ID PTPRZ_HUMAN Reviewed; 2315 AA. AC P23471; A4D0W5; C9JFM0; O76043; Q9UDR6; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 24-MAR-2009, sequence version 4. DT 25-MAY-2022, entry version 223. DE RecName: Full=Receptor-type tyrosine-protein phosphatase zeta; DE Short=R-PTP-zeta; DE EC=3.1.3.48 {ECO:0000250|UniProtKB:Q62656}; DE AltName: Full=Protein-tyrosine phosphatase receptor type Z polypeptide 1; DE AltName: Full=Protein-tyrosine phosphatase receptor type Z polypeptide 2; DE AltName: Full=R-PTP-zeta-2; DE Flags: Precursor; GN Name=PTPRZ1; Synonyms=HTPZP2, PTPRZ, PTPRZ2, PTPZ; 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] (ISOFORM 1), AND VARIANT ASP-1433. RC TISSUE=Brain; RX PubMed=1323835; DOI=10.1073/pnas.89.16.7417; RA Krueger N.X., Saito H.; RT "A human transmembrane protein-tyrosine-phosphatase, PTP zeta, is expressed RT in brain and has an N-terminal receptor domain homologous to carbonic RT anhydrases."; RL Proc. Natl. Acad. Sci. U.S.A. 89:7417-7421(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Brain stem; RX PubMed=8387522; DOI=10.1016/s0021-9258(18)82237-2; RA Levy J.B., Canoll P.D., Silvennoinen O., Barnea G., Morse B., RA Honegger A.M., Huang J.-T., Cannizzaro L.A., Park S.-H., Druck T., RA Huebner K., Sap J., Ehrlich M., Musacchio J.M., Schlessinger J.; RT "The cloning of a receptor-type protein tyrosine phosphatase expressed in RT the central nervous system."; RL J. Biol. Chem. 268:10573-10581(1993). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASP-1433. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASP-1433. 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-999 (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=9653645; DOI=10.1006/geno.1997.5186; RA Onyango P., Lubyova B., Gardellin P., Kurzbauer R., Weith A.; RT "Molecular cloning and expression analysis of five novel genes in RT chromosome 1p36."; RL Genomics 50:187-198(1998). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1480-2092 (ISOFORM 1). RC TISSUE=Liver; RX PubMed=2170109; DOI=10.1002/j.1460-2075.1990.tb07523.x; RA Krueger N.X., Streuli M., Saito H.; RT "Structural diversity and evolution of human receptor-like protein tyrosine RT phosphatases."; RL EMBO J. 9:3241-3252(1990). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1750-1991 AND 2048-2281 (ISOFORM 1). RC TISSUE=Brain stem; RX PubMed=2169617; DOI=10.1073/pnas.87.18.7000; RA Kaplan R., Morse B., Huebner K., Croce C., Howk R., Ravera M., Ricca G., RA Jaye M., Schlessinger J.; RT "Cloning of three human tyrosine phosphatases reveals a multigene family of RT receptor-linked protein-tyrosine-phosphatases expressed in brain."; RL Proc. Natl. Acad. Sci. U.S.A. 87:7000-7004(1990). RN [9] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-105. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [10] RP INTERACTION WITH PTN. RX PubMed=16814777; DOI=10.1016/j.febslet.2006.06.041; RA Fukada M., Fujikawa A., Chow J.P., Ikematsu S., Sakuma S., Noda M.; RT "Protein tyrosine phosphatase receptor type Z is inactivated by ligand- RT induced oligomerization."; RL FEBS Lett. 580:4051-4056(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2055, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302, INTERACTION WITH CNTN1, RP AND DISULFIDE BONDS. RX PubMed=20133774; DOI=10.1073/pnas.0911235107; RA Bouyain S., Watkins D.J.; RT "The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members RT of the contactin family of neural recognition molecules."; RL Proc. Natl. Acad. Sci. U.S.A. 107:2443-2448(2010). CC -!- FUNCTION: Protein tyrosine phosphatase that negatively regulates CC oligodendrocyte precursor proliferation in the embryonic spinal cord. CC Required for normal differentiation of the precursor cells into mature, CC fully myelinating oligodendrocytes. May play a role in protecting CC oligondendrocytes against apoptosis. May play a role in the CC establishment of contextual memory, probably via the dephosphorylation CC of proteins that are part of important signaling cascades (By CC similarity). {ECO:0000250}. 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}; CC -!- SUBUNIT: The carbonic-anhydrase like domain interacts with CNTN1 CC (contactin) (PubMed:20133774). Interacts with PTN (PubMed:16814777). CC Interaction with PTN promotes formation of homooligomers; CC oligomerization impairs phosphatase activity (By similarity). Interacts CC (via chondroitin sulfate chains) with MDK (via C-terminal); this CC interaction is inhibited by PTN; this interaction promotes neuronal CC migration (By similarity). {ECO:0000250|UniProtKB:Q62656, CC ECO:0000269|PubMed:16814777, ECO:0000269|PubMed:20133774}. CC -!- INTERACTION: CC P23471; Q9UM73: ALK; NbExp=2; IntAct=EBI-2263175, EBI-357361; CC P23471; Q12860: CNTN1; NbExp=3; IntAct=EBI-2263175, EBI-5564336; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I CC membrane protein. Secreted {ECO:0000250}. Note=A secreted form is CC apparently generated by shedding of the extracellular domain. CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P23471-1; Sequence=Displayed; CC Name=2; CC IsoId=P23471-2; Sequence=VSP_054062; CC Name=3; CC IsoId=P23471-3; Sequence=VSP_054061, VSP_054062; CC -!- TISSUE SPECIFICITY: Specifically expressed in the central nervous CC system, where it is localized in the Purkinje cell layer of the CC cerebellum, the dentate gyrus, and the subependymal layer of the CC anterior horn of the lateral ventricle. Developmentally regulated in CC the brain. {ECO:0000269|PubMed:9653645}. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. CC Receptor class 5 subfamily. {ECO:0000305}. CC -!- CAUTION: Was termed (PubMed:8387522 and PubMed:2170109) RPTPase beta. CC {ECO:0000305}. CC -!- CAUTION: The human genome was initially thought to contain 2 genes for CC PTPRZ: PTPRZ1 (on chr 7) and PTPRZ2 (on chr 1). However, PTPRZ2 CC probably does not exist and corresponds to PTPRZ1. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC39934.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. The N-terminus may be contaminated with vector sequence.; Evidence={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; M93426; AAA60225.1; -; mRNA. DR EMBL; AC006020; AAF03527.1; -; Genomic_DNA. DR EMBL; AC006353; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC073095; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH236947; EAL24344.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83561.1; -; Genomic_DNA. DR EMBL; U88967; AAC39934.1; ALT_SEQ; mRNA. DR EMBL; X54135; CAA38070.1; -; mRNA. DR CCDS; CCDS34740.1; -. [P23471-1] DR CCDS; CCDS56505.1; -. [P23471-3] DR PIR; A46151; A46151. DR RefSeq; NP_001193767.1; NM_001206838.1. DR RefSeq; NP_001193768.1; NM_001206839.1. [P23471-3] DR RefSeq; NP_002842.2; NM_002851.2. [P23471-1] DR RefSeq; XP_005250576.1; XM_005250519.1. DR PDB; 3JXF; X-ray; 2.00 A; A/B=34-302. DR PDB; 3S97; X-ray; 2.30 A; A/B=34-302. DR PDB; 5AWX; X-ray; 1.86 A; A=1698-2000. DR PDB; 5H08; X-ray; 2.53 A; A=1698-2000. DR PDBsum; 3JXF; -. DR PDBsum; 3S97; -. DR PDBsum; 5AWX; -. DR PDBsum; 5H08; -. DR AlphaFoldDB; P23471; -. DR SMR; P23471; -. DR BioGRID; 111767; 30. DR DIP; DIP-42063N; -. DR IntAct; P23471; 13. DR MINT; P23471; -. DR STRING; 9606.ENSP00000377047; -. DR BindingDB; P23471; -. DR ChEMBL; CHEMBL4295730; -. DR DEPOD; PTPRZ1; -. DR GlyConnect; 2068; 2 N-Linked glycans (1 site). DR GlyGen; P23471; 25 sites, 4 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; P23471; -. DR PhosphoSitePlus; P23471; -. DR BioMuta; PTPRZ1; -. DR DMDM; 229485537; -. DR EPD; P23471; -. DR jPOST; P23471; -. DR MassIVE; P23471; -. DR PaxDb; P23471; -. DR PeptideAtlas; P23471; -. DR PRIDE; P23471; -. DR ProteomicsDB; 10007; -. DR ProteomicsDB; 54112; -. [P23471-1] DR ProteomicsDB; 54113; -. [P23471-2] DR ABCD; P23471; 7 sequenced antibodies. DR Antibodypedia; 2175; 213 antibodies from 26 providers. DR DNASU; 5803; -. DR Ensembl; ENST00000393386.7; ENSP00000377047.2; ENSG00000106278.12. DR Ensembl; ENST00000449182.1; ENSP00000410000.1; ENSG00000106278.12. [P23471-3] DR Ensembl; ENST00000652298.1; ENSP00000499137.1; ENSG00000106278.12. [P23471-2] DR GeneID; 5803; -. DR KEGG; hsa:5803; -. DR MANE-Select; ENST00000393386.7; ENSP00000377047.2; NM_002851.3; NP_002842.2. DR UCSC; uc003vjy.4; human. [P23471-1] DR CTD; 5803; -. DR DisGeNET; 5803; -. DR GeneCards; PTPRZ1; -. DR HGNC; HGNC:9685; PTPRZ1. DR HPA; ENSG00000106278; Tissue enhanced (brain, skin). DR MIM; 176891; gene. DR MIM; 604008; gene. DR neXtProt; NX_P23471; -. DR OpenTargets; ENSG00000106278; -. DR PharmGKB; PA34029; -. DR VEuPathDB; HostDB:ENSG00000106278; -. DR eggNOG; KOG0789; Eukaryota. DR GeneTree; ENSGT00940000155529; -. DR HOGENOM; CLU_001120_1_0_1; -. DR InParanoid; P23471; -. DR OMA; EIHETVC; -. DR OrthoDB; 251520at2759; -. DR PhylomeDB; P23471; -. DR TreeFam; TF351978; -. DR BRENDA; 3.1.3.48; 2681. DR PathwayCommons; P23471; -. DR Reactome; R-HSA-201556; Signaling by ALK. DR Reactome; R-HSA-449836; Other interleukin signaling. DR SignaLink; P23471; -. DR SIGNOR; P23471; -. DR BioGRID-ORCS; 5803; 11 hits in 1070 CRISPR screens. DR ChiTaRS; PTPRZ1; human. DR EvolutionaryTrace; P23471; -. DR GeneWiki; PTPRZ1; -. DR GenomeRNAi; 5803; -. DR Pharos; P23471; Tchem. DR PRO; PR:P23471; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P23471; protein. DR Bgee; ENSG00000106278; Expressed in ventricular zone and 192 other tissues. DR ExpressionAtlas; P23471; baseline and differential. DR Genevisible; P23471; HS. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB. DR GO; GO:0072534; C:perineuronal net; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:Ensembl. DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB. DR GO; GO:0005001; F:transmembrane receptor protein tyrosine phosphatase activity; TAS:ProtInc. DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl. DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0007611; P:learning or memory; ISS:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB. DR GO; GO:0048709; P:oligodendrocyte differentiation; ISS:UniProtKB. DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISS:UniProtKB. DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISS:UniProtKB. DR GO; GO:0006470; P:protein dephosphorylation; IBA:GO_Central. DR GO; GO:0031641; P:regulation of myelination; ISS:UniProtKB. DR GO; GO:0070445; P:regulation of oligodendrocyte progenitor proliferation; ISS:UniProtKB. DR CDD; cd03122; alpha_CARP_receptor_like; 1. DR CDD; cd00063; FN3; 1. DR Gene3D; 2.60.40.10; -; 1. DR Gene3D; 3.10.200.10; -; 1. DR Gene3D; 3.90.190.10; -; 2. DR InterPro; IPR041887; Alpha_CARP_receptor-type. DR InterPro; IPR001148; CA_dom. DR InterPro; IPR036398; CA_dom_sf. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR000242; PTP_cat. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR003595; Tyr_Pase_cat. DR InterPro; IPR000387; Tyr_Pase_dom. DR Pfam; PF00194; Carb_anhydrase; 1. DR Pfam; PF00041; fn3; 1. DR Pfam; PF00102; Y_phosphatase; 2. DR PRINTS; PR00700; PRTYPHPHTASE. DR SMART; SM01057; Carb_anhydrase; 1. DR SMART; SM00060; FN3; 1. DR SMART; SM00194; PTPc; 2. DR SMART; SM00404; PTPc_motif; 2. DR SUPFAM; SSF49265; SSF49265; 1. DR SUPFAM; SSF51069; SSF51069; 1. DR SUPFAM; SSF52799; SSF52799; 2. DR PROSITE; PS51144; ALPHA_CA_2; 1. DR PROSITE; PS50853; FN3; 1. DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 2. DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond; KW Glycoprotein; Hydrolase; Membrane; Phosphoprotein; Protein phosphatase; KW Proteoglycan; Reference proteome; Repeat; Secreted; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..24 FT /evidence="ECO:0000250" FT CHAIN 25..2315 FT /note="Receptor-type tyrosine-protein phosphatase zeta" FT /id="PRO_0000025468" FT TOPO_DOM 25..1636 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1637..1662 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1663..2315 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 36..300 FT /note="Alpha-carbonic anhydrase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01134" FT DOMAIN 314..413 FT /note="Fibronectin type-III" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1717..1992 FT /note="Tyrosine-protein phosphatase 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT DOMAIN 2023..2282 FT /note="Tyrosine-protein phosphatase 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 442..462 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 477..507 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 628..650 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1123..1160 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1397..1523 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1543..1572 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1584..1621 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1933..1939 FT /note="Substrate binding" FT /evidence="ECO:0000250" FT COMPBIAS 446..462 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 628..644 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1416..1432 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1462..1513 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1544..1569 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1591..1621 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 1933 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160, FT ECO:0000255|PROSITE-ProRule:PRU10044" FT BINDING 1901 FT /note="Substrate" FT /evidence="ECO:0000250" FT BINDING 1977 FT /note="Substrate" FT /evidence="ECO:0000250" FT SITE 2223 FT /note="Ancestral active site" FT MOD_RES 637 FT /note="Phosphoserine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q62656" FT MOD_RES 639 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62656" FT MOD_RES 1684 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:B9EKR1" FT MOD_RES 1687 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q62656" FT MOD_RES 2055 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT CARBOHYD 105 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 223 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 232 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 324 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 381 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 497 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 501 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 552 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 587 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000255" FT CARBOHYD 602 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 629 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 637 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine; FT alternate" FT /evidence="ECO:0000255" FT CARBOHYD 677 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 997 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000255" FT CARBOHYD 1017 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1050 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1082 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1122 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1457 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1549 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000255" FT CARBOHYD 1551 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000255" FT CARBOHYD 1562 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1618 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 56..240 FT /evidence="ECO:0000269|PubMed:20133774" FT DISULFID 133..264 FT /evidence="ECO:0000269|PubMed:20133774" FT VAR_SEQ 755..1614 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8387522" FT /id="VSP_054061" FT VAR_SEQ 1723..1729 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:8387522" FT /id="VSP_054062" FT VARIANT 3 FT /note="I -> S (in dbSNP:rs740965)" FT /id="VAR_038942" FT VARIANT 6 FT /note="R -> L (in dbSNP:rs11980387)" FT /id="VAR_038943" FT VARIANT 1433 FT /note="G -> D (in dbSNP:rs1147504)" FT /evidence="ECO:0000269|PubMed:12690205, FT ECO:0000269|PubMed:1323835, ECO:0000269|Ref.5" FT /id="VAR_038944" FT CONFLICT 310 FT /note="V -> A (in Ref. 6; AAC39934)" FT /evidence="ECO:0000305" FT CONFLICT 312 FT /note="S -> R (in Ref. 6; AAC39934)" FT /evidence="ECO:0000305" FT CONFLICT 1426 FT /note="Missing (in Ref. 1; AAA60225, 2, 4; EAL24344 and 5; FT EAW83561)" FT /evidence="ECO:0000305" FT STRAND 40..42 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 46..48 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 49..52 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 54..57 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 58..60 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 68..70 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 71..73 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 78..84 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 94..97 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 102..105 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 111..116 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 121..134 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 141..144 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 150..158 FT /evidence="ECO:0007829|PDB:3JXF" FT TURN 160..162 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 166..171 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 176..185 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 191..193 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 194..202 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 209..211 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 217..220 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 226..233 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 244..251 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 253..255 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 257..261 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 262..265 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 267..272 FT /evidence="ECO:0007829|PDB:3JXF" FT STRAND 275..280 FT /evidence="ECO:0007829|PDB:3JXF" FT HELIX 1701..1703 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1704..1713 FT /evidence="ECO:0007829|PDB:5AWX" FT TURN 1714..1716 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1717..1722 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1730..1733 FT /evidence="ECO:0007829|PDB:5AWX" FT TURN 1734..1737 FT /evidence="ECO:0007829|PDB:5AWX" FT TURN 1743..1746 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1748..1753 FT /evidence="ECO:0007829|PDB:5AWX" FT TURN 1763..1765 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1766..1768 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1781..1790 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1793..1800 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1805..1807 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1808..1817 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1822..1825 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1829..1831 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1843..1849 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1852..1861 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1863..1874 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1889..1896 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1901..1903 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1908..1921 FT /evidence="ECO:0007829|PDB:5AWX" FT TURN 1922..1924 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1929..1932 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1934..1937 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1938..1956 FT /evidence="ECO:0007829|PDB:5AWX" FT STRAND 1957..1959 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1961..1968 FT /evidence="ECO:0007829|PDB:5AWX" FT TURN 1969..1971 FT /evidence="ECO:0007829|PDB:5AWX" FT HELIX 1979..1994 FT /evidence="ECO:0007829|PDB:5AWX" SQ SEQUENCE 2315 AA; 254587 MW; ED9DD98D4CCA2883 CRC64; MRILKRFLAC IQLLCVCRLD WANGYYRQQR KLVEEIGWSY TGALNQKNWG KKYPTCNSPK QSPINIDEDL TQVNVNLKKL KFQGWDKTSL ENTFIHNTGK TVEINLTNDY RVSGGVSEMV FKASKITFHW GKCNMSSDGS EHSLEGQKFP LEMQIYCFDA DRFSSFEEAV KGKGKLRALS ILFEVGTEEN LDFKAIIDGV ESVSRFGKQA ALDPFILLNL LPNSTDKYYI YNGSLTSPPC TDTVDWIVFK DTVSISESQL AVFCEVLTMQ QSGYVMLMDY LQNNFREQQY KFSRQVFSSY TGKEEIHEAV CSSEPENVQA DPENYTSLLV TWERPRVVYD TMIEKFAVLY QQLDGEDQTK HEFLTDGYQD LGAILNNLLP NMSYVLQIVA ICTNGLYGKY SDQLIVDMPT DNPELDLFPE LIGTEEIIKE EEEGKDIEEG AIVNPGRDSA TNQIRKKEPQ ISTTTHYNRI GTKYNEAKTN RSPTRGSEFS GKGDVPNTSL NSTSQPVTKL ATEKDISLTS QTVTELPPHT VEGTSASLND GSKTVLRSPH MNLSGTAESL NTVSITEYEE ESLLTSFKLD TGAEDSSGSS PATSAIPFIS ENISQGYIFS SENPETITYD VLIPESARNA SEDSTSSGSE ESLKDPSMEG NVWFPSSTDI TAQPDVGSGR ESFLQTNYTE IRVDESEKTT KSFSAGPVMS QGPSVTDLEM PHYSTFAYFP TEVTPHAFTP SSRQQDLVST VNVVYSQTTQ PVYNGETPLQ PSYSSEVFPL VTPLLLDNQI LNTTPAASSS DSALHATPVF PSVDVSFESI LSSYDGAPLL PFSSASFSSE LFRHLHTVSQ ILPQVTSATE SDKVPLHASL PVAGGDLLLE PSLAQYSDVL STTHAASETL EFGSESGVLY KTLMFSQVEP PSSDAMMHAR SSGPEPSYAL SDNEGSQHIF TVSYSSAIPV HDSVGVTYQG SLFSGPSHIP IPKSSLITPT ASLLQPTHAL SGDGEWSGAS SDSEFLLPDT DGLTALNISS PVSVAEFTYT TSVFGDDNKA LSKSEIIYGN ETELQIPSFN EMVYPSESTV MPNMYDNVNK LNASLQETSV SISSTKGMFP GSLAHTTTKV FDHEISQVPE NNFSVQPTHT VSQASGDTSL KPVLSANSEP ASSDPASSEM LSPSTQLLFY ETSASFSTEV LLQPSFQASD VDTLLKTVLP AVPSDPILVE TPKVDKISST MLHLIVSNSA SSENMLHSTS VPVFDVSPTS HMHSASLQGL TISYASEKYE PVLLKSESSH QVVPSLYSND ELFQTANLEI NQAHPPKGRH VFATPVLSID EPLNTLINKL IHSDEILTST KSSVTGKVFA GIPTVASDTF VSTDHSVPIG NGHVAITAVS PHRDGSVTST KLLFPSKATS ELSHSAKSDA GLVGGGEDGD TDDDGDDDDD DRGSDGLSIH KCMSCSSYRE SQEKVMNDSD THENSLMDQN NPISYSLSEN SEEDNRVTSV SSDSQTGMDR SPGKSPSANG LSQKHNDGKE ENDIQTGSAL LPLSPESKAW AVLTSDEESG SGQGTSDSLN ENETSTDFSF ADTNEKDADG ILAAGDSEIT PGFPQSPTSS VTSENSEVFH VSEAEASNSS HESRIGLAEG LESEKKAVIP LVIVSALTFI CLVVLVGILI YWRKCFQTAH FYLEDSTSPR VISTPPTPIF PISDDVGAIP IKHFPKHVAD LHASSGFTEE FETLKEFYQE VQSCTVDLGI TADSSNHPDN KHKNRYINIV AYDHSRVKLA QLAEKDGKLT DYINANYVDG YNRPKAYIAA QGPLKSTAED FWRMIWEHNV EVIVMITNLV EKGRRKCDQY WPADGSEEYG NFLVTQKSVQ VLAYYTVRNF TLRNTKIKKG SQKGRPSGRV VTQYHYTQWP DMGVPEYSLP VLTFVRKAAY AKRHAVGPVV VHCSAGVGRT GTYIVLDSML QQIQHEGTVN IFGFLKHIRS QRNYLVQTEE QYVFIHDTLV EAILSKETEV LDSHIHAYVN ALLIPGPAGK TKLEKQFQLL SQSNIQQSDY SAALKQCNRE KNRTSSIIPV ERSRVGISSL SGEGTDYINA SYIMGYYQSN EFIITQHPLL HTIKDFWRMI WDHNAQLVVM IPDGQNMAED EFVYWPNKDE PINCESFKVT LMAEEHKCLS NEEKLIIQDF ILEATQDDYV LEVRHFQCPK WPNPDSPISK TFELISVIKE EAANRDGPMI VHDEHGGVTA GTFCALTTLM HQLEKENSVD VYQVAKMINL MRPGVFADIE QYQFLYKVIL SLVSTRQEEN PSTSLDSNGA ALPDGNIAES LESLV //