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Q9Y2R2 (PTN22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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:
Tyrosine-protein phosphatase non-receptor type 22

EC=3.1.3.48
Alternative name(s):
Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP
Lymphoid phosphatase
Short name=LyP
PEST-domain phosphatase
Short name=PEP
Gene names
Name:PTPN22
Synonyms:PTPN8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length807 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-493' residue. Dephosphorylates the immune system activator SKAP2. Ref.9 Ref.12 Ref.14 Ref.16

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Enzyme regulation

Down-regulated by phosphorylation.

Subunit structure

Interacts with CSK. Interacts with LPXN By similarity. Interacts with CBL. Ref.1

Subcellular location

Cytoplasm By similarity.

Tissue specificity

Predominantly expressed in lymphoid tissues and cells. Isoform 1 is expressed in thymocytes and both mature B and T-cells.

Post-translational modification

Phosphorylation on Ser-35 by PKC/PRKCD abrogates its ability to dephosphorylate and inactivate the SRC family kinases.

Involvement in disease

Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.17

Sequence similarities

Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.

Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
   Biological processImmunity
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseSystemic lupus erythematosus
   Molecular functionHydrolase
Protein phosphatase
   PTMDisulfide bond
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

T cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell activation

Inferred from mutant phenotype PubMed 18299186. Source: BHF-UCL

negative regulation of T cell receptor signaling pathway

Inferred from direct assay Ref.12. Source: UniProtKB

peptidyl-tyrosine dephosphorylation

Inferred from direct assay Ref.1Ref.9Ref.12. Source: GOC

phosphoanandamide dephosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

protein dephosphorylation

Inferred from direct assay Ref.1. Source: BHF-UCL

regulation of B cell receptor signaling pathway

Non-traceable author statement PubMed 19265110. Source: BHF-UCL

regulation of innate immune response

Inferred by curator PubMed 20522204. Source: BHF-UCL

regulation of natural killer cell proliferation

Inferred from direct assay PubMed 20522204. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10940933. Source: UniProtKB

cytoplasmic side of plasma membrane

Inferred from direct assay PubMed 10940933. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 10940933. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.1. Source: BHF-UCL

   Molecular_functionSH3 domain binding

Inferred from sequence or structural similarity. Source: BHF-UCL

kinase binding

Inferred from sequence or structural similarity. Source: BHF-UCL

protein tyrosine phosphatase activity

Inferred from direct assay Ref.12. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y2R2-1)

Also known as: LyP1;

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: Q9Y2R2-2)

Also known as: LyP2;

The sequence of this isoform differs from the canonical sequence as follows:
     685-807: ELHQDRSSPP...PRNPPPTWNI → GKNFSWL
Note: Due to intron retention.
Isoform 3 (identifier: Q9Y2R2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     251-305: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q9Y2R2-4)

Also known as: LYP3;

The sequence of this isoform differs from the canonical sequence as follows:
     647-674: Missing.
Note: No experimental confirmation available.
Isoform 5 (identifier: Q9Y2R2-5)

The sequence of this isoform differs from the canonical sequence as follows:
     137-160: Missing.
     181-203: ETRTIYQFHYKNWPDHDVPSSID → VSVILAHQTSLQNLFSQITPAHF
     204-807: Missing.
Note: No experimental confirmation available.
Isoform 6 (identifier: Q9Y2R2-6)

Also known as: PTPN22.6;

The sequence of this isoform differs from the canonical sequence as follows:
     124-250: Missing.
     788-807: FANRFSKPKGPRNPPPTWNI → MCVILLKS
Note: Lacks most of the phosphatase domain and functions as a dominant negative isoform of the full length PTPN22.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 807807Tyrosine-protein phosphatase non-receptor type 22
PRO_0000094775

Regions

Domain24 – 289266Tyrosine-protein phosphatase
Region227 – 2337Substrate binding

Sites

Active site2271Phosphocysteine intermediate By similarity
Binding site1951Substrate By similarity
Binding site2741Substrate

Amino acid modifications

Modified residue351Phosphoserine; by PKC/PRKCD Ref.12
Modified residue6351Phosphoserine By similarity
Modified residue6841Phosphoserine By similarity
Modified residue6921Phosphoserine By similarity
Disulfide bond129 ↔ 227 Ref.13

Natural variations

Alternative sequence124 – 250127Missing in isoform 6.
VSP_044428
Alternative sequence137 – 16024Missing in isoform 5.
VSP_039725
Alternative sequence181 – 20323ETRTI…PSSID → VSVILAHQTSLQNLFSQITP AHF in isoform 5.
VSP_039726
Alternative sequence204 – 807604Missing in isoform 5.
VSP_039727
Alternative sequence251 – 30555Missing in isoform 3.
VSP_039728
Alternative sequence647 – 67428Missing in isoform 4.
VSP_039729
Alternative sequence685 – 807123ELHQD…PTWNI → GKNFSWL in isoform 2.
VSP_005134
Alternative sequence788 – 80720FANRF…PTWNI → MCVILLKS in isoform 6.
VSP_044429
Natural variant6201R → W Confers susceptibility to systemic lupus erythematosus and type 1 diabetes mellitus; affects CSK kinase binding. Ref.2 Ref.3 Ref.6 Ref.7 Ref.17 Ref.18
Corresponds to variant rs2476601 [ dbSNP | Ensembl ].
VAR_022605

Experimental info

Mutagenesis351S → E: Loss of phosphorylation by PKC/PRKCD. Ref.12
Mutagenesis361T → E: No effect on phosphorylation by PKC/PRKCD. Ref.12
Mutagenesis1291C → S: Decreases activity 2 fold. Ref.13
Mutagenesis2311C → S: Decreases activity 7 fold. Ref.13
Sequence conflict51 – 522KP → NA in AAD00904. Ref.1
Sequence conflict51 – 522KP → NA in AAD00905. Ref.1
Sequence conflict1261V → G in AAD27764. Ref.2
Sequence conflict1471G → V in AAD27764. Ref.2
Sequence conflict2401I → IV in AAD00905. Ref.1
Sequence conflict3721A → V in AK310570. Ref.4
Sequence conflict4201L → P in AAD27764. Ref.2
Sequence conflict7421P → S in AAD27764. Ref.2

Secondary structure

....................................................... 807
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (LyP1) [UniParc].

Last modified March 27, 2002. Version 2.
Checksum: 1ABE8AE89C9D9FBF

FASTA80791,705
        10         20         30         40         50         60 
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE KPKNIKKNRY 

        70         80         90        100        110        120 
KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI ATQGPLSTTL LDFWRMIWEY 

       130        140        150        160        170        180 
SVLIIVMACM EYEMGKKKCE RYWAEPGEMQ LEFGPFSVSC EAEKRKSDYI IRTLKVKFNS 

       190        200        210        220        230        240 
ETRTIYQFHY KNWPDHDVPS SIDPILELIW DVRCYQEDDS VPICIHCSAG CGRTGVICAI 

       250        260        270        280        290        300 
DYTWMLLKDG IIPENFSVFS LIREMRTQRP SLVQTQEQYE LVYNAVLELF KRQMDVIRDK 

       310        320        330        340        350        360 
HSGTESQAKH CIPEKNHTLQ ADSYSPNLPK STTKAAKMMN QQRTKMEIKE SSSFDFRTSE 

       370        380        390        400        410        420 
ISAKEELVLH PAKSSTSFDF LELNYSFDKN ADTTMKWQTK AFPIVGEPLQ KHQSLDLGSL 

       430        440        450        460        470        480 
LFEGCSNSKP VNAAGRYFNS KVPITRTKST PFELIQQRET KEVDSKENFS YLESQPHDSC 

       490        500        510        520        530        540 
FVEMQAQKVM HVSSAELNYS LPYDSKHQIR NASNVKHHDS SALGVYSYIP LVENPYFSSW 

       550        560        570        580        590        600 
PPSGTSSKMS LDLPEKQDGT VFPSSLLPTS STSLFSYYNS HDSLSLNSPT NISSLLNQES 

       610        620        630        640        650        660 
AVLATAPRID DEIPPPLPVR TPESFIVVEE AGEFSPNVPK SLSSAVKVKI GTSLEWGGTS 

       670        680        690        700        710        720 
EPKKFDDSVI LRPSKSVKLR SPKSELHQDR SSPPPPLPER TLESFFLADE DCMQAQSIET 

       730        740        750        760        770        780 
YSTSYPDTME NSTSSKQTLK TPGKSFTRSK SLKILRNMKK SICNSCPPNK PAESVQSNNS 

       790        800 
SSFLNFGFAN RFSKPKGPRN PPPTWNI 

« Hide

Isoform 2 (LyP2) [UniParc].

Checksum: A85EF69FDFDE9D58
Show »

FASTA69178,769
Isoform 3 [UniParc].

Checksum: 826CAD31B7C20983
Show »

FASTA75285,138
Isoform 4 (LYP3) [UniParc].

Checksum: AEA60DFC0BB05C11
Show »

FASTA77988,647
Isoform 5 [UniParc].

Checksum: E5F9FFCC426C6E2C
Show »

FASTA17920,932
Isoform 6 (PTPN22.6) [UniParc].

Checksum: 93025ACF91033DAA
Show »

FASTA66875,488

References

« Hide 'large scale' references
[1]"Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp."
Cohen S., Dadi H., Shaoul E., Sharfe N., Roifman C.M.
Blood 93:2013-2024(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH CBL.
[2]"Human protein tyrosine phosphatase (70zpep) homolog."
Liu T., Zhang J., Fu G., Zhang Q., Ye M., Zhou J., Wu J., Shen Y., Yu M., Chen S., Mao M., Chen Z.
Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT TRP-620.
[3]"Identification of a Variant Form of Tyrosine Phosphatase LYP."
Wang S., Dong H., Han J., Ho W.T., Fu X., Zhao Z.J.
Submitted (JAN-2010) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANT TRP-620.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
[5]Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A.
Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"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. expand/collapse author list , 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], VARIANT TRP-620.
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT TRP-620.
[8]"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 3 AND 5).
Tissue: Lymph.
[9]"Identification of substrates of human protein-tyrosine phosphatase PTPN22."
Wu J., Katrekar A., Honigberg L.A., Smith A.M., Conn M.T., Tang J., Jeffery D., Mortara K., Sampang J., Williams S.R., Buggy J., Clark J.M.
J. Biol. Chem. 281:11002-11010(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Protein tyrosine phosphatase PTPN22 in human autoimmunity."
Vang T., Miletic A.V., Bottini N., Mustelin T.
Autoimmunity 40:453-461(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[11]"PTPN22.6, a dominant negative isoform of PTPN22 and potential biomarker of rheumatoid arthritis."
Chang H.H., Tai T.S., Lu B., Iannaccone C., Cernadas M., Weinblatt M., Shadick N., Miaw S.C., Ho I.C.
PLoS ONE 7:E33067-E33067(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 6).
[12]"Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases."
Yu X., Sun J.P., He Y., Guo X., Liu S., Zhou B., Hudmon A., Zhang Z.Y.
Proc. Natl. Acad. Sci. U.S.A. 104:19767-19772(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-294 IN COMPLEX WITH INHIBITOR, FUNCTION, PHOSPHORYLATION AT SER-35, MUTAGENESIS OF SER-35 AND THR-36.
[13]"Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation."
Tsai S.J., Sen U., Zhao L., Greenleaf W.B., Dasgupta J., Fiorillo E., Orru V., Bottini N., Chen X.S.
Biochemistry 48:4838-4845(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-302, DISULFIDE BOND, MUTAGENESIS OF CYS-129 AND CYS-231.
[14]"Large-scale structural analysis of the classical human protein tyrosine phosphatome."
Barr A.J., Ugochukwu E., Lee W.H., King O.N.F., Filippakopoulos P., Alfano I., Savitsky P., Burgess-Brown N.A., Mueller S., Knapp S.
Cell 136:352-363(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-302, FUNCTION.
[15]"Lyp/PTPN22 phosphatase domain: substrate recognition and specificity for Src family kinases."
Seidel R.D., Love J., Piserchio A., Cowburn D.
Submitted (DEC-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-310 IN COMPLEX WITH SUBSTRATE.
[16]"Substrate specificity of lymphoid-specific tyrosine phosphatase (Lyp) and identification of Src kinase-associated protein of 55 kDa homolog (SKAP-HOM) as a Lyp substrate."
Yu X., Chen M., Zhang S., Yu Z.H., Sun J.P., Wang L., Liu S., Imasaki T., Takagi Y., Zhang Z.Y.
J. Biol. Chem. 286:30526-30534(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-294 OF MUTANT SER-227 ALONE AND IN COMPLEX WITH SKAP2 PEPTIDE, SUBSTRATE SPECIFICITY, FUNCTION.
[17]"Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE."
Kyogoku C., Langefeld C.D., Ortmann W.A., Lee A., Selby S., Carlton V.E.H., Chang M., Ramos P., Baechler E.C., Batliwalla F.M., Novitzke J., Williams A.H., Gillett C., Rodine P., Graham R.R., Ardlie K.G., Gaffney P.M., Moser K.L. expand/collapse author list , Petri M., Begovich A.B., Gregersen P.K., Behrens T.W.
Am. J. Hum. Genet. 75:504-507(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TRP-620, INVOLVEMENT IN SLE.
[18]"A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes."
Bottini N., Musumeci L., Alonso A., Rahmouni S., Nika K., Rostamkhani M., MacMurray J., Meloni G.F., Lucarelli P., Pellecchia M., Eisenbarth G.S., Comings D., Mustelin T.
Nat. Genet. 36:337-338(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TRP-620, CHARACTERIZATION OF VARIANT TRP-620.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF001846 mRNA. Translation: AAD00904.1.
AF001847 mRNA. Translation: AAD00905.1.
AF077031 mRNA. Translation: AAD27764.1.
GU479452 mRNA. Translation: ADD59979.1.
AK310570 mRNA. No translation available.
EF064714 Genomic DNA. Translation: ABK41897.1.
AL137856 Genomic DNA. Translation: CAI19068.1.
CH471122 Genomic DNA. Translation: EAW56575.1.
CH471122 Genomic DNA. Translation: EAW56576.1.
BC017785 mRNA. Translation: AAH17785.1.
BC071670 mRNA. Translation: AAH71670.1.
RefSeqNP_001180360.1. NM_001193431.1.
NP_036543.4. NM_012411.4.
NP_057051.3. NM_015967.5.
UniGeneHs.535276.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2P6XX-ray1.90A/B1-302[»]
2QCJX-ray3.00A/B1-294[»]
2QCTX-ray2.80A/B1-294[»]
3BRHX-ray2.20A/B1-310[»]
3H2XX-ray2.20A1-302[»]
3OLRX-ray2.50A/B/C/D1-294[»]
3OMHX-ray2.90A/B/C/D1-294[»]
4J51X-ray2.30A/B1-303[»]
ProteinModelPortalQ9Y2R2.
SMRQ9Y2R2. Positions 1-335.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117604. 12 interactions.
DIPDIP-29953N.
IntActQ9Y2R2. 16 interactions.
STRING9606.ENSP00000352833.

Chemistry

BindingDBQ9Y2R2.
ChEMBLCHEMBL2889.

PTM databases

PhosphoSiteQ9Y2R2.

Polymorphism databases

DMDM20139861.

Proteomic databases

PaxDbQ9Y2R2.
PRIDEQ9Y2R2.

Protocols and materials databases

DNASU26191.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000460620; ENSP00000433141; ENSG00000134242. [Q9Y2R2-5]
GeneID26191.
KEGGhsa:26191.
UCSCuc001eds.3. human. [Q9Y2R2-1]
uc001edt.3. human. [Q9Y2R2-5]
uc009wgq.3. human. [Q9Y2R2-3]
uc009wgs.2. human. [Q9Y2R2-6]
uc021orx.1. human. [Q9Y2R2-4]

Organism-specific databases

CTD26191.
GeneCardsGC01M114356.
HGNCHGNC:9652. PTPN22.
HPACAB012209.
HPA004912.
HPA013350.
MIM152700. phenotype.
600716. gene.
neXtProtNX_Q9Y2R2.
Orphanet397. Giant cell arteritis.
900. Granulomatosis with polyangiitis.
85408. Juvenile rheumatoid factor-negative polyarthritis.
85410. Oligoarticular juvenile arthritis.
93552. Pediatric systemic lupus erythematosus.
536. Systemic lupus erythematosus.
PharmGKBPA33995.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5599.
HOVERGENHBG103877.
InParanoidQ9Y2R2.
KOK18024.
OrthoDBEOG744T8Z.
PhylomeDBQ9Y2R2.
TreeFamTF351977.

Enzyme and pathway databases

SignaLinkQ9Y2R2.

Gene expression databases

ArrayExpressQ9Y2R2.
BgeeQ9Y2R2.
CleanExHS_PTPN22.
GenevestigatorQ9Y2R2.

Family and domain databases

InterProIPR016276. Non-rcpt_Tyr_Pase_8/22.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PfamPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFPIRSF000930. PTPN8_PTPN22. 1 hit.
PRINTSPR00700. PRTYPHPHTASE.
SMARTSM00194. PTPc. 1 hit.
[Graphical view]
PROSITEPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9Y2R2.
GeneWikiPTPN22.
GenomeRNAi26191.
NextBio35504118.
PROQ9Y2R2.
SOURCESearch...

Entry information

Entry namePTN22_HUMAN
AccessionPrimary (citable) accession number: Q9Y2R2
Secondary accession number(s): A0N0K6 expand/collapse secondary AC list , B1ALC8, D4NZ71, E9PPI1, O95063, O95064, Q6IPX8, Q8WVM1
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: March 27, 2002
Last modified: April 16, 2014
This is version 126 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 1

Human chromosome 1: entries, gene names and cross-references to MIM