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Protein

Receptor-type tyrosine-protein phosphatase H

Gene

PTPRH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protein phosphatase that may contribute to contact inhibition of cell growth and motility by mediating the dephosphorylation of focal adhesion-associated substrates and thus negatively regulating integrin-promoted signaling processes. Induces apoptotic cell death by at least two distinct mechanisms: inhibition of cell survival signaling mediated by PI 3-kinase, Akt, and ILK and activation of a caspase-dependent proapoptotic pathway. Inhibits the basal activity of LCK and its activation in response to TCR stimulation and TCR-induced activation of MAP kinase and surface expression of CD69. Inhibits TCR-induced tyrosine phosphorylation of LAT and ZAP70. Inhibits both basal activity of DOK1 and its CD2-induced tyrosine phosphorylation. Induces dephosphorylation of BCAR1, focal adhesion kinase and SRC. Reduces migratory activity of activity of Jurkat cells. Reduces tyrosine phosphorylation of CEACAM20 and thereby contributes to suppress the intestinal immune response CEACAM20 (By similarity).By similarity4 Publications

Catalytic activityi

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

Enzyme regulationi

Regulated by reversible dimerization. Dimerization reduces its catalytic activity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1020Phosphocysteine intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • transmembrane receptor protein tyrosine phosphatase activity Source: ProtInc

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • protein dephosphorylation Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BioCyciZFISH:HS01346-MONOMER.
BRENDAi3.1.3.48. 2681.
SIGNORiQ9HD43.

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein phosphatase H (EC:3.1.3.48)
Short name:
R-PTP-H
Alternative name(s):
Stomach cancer-associated protein tyrosine phosphatase 1
Short name:
SAP-1
Transmembrane-type protein-tyrosine phosphatase type H
Gene namesi
Name:PTPRH
Synonyms:SAP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:9672. PTPRH.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 754ExtracellularSequence analysisAdd BLAST727
Transmembranei755 – 775HelicalSequence analysisAdd BLAST21
Topological domaini776 – 1115CytoplasmicSequence analysisAdd BLAST340

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi986D → A: Loss of activity. Acts as a dominant negative mutant. 1 Publication1
Mutagenesisi1020C → S: Loss of activity. No induction of apoptosis. 2 Publications1

Organism-specific databases

DisGeNETi5794.
PharmGKBiPA34017.

Polymorphism and mutation databases

BioMutaiPTPRH.
DMDMi296452983.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000031895028 – 1115Receptor-type tyrosine-protein phosphatase HAdd BLAST1088

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi35N-linked (GlcNAc...)Sequence analysis1
Glycosylationi83N-linked (GlcNAc...)Sequence analysis1
Glycosylationi172N-linked (GlcNAc...)Sequence analysis1
Glycosylationi256N-linked (GlcNAc...)Sequence analysis1
Glycosylationi285N-linked (GlcNAc...)Sequence analysis1
Glycosylationi350N-linked (GlcNAc...)Sequence analysis1
Glycosylationi434N-linked (GlcNAc...)Sequence analysis1
Glycosylationi468N-linked (GlcNAc...)Sequence analysis1
Glycosylationi556N-linked (GlcNAc...)Sequence analysis1
Glycosylationi642N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9HD43.
PaxDbiQ9HD43.
PeptideAtlasiQ9HD43.
PRIDEiQ9HD43.

PTM databases

DEPODiQ9HD43.
iPTMnetiQ9HD43.
PhosphoSitePlusiQ9HD43.

Expressioni

Tissue specificityi

Expressed at high levels in the brain, spleen and liver and at lower levels in the heart and stomach. Expressed in pancreatic and colorectal cancer cells, but not in normal pancreas or colon. Expression in hepatocellular carcinoma is related to the differentiation status of the tumor and expression is inversely related to tumor aggressiveness.3 Publications

Inductioni

Induced at the early stage of hepatocellular carcinoma and is suppressed at later stages.1 Publication

Gene expression databases

BgeeiENSG00000080031.
CleanExiHS_PTPRH.
GenevisibleiQ9HD43. HS.

Organism-specific databases

HPAiHPA042300.

Interactioni

Subunit structurei

Homodimer; disulfide-linked (Probable). Interacts with LCK (PubMed:12837766). Interacts (phosphorylated form) with GRB2 (via SH2 domain) (By similarity). Interacts (phosphorylated form) with FYN (via SH2 domain) (By similarity). Interacts (via extracellular domain) with CEACAM20 (via extracellular domain); the interaction dephosphorylates CEACAM20 (By similarity).By similarity1 Publication1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
DHPSP493663EBI-1267176,EBI-741925
GHRP109124EBI-1267176,EBI-286316
KRTAP10-8P604103EBI-1267176,EBI-10171774

Protein-protein interaction databases

IntActiQ9HD43. 6 interactors.
MINTiMINT-1349530.
STRINGi9606.ENSP00000365528.

Structurei

3D structure databases

ProteinModelPortaliQ9HD43.
SMRiQ9HD43.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 121Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST90
Domaini122 – 209Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST88
Domaini210 – 299Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST90
Domaini300 – 387Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST88
Domaini388 – 477Fibronectin type-III 5PROSITE-ProRule annotationAdd BLAST90
Domaini478 – 563Fibronectin type-III 6PROSITE-ProRule annotationAdd BLAST86
Domaini564 – 666Fibronectin type-III 7PROSITE-ProRule annotationAdd BLAST103
Domaini665 – 749Fibronectin type-III 8PROSITE-ProRule annotationAdd BLAST85
Domaini820 – 1079Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST260

Domaini

The extracellular domain mediates homodimerization. One or more cysteines in the extracellular domain is essential for the formation of dimers probably by forming a disulfide bond.
The cytoplasmic domain mediates the interaction with LCK.

Sequence similaritiesi

Contains 8 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0791. Eukaryota.
COG5599. LUCA.
HOGENOMiHOG000170539.
HOVERGENiHBG108307.
InParanoidiQ9HD43.
OrthoDBiEOG091G08FR.
PhylomeDBiQ9HD43.
TreeFamiTF351926.

Family and domain databases

CDDicd00063. FN3. 7 hits.
Gene3Di2.60.40.10. 7 hits.
3.90.190.10. 1 hit.
InterProiIPR003961. FN3_dom.
IPR013783. Ig-like_fold.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR028855. R-PTP-H.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PANTHERiPTHR19134:SF297. PTHR19134:SF297. 2 hits.
PfamiPF00041. fn3. 6 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00060. FN3. 7 hits.
SM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
SSF52799. SSF52799. 1 hit.
PROSITEiPS50853. FN3. 7 hits.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9HD43-1) [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
MAGAGGGLGV WGNLVLLGLC SWTGARAPAP NPGRNLTVET QTTSSISLSW
60 70 80 90 100
EVPDGLDSQN SNYWVQCTGD GGTTETRNTT ATNVTVDGLG PGSLYTCSVW
110 120 130 140 150
VEKDGVNSSV GTVTTATAPN PVRNLRVEAQ TNSSIALTWE VPDGPDPQNS
160 170 180 190 200
TYGVEYTGDG GRAGTRSTAH TNITVDGLEP GCLYAFSMWV GKNGINSSRE
210 220 230 240 250
TRNATTAHNP VRNLRVEAQT TSSISLSWEV PDGTDPQNST YCVQCTGDGG
260 270 280 290 300
RTETRNTTDT RVTVDGLGPG SLYTCSVWVE KDGVNSSVEI VTSATAPNPV
310 320 330 340 350
RNLTVEAQTN SSIALTWEVP DGPDPQNSTY GVEYTGDGGR AGTRSTAHTN
360 370 380 390 400
ITVDRLEPGC LYVFSVWVGK NGINSSRETR NATTAPNPVR NLHMETQTNS
410 420 430 440 450
SIALCWEVPD GPYPQDYTYW VEYTGDGGGT ETRNTTNTSV TAERLEPGTL
460 470 480 490 500
YTFSVWAEKN GARGSRQNVS ISTVPNAVTS LSKQDWTNST IALRWTAPQG
510 520 530 540 550
PGQSSYSYWV SWVREGMTDP RTQSTSGTDI TLKELEAGSL YHLTVWAERN
560 570 580 590 600
EVRGYNSTLT AATAPNEVTD LQNETQTKNS VMLWWKAPGD PHSQLYVYWV
610 620 630 640 650
QWASKGHPRR GQDPQANWVN QTSRTNETWY KVEALEPGTL YNFTVWAERN
660 670 680 690 700
DVASSTQSLC ASTYPDTVTI TSCVSTSAGY GVNLIWSCPQ GGYEAFELEV
710 720 730 740 750
GGQRGSQDRS SCGEAVSVLG LGPARSYPAT ITTIWDGMKV VSHSVVCHTE
760 770 780 790 800
SAGVIAGAFV GILLFLILVG LLIFFLKRRN KKKQQKPELR DLVFSSPGDI
810 820 830 840 850
PAEDFADHVR KNERDSNCGF ADKYQQLSLV GHSQSQMVAS ASENNAKNRY
860 870 880 890 900
RNVLPYDWSR VPLKPIHEEP GSDYINASFM PGLWSPQEFI ATQGPLPQTV
910 920 930 940 950
GDFWRLVWEQ QSHTLVMLTN CMEAGRVKCE HYWPLDSQPC THGHLRVTLV
960 970 980 990 1000
GEEVMENWTV RELLLLQVEE QKTLSVRQFH YQAWPDHGVP SSPDTLLAFW
1010 1020 1030 1040 1050
RMLRQWLDQT MEGGPPIVHC SAGVGRTGTL IALDVLLRQL QSEGLLGPFS
1060 1070 1080 1090 1100
FVRKMRESRP LMVQTEAQYV FLHQCILRFL QQSAQAPAEK EVPYEDVENL
1110
IYENVAAIQA HKLEV
Length:1,115
Mass (Da):122,352
Last modified:May 18, 2010 - v3
Checksum:iA7A1AB24CFCD3846
GO
Isoform 2 (identifier: Q9HD43-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     84-261: Missing.

Show »
Length:937
Mass (Da):103,483
Checksum:i5E579E14580244FF
GO
Isoform 3 (identifier: Q9HD43-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     126-303: Missing.

Show »
Length:937
Mass (Da):103,412
Checksum:iA444EEE28EA7324C
GO

Sequence cautioni

The sequence BAA03645 differs from that shown. Reason: Frameshift at positions 213, 244, 264, 287 and 291.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti294A → T in BAA03645 (PubMed:8294459).Curated1
Sequence conflicti422E → G in BAA03645 (PubMed:8294459).Curated1
Sequence conflicti951G → D in AAI11716 (PubMed:15489334).Curated1
Sequence conflicti1109Q → K in AAI11716 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_061762232D → N.Corresponds to variant rs55870162dbSNPEnsembl.1
Natural variantiVAR_061763243V → I.Corresponds to variant rs45535035dbSNPEnsembl.1
Natural variantiVAR_038918348H → Y.1 PublicationCorresponds to variant rs2288515dbSNPEnsembl.1
Natural variantiVAR_038919543L → F.Corresponds to variant rs16986309dbSNPEnsembl.1
Natural variantiVAR_038920781K → N.Corresponds to variant rs2288523dbSNPEnsembl.1
Natural variantiVAR_038921823K → E.2 PublicationsCorresponds to variant rs890870dbSNPEnsembl.1
Natural variantiVAR_061764831G → D.Corresponds to variant rs36092369dbSNPEnsembl.1
Natural variantiVAR_0389221076I → V.Corresponds to variant rs2288419dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03131884 – 261Missing in isoform 2. 1 PublicationAdd BLAST178
Alternative sequenceiVSP_054222126 – 303Missing in isoform 3. CuratedAdd BLAST178

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D15049 mRNA. Translation: BAA03645.2. Frameshift.
AF275150
, AF275131, AF275132, AF275133, AF275134, AF275135, AF275136, AF275137, AF275138, AF275139, AF275140, AF275141, AF275142, AF275143, AF275144, AF275145, AF275146, AF275147, AF275148, AF275149 Genomic DNA. Translation: AAF91411.1.
AC010327 Genomic DNA. No translation available.
BC111715 mRNA. Translation: AAI11716.1.
BC111716 mRNA. Translation: AAI11717.1.
CCDSiCCDS33110.1. [Q9HD43-1]
CCDS54321.1. [Q9HD43-3]
PIRiA49724.
UniGeneiHs.179770.

Genome annotation databases

EnsembliENST00000263434; ENSP00000263434; ENSG00000080031.
ENST00000376350; ENSP00000365528; ENSG00000080031.
UCSCiuc002qjq.4. human. [Q9HD43-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D15049 mRNA. Translation: BAA03645.2. Frameshift.
AF275150
, AF275131, AF275132, AF275133, AF275134, AF275135, AF275136, AF275137, AF275138, AF275139, AF275140, AF275141, AF275142, AF275143, AF275144, AF275145, AF275146, AF275147, AF275148, AF275149 Genomic DNA. Translation: AAF91411.1.
AC010327 Genomic DNA. No translation available.
BC111715 mRNA. Translation: AAI11716.1.
BC111716 mRNA. Translation: AAI11717.1.
CCDSiCCDS33110.1. [Q9HD43-1]
CCDS54321.1. [Q9HD43-3]
PIRiA49724.
UniGeneiHs.179770.

3D structure databases

ProteinModelPortaliQ9HD43.
SMRiQ9HD43.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9HD43. 6 interactors.
MINTiMINT-1349530.
STRINGi9606.ENSP00000365528.

PTM databases

DEPODiQ9HD43.
iPTMnetiQ9HD43.
PhosphoSitePlusiQ9HD43.

Polymorphism and mutation databases

BioMutaiPTPRH.
DMDMi296452983.

Proteomic databases

MaxQBiQ9HD43.
PaxDbiQ9HD43.
PeptideAtlasiQ9HD43.
PRIDEiQ9HD43.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263434; ENSP00000263434; ENSG00000080031.
ENST00000376350; ENSP00000365528; ENSG00000080031.
UCSCiuc002qjq.4. human. [Q9HD43-1]

Organism-specific databases

DisGeNETi5794.
GeneCardsiPTPRH.
HGNCiHGNC:9672. PTPRH.
HPAiHPA042300.
MIMi602510. gene.
neXtProtiNX_Q9HD43.
PharmGKBiPA34017.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0791. Eukaryota.
COG5599. LUCA.
HOGENOMiHOG000170539.
HOVERGENiHBG108307.
InParanoidiQ9HD43.
OrthoDBiEOG091G08FR.
PhylomeDBiQ9HD43.
TreeFamiTF351926.

Enzyme and pathway databases

BioCyciZFISH:HS01346-MONOMER.
BRENDAi3.1.3.48. 2681.
SIGNORiQ9HD43.

Miscellaneous databases

PROiQ9HD43.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000080031.
CleanExiHS_PTPRH.
GenevisibleiQ9HD43. HS.

Family and domain databases

CDDicd00063. FN3. 7 hits.
Gene3Di2.60.40.10. 7 hits.
3.90.190.10. 1 hit.
InterProiIPR003961. FN3_dom.
IPR013783. Ig-like_fold.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR028855. R-PTP-H.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PANTHERiPTHR19134:SF297. PTHR19134:SF297. 2 hits.
PfamiPF00041. fn3. 6 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00060. FN3. 7 hits.
SM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
SSF52799. SSF52799. 1 hit.
PROSITEiPS50853. FN3. 7 hits.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTPRH_HUMAN
AccessioniPrimary (citable) accession number: Q9HD43
Secondary accession number(s): C9JCH2
, Q15426, Q2NKN9, Q2NKP0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 130 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. 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.