Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Receptor-type tyrosine-protein phosphatase-like N

Gene

Ptprn

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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:15939893, 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). 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).By similarity6 Publications
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

Caution

Does not possess catalytic activity due to replacement of highly conserved residues in tyrosine-protein phosphatase domain.1 Publication

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
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • positive regulation of type B pancreatic cell proliferation Source: UniProtKB
  • response to reactive oxygen species Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionReceptor
Biological processTranscription, Transcription regulation

Names & Taxonomyi

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

Organism-specific databases

MGIiMGI:102765 Ptprn

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini38 – 575LumenalSequence analysisAdd BLAST538
Transmembranei576 – 600HelicalSequence analysisAdd BLAST25
Topological domaini601 – 979CytoplasmicSequence analysisAdd BLAST379

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Endosome, Membrane, Nucleus, 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)DescriptionActionsGraphical viewLength
Mutagenesisi877A → D: No effect on dephosphorylating activity; increased the dephosphorylating efficiency; when associated with 911-A. 1 Publication1
Mutagenesisi911D → A: Confers dephosphorylating activity; increased the dephosphorylating efficiency; when associated with 877-D. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 37By similarityAdd BLAST37
ChainiPRO_000002545238 – 979Receptor-type tyrosine-protein phosphatase-like NAdd BLAST942
ChainiPRO_000043808238 – 448ICA512-N-terminal fragmentBy similarityAdd BLAST411
ChainiPRO_0000438083449 – 979ICA512-transmembrane fragmentBy similarityAdd BLAST531
ChainiPRO_0000438084659 – 979ICA512-cleaved cytosolic fragmentBy similarityAdd BLAST321

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi43Interchain (with C-43 or C-50); in multimeric formBy similarity
Disulfide bondi50Interchain (with C-43 or C-50); in multimeric formBy similarity
Disulfide bondi56 ↔ 65By similarity
Modified residuei307PhosphoserineCombined sources1
Modified residuei308PhosphoserineCombined sources1
Glycosylationi506N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi524N-linked (GlcNAc...) asparagineSequence analysis1
Cross-linki754Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Subject to proteolytic cleavage at multiple sites. Subject to cleavage on a pair of basic residues. On exocytosis of secretory granules in pancreatic beta-cells ICA512-TMF is transiently inserted in the plasma-membrane and cleaved by mu-type calpain CPN1 to yield ICA512-CCF.By similarity
O-glycosylated.By similarity
N-glycosylated.By similarity
Sumoylated at two sites including Lys-754. Sumoylation decreases interaction with STAT5.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei448 – 449CleavageBy similarity2

Keywords - PTMi

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

Proteomic databases

MaxQBiQ60673
PaxDbiQ60673
PRIDEiQ60673

PTM databases

iPTMnetiQ60673
PhosphoSitePlusiQ60673

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; 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 (By similarity). Interacts with PTPRN2, PTPRA and PTPRE (PubMed:12364328).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ60673, 5 interactors
MINTiQ60673
STRINGi10090.ENSMUSP00000027404

Structurei

3D structure databases

ProteinModelPortaliQ60673
SMRiQ60673
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini709 – 969Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni38 – 134RESP18 homology domainBy similarityAdd BLAST97
Regioni449 – 575Sufficient for dimerization of proICA512By similarityAdd BLAST127
Regioni601 – 732Sufficient for dimerization of proICA512By similarityAdd BLAST132

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0793 Eukaryota
COG5599 LUCA
HOVERGENiHBG053762
InParanoidiQ60673

Family and domain databases

Gene3Di3.30.70.2470, 1 hit
3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR033522 IA-2/IA-2_beta
IPR029021 Prot-tyrosine_phosphatase-like
IPR000242 PTPase_domain
IPR021613 Receptor_IA-2_dom
IPR038112 Receptor_IA-2_ectodomain_sf
IPR029403 RESP18_dom
IPR016130 Tyr_Pase_AS
IPR003595 Tyr_Pase_cat
IPR000387 TYR_PHOSPHATASE_dom
PANTHERiPTHR19134:SF2 PTHR19134:SF2, 1 hit
PfamiView protein in Pfam
PF11548 Receptor_IA-2, 1 hit
PF14948 RESP18, 1 hit
PF00102 Y_phosphatase, 1 hit
PRINTSiPR00700 PRTYPHPHTASE
SMARTiView protein in SMART
SM00194 PTPc, 1 hit
SM00404 PTPc_motif, 1 hit
SUPFAMiSSF52799 SSF52799, 1 hit
PROSITEiView protein in PROSITE
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50055 TYR_PHOSPHATASE_PTP, 1 hit

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 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti166 – 169RSWG → GDGAGA in CAA52453 (PubMed:8526904).Curated4
Sequence conflicti363L → M in AAA52102 (PubMed:7980563).Curated1
Sequence conflicti615L → V in CAA52453 (PubMed:8526904).Curated1
Sequence conflicti675T → S in AAA52102 (PubMed:7980563).Curated1
Sequence conflicti859L → V in CAA52453 (PubMed:8526904).Curated1

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

Similar proteinsi

Entry informationi

Entry nameiPTPRN_MOUSE
AccessioniPrimary (citable) accession number: Q60673
Secondary accession number(s): E9Q746, Q62129
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: April 25, 2018
This is version 136 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health