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Protein

Receptor-type tyrosine-protein phosphatase-like N

Gene

Ptprn

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:12031972, PubMed:21732083). Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain (PubMed:16269463). 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). Seems to lack intrinsic enzyme activity (PubMed:7980563, PubMed:8878556).3 Publications

GO - Molecular functioni

GO - Biological processi

  • dense core granule maturation Source: MGI
  • insulin secretion Source: MGI
  • insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
  • luteinization Source: UniProtKB
  • protein dephosphorylation Source: InterPro
  • response to reactive oxygen species Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein phosphatase-like N
Short name:
R-PTP-N
Alternative name(s):
PTP IA-2Curated
Gene namesi
Name:Ptprn
Synonyms:Ptp35
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:102765. Ptprn.

Subcellular locationi

  • Membrane By similarity; Single-pass type I membrane protein By similarity
  • Cytoplasmic vesiclesecretory vesicle membrane 1 Publication; Single-pass type I membrane protein Curated
  • Perikaryon By similarity
  • Cell projectionaxon By similarity
  • Cell junctionsynapse By similarity
  • Cell membrane By similarity; Single-pass type I membrane protein By similarity
  • Endosome By similarity

  • Note: Detected on neuronal secretory vesicles, but not on synaptic vesicles. Colocalizes with insulin-containing secretory granules. Primarily detected on secretory vesicle membranes. 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 via the Golgi apparatus membranes.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini38 – 575538ExtracellularSequence analysisAdd
BLAST
Transmembranei576 – 60025HelicalSequence analysisAdd
BLAST
Topological domaini601 – 979379CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

Mice are born at the expected Mendelian rate, appear healthy and normal, but show impaired glucose tolerance and impaired insulin secretion in response to glucose (PubMed:12031972). 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).2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi877 – 8771A → D: No effect on dephosphorylating activity; increased the dephosphorylating efficiency; when associated with 911-A. 1 Publication
Mutagenesisi911 – 9111D → A: Confers dephosphorylating activity; increased the dephosphorylating efficiency; when associated with 877-D. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3737By similarityAdd
BLAST
Chaini38 – 979942Receptor-type tyrosine-protein phosphatase-like NPRO_0000025452Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei307 – 3071PhosphoserineCombined sources
Modified residuei308 – 3081PhosphoserineCombined sources
Glycosylationi506 – 5061N-linked (GlcNAc...)Sequence analysis
Glycosylationi524 – 5241N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Subject to proteolytic cleavage at multiple sites. Subject to cleavage on a pair of basic residues.By similarity
O-glycosylated.By similarity
N-glycosylated.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei448 – 4492CleavageBy similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ60673.
PaxDbiQ60673.
PRIDEiQ60673.

PTM databases

iPTMnetiQ60673.
PhosphoSiteiQ60673.

Expressioni

Tissue specificityi

Detected in pituitary (PubMed:16269463). Detected in brain (at protein level) (PubMed:12031972, PubMed:16269463, PubMed:19361477). Detected in brain (PubMed:7980563, PubMed:12031972). Weakly expressed in the colon, intestine, stomach and pancreas (PubMed:7980563).4 Publications

Gene expression databases

CleanExiMM_PTPRN.

Interactioni

Subunit structurei

Homodimer. Interacts with phosphorylated SNTB2; this protects PTPRN against cleavage by CAPN1. Dephosphorylation of SNTB2 upon insulin stimulation disrupts the interaction and results in PTPRN cleavage. Interacts with SNX19.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PtpraP180523EBI-8328895,EBI-6597520
Ptprn2P805604EBI-8328895,EBI-8538944

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ60673. 5 interactions.
MINTiMINT-4109182.
STRINGi10090.ENSMUSP00000027404.

Structurei

3D structure databases

ProteinModelPortaliQ60673.
SMRiQ60673. Positions 468-558, 687-976.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini709 – 969261Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0793. Eukaryota.
COG5599. LUCA.
HOVERGENiHBG053762.
InParanoidiQ60673.

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.

Q60673-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRRPRRPGGS GGSGGSGGLR LLVCLLLLSG RPGGCSAISA HGCLFDRRLC
60 70 80 90 100
SHLEVCIQDG LFGQCQAGVG QARPLLQVTS PVLQRLQGVL RQLMSQGLSW
110 120 130 140 150
HDDLTQHVIS QEMERIPRLR PPEPHPRDRS GLVPRKPGPA GELLTQGNPT
160 170 180 190 200
GSSPAAQGFP RPAGGRSWGG SPLSSLQAEL LPPLLEHLLM PPQPPHPALT
210 220 230 240 250
YEPALLQPYL FHQFGSRDGS RGSESSSGVV GVGHLSKAEG PALFSRSASK
260 270 280 290 300
AILGTHSGHS FGDLTGPSPA QLFQDSGLLY MAQELPVPGR ARAPRLPENG
310 320 330 340 350
GNRAEDSSEG HEEEVLGGRG EKSPPQAAQP ELSLQRLTAV LAGYGVELRQ
360 370 380 390 400
LTPEQFSTLL TLLQLLPKGT GRNLEGAVNV GGADVKKTIQ QMQRGDPAEA
410 420 430 440 450
LPPTPSLPGY LTASPASSEV QQVLSPGFPE PPHTPSPLGS SSVLLEKKSP
460 470 480 490 500
LGQSQPTVVG RPSARPSAEE YGYIVTDQKP LSLVAGVRLL EILAEHVHMS
510 520 530 540 550
SGSFINISVV GPAVTFRIRH NEQNLSLADV TQQAGLVKSE LEAQTGLQIL
560 570 580 590 600
QTGVGQREEA AEVLPRQAHG ISPMRSVLLT LVALAGVAGL LVALAVALCM
610 620 630 640 650
RHHSRQRDKE RLAALGPEGA HGDTTFEYQD LCRQHMATKS LFNRAEGQPE
660 670 680 690 700
PSRVSSVSSQ FSDAAQASPS SHSSTPSWCE EPAQANMDIS TGHMILAYME
710 720 730 740 750
DHLRNRDRLA KEWQALCAYQ AEPNTCAAAQ DESNIKKNRH PDFLPYDHAR
760 770 780 790 800
IKLKVESSPS RSDYINASPI IEHDPRMPAY IATQGPLSHT IADFWQMVWE
810 820 830 840 850
SGCTVIVMLT PLVEDGVKQC DRYWPDEGSS LYHVYEVNLV SEHIWCEDFL
860 870 880 890 900
VRSFYLKNLQ TQETRTLTQF HFLSWPAEGT PASTRPLLDF RRKVNKCYRG
910 920 930 940 950
RSCPIIVHCS DGAGRTGTYI LIDMVLNRMA KGVKEIDIAA TLEHVRDQRP
960 970
GLVRSKDQFE FALTAVAEEV NAILKALPQ
Length:979
Mass (Da):106,083
Last modified:July 27, 2011 - v2
Checksum:iAA3A7E126A3C5F3D
GO

Sequence cautioni

The sequence CAA52453.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti166 – 1694RSWG → GDGAGA in CAA52453 (PubMed:8526904).Curated
Sequence conflicti363 – 3631L → M in AAA52102 (PubMed:7980563).Curated
Sequence conflicti615 – 6151L → V in CAA52453 (PubMed:8526904).Curated
Sequence conflicti675 – 6751T → S in AAA52102 (PubMed:7980563).Curated
Sequence conflicti859 – 8591L → V in CAA52453 (PubMed:8526904).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11812 mRNA. Translation: AAA52102.1.
X74438 mRNA. Translation: CAA52453.1. Different initiation.
AC166150 Genomic DNA. No translation available.
PIRiI48721.
JC2349.
UniGeneiMm.2902.

Genome annotation databases

UCSCiuc011wnn.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11812 mRNA. Translation: AAA52102.1.
X74438 mRNA. Translation: CAA52453.1. Different initiation.
AC166150 Genomic DNA. No translation available.
PIRiI48721.
JC2349.
UniGeneiMm.2902.

3D structure databases

ProteinModelPortaliQ60673.
SMRiQ60673. Positions 468-558, 687-976.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ60673. 5 interactions.
MINTiMINT-4109182.
STRINGi10090.ENSMUSP00000027404.

PTM databases

iPTMnetiQ60673.
PhosphoSiteiQ60673.

Proteomic databases

MaxQBiQ60673.
PaxDbiQ60673.
PRIDEiQ60673.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiuc011wnn.1. mouse.

Organism-specific databases

MGIiMGI:102765. Ptprn.

Phylogenomic databases

eggNOGiKOG0793. Eukaryota.
COG5599. LUCA.
HOVERGENiHBG053762.
InParanoidiQ60673.

Miscellaneous databases

ChiTaRSiPtprn. mouse.
PROiQ60673.
SOURCEiSearch...

Gene expression databases

CleanExiMM_PTPRN.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation, sequence and expression of a novel mouse brain cDNA, mIA-2, and its relatedness to members of the protein tyrosine phosphatase family."
    Lu J., Notkins A.L., Lan M.S.
    Biochem. Biophys. Res. Commun. 204:930-936(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], LACK OF FUNCTION AS PROTEIN TYROSINE PHOSPHATASE, TISSUE SPECIFICITY.
    Tissue: Brain.
  2. "Expression of PTP35, the murine homologue of the protein tyrosine phosphatase-related sequence IA-2, is regulated during cell growth and stimulated by mitogens in 3T3 fibroblasts."
    Magistrelli G., Covini N., Mosca M., Lippoli G., Isacchi A.
    Biochem. Biophys. Res. Commun. 217:154-161(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Swiss Webster.
    Tissue: Fibroblast.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "Substitution of two variant residues in the protein tyrosine phosphatase-like PTP35/IA-2 sequence reconstitutes catalytic activity."
    Magistrelli G., Toma S., Isacchi A.
    Biochem. Biophys. Res. Commun. 227:581-588(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: LACK OF FUNCTION AS PROTEIN TYROSINE PHOSPHATASE, MUTAGENESIS OF ALA-877 AND ASP-911.
  5. "Targeted disruption of the protein tyrosine phosphatase-like molecule IA-2 results in alterations in glucose tolerance tests and insulin secretion."
    Saeki K., Zhu M., Kubosaki A., Xie J., Lan M.S., Notkins A.L.
    Diabetes 51:1842-1850(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
  6. "Disruption of the transmembrane dense core vesicle proteins IA-2 and IA-2beta causes female infertility."
    Kubosaki A., Nakamura S., Clark A., Morris J.F., Notkins A.L.
    Endocrinology 147:811-815(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
  7. "Disturbances in the secretion of neurotransmitters in IA-2/IA-2beta null mice: changes in behavior, learning and lifespan."
    Nishimura T., Kubosaki A., Ito Y., Notkins A.L.
    Neuroscience 159:427-437(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307 AND SER-308, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.
  9. "Deletion of Ia-2 and/or Ia-2beta in mice decreases insulin secretion by reducing the number of dense core vesicles."
    Cai T., Hirai H., Zhang G., Zhang M., Takahashi N., Kasai H., Satin L.S., Leapman R.D., Notkins A.L.
    Diabetologia 54:2347-2357(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.

Entry informationi

Entry nameiPTPRN_MOUSE
AccessioniPrimary (citable) accession number: Q60673
Secondary accession number(s): E9Q746, Q62129
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: May 11, 2016
This is version 125 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.1 Publication

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.