Tyrosine-protein phosphatase non-receptor type 1

Names and origin

Protein names

Recommended name:
    Tyrosine-protein phosphatase non-receptor type 1
    EC=3.1.3.48
Alternative name(s):
    Protein-tyrosine phosphatase 1B
      Short name=PTP-1B

Gene names

Name:	PTPN1
Synonyms:	PTP1B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	435 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	May play an important role in CKII- and p60c-src-induced signal transduction cascades By similarity.
Catalytic activity	Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side.
Post-translational modification	Oxidized on Cys-215; the Cys-SOH formed in response to redox signaling reacts with the alpha-amido of the following residue to form a 4-amino-3-isothiazolidinone serine cross-link, triggering a conformational change that inhibits substrate binding and activity. The active site can be restored by reduction.
Polymorphism	Genetic variation in PTPN1 may influence abdominal body fat distribution [MIM:609830].
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily. Contains 1 tyrosine-protein phosphatase domain.

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Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Oxidation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	protein amino acid dephosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct protein tyrosine phosphatase activity Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACTN1	P12814	1	EBI-968788,EBI-351710
Cdh2	P15116	3	EBI-968788,EBI-397974	From a different organism.
GHR	P10912	2	EBI-968788,EBI-286316
INSR	P06213	1	EBI-968788,EBI-475899
PIAS1	O75925	1	EBI-968788,EBI-629434
Sumo1	P63166	1	EBI-968788,EBI-80152	From a different organism.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 435

435

Tyrosine-protein phosphatase non-receptor type 1

PRO_0000094748

Regions

Domain

3 – 277

275

Tyrosine-protein phosphatase

Sites

Active site

215

1

Phosphocysteine intermediate

Amino acid modifications

Modified residue

1

N-acetylmethionine

Modified residue

20

1

Phosphotyrosine

Modified residue

50

1

Phosphoserine; by PKB/AKT1

Modified residue

295

1

Phosphoserine

Modified residue

352

1

Phosphoserine

Modified residue

378

1

Phosphoserine; by PKC

Modified residue

386

1

Phosphoserine; by CDC2

Modified residue

393

1

Phosphoserine By similarity

Cross-link

215 ↔ 216

4-amino-3-isothiazolidinone serine (Cys-Ser); in inhibited form

Natural variations

Natural variant

381

1

G → S: dbSNP rs16995304.

VAR_022013

Natural variant

387

1

P → L Associated with low glucose tolerance. dbSNP rs16995309.

VAR_022014

Experimental info

Mutagenesis

50

1

S → A or D: No phosphorylation

Secondary structure

1

.

435

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P18031-1 [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: 802377DCD33F41FD
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FASTA

435

49,967

        10         20         30         40         50         60 
MEMEKEFEQI DKSGSWAAIY QDIRHEASDF PCRVAKLPKN KNRNRYRDVS PFDHSRIKLH 

        70         80         90        100        110        120 
QEDNDYINAS LIKMEEAQRS YILTQGPLPN TCGHFWEMVW EQKSRGVVML NRVMEKGSLK 

       130        140        150        160        170        180 
CAQYWPQKEE KEMIFEDTNL KLTLISEDIK SYYTVRQLEL ENLTTQETRE ILHFHYTTWP 

       190        200        210        220        230        240 
DFGVPESPAS FLNFLFKVRE SGSLSPEHGP VVVHCSAGIG RSGTFCLADT CLLLMDKRKD 

       250        260        270        280        290        300 
PSSVDIKKVL LEMRKFRMGL IQTADQLRFS YLAVIEGAKF IMGDSSVQDQ WKELSHEDLE 

       310        320        330        340        350        360 
PPPEHIPPPP RPPKRILEPH NGKCREFFPN HQWVKEETQE DKDCPIKEEK GSPLNAAPYG 

       370        380        390        400        410        420 
IESMSQDTEV RSRVVGGSLR GAQAASPAKG EPSLPEKDED HALSYWKPFL VNMCVATVLT 

       430 
AGAYLCYRFL FNSNT

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a cDNA for a major human protein-tyrosine-phosphatase." Chernoff J., Schievella A.R., Jost C.A., Erikson R.L., Neel B.G. Proc. Natl. Acad. Sci. U.S.A. 87:2735-2739(1990) [PubMed: 2157211] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B." Brown-Shimer S., Johnson K.A., Lawrence J.B., Johnson C., Bruskin A., Green N.R., Hill D.E. Proc. Natl. Acad. Sci. U.S.A. 87:5148-5152(1990) [PubMed: 2164224] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Placenta.
[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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye and Lymph.
[6]	"Human placenta protein-tyrosine-phosphatase: amino acid sequence and relationship to a family of receptor-like proteins." Charbonneau H., Tonks N.K., Kumar S., Diltz C.D., Harrylock M., Cool D.E., Krebs E.G., Fischer E.H., Walsh K.A. Proc. Natl. Acad. Sci. U.S.A. 86:5252-5256(1989) [PubMed: 2546149] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-321. Tissue: Placenta.
[7]	"Multi-site phosphorylation of the protein tyrosine phosphatase, PTP1B: identification of cell cycle regulated and phorbol ester stimulated sites of phosphorylation." Flint A.J., Gebbink M.F.G.B., Franza B.R. Jr., Hill D.E., Tonks N.K. EMBO J. 12:1937-1946(1993) [PubMed: 8491187] [Abstract] Cited for: PHOSPHORYLATION AT SER-352; SER-378 AND SER-386.
[8]	"The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence." Frangioni J.V., Beahm P.H., Shifrin V., Jost C.A., Neel B.G. Cell 68:545-560(1992) [PubMed: 1739967] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to dephosphorylate the insulin receptor." Ravichandran L.V., Chen H., Li Y., Quon M.J. Mol. Endocrinol. 15:1768-1780(2001) [PubMed: 11579209] [Abstract] Cited for: PHOSPHORYLATION AT SER-50, MUTAGENESIS OF SER-50.
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-20, MASS SPECTROMETRY.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50 AND SER-295, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Crystal structure of human protein tyrosine phosphatase 1B." Barford D., Flint A.J., Tonks N.K. Science 263:1397-1404(1994) [PubMed: 8128219] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-321.
[13]	"Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: a paradigm for inhibitor design." Puius Y.A., Zhao Y., Sullivan M., Lawrence D.S., Almo S.C., Zhang Z.Y. Proc. Natl. Acad. Sci. U.S.A. 94:13420-13425(1997) [PubMed: 9391040] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-298 OF MUTANT SER-215.
[14]	"Visualization of the cysteinyl-phosphate intermediate of a protein-tyrosine phosphatase by X-ray crystallography." Pannifer A.D., Flint A.J., Tonks N.K., Barford D. J. Biol. Chem. 273:10454-10462(1998) [PubMed: 9553104] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-285.
[15]	"Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics." Groves M.R., Yao Z.-J., Roller P.P., Burke T.R. Jr., Barford D. Biochemistry 37:17773-17783(1998) [PubMed: 9922143] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-298.
[16]	"Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate." Salmeen A., Andersen J.N., Myers M.P., Meng T.-C., Hinks J.A., Tonks N.K., Barford D. Nature 423:769-773(2003) [PubMed: 12802338] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-321, OXIDATION AT CYS-215, CROSS-LINK 215-CYS-SER-216.
[17]	"Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B." Van Montfort R.L.M., Congreve M., Tisi D., Carr R., Jhoti H. Nature 423:773-777(2003) [PubMed: 12802339] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-321, OXIDATION AT CYS-215, CROSS-LINK 215-CYS-SER-216.
[18]	"Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism." Ukkola O., Rankinen T., Lakka T., Leon A.S., Skinner J.S., Wilmore J.H., Rao D.C., Kesaeniemi Y.A., Bouchard C. Obes. Res. 13:829-834(2005) [PubMed: 15919835] [Abstract] Cited for: ASSOCIATION OF VARIANT LEU-387 WITH LOW GLUCOSE TOLERANCE, INVOLVEMENT IN ABDOMINAL BODY FAT DISTRIBUTION.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

M31724 mRNA. Translation: AAA60223.1.
M33689 mRNA. Translation: AAA60157.1.
M33684

M33685 Genomic DNA. Translation: AAA60158.1.
BT006752 mRNA. Translation: AAP35398.1.
AL133230, AL034429 Genomic DNA. Translation: CAC00618.2.
AL034429, AL133230 Genomic DNA. Translation: CAI23215.1.
BC015660 mRNA. Translation: AAH15660.1.
BC018164 mRNA. Translation: AAH18164.1.

PIR

TPHUN1. A35992.

RefSeq

NP_002818.1.

UniGene

Hs.417549

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A5Y	X-ray	2.50	A	1-330	[»]
1AAX	X-ray	1.90	A	1-321

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases