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Q9HD43 (PTPRH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Receptor-type tyrosine-protein phosphatase H

Short name=R-PTP-H
EC=3.1.3.48
Alternative name(s):
Stomach cancer-associated protein tyrosine phosphatase 1
Short name=SAP-1
Transmembrane-type protein-tyrosine phosphatase type H
Gene names
Name:PTPRH
Synonyms:SAP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1115 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 p130cas, focal adhesion kinase and c-Src. Reduces migratory activity of Jurkat cells. Ref.5 Ref.6 Ref.7 Ref.9

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Enzyme regulation

Regulated by reversible dimerization. Dimerization reduces its catalytic activity. Ref.9

Subunit structure

Homodimer; disulfide-linked Probable. Interacts with LCK. Ref.7 Ref.9

Subcellular location

Membrane; Single-pass type I membrane protein Potential. Cytoplasm Ref.8.

Tissue specificity

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. Ref.1 Ref.7 Ref.8

Induction

Induced at the early stage of hepatocellular carcinoma and is suppressed at later stages. Ref.8 Ref.9

Domain

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. Ref.7 Ref.9

The cytoplasmic domain mediates the interaction with LCK. Ref.7 Ref.9

Sequence similarities

Belongs to the protein-tyrosine phosphatase family. Receptor class 3 subfamily.

Contains 8 fibronectin type-III domains.

Contains 1 tyrosine-protein phosphatase domain.

Sequence caution

The sequence BAA03645.2 differs from that shown. Reason: Frameshift at positions 213, 244, 264, 287 and 291.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GHRP109124EBI-1267176,EBI-286316

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HD43-1)

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.
Isoform 2 (identifier: Q9HD43-2)

The sequence of this isoform differs from the canonical sequence as follows:
     84-261: Missing.
Isoform 3 (identifier: Q9HD43-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 11151088Receptor-type tyrosine-protein phosphatase H
PRO_0000318950

Regions

Topological domain28 – 754727Extracellular Potential
Transmembrane755 – 77521Helical; Potential
Topological domain776 – 1115340Cytoplasmic Potential
Domain32 – 12190Fibronectin type-III 1
Domain122 – 20988Fibronectin type-III 2
Domain210 – 29990Fibronectin type-III 3
Domain300 – 38788Fibronectin type-III 4
Domain388 – 47790Fibronectin type-III 5
Domain478 – 56386Fibronectin type-III 6
Domain564 – 666103Fibronectin type-III 7
Domain665 – 74985Fibronectin type-III 8
Domain820 – 1079260Tyrosine-protein phosphatase

Sites

Active site10201Phosphocysteine intermediate By similarity

Amino acid modifications

Glycosylation351N-linked (GlcNAc...) Potential
Glycosylation831N-linked (GlcNAc...) Potential
Glycosylation1721N-linked (GlcNAc...) Potential
Glycosylation2561N-linked (GlcNAc...) Potential
Glycosylation2851N-linked (GlcNAc...) Potential
Glycosylation3501N-linked (GlcNAc...) Potential
Glycosylation4341N-linked (GlcNAc...) Potential
Glycosylation4681N-linked (GlcNAc...) Potential
Glycosylation5561N-linked (GlcNAc...) Potential
Glycosylation6421N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence84 – 261178Missing in isoform 2.
VSP_031318
Alternative sequence126 – 303178Missing in isoform 3.
VSP_054222
Natural variant2321D → N.
Corresponds to variant rs55870162 [ dbSNP | Ensembl ].
VAR_061762
Natural variant2431V → I.
Corresponds to variant rs45535035 [ dbSNP | Ensembl ].
VAR_061763
Natural variant3481H → Y. Ref.4
Corresponds to variant rs2288515 [ dbSNP | Ensembl ].
VAR_038918
Natural variant5431L → F.
Corresponds to variant rs16986309 [ dbSNP | Ensembl ].
VAR_038919
Natural variant7811K → N.
Corresponds to variant rs2288523 [ dbSNP | Ensembl ].
VAR_038920
Natural variant8231K → E. Ref.1 Ref.4
Corresponds to variant rs890870 [ dbSNP | Ensembl ].
VAR_038921
Natural variant8311G → D.
Corresponds to variant rs36092369 [ dbSNP | Ensembl ].
VAR_061764
Natural variant10761I → V.
Corresponds to variant rs2288419 [ dbSNP | Ensembl ].
VAR_038922

Experimental info

Mutagenesis9861D → A: Loss of activity. Acts as a dominant negative mutant. Ref.5
Mutagenesis10201C → S: Loss of activity. No induction of apoptosis. Ref.5 Ref.6
Sequence conflict2941A → T in BAA03645. Ref.1
Sequence conflict4221E → G in BAA03645. Ref.1
Sequence conflict9511G → D in AAI11716. Ref.4
Sequence conflict11091Q → K in AAI11716. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: A7A1AB24CFCD3846

FASTA1,115122,352
        10         20         30         40         50         60 
MAGAGGGLGV WGNLVLLGLC SWTGARAPAP NPGRNLTVET QTTSSISLSW EVPDGLDSQN 

        70         80         90        100        110        120 
SNYWVQCTGD GGTTETRNTT ATNVTVDGLG PGSLYTCSVW VEKDGVNSSV GTVTTATAPN 

       130        140        150        160        170        180 
PVRNLRVEAQ TNSSIALTWE VPDGPDPQNS TYGVEYTGDG GRAGTRSTAH TNITVDGLEP 

       190        200        210        220        230        240 
GCLYAFSMWV GKNGINSSRE TRNATTAHNP VRNLRVEAQT TSSISLSWEV PDGTDPQNST 

       250        260        270        280        290        300 
YCVQCTGDGG RTETRNTTDT RVTVDGLGPG SLYTCSVWVE KDGVNSSVEI VTSATAPNPV 

       310        320        330        340        350        360 
RNLTVEAQTN SSIALTWEVP DGPDPQNSTY GVEYTGDGGR AGTRSTAHTN ITVDRLEPGC 

       370        380        390        400        410        420 
LYVFSVWVGK NGINSSRETR NATTAPNPVR NLHMETQTNS SIALCWEVPD GPYPQDYTYW 

       430        440        450        460        470        480 
VEYTGDGGGT ETRNTTNTSV TAERLEPGTL YTFSVWAEKN GARGSRQNVS ISTVPNAVTS 

       490        500        510        520        530        540 
LSKQDWTNST IALRWTAPQG PGQSSYSYWV SWVREGMTDP RTQSTSGTDI TLKELEAGSL 

       550        560        570        580        590        600 
YHLTVWAERN EVRGYNSTLT AATAPNEVTD LQNETQTKNS VMLWWKAPGD PHSQLYVYWV 

       610        620        630        640        650        660 
QWASKGHPRR GQDPQANWVN QTSRTNETWY KVEALEPGTL YNFTVWAERN DVASSTQSLC 

       670        680        690        700        710        720 
ASTYPDTVTI TSCVSTSAGY GVNLIWSCPQ GGYEAFELEV GGQRGSQDRS SCGEAVSVLG 

       730        740        750        760        770        780 
LGPARSYPAT ITTIWDGMKV VSHSVVCHTE SAGVIAGAFV GILLFLILVG LLIFFLKRRN 

       790        800        810        820        830        840 
KKKQQKPELR DLVFSSPGDI PAEDFADHVR KNERDSNCGF ADKYQQLSLV GHSQSQMVAS 

       850        860        870        880        890        900 
ASENNAKNRY RNVLPYDWSR VPLKPIHEEP GSDYINASFM PGLWSPQEFI ATQGPLPQTV 

       910        920        930        940        950        960 
GDFWRLVWEQ QSHTLVMLTN CMEAGRVKCE HYWPLDSQPC THGHLRVTLV GEEVMENWTV 

       970        980        990       1000       1010       1020 
RELLLLQVEE QKTLSVRQFH YQAWPDHGVP SSPDTLLAFW RMLRQWLDQT MEGGPPIVHC 

      1030       1040       1050       1060       1070       1080 
SAGVGRTGTL IALDVLLRQL QSEGLLGPFS FVRKMRESRP LMVQTEAQYV FLHQCILRFL 

      1090       1100       1110 
QQSAQAPAEK EVPYEDVENL IYENVAAIQA HKLEV 

« Hide

Isoform 2 [UniParc].

Checksum: 5E579E14580244FF
Show »

FASTA937103,483
Isoform 3 [UniParc].

Checksum: A444EEE28EA7324C
Show »

FASTA937103,412

References

« Hide 'large scale' references
[1]"Molecular cloning of a human transmembrane-type protein tyrosine phosphatase and its expression in gastrointestinal cancers."
Matozaki T., Suzuki T., Uchida T., Inazawa J., Ariyama T., Matsuda K., Horita K., Noguchi H., Mizuno H., Sakamoto C., Kasuga M.
J. Biol. Chem. 269:2075-2081(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT GLU-823.
[2]"Gene for the human transmembrane-type protein tyrosine phosphatase H (PTPRH): genomic structure, fine-mapping and its exclusion as a candidate for Peutz-Jeghers syndrome."
Marneros A.G., Mehenni H., Reichenberger E., Antonarakis S.E., Krieg T., Olsen B.R.
Cytogenet. Cell Genet. 92:213-216(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS TYR-348 AND GLU-823.
[5]"Inhibition of cell growth and spreading by stomach cancer-associated protein-tyrosine phosphatase-1 (SAP-1) through dephosphorylation of p130cas."
Noguchi T., Tsuda M., Takeda H., Takada T., Inagaki K., Yamao T., Fukunaga K., Matozaki T., Kasuga M.
J. Biol. Chem. 276:15216-15224(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-986 AND CYS-1020.
[6]"Induction of apoptosis by stomach cancer-associated protein-tyrosine phosphatase-1."
Takada T., Noguchi T., Inagaki K., Hosooka T., Fukunaga K., Yamao T., Ogawa W., Matozaki T., Kasuga M.
J. Biol. Chem. 277:34359-34366(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-1020.
[7]"Interaction of SAP-1, a transmembrane-type protein-tyrosine phosphatase, with the tyrosine kinase Lck. Roles in regulation of T cell function."
Ito T., Okazawa H., Maruyama K., Tomizawa K., Motegi S., Ohnishi H., Kuwano H., Kosugi A., Matozaki T.
J. Biol. Chem. 278:34854-34863(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN, TISSUE SPECIFICITY, INTERACTION WITH LCK.
[8]"Downregulation of stomach cancer-associated protein tyrosine phosphatase-1 (SAP-1) in advanced human hepatocellular carcinoma."
Nagano H., Noguchi T., Inagaki K., Yoon S., Matozaki T., Itoh H., Kasuga M., Hayashi Y.
Oncogene 22:4656-4663(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
[9]"Sap-1/PTPRH activity is regulated by reversible dimerization."
Waelchli S., Espanel X., Hooft van Huijsduijnen R.
Biochem. Biophys. Res. Commun. 331:497-502(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, ENZYME REGULATION, DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D15049 mRNA. Translation: BAA03645.2. Frameshift.
AF275150 expand/collapse EMBL AC list , 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.
PIRA49724.
UniGeneHs.179770.

3D structure databases

ProteinModelPortalQ9HD43.
SMRQ9HD43. Positions 28-561, 569-651, 800-1081.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111758. 4 interactions.
IntActQ9HD43. 5 interactions.
MINTMINT-1349530.
STRING9606.ENSP00000365528.

PTM databases

PhosphoSiteQ9HD43.

Polymorphism databases

DMDM296452983.

Proteomic databases

PaxDbQ9HD43.
PRIDEQ9HD43.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263434; ENSP00000263434; ENSG00000080031.
ENST00000376350; ENSP00000365528; ENSG00000080031. [Q9HD43-1]
KEGGhsa:5794.
UCSCuc002qjq.3. human. [Q9HD43-1]

Organism-specific databases

CTD5794.
GeneCardsGC19M055692.
HGNCHGNC:9672. PTPRH.
HPAHPA042300.
MIM602510. gene.
neXtProtNX_Q9HD43.
PharmGKBPA34017.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5599.
HOGENOMHOG000170539.
HOVERGENHBG108307.
InParanoidQ9HD43.
KOK18034.
OMAFSVWAEK.
OrthoDBEOG7PCJFZ.
PhylomeDBQ9HD43.
TreeFamTF351926.

Gene expression databases

ArrayExpressQ9HD43.
BgeeQ9HD43.
CleanExHS_PTPRH.
GenevestigatorQ9HD43.

Family and domain databases

Gene3D2.60.40.10. 7 hits.
3.90.190.10. 1 hit.
InterProIPR003961. Fibronectin_type3.
IPR013783. Ig-like_fold.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR028855. R-PTP-H.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PANTHERPTHR19134:SF254. PTHR19134:SF254. 1 hit.
PfamPF00041. fn3. 7 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PRINTSPR00700. PRTYPHPHTASE.
SMARTSM00060. FN3. 7 hits.
SM00194. PTPc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 4 hits.
SSF52799. SSF52799. 1 hit.
PROSITEPS50853. FN3. 7 hits.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPTPRH.
GenomeRNAi5794.
NextBio22560.
PROQ9HD43.
SOURCESearch...

Entry information

Entry namePTPRH_HUMAN
AccessionPrimary (citable) accession number: Q9HD43
Secondary accession number(s): C9JCH2 expand/collapse secondary AC list , Q15426, Q2NKN9, Q2NKP0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 109 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM