PTPR2_MACNE
ID PTPR2_MACNE Reviewed; 1013 AA.
AC O02695;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 124.
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;
DE AltName: Full=M1851;
DE Contains:
DE RecName: Full=IA-2beta60;
DE Flags: Precursor;
GN Name=PTPRN2;
OS Macaca nemestrina (Pig-tailed macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9545;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Pancreatic islet;
RX PubMed=9100223; DOI=10.1007/bf03401670;
RA Lagasse J., Jelinek L., Sexson S., Lofton-Day C.E., Breininger J.,
RA Sheppard P., Kindsvogel W., Hagopian W.A.;
RT "An islet-cell protein tyrosine phosphatase is a likely precursor to the
RT 37-kDa autoantigen in type 1 diabetes: human and macaque sequences, tissue
RT distribution, unique and shared epitopes, and predictive autoantibodies.";
RL Mol. Med. 3:163-173(1997).
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. Has
CC phosphatidylinositol phosphatase activity; the PIPase activity is
CC involved in its ability to regulate insulin secretion. Can
CC dephosphorylate phosphatidylinositol 4,5-biphosphate,
CC phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate.
CC Regulates PI(4,5)P2 level in the plasma membrane and localization of
CC cofilin at the plasma membrane and thus is indirectly involved in
CC regulation of actin dynamics related to cell migration and metastasis;
CC upon hydrolyzation of PI(4,5)P2 cofilin is released from the plasma
CC membrane and acts in the cytoplasm in severing F-actin filaments.
CC {ECO:0000250|UniProtKB:P80560, ECO:0000250|UniProtKB:Q63475,
CC ECO:0000250|UniProtKB:Q92932}.
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). Interacts with AP2M1; indicative for
CC an association with adaptor protein complex 2 (AP-2). Interacts with
CC MYO5A. {ECO:0000250|UniProtKB:P80560, 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. Transiently found
CC at the cell membrane, when secretory vesicles fuse with the cell
CC membrane to release their cargo. Is then endocytosed and recycled to
CC secretory vesicles involving clathrin-dependent AP2-mediated
CC endocytosis. Recycled via STX6- but not TTTGN1/TGN38-containing
CC compartments. {ECO:0000250|UniProtKB:P80560,
CC ECO:0000250|UniProtKB:Q63475}.
CC -!- TISSUE SPECIFICITY: Detected in pancreatic islets and adrenal medulla.
CC {ECO:0000269|PubMed:9100223}.
CC -!- DOMAIN: The tyrosine-based internalization signal is proposed to
CC function in clathrin-mediated endocytosis and recycling.
CC {ECO:0000250|UniProtKB:Q63475}.
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}.
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DR EMBL; U91574; AAC51186.1; -; mRNA.
DR RefSeq; NP_001292849.1; NM_001305920.1.
DR AlphaFoldDB; O02695; -.
DR SMR; O02695; -.
DR STRING; 9545.ENSMNEP00000016459; -.
DR GeneID; 105474981; -.
DR CTD; 5799; -.
DR OrthoDB; 411281at2759; -.
DR Proteomes; UP000233120; Whole Genome Shotgun Assembly.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030667; C:secretory granule membrane; ISS:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISS:UniProtKB.
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:0007269; P:neurotransmitter secretion; ISS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
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 2: Evidence at transcript level;
KW Acetylation; Cytoplasmic vesicle; Glycoprotein; Hydrolase;
KW Lipid metabolism; Membrane; Phospholipid metabolism; Phosphoprotein;
KW Protein phosphatase; Receptor; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1013
FT /note="Receptor-type tyrosine-protein phosphatase N2"
FT /id="PRO_0000025455"
FT CHAIN 500..1013
FT /note="IA-2beta60"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT /id="PRO_0000438069"
FT TOPO_DOM 20..613
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 614..634
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 635..1013
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 743..1003
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 1..419
FT /note="Involved in localization to secretory granules;
FT interaction with CPE"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT REGION 116..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 273..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 342..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 673..717
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 664..673
FT /note="Tyrosine-based internalization motif"
FT /evidence="ECO:0000250|UniProtKB:Q63475"
FT MOTIF 1002..1008
FT /note="Leucine-based sorting signal"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT COMPBIAS 276..294
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..434
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 437..456
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 685..717
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 943
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 911
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 943..949
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 988
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 425..426
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT MOD_RES 690
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63475"
FT MOD_RES 696
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63475"
FT MOD_RES 968
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q92932"
FT CARBOHYD 562
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1013 AA; 111191 MW; 4808D43937A2EF59 CRC64;
MALPLLLLLL LLLPPRVLPA APSSVPHGRQ LPGRLGCLLE EGLCGASEAC VNDGVFGRCQ
KVPAMDFYRY EVSPVALQRL RVALQKLSGT GFTWQDDYTQ YVMDQELADL PKTYLRHPEA
SGPARPSKHS IGSERRYSQE GGAALAKAFR RHLPFLEALS QAPASDALAR TRMAQDRPRA
EGDDRFSKSI LTYVAHTSVL TYPPGPQAQL PEDLLPRTLS QLQPDELSPK VDSSVERHHL
MAALSAYAAQ RPPAPPGKGS LEPQYLLRAP SRMPRPLLSP AVPQKWPSPL GDPEDPPSTG
EGARIHTLLK DLQRQPAEAR GLSDLELDSM AELMAGLMQG MDHRGALGGP GKAALGESGE
QADGPKAALR GESFPDDGVQ DDDDRLYQEV HRLSATLGGL LQDHGSRLSP GALPFAKPLK
MERKKSERPE ASLSSEEETA GVENVKSQTY SKDLLGQQPH SEPGAGAFGE LQNQMPGPSE
EEQSLPAGAQ EALGDGLQLE VKPSEEEARG YIVTDRDPLR PEEGRQLVED VARLLQMPSS
TFADVEVLGP AVTFKVGANV QNVTTADVEK ATVDNKDKLE ETSGLKILQT GVGSKSKLKF
LPPQAEQEDS TKFIALTLVS LACILGVLLA SGLIYCLRHS SQHRLKEKLS GLGRDPGADA
TAAYQELCRQ RMATRPPDRP EGPHTSRISS VSSQFSDGPM PSPSARSSAS SWSEEPVQSN
MDISTGHMIL SYMEDHLKNK NRLEKEWEAL CAYQAEPNSS LVAQKEENVP KNRSLAVLTY
DHSRVLLKAE NSHSHSDYIN ASPIMDHDPR NPAYIATQGP LPATVADFWQ MVWESGCVVI
VMLTPLTENG VRQCYHYWPD EGSNLYHIYE VNLVSEHIWC EDFLVRSFYL KNLQTNETRT
VTQFHFLSWY DRGVPSSSRS LLDFRRKVNK CYRGRSCPII VHCSDGAGRS GTYVLIDMVL
NKMAKGAKEI DIAATLEHLR DQRPGMVQTK EQFEFALTAV AEEVNAILKA LPQ
