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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: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).3 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei899 – 8991SubstrateBy similarity
Active sitei931 – 9311Phosphocysteine intermediatePROSITE-ProRule annotation
Binding sitei976 – 9761SubstrateBy similarity

GO - Molecular functioni

GO - Biological processi

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

Keywords - Molecular functioni

Hydrolase, Protein phosphatase, Receptor

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein phosphatase N2 (EC:3.1.3.48)
Short name:
R-PTP-N2
Alternative name(s):
PTP IA-2beta1 Publication
Protein tyrosine phosphatase-NP
Short name:
PTP-NP1 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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 600573ExtracellularSequence analysisAdd
BLAST
Transmembranei601 – 62121HelicalSequence analysisAdd
BLAST
Topological domaini622 – 1001380CytoplasmicSequence analysisAdd
BLAST

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 islets 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence analysisAdd
BLAST
Chaini28 – 1001974Receptor-type tyrosine-protein phosphatase N2PRO_0000025456Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei339 – 3391PhosphoserineCombined sources
Modified residuei422 – 4221PhosphoserineCombined sources
Modified residuei423 – 4231PhosphoserineCombined sources
Glycosylationi550 – 5501N-linked (GlcNAc...)Sequence analysis
Modified residuei678 – 6781PhosphoserineCombined sources
Modified residuei684 – 6841PhosphoserineBy similarity
Modified residuei956 – 9561N6-acetyllysineBy similarity

Post-translational modificationi

Subject to proteolytic cleavage at multiple sites.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei413 – 4142CleavageBy similarity

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP80560.
PaxDbiP80560.
PRIDEiP80560.

PTM databases

iPTMnetiP80560.
PhosphoSiteiP80560.

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

Gene expression databases

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

Interactioni

Binary interactionsi

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

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP80560.
SMRiP80560. Positions 497-583, 710-996.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini731 – 991261Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni931 – 9377Substrate bindingBy similarity

Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0793. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00820000127032.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti121 – 1211A → T in AAB06945 (PubMed:8681804).Curated
Sequence conflicti266 – 2661A → S in AAB06945 (PubMed:8681804).Curated
Sequence conflicti369 – 3691E → D in AAB06945 (PubMed:8681804).Curated
Sequence conflicti370 – 3712Missing in AAB39996 (PubMed:8637868).Curated
Sequence conflicti395 – 3951P → H in AAB06945 (PubMed:8681804).Curated
Sequence conflicti411 – 4111I → M in AAB39996 (PubMed:8637868).Curated
Sequence conflicti414 – 4141S → L in AAB39996 (PubMed:8637868).Curated
Sequence conflicti586 – 5861L → H in AAB39996 (PubMed:8637868).Curated
Sequence conflicti662 – 6621I → V in AAB06945 (PubMed:8681804).Curated
Sequence conflicti662 – 6621I → V in AAB39996 (PubMed:8637868).Curated

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. Positions 497-583, 710-996.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiP80560.
PhosphoSiteiP80560.

Proteomic databases

MaxQBiP80560.
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.
GeneTreeiENSGT00820000127032.
HOGENOMiHOG000243992.
HOVERGENiHBG105788.
InParanoidiP80560.
KOiK07817.
OMAiEACVNDG.
OrthoDBiEOG091G0LUR.
TreeFamiTF351976.

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: September 7, 2016
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, 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.