PTPR2_RAT
ID PTPR2_RAT Reviewed; 1004 AA.
AC Q63475;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Receptor-type tyrosine-protein phosphatase N2;
DE Short=R-PTP-N2;
DE EC=3.1.3.- {ECO:0000305|PubMed:20097759};
DE EC=3.1.3.48;
DE AltName: Full=PTP NE-6;
DE Short=PTPNE6;
DE AltName: Full=Phogrin {ECO:0000303|PubMed:14597614};
DE Contains:
DE RecName: Full=IA-2beta60;
DE Flags: Precursor;
GN Name=Ptprn2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEOLYTIC PROCESSING.
RC STRAIN=New England Deaconess Hospital; TISSUE=Insulinoma;
RX PubMed=8663434; DOI=10.1074/jbc.271.30.18161;
RA Wasmeier C., Hutton J.C.;
RT "Molecular cloning of phogrin, a protein-tyrosine phosphatase homologue
RT localized to insulin secretory granule membranes.";
RL J. Biol. Chem. 271:18161-18170(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Fitzgerald L.R., Walton K.M., Dixon J.E., Largent B.L.;
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION AT SER-681 AND THR-700.
RX PubMed=11353772; DOI=10.1074/jbc.m102580200;
RA Wasmeier C., Hutton J.C.;
RT "Secretagogue-dependent phosphorylation of the insulin granule membrane
RT protein phogrin is mediated by cAMP-dependent protein kinase.";
RL J. Biol. Chem. 276:31919-31928(2001).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=14597614; DOI=10.1074/jbc.m310104200;
RA Hosaka M., Suda M., Sakai Y., Izumi T., Watanabe T., Takeuchi T.;
RT "Secretogranin III binds to cholesterol in the secretory granule membrane
RT as an adapter for chromogranin A.";
RL J. Biol. Chem. 279:3627-3634(2004).
RN [5]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-655, TYROSINE-BASED
RP INTERNALIZATION MOTIF, AND INTERACTION WITH AP2M1.
RX PubMed=15882444; DOI=10.1111/j.1600-0854.2005.00292.x;
RA Wasmeier C., Burgos P.V., Trudeau T., Davidson H.W., Hutton J.C.;
RT "An extended tyrosine-targeting motif for endocytosis and recycling of the
RT dense-core vesicle membrane protein phogrin.";
RL Traffic 6:474-487(2005).
RN [6]
RP FUNCTION AS PHOSPHATIDYLINOSITOL PHOSPHATASE, CATALYTIC ACTIVITY, AND LACK
RP OF FUNCTION AS PROTEIN TYROSINE PHOSPHATASE.
RX PubMed=20097759; DOI=10.1074/jbc.m109.066563;
RA Caromile L.A., Oganesian A., Coats S.A., Seifert R.A., Bowen-Pope D.F.;
RT "The neurosecretory vesicle protein phogrin functions as a
RT phosphatidylinositol phosphatase to regulate insulin secretion.";
RL J. Biol. Chem. 285:10487-10496(2010).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340 AND SER-687, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP INTERACTION WITH MYO5A.
RX PubMed=25744490; DOI=10.1007/s00418-015-1311-9;
RA Wang Z., Peng T., Wu H., He J., Li H.;
RT "HAP1 helps to regulate actin-based transport of insulin-containing
RT granules in pancreatic beta cells.";
RL Histochem. Cell Biol. 144:39-48(2015).
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). Required to maintain normal levels of renin
CC expression and renin release. May regulate catalytic active protein-
CC tyrosine phosphatases such as PTPRA through dimerization (By
CC similarity). Has phosphatidylinositol phosphatase activity; the PIPase
CC activity is involved in its ability to regulate insulin secretion. Can
CC dephosphorylate phosphatidylinositol 4,5-biphosphate,
CC phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate
CC (PubMed:20097759). Regulates PI(4,5)P2 level in the plasma membrane and
CC localization of cofilin at the plasma membrane and thus is indirectly
CC involved in regulation of actin dynamics related to cell migration and
CC metastasis; upon hydrolyzation of PI(4,5)P2 cofilin is released from
CC the plasma membrane and acts in the cytoplasm in severing F-actin
CC filaments (By similarity). {ECO:0000250|UniProtKB:P80560,
CC ECO:0000269|PubMed:20097759}.
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: 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 (PubMed:15882444). Interacts with MYO5A (PubMed:25744490).
CC {ECO:0000250|UniProtKB:P80560, ECO:0000269|PubMed:25744490}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000269|PubMed:14597614}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:14597614}. 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 (PubMed:15882444). Recycled via STX6- but not
CC TTTGN1/TGN38-containing compartments (By similarity).
CC {ECO:0000250|UniProtKB:P80560, ECO:0000269|PubMed:15882444,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [IA-2beta60]: Cytoplasmic vesicle, secretory
CC vesicle membrane {ECO:0000305}.
CC -!- DOMAIN: The tyrosine-based internalization signal is proposed to
CC function at the level of clathrin-mediated endocytosis and recycling.
CC {ECO:0000305|PubMed:15882444}.
CC -!- DOMAIN: The leucine-based sorting signal is proposed to function in
CC trafficking at the plasma membrane. {ECO:0000250|UniProtKB:P80560}.
CC -!- PTM: Subject to proteolytic cleavage at multiple sites.
CC {ECO:0000250|UniProtKB:P80560}.
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
CC for the human protein at acidic conditions (pH 4.5) is questioned. This
CC catalytic activity seems to be affected by the replacement of a highly
CC conserved residue in the tyrosine-protein phosphatase domain.
CC {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; Z50735; CAA90600.1; -; mRNA.
DR EMBL; U73458; AAC08036.1; -; mRNA.
DR RefSeq; NP_113788.1; NM_031600.1.
DR AlphaFoldDB; Q63475; -.
DR SMR; Q63475; -.
DR STRING; 10116.ENSRNOP00000006942; -.
DR GlyGen; Q63475; 1 site.
DR iPTMnet; Q63475; -.
DR PhosphoSitePlus; Q63475; -.
DR SwissPalm; Q63475; -.
DR jPOST; Q63475; -.
DR PaxDb; Q63475; -.
DR PRIDE; Q63475; -.
DR Ensembl; ENSRNOT00000006942; ENSRNOP00000006942; ENSRNOG00000005003.
DR GeneID; 29714; -.
DR KEGG; rno:29714; -.
DR UCSC; RGD:61904; rat.
DR CTD; 5799; -.
DR RGD; 61904; Ptprn2.
DR eggNOG; KOG0793; Eukaryota.
DR GeneTree; ENSGT00940000154095; -.
DR HOGENOM; CLU_007905_0_0_1; -.
DR InParanoid; Q63475; -.
DR OMA; PDNGVHE; -.
DR OrthoDB; 411281at2759; -.
DR PhylomeDB; Q63475; -.
DR TreeFam; TF351976; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:Q63475; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000005003; Expressed in frontal cortex and 9 other tissues.
DR Genevisible; Q63475; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:RGD.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0030141; C:secretory granule; IDA:RGD.
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:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC.
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:0034260; P:negative regulation of GTPase activity; IDA:RGD.
DR GO; GO:0007269; P:neurotransmitter secretion; ISS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
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; 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; 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 Acetylation; Cytoplasmic vesicle; Glycoprotein; Hydrolase;
KW Lipid metabolism; Membrane; Methylation; Phospholipid metabolism;
KW Phosphoprotein; Protein phosphatase; Receptor; Reference proteome; Signal;
KW Synapse; Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..1004
FT /note="Receptor-type tyrosine-protein phosphatase N2"
FT /id="PRO_0000025457"
FT CHAIN 491..1004
FT /note="IA-2beta60"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT /id="PRO_0000438073"
FT TOPO_DOM 28..603
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 604..624
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 625..1004
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 734..994
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 1..409
FT /note="Involved in localization to secretory granules;
FT interaction with CPE"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT REGION 274..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 393..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 665..710
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 655..664
FT /note="Tyrosine-based internalization motif"
FT /evidence="ECO:0000305|PubMed:15882444"
FT MOTIF 993..999
FT /note="Leucine-based sorting signal"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT COMPBIAS 407..454
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..710
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 934
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 902
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 934..940
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 979
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 415..416
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT MOD_RES 259
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT MOD_RES 681
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:11353772"
FT MOD_RES 687
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 700
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000269|PubMed:11353772"
FT MOD_RES 959
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q92932"
FT CARBOHYD 553
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 655
FT /note="Y->A: Impairs internalization; decreases interaction
FT with AP2M1."
FT /evidence="ECO:0000269|PubMed:15882444"
SQ SEQUENCE 1004 AA; 111863 MW; A73929E11B486FB2 CRC64;
MGLPLPLLLL LLLPPPLPRA LPAPASARGR QLPGRLGCLF EDGLCGSLET CVNDGVFGRC
QKVPALDTYR YEVSPGALLH LRIILQKLSR TGFTWQDDYT QRVIAQELSN LPKAYLWHEE
ASSPARSLQQ NADNEKWFSL ESEVALAKTL RRYLPYLELL SQAPTANAHP RIDHETRPVK
GEDSSPENIL TYVAHTSALT YPPATRVKYP DNLLRPLSRL QPDELSPKVD SDIDKQKLIA
ALGAYTAQRP PGENDPEPRY LVHSPMRAPR PFAAPALSQR WPLPPGDSKD SLSMGDDTLL
RSLLKDLQQQ AEVDRLGSLK LEEQADSIAG AIQSDPVEGS QESHGRGAEG QLREQADAPE
EMLQDHRLPE VDDPAAYKEV SRLSFKLGDL LKDHGSPLLP EAPLLEKSSR AEMKKSEQPE
EVLSSEEETA GVEHVKSRTY SKDLLERKPN SEPQPWRLED QFQNRAPEVW EDEQNLKLAA
QGPPSGGLQL EVQPSEEEQQ GYILTGNNPL SPEKGKQLMD EVAHLLRVPS SFFADVKVLG
PAVIFKVSAN IQNMTTADVT KAAVDNKDEL EKATGLTILQ SGIRPKGKLK LLPHPEEQED
STKFIVLTFL SIACILAVLL ASSLAYCLRH NSHYKLKEKL SGLGADPSAD ATEAYQELCR
QRMAVRPQDH SEGPHTSRIN SVSSQLSDGP MPSPSARSST SSWSEEPAQS NMDISTGHMI
LAYMEDHLKN KNRLEKEWEA LCAYQAEPDS SLVAQREENA PKNRSLAVLT YDHSRILLKS
ENSHSNSDYI NASPIMDHDP RNPAYIATQG PLPATVADFW QMVWESGCAV IVMLTPLSEN
GVRQCHHYWP DEGSNVYHVY EVNLVSEHIW CQDFLVRSFY LKNLQTNETR TVTQFHFLSW
YDQGVPSSTR SLLDFRRKVN KCYRGRSCPI IVHCSDGAGR SGTYVLIDMV LNKMAKGAKE
IDIAATLEHL RDQRPGMVQT KEQFEFALTA VAEEVNAILK ALPQ
