PTPRN_BOVIN
ID PTPRN_BOVIN Reviewed; 979 AA.
AC P56722; Q0VD45;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Receptor-type tyrosine-protein phosphatase-like N;
DE Short=R-PTP-N;
DE AltName: Full=Islet cell autoantigen 512;
DE Short=ICA512 {ECO:0000303|PubMed:10457160};
DE Contains:
DE RecName: Full=ICA512-N-terminal fragment;
DE Short=ICA512-NTF;
DE Contains:
DE RecName: Full=ICA512-transmembrane fragment;
DE Short=ICA512-TMF;
DE Contains:
DE RecName: Full=ICA512-cleaved cytosolic fragment;
DE Short=ICA512-CCF;
DE Flags: Precursor;
GN Name=PTPRN;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hermel J.-M., Dirkx R., Solimena M.;
RT "Biochemical analysis of the IDDM autoantigen ICA512.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hippocampus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 449-463, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE,
RP AND TISSUE SPECIFICITY.
RX PubMed=8641276; DOI=10.1002/j.1460-2075.1996.tb00564.x;
RA Solimena M., Dirkx R. Jr., Hermel J.-M., Pleasic-Williams S., Shapiro J.A.,
RA Caron L., Rabin D.U.;
RT "ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane
RT protein of neurosecretory granules.";
RL EMBO J. 15:2102-2114(1996).
RN [4]
RP PROTEIN SEQUENCE OF N-TERMINUS, CHARACTERIZATION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=10457160; DOI=10.1046/j.1460-9568.1999.00677.x;
RA Hermel J.-M., Dirkx R., Solimena M.;
RT "Post-translational modifications of ICA512, a receptor tyrosine
RT phosphatase-like protein of secretory granules.";
RL Eur. J. Neurosci. 11:2609-2620(1999).
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. Seems to lack intrinsic enzyme activity.
CC May regulate catalytic active protein-tyrosine phosphatases such as
CC PTPRA through dimerization. {ECO:0000250|UniProtKB:Q16849,
CC ECO:0000250|UniProtKB:Q60673}.
CC -!- FUNCTION: [ICA512-transmembrane fragment]: ICA512-TMF regulates
CC dynamics and exocytosis of insulin secretory granules (SGs); binding of
CC ICA512-TMF to SNTB2/beta-2-syntrophin is proposed to restrain SGs
CC mobility and exocytosis by tethering them to the actin cytoskeleton
CC depending on UTRN; the function is inhibited by cytoplasmic ICA512-CFF
CC dimerizing with ICA512-TMF and displacing SNTB2.
CC {ECO:0000250|UniProtKB:Q16849, ECO:0000250|UniProtKB:Q60673}.
CC -!- FUNCTION: [ICA512-cleaved cytosolic fragment]: ICA512-CCF translocated
CC to the nucleus promotes expression of insulin and other granule-related
CC genes; the function implicates binding to and regulating activity of
CC STAT5B probably by preventing its dephosphorylation and potentially by
CC inducing its sumoylation by recruiting PIAS4. Enhances pancreatic beta-
CC cell proliferation by converging with signaling by STAT5B and STAT3.
CC ICA512-CCF located in the cytoplasm regulates dynamics and exocytosis
CC of insulin secretory granules (SGs) by dimerizing with ICA512-TMF and
CC displacing SNTB2 thus enhancing SGs mobility and exocytosis.
CC {ECO:0000250|UniProtKB:Q16849}.
CC -!- SUBUNIT: Homodimer; shown for the unprocessed protein (proICA512) in
CC the endoplasmic reticulum and resolved during protein maturation as
CC ICA512-TMF seems to be predominantly monomeric in secretory granules;
CC however, ICA512-CCF interacts with ICA512-TMF disrupting the ICA512-
CC TMF:SNTB2 complex. The isolated lumenal RESP18 homology domain has been
CC shown to form disulfide-linked homooligomers. Interacts (via
CC cytoplasmic domain) with phosphorylated SNTB2; this protects PTPRN
CC against cleavage by CAPN1 to produce ICA512-CCF. Dephosphorylation of
CC SNTB2 upon insulin stimulation disrupts the interaction and results in
CC PTPRN cleavage. Interacts with SNX19. ICA512-CCF interacts with PIAS4;
CC in the nucleus. Interacts with STAT5B (phosphorylated); down-regulated
CC by ICA512-CCF sumoylation; ICA512-CCF prevents STAT5B
CC dephosphorylation; ICA512-CCF mediates interaction of STAT5B with
CC PIAS4. Interacts (via RESP18 homology domain) with insulin and
CC proinsulin. Interacts with PTPRN2, PTPRA and PTPRE.
CC {ECO:0000250|UniProtKB:Q16849, ECO:0000250|UniProtKB:Q60673}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:8641276,
CC ECO:0000269|Ref.1}; Single-pass type I membrane protein
CC {ECO:0000305|PubMed:10457160}. Cytoplasmic vesicle, secretory vesicle
CC membrane {ECO:0000269|PubMed:8641276}; Single-pass type I membrane
CC protein {ECO:0000305}. Perikaryon {ECO:0000250|UniProtKB:Q63259}. Cell
CC projection, axon {ECO:0000250|UniProtKB:Q63259}. Synapse
CC {ECO:0000250|UniProtKB:Q63259}. Cell membrane
CC {ECO:0000250|UniProtKB:Q63259}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q63259}. Endosome {ECO:0000269|PubMed:8641276}.
CC Note=Detected on neuronal secretory vesicles, but not on synaptic
CC vesicles (PubMed:8641276). Colocalizes with insulin-containing
CC secretory granules. Primarily detected on secretory vesicle membranes.
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 via the Golgi apparatus membranes.
CC {ECO:0000250|UniProtKB:Q63259, ECO:0000269|PubMed:8641276}.
CC -!- SUBCELLULAR LOCATION: [ICA512-transmembrane fragment]: Cytoplasmic
CC vesicle, secretory vesicle membrane {ECO:0000269|PubMed:8641276}.
CC -!- SUBCELLULAR LOCATION: [ICA512-cleaved cytosolic fragment]: Nucleus
CC {ECO:0000250|UniProtKB:Q16849}.
CC -!- TISSUE SPECIFICITY: Detected in pituitary (at protein level).
CC {ECO:0000269|PubMed:10457160, ECO:0000269|PubMed:8641276}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10457160}.
CC -!- PTM: O-glycosylated. {ECO:0000250|UniProtKB:Q16849}.
CC -!- PTM: Subject to proteolytic cleavage at multiple sites
CC (PubMed:10457160). Subject to cleavage on a pair of basic residues. On
CC exocytosis of secretory granules in pancreatic beta-cells ICA512-TMF is
CC transiently inserted in the plasma-membrane and cleaved by mu-type
CC calpain CPN1 to yield ICA512-CCF (By similarity).
CC {ECO:0000250|UniProtKB:Q16849, ECO:0000250|UniProtKB:Q63259,
CC ECO:0000269|PubMed:10457160, ECO:0000269|PubMed:8641276}.
CC -!- PTM: Sumoylated at two sites including Lys-754. Sumoylation decreases
CC interaction with STAT5. {ECO:0000250|UniProtKB:Q16849}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC Receptor class 8 subfamily. {ECO:0000305}.
CC -!- CAUTION: Does not possess catalytic activity due to replacement of
CC highly conserved residues in tyrosine-protein phosphatase domain.
CC {ECO:0000305}.
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DR EMBL; AF075170; AAD41665.1; -; mRNA.
DR EMBL; BC119839; AAI19840.1; -; mRNA.
DR RefSeq; NP_001068599.1; NM_001075131.1.
DR AlphaFoldDB; P56722; -.
DR SMR; P56722; -.
DR STRING; 9913.ENSBTAP00000018336; -.
DR PaxDb; P56722; -.
DR PRIDE; P56722; -.
DR Ensembl; ENSBTAT00000018336; ENSBTAP00000018336; ENSBTAG00000013798.
DR GeneID; 286810; -.
DR KEGG; bta:286810; -.
DR CTD; 5798; -.
DR VEuPathDB; HostDB:ENSBTAG00000013798; -.
DR VGNC; VGNC:33554; PTPRN.
DR eggNOG; KOG0793; Eukaryota.
DR GeneTree; ENSGT00940000154095; -.
DR HOGENOM; CLU_007905_2_0_1; -.
DR InParanoid; P56722; -.
DR OMA; AQTGFQI; -.
DR OrthoDB; 411281at2759; -.
DR TreeFam; TF351976; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000013798; Expressed in adenohypophysis and 54 other tissues.
DR ExpressionAtlas; P56722; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043679; C:axon terminus; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030507; F:spectrin binding; IEA:Ensembl.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IEA:Ensembl.
DR GO; GO:1990502; P:dense core granule maturation; IEA:Ensembl.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0001553; P:luteinization; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:1904692; P:positive regulation of type B pancreatic cell proliferation; IEA:Ensembl.
DR GO; GO:0051046; P:regulation of secretion; IBA:GO_Central.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS:UniProtKB.
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 Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Endosome; Glycoprotein;
KW Isopeptide bond; Membrane; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Signal; Synapse; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..34
FT /evidence="ECO:0000269|PubMed:10457160"
FT CHAIN 35..979
FT /note="Receptor-type tyrosine-protein phosphatase-like N"
FT /id="PRO_0000025450"
FT CHAIN 35..448
FT /note="ICA512-N-terminal fragment"
FT /evidence="ECO:0000269|PubMed:8641276"
FT /id="PRO_0000438076"
FT CHAIN 449..979
FT /note="ICA512-transmembrane fragment"
FT /evidence="ECO:0000269|PubMed:8641276"
FT /id="PRO_0000438077"
FT CHAIN 659..979
FT /note="ICA512-cleaved cytosolic fragment"
FT /evidence="ECO:0000250|UniProtKB:Q16849"
FT /id="PRO_0000438078"
FT TOPO_DOM 35..575
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 576..600
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 601..979
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 709..969
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 35..131
FT /note="RESP18 homology domain"
FT /evidence="ECO:0000250|UniProtKB:Q16849"
FT REGION 113..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 248..272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 285..332
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 449..575
FT /note="Sufficient for dimerization of proICA512"
FT /evidence="ECO:0000250|UniProtKB:Q16849"
FT REGION 601..732
FT /note="Sufficient for dimerization of proICA512"
FT /evidence="ECO:0000250|UniProtKB:P80560"
FT REGION 643..680
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 113..129
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..327
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 411..426
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 448..464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 652..680
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 448..449
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:10457160,
FT ECO:0000269|PubMed:8641276"
FT MOD_RES 308
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60673"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60673"
FT CARBOHYD 506
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 524
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40
FT /note="Interchain (with C-40 or C-47); in multimeric form"
FT /evidence="ECO:0000250|UniProtKB:Q16849"
FT DISULFID 47
FT /note="Interchain (with C-40 or C-47); in multimeric form"
FT /evidence="ECO:0000250|UniProtKB:Q16849"
FT DISULFID 53..62
FT /evidence="ECO:0000250|UniProtKB:Q16849"
FT CROSSLNK 754
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q16849"
SQ SEQUENCE 979 AA; 105908 MW; 288DA2DBE780CB67 CRC64;
MRLPGRPGGP GGSGGLRVLL CLLLLGSRPG GCNAISAHGC LFDRRLCSHL EVCIQDGLFG
QCQVGVGQAR PLLQVTSPVL QRLQGVLRQL MSQGLSWHDD LTQYVISQEM ERIPRLRPPE
PHPRDRSGLV PRRPGPAGEL LLQGIPTGSA PALQHRLPRP SVGGGRAGAG SPLSPLQAEL
LPPLLEHLLL PPQPPHPALS YEPALLQPYL FHQFGSRDGS RGSESSPGMV SVDPLPKAEA
PAFLSRAGSK GMFGAHPGHS YGDPPGPPPA QLFQESELFY LAQESQVPSR TRAPRLPEPG
GSSRAGDSSE GYEEEGLEGR EEKPPAPAEQ PDVTLQRVAA VLAGYGVELH QLTPEQLSTL
STLLQLLPKG SRQNPGGAVN VGADIKKTME EQVQGEDPAE PPPPMPSLPG SPTGSSTSNK
AQKELSTGAS EPPKAAGPPA TPVLVEKKSP LGQNQPTMAG QPSTRPSAEE YGYIVTDQKP
LSLAAGVRLL EILAEHVHMS SGSFINISVV GPALTFRIRH NEQNLSLADV TQQAGLVKSE
LEAQTGLQIL QTGVGQREEA AAILPRPAHS TSPMRSVLLT LVALAGVAGL LVALAVALCV
RQHARQRDKE RLAALGPEGA HGDTTFEYQD LCRQHMATKS LFNRAEGPPE PSRVSSVSSQ
FSDAAQASPS SHSSTPSWCE EPAQANMDIS TGHMILAYME DHLRNRDRLA KEWQALCAYQ
AEPNTCATAQ GEGNIKKNRH PDFLPYDHAR IKLKVESSPS RSDYINASPI IEHDPRMPAY
IATQGPLSHT IADFWQMVWE SGCTVIVMLT PLVEDGVKQC DRYWPDEGSS LYHVYEVNLV
SEHIWCEDFL VRSFYLKNVQ TQETRTLTQF HFLSWPAEGT PASTRPLLDF RRKVNKCYRG
RSCPIIVHCS DGAGRTGTYI LIDMVLNRMA KGVKEIDIAA TLEHVRDQRP GLVRSKDQFE
FALTAVAEEV NAILKALPQ
