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Protein

Receptor-type tyrosine-protein phosphatase N2

Gene

Ptprn2

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. May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (By similarity). Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate, phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate (PubMed:20097759). Regulates PI(4,5)P2 level in the plasma membrane and localization of cofilin at the plasma membrane and thus is indirectly involved in regulation of actin dynamics related to cell migration and metastasis; upon hydrolyzation of PI(4,5)P2 cofilin is released from the plasma membrane and acts in the cytoplasm in severing F-actin filaments (By similarity).By similarity1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei902SubstrateBy similarity1
Active sitei934Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei979SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase, Receptor

Keywords - Biological processi

Lipid metabolism, Phospholipid metabolism

Enzyme and pathway databases

ReactomeiR-RNO-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein phosphatase N2 (EC:3.1.3.-1 Publication, EC:3.1.3.48)
Short name:
R-PTP-N2
Alternative name(s):
PTP NE-6
Short name:
PTPNE6
Phogrin1 Publication
Cleaved into the following chain:
Gene namesi
Name:Ptprn2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi61904. Ptprn2.

Subcellular locationi

  • Cytoplasmic vesiclesecretory vesicle membrane 1 Publication; Single-pass type I membrane protein 1 Publication
  • Cytoplasmic vesiclesecretory vesiclesynaptic vesicle membrane By similarity; Single-pass type I membrane protein By similarity

  • Note: Predominantly found on dense-core secretory granules. Sorting to secretory granules in part is dependent of the N-terminal propeptide domain of the precursor and its interaction with CPE (By similarity). Transiently found at the cell membrane, when secretory vesicles fuse with the cell membrane to release their cargo. Is then endocytosed and recycled to secretory vesicles involving clathrin-dependent AP2-mediated endocytosis (PubMed:15882444). Recycled via STX6- but not TTTGN1/TGN38-containing compartments (By similarity).By similarityCurated1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 603ExtracellularSequence analysisAdd BLAST576
Transmembranei604 – 624HelicalSequence analysisAdd BLAST21
Topological domaini625 – 1004CytoplasmicSequence analysisAdd BLAST380

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: RGD
  • endoplasmic reticulum lumen Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • receptor complex Source: Ensembl
  • secretory granule Source: RGD
  • secretory granule membrane Source: UniProtKB
  • synaptic vesicle membrane Source: UniProtKB
  • terminal bouton Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasmic vesicle, Membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi655Y → A: Impairs internalization; decreases interaction with AP2M1. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000002545728 – 1004Receptor-type tyrosine-protein phosphatase N2Add BLAST977
ChainiPRO_0000438073491 – 1004IA-2beta60By similarityAdd BLAST514

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei259Omega-N-methylarginineBy similarity1
Modified residuei340PhosphoserineCombined sources1
Modified residuei424PhosphoserineBy similarity1
Modified residuei425PhosphoserineBy similarity1
Glycosylationi553N-linked (GlcNAc...)Sequence analysis1
Modified residuei681Phosphoserine; by PKABy similarity1 Publication1
Modified residuei687PhosphoserineCombined sources1
Modified residuei700Phosphothreonine; by PKA1 Publication1
Modified residuei959N6-acetyllysineBy similarity1

Post-translational modificationi

Subject to proteolytic cleavage at multiple sites.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei415 – 416CleavageBy similarity2

Keywords - PTMi

Acetylation, Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ63475.
PRIDEiQ63475.

PTM databases

iPTMnetiQ63475.
PhosphoSitePlusiQ63475.
SwissPalmiQ63475.

Expressioni

Gene expression databases

BgeeiENSRNOG00000005003.
GenevisibleiQ63475. RN.

Interactioni

Subunit structurei

Self-associates. Interacts (via cytoplasmic domain) with PTPRN (via cytoplasmic domain). Interacts (precursor form) with CPE. Interacts with HAP1. Interacts with AP2A1 or AP2A2 and AP1G1; indicative for an association with adaptor protein complex 2 (AP-2) and adaptor protein complex 1 (AP-1) (By similarity). Interacts with AP2M1; indicative for an association with adaptor protein complex 2 (AP-2) (PubMed:15882444). Interacts with MYO5A (PubMed:25744490).By similarity1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000006942.

Structurei

3D structure databases

ProteinModelPortaliQ63475.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini734 – 994Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 409Involved in localization to secretory granules; interaction with CPEBy similarityAdd BLAST409
Regioni934 – 940Substrate bindingBy similarity7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi655 – 664Tyrosine-based internalization motif1 Publication10
Motifi993 – 999Leucine-based sorting signalBy similarity7

Domaini

The tyrosine-based internalization signal is proposed to function at the level of clathrin-mediated endocytosis and recycling.1 Publication
The leucine-based sorting signal is proposed to function in trafficking at the plasma membrane.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.
HOVERGENiHBG105788.
InParanoidiQ63475.
KOiK07817.
OMAiEACVNDG.
OrthoDBiEOG091G0LUR.
PhylomeDBiQ63475.
TreeFamiTF351976.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR021613. Receptor_IA-2_dom.
IPR029403. RESP18_dom.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
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.

Q63475-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGLPLPLLLL LLLPPPLPRA LPAPASARGR QLPGRLGCLF EDGLCGSLET
60 70 80 90 100
CVNDGVFGRC QKVPALDTYR YEVSPGALLH LRIILQKLSR TGFTWQDDYT
110 120 130 140 150
QRVIAQELSN LPKAYLWHEE ASSPARSLQQ NADNEKWFSL ESEVALAKTL
160 170 180 190 200
RRYLPYLELL SQAPTANAHP RIDHETRPVK GEDSSPENIL TYVAHTSALT
210 220 230 240 250
YPPATRVKYP DNLLRPLSRL QPDELSPKVD SDIDKQKLIA ALGAYTAQRP
260 270 280 290 300
PGENDPEPRY LVHSPMRAPR PFAAPALSQR WPLPPGDSKD SLSMGDDTLL
310 320 330 340 350
RSLLKDLQQQ AEVDRLGSLK LEEQADSIAG AIQSDPVEGS QESHGRGAEG
360 370 380 390 400
QLREQADAPE EMLQDHRLPE VDDPAAYKEV SRLSFKLGDL LKDHGSPLLP
410 420 430 440 450
EAPLLEKSSR AEMKKSEQPE EVLSSEEETA GVEHVKSRTY SKDLLERKPN
460 470 480 490 500
SEPQPWRLED QFQNRAPEVW EDEQNLKLAA QGPPSGGLQL EVQPSEEEQQ
510 520 530 540 550
GYILTGNNPL SPEKGKQLMD EVAHLLRVPS SFFADVKVLG PAVIFKVSAN
560 570 580 590 600
IQNMTTADVT KAAVDNKDEL EKATGLTILQ SGIRPKGKLK LLPHPEEQED
610 620 630 640 650
STKFIVLTFL SIACILAVLL ASSLAYCLRH NSHYKLKEKL SGLGADPSAD
660 670 680 690 700
ATEAYQELCR QRMAVRPQDH SEGPHTSRIN SVSSQLSDGP MPSPSARSST
710 720 730 740 750
SSWSEEPAQS NMDISTGHMI LAYMEDHLKN KNRLEKEWEA LCAYQAEPDS
760 770 780 790 800
SLVAQREENA PKNRSLAVLT YDHSRILLKS ENSHSNSDYI NASPIMDHDP
810 820 830 840 850
RNPAYIATQG PLPATVADFW QMVWESGCAV IVMLTPLSEN GVRQCHHYWP
860 870 880 890 900
DEGSNVYHVY EVNLVSEHIW CQDFLVRSFY LKNLQTNETR TVTQFHFLSW
910 920 930 940 950
YDQGVPSSTR SLLDFRRKVN KCYRGRSCPI IVHCSDGAGR SGTYVLIDMV
960 970 980 990 1000
LNKMAKGAKE IDIAATLEHL RDQRPGMVQT KEQFEFALTA VAEEVNAILK

ALPQ
Length:1,004
Mass (Da):111,863
Last modified:November 1, 1996 - v1
Checksum:iA73929E11B486FB2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z50735 mRNA. Translation: CAA90600.1.
U73458 mRNA. Translation: AAC08036.1.
RefSeqiNP_113788.1. NM_031600.1.
UniGeneiRn.11044.

Genome annotation databases

EnsembliENSRNOT00000006942; ENSRNOP00000006942; ENSRNOG00000005003.
GeneIDi29714.
KEGGirno:29714.
UCSCiRGD:61904. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z50735 mRNA. Translation: CAA90600.1.
U73458 mRNA. Translation: AAC08036.1.
RefSeqiNP_113788.1. NM_031600.1.
UniGeneiRn.11044.

3D structure databases

ProteinModelPortaliQ63475.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000006942.

PTM databases

iPTMnetiQ63475.
PhosphoSitePlusiQ63475.
SwissPalmiQ63475.

Proteomic databases

PaxDbiQ63475.
PRIDEiQ63475.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000006942; ENSRNOP00000006942; ENSRNOG00000005003.
GeneIDi29714.
KEGGirno:29714.
UCSCiRGD:61904. rat.

Organism-specific databases

CTDi5799.
RGDi61904. Ptprn2.

Phylogenomic databases

eggNOGiKOG0793. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000243992.
HOVERGENiHBG105788.
InParanoidiQ63475.
KOiK07817.
OMAiEACVNDG.
OrthoDBiEOG091G0LUR.
PhylomeDBiQ63475.
TreeFamiTF351976.

Enzyme and pathway databases

ReactomeiR-RNO-6798695. Neutrophil degranulation.

Miscellaneous databases

PROiQ63475.

Gene expression databases

BgeeiENSRNOG00000005003.
GenevisibleiQ63475. RN.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR021613. Receptor_IA-2_dom.
IPR029403. RESP18_dom.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
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 nameiPTPR2_RAT
AccessioniPrimary (citable) accession number: Q63475
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Has no tyrosine-protein phosphatase activity at mild acidic conditions (pH 5.5). The in vivo relevance of the low PPase activity for the human protein at acidic conditions (pH 4.5) is questioned. This catalytic activity seems to be affected by the replacement of a highly conserved residue in the 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.