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Protein

Receptor-type tyrosine-protein phosphatase U

Gene

PTPRU

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Tyrosine-protein phosphatase which dephosphorylates CTNNB1. Regulates CTNNB1 function both in cell adhesion and signaling. May function in cell proliferation and migration and play a role in the maintenance of epithelial integrity. May play a role in megakaryocytopoiesis.3 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1053SubstrateSequence analysis1
Active sitei1085Phosphocysteine intermediateBy similarity1
Binding sitei1129SubstrateBy similarity1
Active sitei1380Phosphocysteine intermediateBy similarity1

GO - Molecular functioni

  • beta-catenin binding Source: UniProtKB
  • protein tyrosine phosphatase activity Source: UniProtKB
  • transmembrane receptor protein tyrosine phosphatase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase, Receptor
Biological processCell adhesion, Differentiation

Enzyme and pathway databases

BRENDAi3.1.3.48 2681
ReactomeiR-HSA-1433557 Signaling by SCF-KIT

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein phosphatase U (EC:3.1.3.48)
Short name:
R-PTP-U
Alternative name(s):
Pancreatic carcinoma phosphatase 2
Short name:
PCP-2
Protein-tyrosine phosphatase J
Short name:
PTP-J
Short name:
hPTP-J
Protein-tyrosine phosphatase pi
Short name:
PTP pi
Protein-tyrosine phosphatase receptor omicron
Short name:
PTP-RO
Receptor-type protein-tyrosine phosphatase psi
Short name:
R-PTP-psi
Gene namesi
Name:PTPRU
Synonyms:FMI, PCP2, PTPRO
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000060656.19
HGNCiHGNC:9683 PTPRU
MIMi602454 gene
neXtProtiNX_Q92729

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 domaini19 – 749ExtracellularSequence analysisAdd BLAST731
Transmembranei750 – 770HelicalSequence analysisAdd BLAST21
Topological domaini771 – 1446CytoplasmicSequence analysisAdd BLAST676

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1085C → S: Loss of phosphatase activity toward CTNNB1. Loss of the inhibitory effect on CTNNB1 transcriptional activity without effect on interaction with CTNNB1; when associated with S-1380. 2 Publications1
Mutagenesisi1380C → S: No effect on phosphatase activity toward CTNNB1. Loss of the inhibitory effect on CTNNB1 transcriptional activity without effect on interaction with CTNNB1; when associated with S-1085. 2 Publications1

Organism-specific databases

DisGeNETi10076
OpenTargetsiENSG00000060656
PharmGKBiPA34028

Chemistry databases

ChEMBLiCHEMBL1961785

Polymorphism and mutation databases

BioMutaiPTPRU
DMDMi229462800

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000037165819 – 1446Receptor-type tyrosine-protein phosphatase UAdd BLAST1428

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi75N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi210 ↔ 264Sequence analysis
Glycosylationi410N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi685N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei848PhosphoserineCombined sources1
Modified residuei853PhosphoserineCombined sources1
Modified residuei863PhosphoserineBy similarity1
Modified residuei865PhosphotyrosineBy similarity1

Post-translational modificationi

The extracellular domain is proteolytically processed through cleavage within the fibronectin type-III 4 domain (By similarity). In addition to the 190 kDa full-length protein, proteolytic products of 100 kDa, 80 kDa and 73 kDa are observed.By similarity1 Publication
N-glycosylated.1 Publication
Phosphorylated on tyrosine residues upon activation of KIT with stem cell factor (SCF). The 73 kDa proteolytic product is not phosphorylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ92729
MaxQBiQ92729
PaxDbiQ92729
PeptideAtlasiQ92729
PRIDEiQ92729
ProteomicsDBi75416
75417 [Q92729-2]
75418 [Q92729-3]
75419 [Q92729-4]

PTM databases

DEPODiQ92729
iPTMnetiQ92729
PhosphoSitePlusiQ92729

Expressioni

Tissue specificityi

High levels in brain, pancreas, and skeletal muscle; less in colon, kidney, liver, stomach, and uterus; not expressed in placenta and spleen. Also detected in heart, prostate, lung, thymus, testis and ovary. Ubiquitously expressed in brain. Expressed by hematopoietic stem cells.4 Publications

Developmental stagei

Expressed in fetal brain, lung and kidney.1 Publication

Inductioni

Up-regulated upon cell contact (at protein level). Down-regulated by phorbol ester (at protein level) and calcium ionophore but up-regulated by phorbol ester in megakaryocytic cells (PubMed:10397721).4 Publications

Gene expression databases

BgeeiENSG00000060656 Expressed in 199 organ(s), highest expression level in epithelium of bronchus
CleanExiHS_PCP2
HS_PTPRU
GenevisibleiQ92729 HS

Organism-specific databases

HPAiCAB011476
HPA039832

Interactioni

Subunit structurei

Forms homooligomeric complexes which mediate cell homotypic adhesion (Probable). Interacts (via the cytoplasmic juxtamembrane domain) with CTNNB1; may mediate interaction with the cadherin/catenin adhesion complex. Interacts with KIT. May interact with AP3B1.Curated4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KITP107212EBI-7052301,EBI-1379503

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115386, 27 interactors
IntActiQ92729, 1 interactor
MINTiQ92729
STRINGi9606.ENSP00000334941

Structurei

3D structure databases

ProteinModelPortaliQ92729
SMRiQ92729
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 188MAMPROSITE-ProRule annotationAdd BLAST164
Domaini190 – 275Ig-like C2-typeAdd BLAST86
Domaini288 – 383Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST96
Domaini386 – 484Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST99
Domaini485 – 591Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST107
Domaini592 – 674Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST83
Domaini888 – 1144Tyrosine-protein phosphatase 1PROSITE-ProRule annotationAdd BLAST257
Domaini1176 – 1439Tyrosine-protein phosphatase 2PROSITE-ProRule annotationAdd BLAST264

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni771 – 887Mediates interaction with CTNNB1By similarityAdd BLAST117
Regioni1085 – 1091Substrate bindingBy similarity7

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4228 Eukaryota
COG5599 LUCA
GeneTreeiENSGT00760000118900
HOVERGENiHBG062785
InParanoidiQ92729
KOiK16662
OMAiASFQCMA
OrthoDBiEOG091G00CK
PhylomeDBiQ92729
TreeFamiTF312900

Family and domain databases

CDDicd00063 FN3, 3 hits
cd06263 MAM, 1 hit
Gene3Di2.60.40.10, 4 hits
3.90.190.10, 2 hits
InterProiView protein in InterPro
IPR013320 ConA-like_dom_sf
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR000998 MAM_dom
IPR029021 Prot-tyrosine_phosphatase-like
IPR000242 PTPase_domain
IPR016130 Tyr_Pase_AS
IPR003595 Tyr_Pase_cat
IPR000387 TYR_PHOSPHATASE_dom
PfamiView protein in Pfam
PF00041 fn3, 2 hits
PF00629 MAM, 1 hit
PF00102 Y_phosphatase, 2 hits
PRINTSiPR00020 MAMDOMAIN
PR00700 PRTYPHPHTASE
SMARTiView protein in SMART
SM00060 FN3, 3 hits
SM00137 MAM, 1 hit
SM00194 PTPc, 2 hits
SM00404 PTPc_motif, 2 hits
SUPFAMiSSF48726 SSF48726, 1 hit
SSF49265 SSF49265, 2 hits
SSF49899 SSF49899, 1 hit
SSF52799 SSF52799, 2 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 3 hits
PS00740 MAM_1, 1 hit
PS50060 MAM_2, 1 hit
PS00383 TYR_PHOSPHATASE_1, 2 hits
PS50056 TYR_PHOSPHATASE_2, 2 hits
PS50055 TYR_PHOSPHATASE_PTP, 2 hits

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: Q92729-1) [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
MARAQALVLA LTFQLCAPET ETPAAGCTFE EASDPAVPCE YSQAQYDDFQ
60 70 80 90 100
WEQVRIHPGT RAPADLPHGS YLMVNTSQHA PGQRAHVIFQ SLSENDTHCV
110 120 130 140 150
QFSYFLYSRD GHSPGTLGVY VRVNGGPLGS AVWNMTGSHG RQWHQAELAV
160 170 180 190 200
STFWPNEYQV LFEALISPDR RGYMGLDDIL LLSYPCAKAP HFSRLGDVEV
210 220 230 240 250
NAGQNASFQC MAAGRAAEAE RFLLQRQSGA LVPAAGVRHI SHRRFLATFP
260 270 280 290 300
LAAVSRAEQD LYRCVSQAPR GAGVSNFAEL IVKEPPTPIA PPQLLRAGPT
310 320 330 340 350
YLIIQLNTNS IIGDGPIVRK EIEYRMARGP WAEVHAVSLQ TYKLWHLDPD
360 370 380 390 400
TEYEISVLLT RPGDGGTGRP GPPLISRTKC AEPMRAPKGL AFAEIQARQL
410 420 430 440 450
TLQWEPLGYN VTRCHTYTVS LCYHYTLGSS HNQTIRECVK TEQGVSRYTI
460 470 480 490 500
KNLLPYRNVH VRLVLTNPEG RKEGKEVTFQ TDEDVPSGIA AESLTFTPLE
510 520 530 540 550
DMIFLKWEEP QEPNGLITQY EISYQSIESS DPAVNVPGPR RTISKLRNET
560 570 580 590 600
YHVFSNLHPG TTYLFSVRAR TGKGFGQAAL TEITTNISAP SFDYADMPSP
610 620 630 640 650
LGESENTITV LLRPAQGRGA PISVYQVIVE EERARRLRRE PGGQDCFPVP
660 670 680 690 700
LTFEAALARG LVHYFGAELA ASSLPEAMPF TVGDNQTYRG FWNPPLEPRK
710 720 730 740 750
AYLIYFQAAS HLKGETRLNC IRIARKAACK ESKRPLEVSQ RSEEMGLILG
760 770 780 790 800
ICAGGLAVLI LLLGAIIVII RKGRDHYAYS YYPKPVNMTK ATVNYRQEKT
810 820 830 840 850
HMMSAVDRSF TDQSTLQEDE RLGLSFMDTH GYSTRGDQRS GGVTEASSLL
860 870 880 890 900
GGSPRRPCGR KGSPYHTGQL HPAVRVADLL QHINQMKTAE GYGFKQEYES
910 920 930 940 950
FFEGWDATKK KDKVKGSRQE PMPAYDRHRV KLHPMLGDPN ADYINANYID
960 970 980 990 1000
GYHRSNHFIA TQGPKPEMVY DFWRMVWQEH CSSIVMITKL VEVGRVKCSR
1010 1020 1030 1040 1050
YWPEDSDTYG DIKIMLVKTE TLAEYVVRTF ALERRGYSAR HEVRQFHFTA
1060 1070 1080 1090 1100
WPEHGVPYHA TGLLAFIRRV KASTPPDAGP IVIHCSAGTG RTGCYIVLDV
1110 1120 1130 1140 1150
MLDMAECEGV VDIYNCVKTL CSRRVNMIQT EEQYIFIHDA ILEACLCGET
1160 1170 1180 1190 1200
TIPVSEFKAT YKEMIRIDPQ SNSSQLREEF QTLNSVTPPL DVEECSIALL
1210 1220 1230 1240 1250
PRNRDKNRSM DVLPPDRCLP FLISTDGDSN NYINAALTDS YTRSAAFIVT
1260 1270 1280 1290 1300
LHPLQSTTPD FWRLVYDYGC TSIVMLNQLN QSNSAWPCLQ YWPEPGRQQY
1310 1320 1330 1340 1350
GLMEVEFMSG TADEDLVARV FRVQNISRLQ EGHLLVRHFQ FLRWSAYRDT
1360 1370 1380 1390 1400
PDSKKAFLHL LAEVDKWQAE SGDGRTIVHC LNGGGRSGTF CACATVLEMI
1410 1420 1430 1440
RCHNLVDVFF AAKTLRNYKP NMVETMDQYH FCYDVALEYL EGLESR
Length:1,446
Mass (Da):162,423
Last modified:May 5, 2009 - v2
Checksum:i76F9BD6EFABE8663
GO
Isoform 2 (identifier: Q92729-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     774-783: Missing.

Show »
Length:1,436
Mass (Da):161,107
Checksum:iF88BB75170BF3676
GO
Isoform 3 (identifier: Q92729-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     774-783: Missing.
     993-995: Missing.

Show »
Length:1,433
Mass (Da):160,795
Checksum:iBA085FF7C36BB2A8
GO
Isoform 4 (identifier: Q92729-4) [UniParc]FASTAAdd to basket
Also known as: PTPRO

The sequence of this isoform differs from the canonical sequence as follows:
     774-783: Missing.
     950-950: D → DIRINRE
     1329-1330: Missing.

Note: No experimental confirmation available.
Show »
Length:1,440
Mass (Da):161,648
Checksum:iEDE5C3CF8C8C9DA0
GO

Sequence cautioni

The sequence CAA65016 differs from that shown. Several sequencing problems.Curated
The sequence CAA65832 differs from that shown. Several sequencing problems.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti359 – 360LT → S in AAC51938 (PubMed:9434160).Curated2
Sequence conflicti401T → A in AAC51938 (PubMed:9434160).Curated1
Sequence conflicti715E → D in AAB51343 (PubMed:9070223).Curated1
Sequence conflicti840 – 841SG → GW in AAC51938 (PubMed:9434160).Curated2
Sequence conflicti1215P → A in AAB07074 (Ref. 5) Curated1
Sequence conflicti1245A → R in AAC51938 (PubMed:9434160).Curated1
Sequence conflicti1399M → I in AAC51938 (PubMed:9434160).Curated1
Sequence conflicti1436A → V in AAB07074 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05507560T → N. Corresponds to variant dbSNP:rs35332573Ensembl.1
Natural variantiVAR_055076471R → L. Corresponds to variant dbSNP:rs35745442Ensembl.1
Natural variantiVAR_035650830H → Y in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_035651835R → W in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs558954146Ensembl.1
Natural variantiVAR_035652856R → C in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs763868325Ensembl.1
Natural variantiVAR_055077940N → S. Corresponds to variant dbSNP:rs2235937Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_037082774 – 783Missing in isoform 2, isoform 3 and isoform 4. 5 Publications10
Alternative sequenceiVSP_037083950D → DIRINRE in isoform 4. 1 Publication1
Alternative sequenceiVSP_037084993 – 995Missing in isoform 3. 1 Publication3
Alternative sequenceiVSP_0370851329 – 1330Missing in isoform 4. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X95712 mRNA Translation: CAA65016.1 Sequence problems.
X97198 mRNA Translation: CAA65832.1 Sequence problems.
U73727 mRNA Translation: AAB51343.1
U71075 mRNA Translation: AAC51938.1
U60289 Genomic DNA Translation: AAB07074.1
AL645859 Genomic DNA No translation available.
AL590729 Genomic DNA No translation available.
AL049570 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07651.1
CH471059 Genomic DNA Translation: EAX07652.1
BC146655 mRNA Translation: AAI46656.1
AB208855 mRNA Translation: BAD92092.1
CCDSiCCDS334.1 [Q92729-1]
CCDS335.1 [Q92729-2]
CCDS44098.2 [Q92729-4]
CCDS53290.1 [Q92729-3]
PIRiJC5290
S72441
RefSeqiNP_001181930.1, NM_001195001.1 [Q92729-3]
NP_005695.3, NM_005704.4 [Q92729-1]
NP_573438.3, NM_133177.3 [Q92729-4]
NP_573439.2, NM_133178.3 [Q92729-2]
UniGeneiHs.19718

Genome annotation databases

EnsembliENST00000345512; ENSP00000334941; ENSG00000060656 [Q92729-1]
ENST00000373779; ENSP00000362884; ENSG00000060656 [Q92729-2]
ENST00000428026; ENSP00000392332; ENSG00000060656 [Q92729-3]
ENST00000460170; ENSP00000432906; ENSG00000060656 [Q92729-4]
GeneIDi10076
KEGGihsa:10076
UCSCiuc001bru.4 human [Q92729-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPTPRU_HUMAN
AccessioniPrimary (citable) accession number: Q92729
Secondary accession number(s): A6H8L1
, O00197, P78399, Q59HA4, Q5SYU4, Q5SYU5, Q92735, Q92850
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 5, 2009
Last modified: September 12, 2018
This is version 179 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

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

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