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Protein

Receptor-type tyrosine-protein phosphatase N2

Gene

Ptprn2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in vesicle-mediated secretory processes (PubMed:21732083). 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 (PubMed:21732083). Plays a role in insulin secretion in response to glucose stimuli (PubMed:15220191, PubMed:16418280, PubMed:21732083). 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) (PubMed:16269463). Required to maintain normal levels of renin expression and renin release (PubMed:19019914). May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (PubMed:12364328). Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate (By similarity). 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 similarity6 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei899SubstrateBy similarity1
Active sitei931Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei976SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

  • insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
  • lipid metabolic process Source: UniProtKB-KW
  • negative regulation of GTPase activity Source: Ensembl
  • neurotransmitter secretion Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase, Receptor

Keywords - Biological processi

Lipid metabolism, Phospholipid metabolism

Enzyme and pathway databases

ReactomeiR-MMU-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein phosphatase N2 (EC:3.1.3.-, EC:3.1.3.48)
Short name:
R-PTP-N2
Alternative name(s):
PTP IA-2beta1 Publication
Phogrin2 Publications
Protein tyrosine phosphatase-NP
Short name:
PTP-NP1 Publication
Cleaved into the following 3 chains:
IA-2beta711 Publication
IA-2beta641 Publication
IA-2beta601 Publication
Gene namesi
Name:Ptprn2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:107418. Ptprn2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 600ExtracellularSequence analysisAdd BLAST573
Transmembranei601 – 621HelicalSequence analysisAdd BLAST21
Topological domaini622 – 1001CytoplasmicSequence analysisAdd BLAST380

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell junction, Cytoplasmic vesicle, Membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Mice appear healthy and normal, but display mildly decreased glucose tolerance and impaired glucose-stimulated insulin secretion (PubMed:15220191). Pancreatic islRef.?ets from mice lacking both Ptprn and Ptprn2 contain decreased numbers of insulin-containing vesicles and show a further decrease in insulin secretion after glucose stimuli (PubMed:21732083). Mice lacking both Ptprn and Ptprn2 appear normal, but have lower levels of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. Likewise, they have decreased numbers of synaptic vesicles in the hippocampus and show decreased neurotransmitter release after K+ stimulation; basal levels of neurotransmitter release are unaffected. They show increased anxiety-like behavior with strongly decreased exploratory activity and rearing. Besides, they show defects in remembering conditioned learning. With increasing age, mutant mice develop a tendency to suffer seizures and display a reduced life span; roughly half of the mutant mice are dead after 40 weeks (PubMed:19361477). The majority of female mice deficient in both Ptprn and Ptprn2 are infertile or have small litters, due to abnormalities of the estrous cycle and absence of corpora lutea. These defects are due to decreased levels of luteinizing hormone and follicle-stimulating hormone (FSH) in the pituitary and decreased levels of luteinizing hormone (LH) in the blood plasma. In contrast, male mice lacking both Ptprn and Ptprn2 display normal hormone levels and normal fertility (PubMed:16269463).4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi990 – 991EE → AA: Impairs localization to secretory granules, promotes location at the TGN, decreases interaction with alpha- and gamma-type adaptin subunits. 2 Publications2
Mutagenesisi995 – 996IL → AA: Impairs localization to secretory granules, promotes location at the plasma membrane, defective ind gamma endocytosis, highly decreases interaction with alpha- and gamma-type adaptin subunits. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000002545628 – 1001Receptor-type tyrosine-protein phosphatase N2Add BLAST974
ChainiPRO_0000438090414 – 1001IA-2beta711 PublicationAdd BLAST588
ChainiPRO_0000438071464 – 1001IA-2beta641 PublicationAdd BLAST538
ChainiPRO_0000438072489 – 1001IA-2beta601 PublicationAdd BLAST513

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei259Omega-N-methylarginineCombined sources1
Modified residuei339PhosphoserineCombined sources1
Modified residuei422PhosphoserineCombined sources1
Modified residuei423PhosphoserineCombined sources1
Glycosylationi550N-linked (GlcNAc...)Sequence analysis1
Modified residuei678PhosphoserineCombined sourcesBy similarity1
Modified residuei684PhosphoserineBy similarity1
Modified residuei697PhosphothreonineBy similarity1
Modified residuei956N6-acetyllysineBy similarity1

Post-translational modificationi

Subject to proteolytic cleavage at multiple sites during maturation of secretory granules. In the brain at least IA-2beta71, IA-2beta64 and IA-2beta60 have been detected, in the pancreas and a pancreatic beta cell line only IA-2beta60 has been detected.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei413 – 414CleavageBy similarity2

Keywords - PTMi

Acetylation, Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

PaxDbiP80560.
PRIDEiP80560.

PTM databases

iPTMnetiP80560.
PhosphoSitePlusiP80560.

Expressioni

Tissue specificityi

Detected in brain (PubMed:15220191, PubMed:19361477). Detected in pancreas islets (at protein level) (PubMed:8681804). Detected in pancreas and brain (PubMed:8681804, PubMed:8637868).4 Publications

Developmental stagei

Expressed in early stages of pancreatic development. First expressed in day 8.5 embryos (E8.5) in the dorsal part of the midgut endoderm and by E9.5, in the pancreatic rudiment specifically in early endocrine progenitor cells. At later stages expressed in insulin- or glucagon-producing cells. During neural development, the type 2 PTP-NP is expressed in early stages of neurogenesis, and the type 1 weakly in the later stages.1 Publication

Inductioni

By GHRL in brain, pancreas, and insulinoma cell lines.1 Publication

Gene expression databases

BgeeiENSMUSG00000056553.
ExpressionAtlasiP80560. baseline and differential.
GenevisibleiP80560. MM.

Interactioni

Subunit structurei

Self-associates. Interacts (via cytoplasmic domain) with PTPRN (via cytoplasmic domain) (PubMed:12364328). Interacts (precursor form) with CPE (PubMed:21210912). Interacts with HAP1 isoform A (PubMed:21544547). 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) (PubMed:16262730). Interacts with AP2M1; indicative for an association with adaptor protein complex 2 (AP-2). Interacts with MYO5A (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PtprnQ606734EBI-8538944,EBI-8328895

Protein-protein interaction databases

IntActiP80560. 2 interactors.
MINTiMINT-8310377.
STRINGi10090.ENSMUSP00000064046.

Structurei

3D structure databases

ProteinModelPortaliP80560.
SMRiP80560.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini731 – 991Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 407Involved in localization to secretory granules; interaction with CPE1 PublicationAdd BLAST407
Regioni931 – 937Substrate bindingBy similarity7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi652 – 661Tyrosine-based internalization motifBy similarity10
Motifi990 – 996Leucine-based sorting signal1 Publication7

Domaini

The tyrosine-based internalization signal is proposed to function in clathrin-mediated endocytosis and recycling.By similarity
The leucine-based sorting signal is proposed to function in trafficking at the plasma membrane.1 Publication

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.
InParanoidiP80560.
KOiK07817.
OMAiEACVNDG.
OrthoDBiEOG091G0LUR.
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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P80560-1) [UniParc]FASTAAdd to basket
Also known as: Type 1-PTP-NP

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGPPLPLLLL LLLPPPLPRA LPAPASARGR QLPGRLGCLF EDGLCGSLET
60 70 80 90 100
CVNDGVFGRC QKVPVMDTYR YEVPPGALLH LKVTLQKLSR TGFTWQDDYT
110 120 130 140 150
QRVIAQELAN LPKAYLWHGE ASGPARSLQQ NADNEKWFSL EREVALAKTL
160 170 180 190 200
RRYLPYLELL SQTPTANAHS RIDHETRPAK GEDSSPENIL TYVAHTSALT
210 220 230 240 250
YPPATRAKYP DNLLRPFSRL QPDELSPKVD GDIDKQKLIA ALGAYTAQRL
260 270 280 290 300
PGENDPEPRY LVHGSARAPR PFSATALSQR WPPPPGDAKD SPSMDDDTLL
310 320 330 340 350
QSLLKDLQQN SEVDRLGPLK EEKADSVAGA IQSDPAEGSQ ESHGRGAEGQ
360 370 380 390 400
PREQTDAPET MLQDHRLSEV DDPVYKEVNR LSFQLGDLLK DYGSPLLPEG
410 420 430 440 450
PLLEKSSREE IKKSEQPEEV LSSEEETAGV EHVRSRTYSK DLFERKPNSE
460 470 480 490 500
PQPRRLEDQF QNRAPELWED EESLKLAAQG PPSGGLQLEV QPSEEQQGYI
510 520 530 540 550
LTGNNPLSPE KGKQLMDQVA HILRVPSSFF ADIKVLGPAV TFKVSANIQN
560 570 580 590 600
MTTADVIKAA ADNKDQLEKA TGLTILQSGI RPKGKLKLLP HQEEQEDSTK
610 620 630 640 650
FILLTFLSIA CILGVLLASS LAYCLRHNSH YKLKDKLSGL GADPSADATE
660 670 680 690 700
AYQELCRQRM AIRPQDRSEG PHTSRINSVS SQFSDGPMPS PSARSSTSSW
710 720 730 740 750
SEEPVQSNMD ISTGHMILAY MEDHLKNKNR LEKEWEALCA YQAEPNSSLV
760 770 780 790 800
AQREENAPKN RSLAVLTYDH SRILLKSQNS HGSSDYINAS PIMDHDPRNP
810 820 830 840 850
AYIATQGPLP ATVADFWQMV WESGCAVIVM LTPLSENGVR QCHHYWPDEG
860 870 880 890 900
SNLYHVYEVN LVSEHIWCQD FLVRSFYLKN LQTNETRTVT QFHFLSWYDQ
910 920 930 940 950
GVPSSTRSLL DFRRKVNKCY RGRSCPIIVH CSDGAGRSGT YVLIDMVLNK
960 970 980 990 1000
MAKGAKEIDI AATLEHLRDQ RPGMVQTKEQ FEFALTAVAE EVNAILKALP

Q
Length:1,001
Mass (Da):111,497
Last modified:July 27, 2011 - v2
Checksum:i42B590A13CA89CB8
GO
Isoform 2 (identifier: P80560-2)
Also known as: Type 2-PTP-NP
Sequence is not available
Length:
Mass (Da):

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121A → T in AAB06945 (PubMed:8681804).Curated1
Sequence conflicti266A → S in AAB06945 (PubMed:8681804).Curated1
Sequence conflicti369E → D in AAB06945 (PubMed:8681804).Curated1
Sequence conflicti370 – 371Missing in AAB39996 (PubMed:8637868).Curated2
Sequence conflicti395P → H in AAB06945 (PubMed:8681804).Curated1
Sequence conflicti411I → M in AAB39996 (PubMed:8637868).Curated1
Sequence conflicti414S → L in AAB39996 (PubMed:8637868).Curated1
Sequence conflicti586L → H in AAB39996 (PubMed:8637868).Curated1
Sequence conflicti662I → V in AAB06945 (PubMed:8681804).Curated1
Sequence conflicti662I → V in AAB39996 (PubMed:8637868).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U57345 mRNA. Translation: AAB06945.1.
U82439 mRNA. Translation: AAB39996.1.
BN000315
, BN000293, BN000294, BN000295, BN000296, BN000297, BN000298, BN000299, BN000300, BN000301, BN000302, BN000303, BN000304, BN000305, BN000306, BN000307, BN000308, BN000309, BN000310, BN000311, BN000312, BN000313, BN000314 Genomic DNA. Translation: CAG23871.1.
CCDSiCCDS36576.1. [P80560-1]
RefSeqiNP_035345.2. NM_011215.2. [P80560-1]
UniGeneiMm.206054.

Genome annotation databases

EnsembliENSMUST00000070733; ENSMUSP00000064046; ENSMUSG00000056553. [P80560-1]
GeneIDi19276.
KEGGimmu:19276.
UCSCiuc007phx.2. mouse. [P80560-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U57345 mRNA. Translation: AAB06945.1.
U82439 mRNA. Translation: AAB39996.1.
BN000315
, BN000293, BN000294, BN000295, BN000296, BN000297, BN000298, BN000299, BN000300, BN000301, BN000302, BN000303, BN000304, BN000305, BN000306, BN000307, BN000308, BN000309, BN000310, BN000311, BN000312, BN000313, BN000314 Genomic DNA. Translation: CAG23871.1.
CCDSiCCDS36576.1. [P80560-1]
RefSeqiNP_035345.2. NM_011215.2. [P80560-1]
UniGeneiMm.206054.

3D structure databases

ProteinModelPortaliP80560.
SMRiP80560.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP80560. 2 interactors.
MINTiMINT-8310377.
STRINGi10090.ENSMUSP00000064046.

PTM databases

iPTMnetiP80560.
PhosphoSitePlusiP80560.

Proteomic databases

PaxDbiP80560.
PRIDEiP80560.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000070733; ENSMUSP00000064046; ENSMUSG00000056553. [P80560-1]
GeneIDi19276.
KEGGimmu:19276.
UCSCiuc007phx.2. mouse. [P80560-1]

Organism-specific databases

CTDi5799.
MGIiMGI:107418. Ptprn2.

Phylogenomic databases

eggNOGiKOG0793. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000243992.
HOVERGENiHBG105788.
InParanoidiP80560.
KOiK07817.
OMAiEACVNDG.
OrthoDBiEOG091G0LUR.
TreeFamiTF351976.

Enzyme and pathway databases

ReactomeiR-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

PROiP80560.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000056553.
ExpressionAtlasiP80560. baseline and differential.
GenevisibleiP80560. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: P80560
Secondary accession number(s): O09134, P70328, Q1RLJ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 145 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.