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Protein

Receptor-type tyrosine-protein phosphatase-like N

Gene

Ptprn

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in vesicle-mediated secretory processes. Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation. Plays a role in insulin secretion in response to glucose stimuli. Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Required to maintain normal levels of renin expression and renin release. Seems to lack intrinsic enzyme activity.By similarity
ICA512-transmembrane fragment: ICA512-TMF regulates dynamics and exocytosis of insulin secretory granules (SGs); binding of ICA512-TMF to SNTB2/beta-2-syntrophin is proposed to restrain SGs mobility and exocytosis by tethering them to the actin cytoskeleton depending on UTRN; the function is inhibited by cytoplasmic ICA512-CFF dimerizing with ICA512-TMF and displacing SNTB2 (By similarity).By similarity
ICA512-cleaved cytosolic fragment: ICA512-CCF translocated to the nucleus promotes expression of insulin and other granule-related genes; the function implicates binding to and regulating activity of STAT5B probably by preventing its dephosphorylation and potentially by inducing its sumoylation by recruiting PIAS4 (By similarity). Enhances pancreatic beta-cell proliferation by converging with signaling by STAT5B and STAT3 (PubMed:18178618). ICA512-CCF located in the cytoplasm regulates dynamics and exocytosis of insulin secretory granules (SGs) by dimerizing with ICA512-TMF and displacing SNTB2 thus enhancing SGs mobility and exocytosis (By similarity).By similarity1 Publication

GO - Molecular functioni

  • GTPase binding Source: RGD

GO - Biological processi

  • cytokine-mediated signaling pathway Source: RGD
  • dense core granule maturation Source: Ensembl
  • insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
  • luteinization Source: UniProtKB
  • positive regulation of type B pancreatic cell proliferation Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • response to cAMP Source: RGD
  • response to estrogen Source: RGD
  • response to glucose Source: RGD
  • response to insulin Source: RGD
  • response to reactive oxygen species Source: UniProtKB
  • second-messenger-mediated signaling Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein phosphatase-like N
Short name:
R-PTP-N
Alternative name(s):
105 kDa islet cell antigen
BEM-3
Brain-enriched membrane-associated protein tyrosine phosphatase
ICA1051 Publication
ICA5121 Publication
PTP IA-21 Publication
PTPLP
Cleaved into the following 3 chains:
ICA512-N-terminal fragment
Short name:
ICA512-NTF
ICA512-transmembrane fragment
Short name:
ICA512-TMF
ICA512-cleaved cytosolic fragment
Short name:
ICA512-CCF
Gene namesi
Name:Ptprn
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi620777. Ptprn.

Subcellular locationi

ICA512-transmembrane fragment :
ICA512-cleaved cytosolic fragment :
  • Nucleus By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini41 – 579LumenalSequence analysisAdd BLAST539
Transmembranei580 – 604HelicalSequence analysisAdd BLAST25
Topological domaini605 – 983CytoplasmicSequence analysisAdd BLAST379

GO - Cellular componenti

  • axon terminus Source: UniProtKB
  • cell junction Source: UniProtKB-KW
  • endosome Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: RGD
  • neuronal cell body Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • perikaryon Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
  • secretory granule Source: UniProtKB
  • synapse Source: UniProtKB
  • transport vesicle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Endosome, Membrane, Nucleus, Synapse

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 40By similarityAdd BLAST40
ChainiPRO_000002545341 – 983Receptor-type tyrosine-protein phosphatase-like NAdd BLAST943
ChainiPRO_000043808541 – 452ICA512-N-terminal fragmentBy similarityAdd BLAST412
ChainiPRO_0000438086453 – 983ICA512-transmembrane fragmentBy similarityAdd BLAST531
ChainiPRO_0000438087663 – 983ICA512-cleaved cytosolic fragmentBy similarityAdd BLAST321

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi46Interchain (in homooligomer)By similarity
Disulfide bondi53Interchain (in homooligomer)By similarity
Modified residuei311PhosphoserineCombined sources1
Modified residuei312PhosphoserineCombined sources1
Glycosylationi510N-linked (GlcNAc...)Sequence analysis1
Glycosylationi528N-linked (GlcNAc...)Sequence analysis1
Cross-linki758Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Subject to proteolytic cleavage at multiple sites (PubMed:7568143). Subject to cleavage on a pair of basic residues (By similarity). Following exocytosis of secretory granules in pancreatic beta-cells ICA512-TMF located in the plasma-membrane is cleaved by mu-type calpain CPN1 to yield ICA512-CCF (PubMed:15596545).By similarity2 Publications
N-glycosylated.By similarity
O-glycosylated.By similarity
Sumoylated at two sites including Lys-758. Sumoylation decreases interaction with STAT5.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei452 – 453CleavageBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ63259.
PRIDEiQ63259.

PTM databases

iPTMnetiQ63259.
PhosphoSitePlusiQ63259.

Expressioni

Tissue specificityi

Detected in pancreas islets (PubMed:7657822, PubMed:10457160). Detected in pancreas alpha, beta and delta cells, and in chromaffin cells in the adrenal medulla (PubMed:8641276). Detected in amygdala, hypothalamus, autonomous nerve fibers and ganglia, especially at synaptic contacts (PubMed:8641276). Detected in pituitary (at protein level) (PubMed:8641276, PubMed:10457160). Detected in brain, specifically in cerebral cortex, diencephalon and brain stem (PubMed:7887886).4 Publications

Gene expression databases

BgeeiENSRNOG00000019587.
GenevisibleiQ63259. RN.

Interactioni

Subunit structurei

Homodimer; shown for the unprocessed protein (proICA512) in the endoplasmic reticulum and resolved during protein maturation as ICA512-TMF seems to be predominantly monomeric in secretory granules; however, ICA512-CCF interacts with ICA512-TMF disrupting the ICA512-TMF:SNTB2 complex. The isolated lumenal RESP18 homology domain has been shown to form disulfide-linked homooligomers. Interacts (via cytoplasmic domain) with phosphorylated SNTB2; this protects PTPRN against cleavage by CAPN1 to produce ICA512-CCF. Dephosphorylation of SNTB2 upon insulin stimulation disrupts the interaction and results in PTPRN cleavage. Interacts with SNX19. ICA512-CCF interacts with PIAS4; in the nucleus. Interacts with STAT5B (phosphorylated); down-regulated by ICA512-CCF sumoylation; ICA512-CCF prevents STAT5B dephosphorylation; ICA512-CCF mediates interaction of STAT5B with PIAS4. Interacts (via RESP18 homology domain) with insulin and proinsulin. Interacts with PTPRN2, PTPRA and PTPRE.By similarity

GO - Molecular functioni

  • GTPase binding Source: RGD

Protein-protein interaction databases

IntActiQ63259. 2 interactors.
MINTiMINT-4566117.
STRINGi10116.ENSRNOP00000026654.

Structurei

3D structure databases

ProteinModelPortaliQ63259.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini713 – 973Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni41 – 137RESP18 homology domainBy similarityAdd BLAST97
Regioni453 – 579Sufficient for dimerization of proICA512By similarityAdd BLAST127
Regioni605 – 736Sufficient for dimerization of proICA512By similarityAdd BLAST132

Domaini

The RESP18 homology domain is sufficient for targeting proICA512 to secretory granules.By similarity

Sequence similaritiesi

Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0793. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000243992.
HOVERGENiHBG053762.
InParanoidiQ63259.
KOiK07817.
OMAiFLPYDHA.
OrthoDBiEOG091G0LUR.
PhylomeDBiQ63259.
TreeFamiTF351976.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR033522. PTPRN.
IPR021613. Receptor_IA-2_dom.
IPR029403. RESP18_dom.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PANTHERiPTHR19134:SF2. PTHR19134:SF2. 1 hit.
PfamiPF11548. Receptor_IA-2. 1 hit.
PF14948. RESP18. 1 hit.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q63259-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRRPRRPGGP AGCGGSEGSG GLRLLVCLLL LSGRPGGCSA ISAHGCLFDR
60 70 80 90 100
RLCSHLEVCI QDGLFGQCQA GVGQARPLLQ VTSPVLQRLQ GVLRQLMSQG
110 120 130 140 150
LSWHDDLTQY VISQEMERIP RLRPPEPHPR DRSGSVPRRA GPAGELLSQG
160 170 180 190 200
NPTGSSPAVQ GLSRPPGDGN GAGVGSPLSS LQAELLPPLL EHLLMPPQPP
210 220 230 240 250
HPSLTYEPAL LQPYLFQQFG SRDGSRGSES ASGVVGHLAK AEDPVLFSRS
260 270 280 290 300
LSKAILGTHS GHSFGDLTGP SPAQLFQDSG LLYMAQELPV PGRARAPRLP
310 320 330 340 350
EEGGSSRAED SSEGHEEEVL GGHGEKSPPQ AVQADVSLQR LAAVLAGYGV
360 370 380 390 400
ELRQLTPEQL STLLTLLQLL PKGTGRHLGG AVNGGADVKK TIEEQMQRGD
410 420 430 440 450
TADARPPTPL LPGHPTASST SIKVRQVLSP GFPEPPKTSS PLGISAVLLE
460 470 480 490 500
KKSPLGQSQP TVVGQPSARP SAEEYGYIVT DQKPLSLVAG VKLLEILAEH
510 520 530 540 550
VHMTSGSFIN ISVVGPAVTF RIRHNEQNLS LADVTQQAGL VKSELEAQTG
560 570 580 590 600
LQILQTGVGQ REESAAVLPR QAHGISPMRS LLLTLVALAG VAGLLVALAV
610 620 630 640 650
ALCMRHHSKQ RDKERLAALG PEGAHGDTTF EYQDLCRQHM ATKSLFNRAE
660 670 680 690 700
GQPEPSRVSS VSSQFSDAAQ ASPSSHSSTP SWCEEPAQAN MDISTGHMIL
710 720 730 740 750
AYMEDHLRNR DRLAKEWQAL CAYQAEPNTC ATAQGEGNIK KNRHPDFLPY
760 770 780 790 800
DHARIKLKVE SSPSRSDYIN ASPIIEHDPR MPAYIATQGP LSHTIADFWQ
810 820 830 840 850
MVWESGCTVI VMLTPLVEDG VKQCDRYWPD EGSSLYHVYE VNLVSEHIWC
860 870 880 890 900
EDFLVRSFYL KNVQTQETRT LTQFHFLSWP AEGTPASTRP LLDFRRKVNK
910 920 930 940 950
CYRGRSCPII VHCSDGAGRT GTYILIDMVL NRMAKGVKEI DIAATLEHVR
960 970 980
DQRPGLVRSK DQFEFALTAV AEEVNAILKA LPQ
Length:983
Mass (Da):106,228
Last modified:July 15, 1998 - v2
Checksum:iBCD567DAFFFE2A2B
GO

Sequence cautioni

The sequence BAA07397 differs from that shown. Reason: Frameshift at positions 33 and 102.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti466P → T in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti507S → R in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti517A → V in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti520F → S in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti564S → A in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti566A → E in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti574G → R in BAA07397 (PubMed:7887886).Curated1
Sequence conflicti581L → V in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti599A → V in BAA08254 (Ref. 4) Curated1
Sequence conflicti609K → R in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti664Q → K in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti672S → N in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti714A → P in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti716E → K in CAA63313 (PubMed:7568143).Curated1
Sequence conflicti731A → S in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti953 – 955RPG → PTC in AAA83235 (PubMed:7657822).Curated3
Sequence conflicti962Q → K in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti966A → P in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti969A → P in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti971A → G in AAA83235 (PubMed:7657822).Curated1
Sequence conflicti976A → P in AAA83235 (PubMed:7657822).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X92563 mRNA. Translation: CAA63313.1.
D38222 mRNA. Translation: BAA07397.1. Frameshift.
U40652 mRNA. Translation: AAA83235.1.
D45414 mRNA. Translation: BAA08254.1.
PIRiS54342.
RefSeqiNP_446333.1. NM_053881.1.
UniGeneiRn.11097.

Genome annotation databases

EnsembliENSRNOT00000026654; ENSRNOP00000026654; ENSRNOG00000019587.
GeneIDi116660.
KEGGirno:116660.
UCSCiRGD:620777. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X92563 mRNA. Translation: CAA63313.1.
D38222 mRNA. Translation: BAA07397.1. Frameshift.
U40652 mRNA. Translation: AAA83235.1.
D45414 mRNA. Translation: BAA08254.1.
PIRiS54342.
RefSeqiNP_446333.1. NM_053881.1.
UniGeneiRn.11097.

3D structure databases

ProteinModelPortaliQ63259.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ63259. 2 interactors.
MINTiMINT-4566117.
STRINGi10116.ENSRNOP00000026654.

PTM databases

iPTMnetiQ63259.
PhosphoSitePlusiQ63259.

Proteomic databases

PaxDbiQ63259.
PRIDEiQ63259.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000026654; ENSRNOP00000026654; ENSRNOG00000019587.
GeneIDi116660.
KEGGirno:116660.
UCSCiRGD:620777. rat.

Organism-specific databases

CTDi5798.
RGDi620777. Ptprn.

Phylogenomic databases

eggNOGiKOG0793. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000243992.
HOVERGENiHBG053762.
InParanoidiQ63259.
KOiK07817.
OMAiFLPYDHA.
OrthoDBiEOG091G0LUR.
PhylomeDBiQ63259.
TreeFamiTF351976.

Miscellaneous databases

PROiQ63259.

Gene expression databases

BgeeiENSRNOG00000019587.
GenevisibleiQ63259. RN.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR033522. PTPRN.
IPR021613. Receptor_IA-2_dom.
IPR029403. RESP18_dom.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PANTHERiPTHR19134:SF2. PTHR19134:SF2. 1 hit.
PfamiPF11548. Receptor_IA-2. 1 hit.
PF14948. RESP18. 1 hit.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTPRN_RAT
AccessioniPrimary (citable) accession number: Q63259
Secondary accession number(s): Q62883, Q63795, Q64643
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 15, 1998
Last modified: November 30, 2016
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Does not possess catalytic activity due to replacement of highly conserved residues in tyrosine-protein phosphatase domain.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.