PTPR2_HUMAN
ID PTPR2_HUMAN Reviewed; 1015 AA.
AC Q92932; E9PC57; Q8N4I5; Q92662; Q9Y4F8; Q9Y4I6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Receptor-type tyrosine-protein phosphatase N2;
DE Short=R-PTP-N2;
DE EC=3.1.3.-;
DE EC=3.1.3.48 {ECO:0000305|PubMed:8798755};
DE AltName: Full=Islet cell autoantigen-related protein {ECO:0000303|PubMed:8798755};
DE Short=IAR {ECO:0000303|PubMed:8798755};
DE Short=ICAAR {ECO:0000303|PubMed:8954911};
DE AltName: Full=Phogrin {ECO:0000303|PubMed:25421040, ECO:0000303|PubMed:8878534};
DE Contains:
DE RecName: Full=IA-2beta60;
DE Flags: Precursor;
GN Name=PTPRN2; Synonyms=KIAA0387;
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), DOMAIN, ROLE IN DIABETES MELLITUS,
RP AND VARIANT PRO-208.
RC TISSUE=Pancreas;
RX PubMed=8878534; DOI=10.1006/bbrc.1996.1526;
RA Kawasaki E., Hutton J.C., Eisenbarth G.S.;
RT "Molecular cloning and characterization of the human transmembrane protein
RT tyrosine phosphatase homologue, phogrin, an autoantigen of type 1
RT diabetes.";
RL Biochem. Biophys. Res. Commun. 227:440-447(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP VARIANT ASN-325.
RC TISSUE=Fetal brain;
RX PubMed=8954911; DOI=10.1006/bbrc.1996.1817;
RA Smith P.D., Barker K.T., Wang J., Lu Y.-J., Shipley J., Crompton M.R.;
RT "ICAAR, a novel member of a new family of transmembrane, tyrosine
RT phosphatase-like proteins.";
RL Biochem. Biophys. Res. Commun. 229:402-411(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND ROLE IN DIABETES
RP MELLITUS.
RC TISSUE=Brain, and Pancreas;
RX PubMed=8798755; DOI=10.1074/jbc.271.40.24817;
RA Cui L., Yu W.-P., de Aizpurua H.J., Schmidli R.S., Pallen C.J.;
RT "Cloning and characterization of islet cell antigen-related protein-
RT tyrosine phosphatase (PTP), a novel receptor-like PTP and autoantigen in
RT insulin-dependent diabetes.";
RL J. Biol. Chem. 271:24817-24823(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND VARIANTS THR-140; PRO-208 AND
RP ASN-325.
RC TISSUE=Brain;
RA Jiang S., Tulloch G., Fu Y., London R., Hummel G.S., White R.A.,
RA Avraham H., Avraham S.;
RT "Characterization and chromosomal localization of PTPRP, a receptor protein
RT tyrosine phosphatase predominantly expressed in brain and pancreas.";
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANTS PRO-208
RP AND HIS-213.
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [6]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT PRO-208.
RC TISSUE=Brain;
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 DOMAIN, AND ROLE IN DIABETES MELLITUS.
RX PubMed=8637868; DOI=10.1073/pnas.93.6.2307;
RA Lu J., Li Q., Xie H., Chen Z.-J., Borovitskaya A.E., Maclaren N.K.,
RA Notkins A.L., Lan M.S.;
RT "Identification of a second transmembrane protein tyrosine phosphatase, IA-
RT 2beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor
RT of the 37-kDa tryptic fragment.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2307-2311(1996).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-970, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF CYS-945.
RX PubMed=26620550; DOI=10.15252/embj.201591973;
RA Sengelaub C.A., Navrazhina K., Ross J.B., Halberg N., Tavazoie S.F.;
RT "PTPRN2 and PLCbeta1 promote metastatic breast cancer cell migration
RT through PI(4,5)P2-dependent actin remodeling.";
RL EMBO J. 35:62-76(2016).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 715-1010.
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 [13]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 502-599.
RX PubMed=25421040; DOI=10.1007/s10969-014-9191-0;
RA Noguera M.E., Primo M.E., Jakoncic J., Poskus E., Solimena M.,
RA Ermacora M.R.;
RT "X-ray structure of the mature ectodomain of phogrin.";
RL J. Struct. Funct. Genomics 16:1-9(2015).
RN [14]
RP VARIANT [LARGE SCALE ANALYSIS] LYS-716.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Plays a role in vesicle-mediated secretory processes.
CC Required for normal accumulation of secretory vesicles in hippocampus,
CC pituitary and pancreatic islets. Required for the accumulation of
CC normal levels of insulin-containing vesicles and preventing their
CC degradation. Plays a role in insulin secretion in response to glucose
CC stimuli. Required for normal accumulation of the neurotransmitters
CC norepinephrine, dopamine and serotonin in the brain. In females, but
CC not in males, required for normal accumulation and secretion of
CC pituitary hormones, such as luteinizing hormone (LH) and follicle-
CC stimulating hormone (FSH) (By similarity). Required to maintain normal
CC levels of renin expression and renin release (By similarity). May
CC regulate catalytic active protein-tyrosine phosphatases such as PTPRA
CC through dimerization (By similarity). Has phosphatidylinositol
CC phosphatase activity; the PIPase activity is involved in its ability to
CC regulate insulin secretion. Can dephosphorylate phosphatidylinositol
CC 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate and
CC phosphatidylinositol 3-phosphate (By similarity). Regulates PI(4,5)P2
CC level in the plasma membrane and localization of cofilin at the plasma
CC membrane and thus is indirectly involved in regulation of actin
CC dynamics related to cell migration and metastasis; upon hydrolyzation
CC of PI(4,5)P2 cofilin is released from the plasma membrane and acts in
CC the cytoplasm in severing F-actin filaments (PubMed:26620550).
CC {ECO:0000250|UniProtKB:P80560, ECO:0000250|UniProtKB:Q63475,
CC ECO:0000269|PubMed:26620550}.
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:0000305|PubMed:8798755};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 4.5. {ECO:0000269|PubMed:8798755};
CC -!- SUBUNIT: Self-associates. Interacts (via cytoplasmic domain) with PTPRN
CC (via cytoplasmic domain). Interacts (precursor form) with CPE.
CC Interacts with HAP1. Interacts with AP2A1 or AP2A2 and AP1G1;
CC indicative for an association with adaptor protein complex 2 (AP-2) and
CC adaptor protein complex 1 (AP-1) (By similarity). Interacts with AP2M1;
CC indicative for an association with adaptor protein complex 2 (AP-2).
CC Interacts with MYO5A (By similarity). {ECO:0000250|UniProtKB:P80560,
CC ECO:0000250|UniProtKB:Q63475}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000250|UniProtKB:P80560}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P80560}. Cytoplasmic vesicle, secretory vesicle,
CC synaptic vesicle membrane {ECO:0000250|UniProtKB:P80560}; Single-pass
CC type I membrane protein {ECO:0000250|UniProtKB:P80560}.
CC Note=Predominantly found on dense-core secretory granules. Sorting to
CC secretory granules in part is dependent of the N-terminal propeptide
CC domain of the precursor and its interaction with CPE (By similarity).
CC Transiently found at the cell membrane, when secretory vesicles fuse
CC with the cell membrane to release their cargo. Is then endocytosed and
CC recycled to secretory vesicles involving clathrin-dependent AP2-
CC mediated endocytosis. Recycled via STX6- but not TTTGN1/TGN38-
CC containing compartments (By similarity). {ECO:0000250|UniProtKB:P80560,
CC ECO:0000250|UniProtKB:Q63475}.
CC -!- SUBCELLULAR LOCATION: [IA-2beta60]: Cytoplasmic vesicle, secretory
CC vesicle membrane {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q92932-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92932-2; Sequence=VSP_007779;
CC Name=3;
CC IsoId=Q92932-3; Sequence=VSP_035264;
CC Name=4;
CC IsoId=Q92932-4; Sequence=VSP_045032;
CC -!- TISSUE SPECIFICITY: Highest levels in brain and pancreas
CC (PubMed:8954911, PubMed:8798755). Lower levels in trachea, prostate,
CC stomach and spinal cord (PubMed:8798755). {ECO:0000269|PubMed:8798755,
CC ECO:0000269|PubMed:8954911}.
CC -!- DOMAIN: The cytoplasmic domain appears to contain the autoantigenic
CC epitopes. {ECO:0000269|PubMed:8637868, ECO:0000269|PubMed:8878534}.
CC -!- DOMAIN: The leucine-based sorting signal is proposed to function in
CC trafficking at the plasma membrane. {ECO:0000250|UniProtKB:P80560}.
CC -!- DOMAIN: The tyrosine-based internalization signal is proposed to
CC function at the level of clathrin-mediated endocytosis and recycling.
CC {ECO:0000250|UniProtKB:Q63475}.
CC -!- PTM: Subject to proteolytic cleavage at multiple sites.
CC {ECO:0000250|UniProtKB:P80560}.
CC -!- DISEASE: Note=Autoantigen in insulin-dependent diabetes mellitus
CC (IDDM). {ECO:0000269|PubMed:8637868, ECO:0000269|PubMed:8798755,
CC ECO:0000269|PubMed:8878534}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC Receptor class 8 subfamily. {ECO:0000305}.
CC -!- CAUTION: Has no tyrosine-protein phosphatase activity at mild acidic
CC conditions (pH 5.5). The in vivo relevance of the low PPase activity at
CC acidic conditions (pH 4.5) is questioned. This catalytic activity seems
CC to be affected by the replacement of a highly conserved residue in the
CC tyrosine-protein phosphatase domain. {ECO:0000305,
CC ECO:0000305|PubMed:8798755}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20841.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U66702; AAC50742.1; -; mRNA.
DR EMBL; Y08569; CAA69880.1; -; Genomic_DNA.
DR EMBL; AF007555; AAB63600.1; -; mRNA.
DR EMBL; U81561; AAB68603.1; -; mRNA.
DR EMBL; AB002385; BAA20841.2; ALT_INIT; mRNA.
DR EMBL; AC005481; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006003; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006372; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011899; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC019043; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC078942; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093662; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093856; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC125243; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034040; AAH34040.1; -; mRNA.
DR CCDS; CCDS5947.1; -. [Q92932-1]
DR CCDS; CCDS5948.1; -. [Q92932-4]
DR CCDS; CCDS5949.1; -. [Q92932-2]
DR PIR; JC5062; JC5062.
DR PIR; JC5263; JC5263.
DR RefSeq; NP_001295196.1; NM_001308267.1.
DR RefSeq; NP_001295197.1; NM_001308268.1. [Q92932-3]
DR RefSeq; NP_002838.2; NM_002847.4. [Q92932-1]
DR RefSeq; NP_570857.2; NM_130842.3. [Q92932-4]
DR RefSeq; NP_570858.2; NM_130843.3. [Q92932-2]
DR PDB; 2QEP; X-ray; 2.50 A; A/B=715-1010.
DR PDB; 4HTI; X-ray; 1.95 A; A=502-599.
DR PDB; 4HTJ; X-ray; 2.01 A; A=502-599.
DR PDBsum; 2QEP; -.
DR PDBsum; 4HTI; -.
DR PDBsum; 4HTJ; -.
DR AlphaFoldDB; Q92932; -.
DR SMR; Q92932; -.
DR BioGRID; 111763; 57.
DR IntAct; Q92932; 28.
DR MINT; Q92932; -.
DR STRING; 9606.ENSP00000374069; -.
DR TCDB; 8.A.128.1.12; the signaling adaptor protein karap/dap12/tyrobp (sap) family.
DR DEPOD; PTPRN2; -.
DR GlyGen; Q92932; 1 site.
DR iPTMnet; Q92932; -.
DR PhosphoSitePlus; Q92932; -.
DR BioMuta; PTPRN2; -.
DR DMDM; 116242738; -.
DR jPOST; Q92932; -.
DR MassIVE; Q92932; -.
DR PaxDb; Q92932; -.
DR PeptideAtlas; Q92932; -.
DR PRIDE; Q92932; -.
DR ProteomicsDB; 19372; -.
DR ProteomicsDB; 75611; -. [Q92932-1]
DR ProteomicsDB; 75612; -. [Q92932-2]
DR ProteomicsDB; 75613; -. [Q92932-3]
DR Antibodypedia; 1539; 378 antibodies from 31 providers.
DR DNASU; 5799; -.
DR Ensembl; ENST00000389413.7; ENSP00000374064.3; ENSG00000155093.19. [Q92932-2]
DR Ensembl; ENST00000389416.8; ENSP00000374067.4; ENSG00000155093.19. [Q92932-4]
DR Ensembl; ENST00000389418.9; ENSP00000374069.4; ENSG00000155093.19. [Q92932-1]
DR GeneID; 5799; -.
DR KEGG; hsa:5799; -.
DR MANE-Select; ENST00000389418.9; ENSP00000374069.4; NM_002847.5; NP_002838.2.
DR UCSC; uc003wno.4; human. [Q92932-1]
DR CTD; 5799; -.
DR DisGeNET; 5799; -.
DR GeneCards; PTPRN2; -.
DR HGNC; HGNC:9677; PTPRN2.
DR HPA; ENSG00000155093; Tissue enhanced (brain, pancreas).
DR MIM; 601698; gene.
DR neXtProt; NX_Q92932; -.
DR OpenTargets; ENSG00000155093; -.
DR PharmGKB; PA34022; -.
DR VEuPathDB; HostDB:ENSG00000155093; -.
DR eggNOG; KOG0793; Eukaryota.
DR GeneTree; ENSGT00940000154095; -.
DR HOGENOM; CLU_007905_0_0_1; -.
DR InParanoid; Q92932; -.
DR OMA; PDNGVHE; -.
DR PhylomeDB; Q92932; -.
DR TreeFam; TF351976; -.
DR BRENDA; 3.1.3.48; 2681.
DR PathwayCommons; Q92932; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q92932; -.
DR BioGRID-ORCS; 5799; 8 hits in 1072 CRISPR screens.
DR ChiTaRS; PTPRN2; human.
DR EvolutionaryTrace; Q92932; -.
DR GeneWiki; PTPRN2; -.
DR GenomeRNAi; 5799; -.
DR Pharos; Q92932; Tbio.
DR PRO; PR:Q92932; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q92932; protein.
DR Bgee; ENSG00000155093; Expressed in lateral nuclear group of thalamus and 183 other tissues.
DR ExpressionAtlas; Q92932; baseline and differential.
DR Genevisible; Q92932; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0030667; C:secretory granule membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0005001; F:transmembrane receptor protein tyrosine phosphatase activity; TAS:ProtInc.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0007269; P:neurotransmitter secretion; ISS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc.
DR GO; GO:0051046; P:regulation of secretion; IBA:GO_Central.
DR Gene3D; 3.30.70.2470; -; 1.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR033522; IA-2/IA-2_beta.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR021613; Receptor_IA-2_dom.
DR InterPro; IPR038112; Receptor_IA-2_ectodomain_sf.
DR InterPro; IPR029403; RESP18_dom.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR PANTHER; PTHR46106; PTHR46106; 1.
DR Pfam; PF11548; Receptor_IA-2; 1.
DR Pfam; PF14948; RESP18; 1.
DR Pfam; PF00102; Y_phosphatase; 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; Acetylation; Alternative splicing; Cytoplasmic vesicle;
KW Diabetes mellitus; Glycoprotein; Hydrolase; Lipid metabolism; Membrane;
KW Phospholipid metabolism; Phosphoprotein; Protein phosphatase; Receptor;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1015
FT /note="Receptor-type tyrosine-protein phosphatase N2"
FT /id="PRO_0000025454"
FT CHAIN 502..1015
FT /note="IA-2beta60"
FT /evidence="ECO:0000250|UniProtKB:P80560,
FT ECO:0000250|UniProtKB:Q63475"
FT /id="PRO_0000438088"
FT TOPO_DOM 22..615
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 616..636
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 637..1015
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 745..1005
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 1..421
FT /note="Involved in localization to secretory granules;
FT interaction with CPE"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT REGION 117..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..305
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 350..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 675..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 666..675
FT /note="Tyrosine-based internalization motif"
FT /evidence="ECO:0000250|UniProtKB:Q63475"
FT MOTIF 1004..1010
FT /note="Leucine-based sorting signal"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT COMPBIAS 421..436
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 437..458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 687..719
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 945
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 913
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 945..951
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 990
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 427..428
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT MOD_RES 436
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT MOD_RES 692
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63475"
FT MOD_RES 698
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63475"
FT MOD_RES 970
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CARBOHYD 564
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..37
FT /note="MGPPLPLLLLLLLLLPPRVLPAAPSSVPRGRQLPGRL -> MAVESEYSLLR
FT TEASFPTMKMFCVSHTLPRVEVMFVSGPQTRERTEPVDPRWQCLVQMWA (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:9205841"
FT /id="VSP_035264"
FT VAR_SEQ 38..54
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_045032"
FT VAR_SEQ 519..547
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007779"
FT VARIANT 140
FT /note="S -> T (in dbSNP:rs3800855)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_027955"
FT VARIANT 208
FT /note="S -> P (in dbSNP:rs1130495)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8878534, ECO:0000269|PubMed:9205841,
FT ECO:0000269|Ref.4"
FT /id="VAR_046301"
FT VARIANT 213
FT /note="R -> H (in dbSNP:rs1130496)"
FT /evidence="ECO:0000269|PubMed:9205841"
FT /id="VAR_027956"
FT VARIANT 325
FT /note="S -> N (in dbSNP:rs1130499)"
FT /evidence="ECO:0000269|PubMed:8954911, ECO:0000269|Ref.4"
FT /id="VAR_020302"
FT VARIANT 343
FT /note="V -> M (in dbSNP:rs3752368)"
FT /id="VAR_022015"
FT VARIANT 388
FT /note="L -> H (in dbSNP:rs7456452)"
FT /id="VAR_046302"
FT VARIANT 716
FT /note="E -> K (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs577236042)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035648"
FT MUTAGEN 945
FT /note="C->A: No effect to increase invasion, migration, and
FT metastatic lung colonization in mice breast cancer model."
FT /evidence="ECO:0000269|PubMed:26620550"
FT MUTAGEN 945
FT /note="C->S: Loss of activity."
FT CONFLICT 160
FT /note="A -> D (in Ref. 4; AAB68603)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="S -> G (in Ref. 2; CAA69880)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="G -> R (in Ref. 2; CAA69880)"
FT /evidence="ECO:0000305"
FT STRAND 512..517
FT /evidence="ECO:0007829|PDB:4HTI"
FT HELIX 523..536
FT /evidence="ECO:0007829|PDB:4HTI"
FT HELIX 541..543
FT /evidence="ECO:0007829|PDB:4HTI"
FT STRAND 544..550
FT /evidence="ECO:0007829|PDB:4HTI"
FT STRAND 553..558
FT /evidence="ECO:0007829|PDB:4HTI"
FT HELIX 567..576
FT /evidence="ECO:0007829|PDB:4HTI"
FT HELIX 578..585
FT /evidence="ECO:0007829|PDB:4HTI"
FT STRAND 589..594
FT /evidence="ECO:0007829|PDB:4HTI"
FT HELIX 725..738
FT /evidence="ECO:0007829|PDB:2QEP"
FT HELIX 742..754
FT /evidence="ECO:0007829|PDB:2QEP"
FT TURN 763..766
FT /evidence="ECO:0007829|PDB:2QEP"
FT TURN 768..770
FT /evidence="ECO:0007829|PDB:2QEP"
FT HELIX 771..773
FT /evidence="ECO:0007829|PDB:2QEP"
FT HELIX 783..785
FT /evidence="ECO:0007829|PDB:2QEP"
FT TURN 791..793
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 795..797
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 802..806
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 811..813
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 815..819
FT /evidence="ECO:0007829|PDB:2QEP"
FT HELIX 824..826
FT /evidence="ECO:0007829|PDB:2QEP"
FT HELIX 827..836
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 841..844
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 848..850
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 862..868
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 871..882
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 885..894
FT /evidence="ECO:0007829|PDB:2QEP"
FT TURN 895..898
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 899..908
FT /evidence="ECO:0007829|PDB:2QEP"
FT HELIX 920..934
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 941..944
FT /evidence="ECO:0007829|PDB:2QEP"
FT STRAND 946..949
FT /evidence="ECO:0007829|PDB:2QEP"
FT HELIX 950..966
FT /evidence="ECO:0007829|PDB:2QEP"
FT HELIX 974..982
FT /evidence="ECO:0007829|PDB:2QEP"
FT HELIX 992..1010
FT /evidence="ECO:0007829|PDB:2QEP"
SQ SEQUENCE 1015 AA; 111271 MW; 950C15CA89DBC029 CRC64;
MGPPLPLLLL LLLLLPPRVL PAAPSSVPRG RQLPGRLGCL LEEGLCGASE ACVNDGVFGR
CQKVPAMDFY RYEVSPVALQ RLRVALQKLS GTGFTWQDDY TQYVMDQELA DLPKTYLRRP
EASSPARPSK HSVGSERRYS REGGAALANA LRRHLPFLEA LSQAPASDVL ARTHTAQDRP
PAEGDDRFSE SILTYVAHTS ALTYPPGSRT QLREDLLPRT LGQLQPDELS PKVDSGVDRH
HLMAALSAYA AQRPPAPPGE GSLEPQYLLR APSRMPRPLL APAAPQKWPS PLGDSEDPSS
TGDGARIHTL LKDLQRQPAE VRGLSGLELD GMAELMAGLM QGVDHGVARG SPGRAALGES
GEQADGPKAT LRGDSFPDDG VQDDDDRLYQ EVHRLSATLG GLLQDHGSRL LPGALPFARP
LDMERKKSEH PESSLSSEEE TAGVENVKSQ TYSKDLLGQQ PHSEPGAAAF GELQNQMPGP
SKEEQSLPAG AQEALSDGLQ LEVQPSEEEA RGYIVTDRDP LRPEEGRRLV EDVARLLQVP
SSAFADVEVL GPAVTFKVSA NVQNVTTEDV EKATVDNKDK LEETSGLKIL QTGVGSKSKL
KFLPPQAEQE DSTKFIALTL VSLACILGVL LASGLIYCLR HSSQHRLKEK LSGLGGDPGA
DATAAYQELC RQRMATRPPD RPEGPHTSRI SSVSSQFSDG PIPSPSARSS ASSWSEEPVQ
SNMDISTGHM ILSYMEDHLK NKNRLEKEWE ALCAYQAEPN SSFVAQREEN VPKNRSLAVL
TYDHSRVLLK AENSHSHSDY INASPIMDHD PRNPAYIATQ GPLPATVADF WQMVWESGCV
VIVMLTPLAE NGVRQCYHYW PDEGSNLYHI YEVNLVSEHI WCEDFLVRSF YLKNLQTNET
RTVTQFHFLS WYDRGVPSSS RSLLDFRRKV NKCYRGRSCP IIVHCSDGAG RSGTYVLIDM
VLNKMAKGAK EIDIAATLEH LRDQRPGMVQ TKEQFEFALT AVAEEVNAIL KALPQ
