Q9HD43 (PTPRH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1115 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Hydrolase Protein phosphatase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc mitochondrion Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	transmembrane receptor protein tyrosine phosphatase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GHR	P10912	4	EBI-1267176,EBI-286316

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 1115	1088	Receptor-type tyrosine-protein phosphatase H		PRO_0000318950
Regions
	Topological domain	28 – 754	727	Extracellular Potential
	Transmembrane	755 – 775	21	Helical; Potential
	Topological domain	776 – 1115	340	Cytoplasmic Potential
	Domain	30 – 117	88	Fibronectin type-III 1
	Domain	119 – 206	88	Fibronectin type-III 2
	Domain	207 – 296	90	Fibronectin type-III 3
	Domain	297 – 384	88	Fibronectin type-III 4
	Domain	386 – 473	88	Fibronectin type-III 5
	Domain	475 – 563	89	Fibronectin type-III 6
	Domain	565 – 663	99	Fibronectin type-III 7
	Domain	665 – 749	85	Fibronectin type-III 8
	Domain	820 – 1079	260	Tyrosine-protein phosphatase
Sites
	Active site	1020	1	Phosphocysteine intermediate By similarity
Amino acid modifications
	Glycosylation	35	1	N-linked (GlcNAc...) Potential
	Glycosylation	83	1	N-linked (GlcNAc...) Potential
	Glycosylation	172	1	N-linked (GlcNAc...) Potential
	Glycosylation	256	1	N-linked (GlcNAc...) Potential
	Glycosylation	285	1	N-linked (GlcNAc...) Potential
	Glycosylation	350	1	N-linked (GlcNAc...) Potential
	Glycosylation	434	1	N-linked (GlcNAc...) Potential
	Glycosylation	468	1	N-linked (GlcNAc...) Potential
	Glycosylation	556	1	N-linked (GlcNAc...) Potential
	Glycosylation	642	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	84 – 261	178	Missing in isoform 2.		VSP_031318
	Natural variant	232	1	D → N. Corresponds to variant rs55870162 [ dbSNP | Ensembl ].		VAR_061762
	Natural variant	243	1	V → I. Corresponds to variant rs45535035 [ dbSNP | Ensembl ].		VAR_061763
	Natural variant	348	1	H → Y. Ref.4 Corresponds to variant rs2288515 [ dbSNP | Ensembl ].		VAR_038918
	Natural variant	543	1	L → F. Corresponds to variant rs16986309 [ dbSNP | Ensembl ].		VAR_038919
	Natural variant	781	1	K → N. Corresponds to variant rs2288523 [ dbSNP | Ensembl ].		VAR_038920
	Natural variant	823	1	K → E. Ref.1 Ref.4 Corresponds to variant rs890870 [ dbSNP | Ensembl ].		VAR_038921
	Natural variant	831	1	G → D. Corresponds to variant rs36092369 [ dbSNP | Ensembl ].		VAR_061764
	Natural variant	1076	1	I → V. Corresponds to variant rs2288419 [ dbSNP | Ensembl ].		VAR_038922
Experimental info
	Mutagenesis	986	1	D → A: Loss of activity. Acts as a dominant negative mutant. Ref.5
	Mutagenesis	1020	1	C → S: Loss of activity. No induction of apoptosis. Ref.5 Ref.6
	Sequence conflict	294	1	A → T in BAA03645. Ref.1
	Sequence conflict	422	1	E → G in BAA03645. Ref.1
	Sequence conflict	951	1	G → D in AAI11716. Ref.4
	Sequence conflict	1109	1	Q → K in AAI11716. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: A7A1AB24CFCD3846	FASTA	1,115	122,352
	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
	Isoform 2 [UniParc]. Checksum: 5E579E14580244FF	FASTA	937	103,483
	10 20 30 40 50 60 MAGAGGGLGV WGNLVLLGLC SWTGARAPAP NPGRNLTVET QTTSSISLSW EVPDGLDSQN 70 80 90 100 110 120 SNYWVQCTGD GGTTETRNTT ATNVTVDGLG PGSLYTCSVW VEKDGVNSSV EIVTSATAPN 130 140 150 160 170 180 PVRNLTVEAQ TNSSIALTWE VPDGPDPQNS TYGVEYTGDG GRAGTRSTAH TNITVDRLEP 190 200 210 220 230 240 GCLYVFSVWV GKNGINSSRE TRNATTAPNP VRNLHMETQT NSSIALCWEV PDGPYPQDYT 250 260 270 280 290 300 YWVEYTGDGG GTETRNTTNT SVTAERLEPG TLYTFSVWAE KNGARGSRQN VSISTVPNAV 310 320 330 340 350 360 TSLSKQDWTN STIALRWTAP QGPGQSSYSY WVSWVREGMT DPRTQSTSGT DITLKELEAG 370 380 390 400 410 420 SLYHLTVWAE RNEVRGYNST LTAATAPNEV TDLQNETQTK NSVMLWWKAP GDPHSQLYVY 430 440 450 460 470 480 WVQWASKGHP RRGQDPQANW VNQTSRTNET WYKVEALEPG TLYNFTVWAE RNDVASSTQS 490 500 510 520 530 540 LCASTYPDTV TITSCVSTSA GYGVNLIWSC PQGGYEAFEL EVGGQRGSQD RSSCGEAVSV 550 560 570 580 590 600 LGLGPARSYP ATITTIWDGM KVVSHSVVCH TESAGVIAGA FVGILLFLIL VGLLIFFLKR 610 620 630 640 650 660 RNKKKQQKPE LRDLVFSSPG DIPAEDFADH VRKNERDSNC GFADKYQQLS LVGHSQSQMV 670 680 690 700 710 720 ASASENNAKN RYRNVLPYDW SRVPLKPIHE EPGSDYINAS FMPGLWSPQE FIATQGPLPQ 730 740 750 760 770 780 TVGDFWRLVW EQQSHTLVML TNCMEAGRVK CEHYWPLDSQ PCTHGHLRVT LVGEEVMENW 790 800 810 820 830 840 TVRELLLLQV EEQKTLSVRQ FHYQAWPDHG VPSSPDTLLA FWRMLRQWLD QTMEGGPPIV 850 860 870 880 890 900 HCSAGVGRTG TLIALDVLLR QLQSEGLLGP FSFVRKMRES RPLMVQTEAQ YVFLHQCILR 910 920 930 FLQQSAQAPA EKEVPYEDVE NLIYENVAAI QAHKLEV

References

	« Hide 'large scale' referencesShow '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. , 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 , 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.
IPI	IPI00718801. IPI00760988.
PIR	A49724.
RefSeq	NP_001154912.1. NM_001161440.1. NP_002833.3. NM_002842.3.
UniGene	Hs.179770. Hs.657630.
3D structure databases
HSSP	HSSP built from PDB template 2G59 based on UniProtKB Q16827.
ProteinModelPortal	Q9HD43.
SMR	Q9HD43. Positions 28-588, 800-1081.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HD43. 5 interactions.
MINT	MINT-1349530.
STRING	9606.ENSP00000365528.
PTM databases
PhosphoSite	Q9HD43.
Polymorphism databases
DMDM	296452983.
Proteomic databases
PaxDb	Q9HD43.
PRIDE	Q9HD43.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000376350; ENSP00000365528; ENSG00000080031.
GeneID	5794.
KEGG	hsa:5794.
UCSC	uc002qjq.3. human.
Organism-specific databases
CTD	5794.
GeneCards	GC19M055692.
HGNC	HGNC:9672. PTPRH.
HPA	HPA042300.
MIM	602510. gene.
neXtProt	NX_Q9HD43.
PharmGKB	PA34017.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5599.
HOGENOM	HOG000170539.
HOVERGEN	HBG108307.
InParanoid	Q9HD43.
KO	K01104.
OMA	FSVWAEK.
OrthoDB	EOG4JQ3XS.
Gene expression databases
ArrayExpress	Q9HD43.
Bgee	Q9HD43.
CleanEx	HS_PTPRH.
Genevestigator	Q9HD43.
Family and domain databases
Gene3D	2.60.40.10. 7 hits.
InterPro	IPR003961. Fibronectin_type3. IPR013783. Ig-like_fold. IPR000387. Tyr/Dual-sp_Pase. IPR016130. Tyr_Pase_AS. IPR000242. Tyr_Pase_rcpt/non-rcpt. [Graphical view]
Pfam	PF00041. fn3. 7 hits. PF00102. Y_phosphatase. 1 hit. [Graphical view]
PRINTS	PR00700. PRTYPHPHTASE.
SMART	SM00060. FN3. 7 hits. SM00194. PTPc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 7 hits.
PROSITE	PS50853. FN3. 8 hits. PS00383. TYR_PHOSPHATASE_1. 1 hit. PS50056. TYR_PHOSPHATASE_2. 1 hit. PS50055. TYR_PHOSPHATASE_PTP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5794.
NextBio	22560.
SOURCE	Search...

Entry information

Entry name

PTPRH_HUMAN

Accession

Primary (citable) accession number: Q9HD43
Secondary accession number(s): Q15426, Q2NKN9, Q2NKP0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 96 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.