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Protein

Receptor-type tyrosine-protein phosphatase N2

Gene

PTPRN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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) (By similarity). Required to maintain normal levels of renin expression and renin release (By similarity). 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 (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 (PubMed:26620550).By similarity1 Publication

Caution

Has no tyrosine-protein phosphatase activity at mild acidic conditions (pH 5.5). The in vivo relevance of the low PPase activity 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

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation1 Publication

pH dependencei

Optimum pH is 4.5.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei913SubstrateBy similarity1
Active sitei945Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei990SubstrateBy similarity1

GO - Molecular functioni

  • transmembrane receptor protein tyrosine phosphatase activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase, Receptor
Biological processLipid metabolism, Phospholipid metabolism

Enzyme and pathway databases

BRENDAi3.1.3.48 2681
ReactomeiR-HSA-6798695 Neutrophil degranulation

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein phosphatase N2 (EC:3.1.3.-, EC:3.1.3.481 Publication)
Short name:
R-PTP-N2
Alternative name(s):
Islet cell autoantigen-related protein1 Publication
Short name:
IAR1 Publication
Short name:
ICAAR1 Publication
Phogrin2 Publications
Cleaved into the following chain:
Gene namesi
Name:PTPRN2
Synonyms:KIAA0387
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000155093.17
HGNCiHGNC:9677 PTPRN2
MIMi601698 gene
neXtProtiNX_Q92932

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 domaini22 – 615ExtracellularSequence analysisAdd BLAST594
Transmembranei616 – 636HelicalSequence analysisAdd BLAST21
Topological domaini637 – 1015CytoplasmicSequence analysisAdd BLAST379

Keywords - Cellular componenti

Cell junction, Cytoplasmic vesicle, Membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Autoantigen in insulin-dependent diabetes mellitus (IDDM).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi945C → A: No effect to increase invasion, migration, and metastatic lung colonization in mice breast cancer model. 1 Publication1
Mutagenesisi945C → S: Loss of activity. 1

Keywords - Diseasei

Diabetes mellitus

Organism-specific databases

DisGeNETi5799
OpenTargetsiENSG00000155093
PharmGKBiPA34022

Polymorphism and mutation databases

BioMutaiPTPRN2
DMDMi116242738

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000002545422 – 1015Receptor-type tyrosine-protein phosphatase N2Add BLAST994
ChainiPRO_0000438088502 – 1015IA-2beta60By similarityAdd BLAST514

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei436PhosphoserineBy similarity1
Modified residuei437PhosphoserineBy similarity1
Glycosylationi564N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei692PhosphoserineBy similarity1
Modified residuei698PhosphoserineBy similarity1
Modified residuei970N6-acetyllysineCombined sources1

Post-translational modificationi

Subject to proteolytic cleavage at multiple sites.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei427 – 428CleavageSequence analysis2

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ92932
PeptideAtlasiQ92932
PRIDEiQ92932
ProteomicsDBi75611
75612 [Q92932-2]
75613 [Q92932-3]

PTM databases

DEPODiQ92932
iPTMnetiQ92932
PhosphoSitePlusiQ92932

Expressioni

Tissue specificityi

Highest levels in brain and pancreas (PubMed:8954911, PubMed:8798755). Lower levels in trachea, prostate, stomach and spinal chord (PubMed:8798755).2 Publications

Gene expression databases

BgeeiENSG00000155093
CleanExiHS_PTPRN2
ExpressionAtlasiQ92932 baseline and differential
GenevisibleiQ92932 HS

Organism-specific databases

HPAiHPA006900
HPA026656

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). Interacts with MYO5A (By similarity).By similarity

Protein-protein interaction databases

BioGridi111763, 25 interactors
IntActiQ92932, 7 interactors
MINTiQ92932
STRINGi9606.ENSP00000374069

Structurei

Secondary structure

11015
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi512 – 517Combined sources6
Helixi523 – 536Combined sources14
Helixi541 – 543Combined sources3
Beta strandi544 – 550Combined sources7
Beta strandi553 – 558Combined sources6
Helixi567 – 576Combined sources10
Helixi578 – 585Combined sources8
Beta strandi589 – 594Combined sources6
Helixi725 – 738Combined sources14
Helixi742 – 754Combined sources13
Turni763 – 766Combined sources4
Turni768 – 770Combined sources3
Helixi771 – 773Combined sources3
Helixi783 – 785Combined sources3
Turni791 – 793Combined sources3
Beta strandi795 – 797Combined sources3
Beta strandi802 – 806Combined sources5
Beta strandi811 – 813Combined sources3
Beta strandi815 – 819Combined sources5
Helixi824 – 826Combined sources3
Helixi827 – 836Combined sources10
Beta strandi841 – 844Combined sources4
Beta strandi848 – 850Combined sources3
Beta strandi862 – 868Combined sources7
Beta strandi871 – 882Combined sources12
Beta strandi885 – 894Combined sources10
Turni895 – 898Combined sources4
Beta strandi899 – 908Combined sources10
Helixi920 – 934Combined sources15
Beta strandi941 – 944Combined sources4
Beta strandi946 – 949Combined sources4
Helixi950 – 966Combined sources17
Helixi974 – 982Combined sources9
Helixi992 – 1010Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QEPX-ray2.50A/B715-1010[»]
4HTIX-ray1.95A502-599[»]
4HTJX-ray2.01A502-599[»]
ProteinModelPortaliQ92932
SMRiQ92932
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92932

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini745 – 1005Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 421Involved in localization to secretory granules; interaction with CPEBy similarityAdd BLAST421
Regioni945 – 951Substrate bindingBy similarity7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi666 – 675Tyrosine-based internalization motifBy similarity10
Motifi1004 – 1010Leucine-based sorting signalBy similarity7

Domaini

The cytoplasmic domain appears to contain the autoantigenic epitopes.2 Publications
The leucine-based sorting signal is proposed to function in trafficking at the plasma membrane.By similarity
The tyrosine-based internalization signal is proposed to function at the level of clathrin-mediated endocytosis and recycling.By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0793 Eukaryota
COG5599 LUCA
GeneTreeiENSGT00920000148980
HOGENOMiHOG000243992
HOVERGENiHBG105788
InParanoidiQ92932
KOiK07817
OMAiETCVNDG
OrthoDBiEOG091G0LUR
PhylomeDBiQ92932
TreeFamiTF351976

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:SF266 PTHR19134:SF266, 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

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92932-1) [UniParc]FASTAAdd to basket

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 LLLLLPPRVL PAAPSSVPRG RQLPGRLGCL LEEGLCGASE
60 70 80 90 100
ACVNDGVFGR CQKVPAMDFY RYEVSPVALQ RLRVALQKLS GTGFTWQDDY
110 120 130 140 150
TQYVMDQELA DLPKTYLRRP EASSPARPSK HSVGSERRYS REGGAALANA
160 170 180 190 200
LRRHLPFLEA LSQAPASDVL ARTHTAQDRP PAEGDDRFSE SILTYVAHTS
210 220 230 240 250
ALTYPPGSRT QLREDLLPRT LGQLQPDELS PKVDSGVDRH HLMAALSAYA
260 270 280 290 300
AQRPPAPPGE GSLEPQYLLR APSRMPRPLL APAAPQKWPS PLGDSEDPSS
310 320 330 340 350
TGDGARIHTL LKDLQRQPAE VRGLSGLELD GMAELMAGLM QGVDHGVARG
360 370 380 390 400
SPGRAALGES GEQADGPKAT LRGDSFPDDG VQDDDDRLYQ EVHRLSATLG
410 420 430 440 450
GLLQDHGSRL LPGALPFARP LDMERKKSEH PESSLSSEEE TAGVENVKSQ
460 470 480 490 500
TYSKDLLGQQ PHSEPGAAAF GELQNQMPGP SKEEQSLPAG AQEALSDGLQ
510 520 530 540 550
LEVQPSEEEA RGYIVTDRDP LRPEEGRRLV EDVARLLQVP SSAFADVEVL
560 570 580 590 600
GPAVTFKVSA NVQNVTTEDV EKATVDNKDK LEETSGLKIL QTGVGSKSKL
610 620 630 640 650
KFLPPQAEQE DSTKFIALTL VSLACILGVL LASGLIYCLR HSSQHRLKEK
660 670 680 690 700
LSGLGGDPGA DATAAYQELC RQRMATRPPD RPEGPHTSRI SSVSSQFSDG
710 720 730 740 750
PIPSPSARSS ASSWSEEPVQ SNMDISTGHM ILSYMEDHLK NKNRLEKEWE
760 770 780 790 800
ALCAYQAEPN SSFVAQREEN VPKNRSLAVL TYDHSRVLLK AENSHSHSDY
810 820 830 840 850
INASPIMDHD PRNPAYIATQ GPLPATVADF WQMVWESGCV VIVMLTPLAE
860 870 880 890 900
NGVRQCYHYW PDEGSNLYHI YEVNLVSEHI WCEDFLVRSF YLKNLQTNET
910 920 930 940 950
RTVTQFHFLS WYDRGVPSSS RSLLDFRRKV NKCYRGRSCP IIVHCSDGAG
960 970 980 990 1000
RSGTYVLIDM VLNKMAKGAK EIDIAATLEH LRDQRPGMVQ TKEQFEFALT
1010
AVAEEVNAIL KALPQ
Length:1,015
Mass (Da):111,271
Last modified:October 17, 2006 - v2
Checksum:i950C15CA89DBC029
GO
Isoform 2 (identifier: Q92932-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     519-547: Missing.

Note: No experimental confirmation available.
Show »
Length:986
Mass (Da):108,054
Checksum:i6AECE2238F5E1DAE
GO
Isoform 3 (identifier: Q92932-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: MGPPLPLLLL...PRGRQLPGRL → MAVESEYSLL...RWQCLVQMWA

Note: No experimental confirmation available.
Show »
Length:1,038
Mass (Da):114,360
Checksum:iDB2F9170755B08A6
GO
Isoform 4 (identifier: Q92932-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     38-54: Missing.

Note: No experimental confirmation available.
Show »
Length:998
Mass (Da):109,622
Checksum:iDD03BB2583397566
GO

Sequence cautioni

The sequence BAA20841 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti160A → D in AAB68603 (Ref. 4) Curated1
Sequence conflicti247S → G in CAA69880 (PubMed:8954911).Curated1
Sequence conflicti323G → R in CAA69880 (PubMed:8954911).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027955140S → T1 PublicationCorresponds to variant dbSNP:rs3800855Ensembl.1
Natural variantiVAR_046301208S → P4 PublicationsCorresponds to variant dbSNP:rs1130495Ensembl.1
Natural variantiVAR_027956213R → H1 PublicationCorresponds to variant dbSNP:rs1130496Ensembl.1
Natural variantiVAR_020302325S → N2 PublicationsCorresponds to variant dbSNP:rs1130499Ensembl.1
Natural variantiVAR_022015343V → M. Corresponds to variant dbSNP:rs3752368Ensembl.1
Natural variantiVAR_046302388L → H. Corresponds to variant dbSNP:rs7456452Ensembl.1
Natural variantiVAR_035648716E → K in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs577236042Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0352641 – 37MGPPL…LPGRL → MAVESEYSLLRTEASFPTMK MFCVSHTLPRVEVMFVSGPQ TRERTEPVDPRWQCLVQMWA in isoform 3. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_04503238 – 54Missing in isoform 4. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_007779519 – 547Missing in isoform 2. 1 PublicationAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U66702 mRNA Translation: AAC50742.1
Y08569 Genomic DNA Translation: CAA69880.1
AF007555 mRNA Translation: AAB63600.1
U81561 mRNA Translation: AAB68603.1
AB002385 mRNA Translation: BAA20841.2 Different initiation.
AC005481 Genomic DNA No translation available.
AC006003 Genomic DNA No translation available.
AC006372 Genomic DNA No translation available.
AC011899 Genomic DNA No translation available.
AC019043 Genomic DNA No translation available.
AC078942 Genomic DNA No translation available.
AC093662 Genomic DNA No translation available.
AC093856 Genomic DNA No translation available.
AC125243 Genomic DNA No translation available.
BC034040 mRNA Translation: AAH34040.1
CCDSiCCDS5947.1 [Q92932-1]
CCDS5948.1 [Q92932-4]
CCDS5949.1 [Q92932-2]
PIRiJC5062
JC5263
RefSeqiNP_001295196.1, NM_001308267.1
NP_001295197.1, NM_001308268.1 [Q92932-3]
NP_002838.2, NM_002847.4 [Q92932-1]
NP_570857.2, NM_130842.3 [Q92932-4]
NP_570858.2, NM_130843.3 [Q92932-2]
UniGeneiHs.490789

Genome annotation databases

EnsembliENST00000389413; ENSP00000374064; ENSG00000155093 [Q92932-2]
ENST00000389416; ENSP00000374067; ENSG00000155093 [Q92932-4]
ENST00000389418; ENSP00000374069; ENSG00000155093 [Q92932-1]
GeneIDi5799
KEGGihsa:5799
UCSCiuc003wno.4 human [Q92932-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPTPR2_HUMAN
AccessioniPrimary (citable) accession number: Q92932
Secondary accession number(s): E9PC57
, Q8N4I5, Q92662, Q9Y4F8, Q9Y4I6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 17, 2006
Last modified: June 20, 2018
This is version 167 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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