein.
DR Bgee; ENSG00000134242; Expressed in bone marrow cell and 116 other tissues.
DR ExpressionAtlas; Q9Y2R2; baseline and differential.
DR Genevisible; Q9Y2R2; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0019900; F:kinase binding; ISS:BHF-UCL.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0016791; F:phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; ISS:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; IMP:UniProtKB.
DR GO; GO:0043508; P:negative regulation of JUN kinase activity; IMP:UniProtKB.
DR GO; GO:0070433; P:negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; IMP:UniProtKB.
DR GO; GO:1903753; P:negative regulation of p38MAPK cascade; IMP:UniProtKB.
DR GO; GO:0050868; P:negative regulation of T cell activation; IMP:BHF-UCL.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IBA:GO_Central.
DR GO; GO:0035644; P:phosphoanandamide dephosphorylation; ISS:BHF-UCL.
DR GO; GO:2000566; P:positive regulation of CD8-positive, alpha-beta T cell proliferation; IBA:GO_Central.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0071663; P:positive regulation of granzyme B production; IBA:GO_Central.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IMP:UniProtKB.
DR GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0034141; P:positive regulation of toll-like receptor 3 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034157; P:positive regulation of toll-like receptor 7 signaling pathway; IBA:GO_Central.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; IBA:GO_Central.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IMP:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:BHF-UCL.
DR GO; GO:0050855; P:regulation of B cell receptor signaling pathway; NAS:BHF-UCL.
DR GO; GO:0045088; P:regulation of innate immune response; IC:BHF-UCL.
DR GO; GO:0032817; P:regulation of natural killer cell proliferation; IDA:BHF-UCL.
DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; ISS:BHF-UCL.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR016276; PTPN22.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PIRSF; PIRSF000930; PTPN8_PTPN22; 1.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR SMART; SM00194; PTPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
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 3D-structure; Alternative splicing; Autophagy; Cytoplasm;
KW Diabetes mellitus; Disease variant; Disulfide bond; Hydrolase; Immunity;
KW Lipid metabolism; Phosphoprotein; Protein phosphatase; Reference proteome;
KW Systemic lupus erythematosus.
FT CHAIN 1..807
FT /note="Tyrosine-protein phosphatase non-receptor type 22"
FT /id="PRO_0000094775"
FT DOMAIN 24..289
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 676..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 724..746
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 227
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 195
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 227..233
FT /ligand="substrate"
FT BINDING 274
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.19"
FT MOD_RES 35
FT /note="Phosphoserine; by PKC/PRKCD"
FT /evidence="ECO:0000269|PubMed:18056643"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 635
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29352"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29352"
FT MOD_RES 692
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29352"
FT DISULFID 129..227
FT /evidence="ECO:0000269|PubMed:19371084"
FT VAR_SEQ 124..250
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044428"
FT VAR_SEQ 137..160
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039725"
FT VAR_SEQ 181..203
FT /note="ETRTIYQFHYKNWPDHDVPSSID -> VSVILAHQTSLQNLFSQITPAHF
FT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039726"
FT VAR_SEQ 204..807
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039727"
FT VAR_SEQ 251..305
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039728"
FT VAR_SEQ 647..674
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:21044313"
FT /id="VSP_039729"
FT VAR_SEQ 685..807
FT /note="ELHQDRSSPPPPLPERTLESFFLADEDCMQAQSIETYSTSYPDTMENSTSSK
FT QTLKTPGKSFTRSKSLKILRNMKKSICNSCPPNKPAESVQSNNSSSFLNFGFANRFSKP
FT KGPRNPPPTWNI -> GKNFSWL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10068674"
FT /id="VSP_005134"
FT VAR_SEQ 788..807
FT /note="FANRFSKPKGPRNPPPTWNI -> MCVILLKS (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044429"
FT VARIANT 201
FT /note="S -> F (moderately reduces phosphatase activity;
FT dbSNP:rs7416347)"
FT /evidence="ECO:0000269|PubMed:22952725"
FT /id="VAR_072629"
FT VARIANT 263
FT /note="R -> Q (reduces risk of SLE and RA but not IDDM;
FT associated with reduced risk of ulcerative colitis but not
FT of Crohn disease; severely reduces phosphatase activity;
FT dbSNP:rs33996649)"
FT /evidence="ECO:0000269|PubMed:18981062,
FT ECO:0000269|PubMed:21287672, ECO:0000269|PubMed:22952725"
FT /id="VAR_072630"
FT VARIANT 266
FT /note="R -> W (severely reduces phosphatase activity;
FT dbSNP:rs72650670)"
FT /evidence="ECO:0000269|PubMed:22952725"
FT /id="VAR_072631"
FT VARIANT 620
FT /note="R -> W (in IDDM, RA, SLE and VTLG; also found in
FT patients with Graves disease, Hashimoto thyroiditis and
FT Addison disease; associated with reduced risk of Crohn
FT disease but not of ulcerative colitis; affects CSK kinase
FT binding; alters B cell receptor signaling and memory B cell
FT proliferation; dbSNP:rs2476601)"
FT /evidence="ECO:0000269|PubMed:15004560,
FT ECO:0000269|PubMed:15208781, ECO:0000269|PubMed:15273934,
FT ECO:0000269|PubMed:15531553, ECO:0000269|PubMed:15719322,
FT ECO:0000269|PubMed:16015369, ECO:0000269|PubMed:16710414,
FT ECO:0000269|PubMed:19265110, ECO:0000269|PubMed:21044313,
FT ECO:0000269|PubMed:21287672, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.7"
FT /id="VAR_022605"
FT MUTAGEN 35
FT /note="S->E: Loss of phosphorylation by PKC/PRKCD."
FT /evidence="ECO:0000269|PubMed:18056643"
FT MUTAGEN 36
FT /note="T->E: No effect on phosphorylation by PKC/PRKCD."
FT /evidence="ECO:0000269|PubMed:18056643"
FT MUTAGEN 129
FT /note="C->S: Decreases activity 2 fold."
FT /evidence="ECO:0000269|PubMed:19371084"
FT MUTAGEN 231
FT /note="C->S: Decreases activity 7 fold."
FT /evidence="ECO:0000269|PubMed:19371084"
FT CONFLICT 51..52
FT /note="KP -> NA (in Ref. 1; AAD00904/AAD00905)"
FT /evidence="ECO:0000305"
FT CONFLICT 126
FT /note="V -> G (in Ref. 2; AAD27764)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="G -> V (in Ref. 2; AAD27764)"
FT /evidence="ECO:0000305"
FT CONFLICT 240
FT /note="I -> IV (in Ref. 1; AAD00905)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="A -> V (in Ref. 4; AK310570)"
FT /evidence="ECO:0000305"
FT CONFLICT 420
FT /note="L -> P (in Ref. 2; AAD27764)"
FT /evidence="ECO:0000305"
FT CONFLICT 742
FT /note="P -> S (in Ref. 2; AAD27764)"
FT /evidence="ECO:0000305"
FT HELIX 3..16
FT /evidence="ECO:0007829|PDB:2P6X"
FT HELIX 21..40
FT /evidence="ECO:0007829|PDB:2P6X"
FT HELIX 47..50
FT /evidence="ECO:0007829|PDB:2P6X"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:3OMH"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:4J51"
FT TURN 80..83
FT /evidence="ECO:0007829|PDB:4J51"
FT STRAND 86..92
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:2P6X"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:2P6X"
FT HELIX 110..119
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:3BRH"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:2QCJ"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 156..165
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 167..178
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 181..190
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:2QCJ"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:2P6X"
FT HELIX 203..215
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:3BRH"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:2P6X"
FT STRAND 228..232
FT /evidence="ECO:0007829|PDB:2P6X"
FT HELIX 233..248
FT /evidence="ECO:0007829|PDB:2P6X"
FT HELIX 258..266
FT /evidence="ECO:0007829|PDB:2P6X"
FT HELIX 276..301
FT /evidence="ECO:0007829|PDB:2P6X"
SQ SEQUENCE 807 AA; 91705 MW; 1ABE8AE89C9D9FBF CRC64;
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE KPKNIKKNRY
KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI ATQGPLSTTL LDFWRMIWEY
SVLIIVMACM EYEMGKKKCE RYWAEPGEMQ LEFGPFSVSC EAEKRKSDYI IRTLKVKFNS
ETRTIYQFHY KNWPDHDVPS SIDPILELIW DVRCYQEDDS VPICIHCSAG CGRTGVICAI
DYTWMLLKDG IIPENFSVFS LIREMRTQRP SLVQTQEQYE LVYNAVLELF KRQMDVIRDK
HSGTESQAKH CIPEKNHTLQ ADSYSPNLPK STTKAAKMMN QQRTKMEIKE SSSFDFRTSE
ISAKEELVLH PAKSSTSFDF LELNYSFDKN ADTTMKWQTK AFPIVGEPLQ KHQSLDLGSL
LFEGCSNSKP VNAAGRYFNS KVPITRTKST PFELIQQRET KEVDSKENFS YLESQPHDSC
FVEMQAQKVM HVSSAELNYS LPYDSKHQIR NASNVKHHDS SALGVYSYIP LVENPYFSSW
PPSGTSSKMS LDLPEKQDGT VFPSSLLPTS STSLFSYYNS HDSLSLNSPT NISSLLNQES
AVLATAPRID DEIPPPLPVR TPESFIVVEE AGEFSPNVPK SLSSAVKVKI GTSLEWGGTS
EPKKFDDSVI LRPSKSVKLR SPKSELHQDR SSPPPPLPER TLESFFLADE DCMQAQSIET
YSTSYPDTME NSTSSKQTLK TPGKSFTRSK SLKILRNMKK SICNSCPPNK PAESVQSNNS
SSFLNFGFAN RFSKPKGPRN PPPTWNI
