P35236 (PTN7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein phosphatase non-receptor type 7
EC=3.1.3.48

Alternative name(s):
Hematopoietic protein-tyrosine phosphatase
Short name=HEPTP
Protein-tyrosine phosphatase LC-PTP

Gene names

Name:

PTPN7

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	360 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protein phosphatase that acts preferentially on tyrosine-phosphorylated MAPK1. Plays a role in the regulation of T and B-lymphocyte development and signal transduction. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Ref.9
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
Enzyme regulation	Inhibited in cells after FCER1A triggering By similarity.
Subunit structure	Monomer. Interacts with MAPK1, MAPK3 and several other MAP kinases. Ref.6 Ref.7 Ref.8 Ref.9 Ref.15
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton By similarity Ref.10.
Tissue specificity	Expressed exclusively in thymus and spleen. Ref.1 Ref.2
Post-translational modification	Phosphorylated on serine residues in resting T-cells. Phosphorylation increases upon exposure to stimuli that increase intracellular cAMP levels. Phosphorylation leads to dissociation of bound MAP kinases. Ref.7 Ref.8 Ref.10 Oxidized at active site cysteine. Treatment with pervanadate (vanadate and H2O2) or with antigen enhanced oxidation of active site cysteine By similarity.
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily. Contains 1 tyrosine-protein phosphatase domain.
Sequence caution	The sequence AAA59531.1 differs from that shown. Reason: Frameshift at position 5.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protein phosphatase
PTM	Oxidation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from direct assay PubMed 10940933. Source: BHF-UCL internal side of plasma membrane Inferred from direct assay PubMed 10940933. Source: UniProtKB
Molecular_function	protein tyrosine phosphatase activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P35236-1)

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: P35236-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGASFWPIRQAREQQRRALSFRQTSWLSEPPLGPAPHLSM

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 360

360

Tyrosine-protein phosphatase non-receptor type 7

PRO_0000094761

Regions

Domain

97 – 350

254

Tyrosine-protein phosphatase

Region

38 – 51

14

Interaction with MAP kinases

Region

291 – 297

7

Substrate binding

Sites

Active site

291

1

Phosphocysteine intermediate Ref.6

Binding site

257

1

Substrate

Binding site

335

1

Substrate

Amino acid modifications

Modified residue

44

1

Phosphoserine Ref.8 Ref.10 Ref.13

Modified residue

66

1

Phosphothreonine Ref.7 Ref.12

Modified residue

93

1

Phosphoserine Ref.7

Modified residue

143

1

Phosphoserine Ref.13

Modified residue

291

1

Cysteine sulfenic acid (-SOH) By similarity

Natural variations

Alternative sequence

1

1

M → MGASFWPIRQAREQQRRALS FRQTSWLSEPPLGPAPHLSM in isoform 2.

VSP_026925

Experimental info

Mutagenesis

44

1

S → A: Prevents dissociation of bound MAP kinase and enhances their dephosphorylation. Ref.10

Mutagenesis

44

1

S → D: Reduces binding of MAP kinase. Ref.10

Mutagenesis

66

1

T → A: Prevents dissociation of bound MAP kinase and enhances their dephosphorylation; when associated with A-93. Ref.7

Mutagenesis

93

1

S → A: Prevents dissociation of bound MAP kinase and enhances their dephosphorylation; when associated with A-66. Ref.7

Mutagenesis

125

1

Y → A: Strongly reduced catalytic activity. Ref.11

Mutagenesis

257

1

D → A: Loss of catalytic activity. Ref.11

Mutagenesis

291

1

C → S: Loss of catalytic activity. Ref.6

Mutagenesis

335

1

Q → A: Reduced catalytic activity. Ref.11

Sequence conflict

235 – 236

2

QL → HV in AAA59531. Ref.2

Sequence conflict

337

1

A → D in BAA01946. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

360

Helix Strand Turn

Details...

Helix

38 – 41

4

Helix

67 – 77

11

Beta strand

81 – 83

3

Helix

84 – 89

6

Helix

94 – 103

10

Helix

111 – 113

3

Helix

119 – 122

4

Helix

132 – 134

3

Beta strand

135 – 137

3

Beta strand

149 – 155

7

Helix

158 – 160

3

Beta strand

164 – 169

6

Helix

173 – 175

3

Helix

176 – 185

10

Beta strand

190 – 194

5

Beta strand

199 – 201

3

Beta strand

210 – 215

6

Beta strand

218 – 227

10

Beta strand

229 – 240

12

Beta strand

243 – 252

10

Helix

264 – 275

12

Beta strand

281 – 283

3

Beta strand

287 – 295

9

Helix

296 – 314

19

Beta strand

315 – 317

3

Helix

319 – 329

11

Helix

337 – 353

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2002. Version 3. Checksum: 388A154CC55AC0EE	FASTA	360	40,529
	10 20 30 40 50 60 MVQAHGGRSR AQPLTLSLGA AMTQPPPEKT PAKKHVRLQE RRGSNVALML DVRSLGAVEP 70 80 90 100 110 120 ICSVNTPREV TLHFLRTAGH PLTRWALQRQ PPSPKQLEEE FLKIPSNFVS PEDLDIPGHA 130 140 150 160 170 180 SKDRYKTILP NPQSRVCLGR AQSQEDGDYI NANYIRGYDG KEKVYIATQG PMPNTVSDFW 190 200 210 220 230 240 EMVWQEEVSL IVMLTQLREG KEKCVHYWPT EEETYGPFQI RIQDMKECPE YTVRQLTIQY 250 260 270 280 290 300 QEERRSVKHI LFSAWPDHQT PESAGPLLRL VAEVEESPET AAHPGPIVVH CSAGIGRTGC 310 320 330 340 350 360 FIATRIGCQQ LKARGEVDIL GIVCQLRLDR GGMIQTAEQY QFLHHTLALY AGQLPEEPSP
	Isoform 2 [UniParc]. Checksum: 16690FDF358E20C8	FASTA	399	45,002
	10 20 30 40 50 60 MGASFWPIRQ AREQQRRALS FRQTSWLSEP PLGPAPHLSM VQAHGGRSRA QPLTLSLGAA 70 80 90 100 110 120 MTQPPPEKTP AKKHVRLQER RGSNVALMLD VRSLGAVEPI CSVNTPREVT LHFLRTAGHP 130 140 150 160 170 180 LTRWALQRQP PSPKQLEEEF LKIPSNFVSP EDLDIPGHAS KDRYKTILPN PQSRVCLGRA 190 200 210 220 230 240 QSQEDGDYIN ANYIRGYDGK EKVYIATQGP MPNTVSDFWE MVWQEEVSLI VMLTQLREGK 250 260 270 280 290 300 EKCVHYWPTE EETYGPFQIR IQDMKECPEY TVRQLTIQYQ EERRSVKHIL FSAWPDHQTP 310 320 330 340 350 360 ESAGPLLRLV AEVEESPETA AHPGPIVVHC SAGIGRTGCF IATRIGCQQL KARGEVDILG 370 380 390 IVCQLRLDRG GMIQTAEQYQ FLHHTLALYA GQLPEEPSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and chromosomal mapping of a human protein-tyrosine phosphatase LC-PTP." Adachi M., Sekiya M., Isobe M., Kumura Y., Ogita Z.I., Hinoda Y., Imai K., Yachi A. Biochem. Biophys. Res. Commun. 186:1607-1615(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION.
[2]	"Cloning and expression of an inducible lymphoid-specific, protein tyrosine phosphatase (HePTPase)." Zanke B., Suzuki H., Kishihara K., Mizzen L., Minden M., Pawson A., Mak T.W. Eur. J. Immunol. 22:235-239(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Tissue: Lymphocyte.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING.
[5]	"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] (ISOFORM 2). Tissue: Lymph.
[6]	"Negative regulation of T cell antigen receptor signal transduction by hematopoietic tyrosine phosphatase (HePTP)." Saxena M., Williams S., Gilman J., Mustelin T. J. Biol. Chem. 273:15340-15344(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAPK1, ACTIVE SITE, MUTAGENESIS OF CYS-291.
[7]	"Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)." Saxena M., Williams S., Brockdorff J., Gilman J., Mustelin T. J. Biol. Chem. 274:11693-11700(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAPK1 AND MAPK3, PHOSPHORYLATION AT THR-66 AND SER-93, MUTAGENESIS OF THR-66 AND SER-93.
[8]	"Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase." Saxena M., Williams S., Tasken K., Mustelin T. Nat. Cell Biol. 1:305-311(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAPK1, PHOSPHORYLATION AT SER-44.
[9]	"The MAP-kinase ERK2 is a specific substrate of the protein tyrosine phosphatase HePTP." Pettiford S.M., Herbst R. Oncogene 19:858-869(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAPK1 AND MAPK3.
[10]	"Haematopoietic protein tyrosine phosphatase (HePTP) phosphorylation by cAMP-dependent protein kinase in T-cells: dynamics and subcellular location." Nika K., Hyunh H., Williams S., Paul S., Bottini N., Tasken K., Lombroso P.J., Mustelin T. Biochem. J. 378:335-342(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-44, MUTAGENESIS OF SER-44.
[11]	"Molecular determinants of substrate recognition in hematopoietic protein-tyrosine phosphatase." Huang Z., Zhou B., Zhang Z.-Y. J. Biol. Chem. 279:52150-52159(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-125; ASP-257 AND GLN-335.
[12]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-66, MASS SPECTROMETRY. Tissue: Platelet.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND SER-143, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site." Mustelin T., Tautz L., Page R. J. Mol. Biol. 354:150-163(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 65-360 OF MUTANT ASP-246 IN COMPLEX WITH SUBSTRATE ANALOG.
[15]	"Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases." Eswaran J., von Kries J.P., Marsden B., Longman E., Debreczeni J.E., Ugochukwu E., Turnbull A., Lee W.H., Knapp S., Barr A.J. Biochem. J. 395:483-491(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 65-358 IN COMPLEX WITH SUBSTRATE ANALOG, SUBUNIT.
[16]	"Docking interactions induce exposure of activation loop in the MAP kinase ERK2." Zhou T., Sun L., Humphreys J., Goldsmith E.J. Structure 14:1011-1019(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 37-52 IN COMPLEX WITH MAPK1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D11327 mRNA. Translation: BAA01946.1.
M64322 mRNA. Translation: AAA59531.1. Frameshift.
BT009848 mRNA. Translation: AAP88850.1.
AL592300 Genomic DNA. Translation: CAI13108.1.
BC001746 mRNA. Translation: AAH01746.2.

IPI

IPI00081833.
IPI00946771.

PIR

JH0692.

RefSeq

NP_542155.1. NM_080588.2.

UniGene

Hs.402773.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZC0	X-ray	1.85	A	65-360	[»]
2A3K	X-ray	2.55	A	65-358	[»]
2GP0	X-ray	2.05	A	65-360	[»]
2GPH	X-ray	1.90	B	37-51	[»]
2HVL	X-ray	2.40	A	65-360	[»]
2QDC	X-ray	2.00	A	65-360	[»]
2QDM	X-ray	2.05	A	65-360	[»]
2QDP	X-ray	2.72	A	65-360	[»]
3D42	X-ray	2.46	A	65-360	[»]
3D44	X-ray	1.90	A	65-360	[»]
3O4S	X-ray	1.90	A	65-360	[»]
3O4T	X-ray	2.60	A	65-360	[»]
3O4U	X-ray	2.25	A	65-360	[»]

ProteinModelPortal

P35236.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29118N.

IntAct

P35236. 1 interaction.

STRING

9606.ENSP00000356248.

PTM databases

PhosphoSite

P35236.

Proteomic databases

PaxDb

P35236.

PRIDE

P35236.

Protocols and materials databases

DNASU

5778.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000308986; ENSP00000311133; ENSG00000143851.
ENST00000367279; ENSP00000356248; ENSG00000143851.
ENST00000495688; ENSP00000420506; ENSG00000143851.

GeneID

5778.

KEGG

hsa:5778.

UCSC

uc001gxl.2. human.
uc001gxn.2. human.

Organism-specific databases

CTD

5778.

GeneCards

GC01M202116.

H-InvDB

HIX0001472.

HGNC

HGNC:9659. PTPN7.

HPA

CAB009530.
HPA019118.

MIM

176889. gene.

neXtProt

NX_P35236.

PharmGKB

PA34003.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5599.

HOGENOM

HOG000294188.

HOVERGEN

HBG001594.

InParanoid

P35236.

KO

K04458.

OrthoDB

EOG4DJJWN.

Enzyme and pathway databases

BRENDA

3.1.3.48. 2681.

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
tcrraspathway. Ras signaling in the CD4+ TCR pathway.

Gene expression databases

ArrayExpress

P35236.

Bgee

P35236.

CleanEx

HS_PTPN7.

Genevestigator

P35236.

GermOnline

ENSG00000143851. Homo sapiens.

Family and domain databases

InterPro

IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR008356. Tyr_Pase_KIM-con.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]

Pfam

PF00102. Y_phosphatase. 1 hit.
[Graphical view]

PRINTS

PR01778. KIMPTPASE.
PR00700. PRTYPHPHTASE.

SMART

SM00194. PTPc. 1 hit.
[Graphical view]

PROSITE

PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P35236.

ChEMBL

CHEMBL2219.

ChiTaRS

PTPN7. human.

EvolutionaryTrace

P35236.

GenomeRNAi

5778.

NextBio

22472.

SOURCE

Search...

Entry information

Entry name

PTN7_HUMAN

Accession

Primary (citable) accession number: P35236
Secondary accession number(s): Q53XK4, Q5SXQ1, Q9BV05

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	January 23, 2002
Last modified:	May 1, 2013
This is version 129 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.