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Protein

Tyrosine-protein phosphatase non-receptor type 22

Gene

PTPN22

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:16461343, PubMed:18056643). Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue (PubMed:21719704). Dephosphorylates ZAP70 at its activating 'Tyr-493' residue (PubMed:16461343). Dephosphorylates the immune system activator SKAP2 (PubMed:21719704). Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208). Promotes host antiviral responses mediated by type 1 interferon (By similarity). Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy (PubMed:23991106).By similarity6 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation1 Publication

Enzyme regulationi

Down-regulated by phosphorylation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei195SubstrateBy similarity1
Active sitei227Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei274Substrate1 Publication1

GO - Molecular functioni

  • kinase binding Source: BHF-UCL
  • phosphatase activity Source: UniProtKB
  • protein tyrosine phosphatase activity Source: UniProtKB
  • SH3 domain binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • cellular response to muramyl dipeptide Source: UniProtKB
  • lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • negative regulation of autophagy Source: UniProtKB
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of interleukin-6 secretion Source: UniProtKB
  • negative regulation of interleukin-8 secretion Source: UniProtKB
  • negative regulation of JUN kinase activity Source: UniProtKB
  • negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
  • negative regulation of p38MAPK cascade Source: UniProtKB
  • negative regulation of T cell activation Source: BHF-UCL
  • negative regulation of T cell receptor signaling pathway Source: UniProtKB
  • negative regulation of tumor necrosis factor production Source: UniProtKB
  • phosphoanandamide dephosphorylation Source: BHF-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of interferon-gamma secretion Source: UniProtKB
  • positive regulation of protein K63-linked ubiquitination Source: UniProtKB
  • positive regulation of toll-like receptor 3 signaling pathway Source: UniProtKB
  • positive regulation of toll-like receptor 4 signaling pathway Source: UniProtKB
  • positive regulation of type I interferon production Source: UniProtKB
  • protein dephosphorylation Source: BHF-UCL
  • regulation of B cell receptor signaling pathway Source: BHF-UCL
  • regulation of innate immune response Source: BHF-UCL
  • regulation of natural killer cell proliferation Source: BHF-UCL
  • regulation of NIK/NF-kappaB signaling Source: UniProtKB
  • response to lipopolysaccharide Source: UniProtKB
  • T cell differentiation Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Autophagy, Immunity

Enzyme and pathway databases

BioCyciZFISH:HS05837-MONOMER.
BRENDAi3.1.3.48. 2681.
ReactomeiR-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
R-HSA-202430. Translocation of ZAP-70 to Immunological synapse.
SignaLinkiQ9Y2R2.
SIGNORiQ9Y2R2.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type 22 (EC:3.1.3.481 Publication)
Alternative name(s):
Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP
Lymphoid phosphatase
Short name:
LyP
PEST-domain phosphatase
Short name:
PEP
Gene namesi
Name:PTPN22
Synonyms:PTPN8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:9652. PTPN22.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic side of plasma membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Systemic lupus erythematosus (SLE)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:152700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072630263R → Q Polymorphism; reduces risk of SLE and RA but not IDDM; associated with reduced risk of ulcerative colitis but not of Crohn disease; severely reduces phosphatase activity. 3 PublicationsCorresponds to variant rs33996649dbSNPEnsembl.1
Natural variantiVAR_022605620R → W in IDDM, RA, SLE and VTLG; also found in patients with Graves disease, Hashimoto thyroiditis and Addison disease; associated with reduced risk of Crohn disease but not of ulcerative colitis; affects CSK kinase binding; alters B cell receptor signaling and memory B cell proliferation. 12 PublicationsCorresponds to variant rs2476601dbSNPEnsembl.1
Diabetes mellitus, insulin-dependent (IDDM)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
See also OMIM:222100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072630263R → Q Polymorphism; reduces risk of SLE and RA but not IDDM; associated with reduced risk of ulcerative colitis but not of Crohn disease; severely reduces phosphatase activity. 3 PublicationsCorresponds to variant rs33996649dbSNPEnsembl.1
Natural variantiVAR_022605620R → W in IDDM, RA, SLE and VTLG; also found in patients with Graves disease, Hashimoto thyroiditis and Addison disease; associated with reduced risk of Crohn disease but not of ulcerative colitis; affects CSK kinase binding; alters B cell receptor signaling and memory B cell proliferation. 12 PublicationsCorresponds to variant rs2476601dbSNPEnsembl.1
Rheumatoid arthritis (RA)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionAn inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.
See also OMIM:180300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072630263R → Q Polymorphism; reduces risk of SLE and RA but not IDDM; associated with reduced risk of ulcerative colitis but not of Crohn disease; severely reduces phosphatase activity. 3 PublicationsCorresponds to variant rs33996649dbSNPEnsembl.1
Natural variantiVAR_022605620R → W in IDDM, RA, SLE and VTLG; also found in patients with Graves disease, Hashimoto thyroiditis and Addison disease; associated with reduced risk of Crohn disease but not of ulcerative colitis; affects CSK kinase binding; alters B cell receptor signaling and memory B cell proliferation. 12 PublicationsCorresponds to variant rs2476601dbSNPEnsembl.1
Vitiligo (VTLG)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA pigmentary disorder of the skin and mucous membranes. It is characterized by circumscribed depigmented macules and patches, commonly on extensor aspects of extremities, on the face or neck and in skin folds. Vitiligo is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. It is a multifactorial disorder with a complex etiology probably including autoimmune mechanisms, and is associated with an elevated risk of other autoimmune diseases.
See also OMIM:193200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022605620R → W in IDDM, RA, SLE and VTLG; also found in patients with Graves disease, Hashimoto thyroiditis and Addison disease; associated with reduced risk of Crohn disease but not of ulcerative colitis; affects CSK kinase binding; alters B cell receptor signaling and memory B cell proliferation. 12 PublicationsCorresponds to variant rs2476601dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi35S → E: Loss of phosphorylation by PKC/PRKCD. 1 Publication1
Mutagenesisi36T → E: No effect on phosphorylation by PKC/PRKCD. 1 Publication1
Mutagenesisi129C → S: Decreases activity 2 fold. 1 Publication1
Mutagenesisi231C → S: Decreases activity 7 fold. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Disease mutation, Systemic lupus erythematosus

Organism-specific databases

DisGeNETi26191.
MalaCardsiPTPN22.
MIMi152700. phenotype.
180300. phenotype.
193200. phenotype.
222100. phenotype.
OpenTargetsiENSG00000134242.
Orphaneti397. 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.
3437. Vogt-Koyanagi-Harada disease.
PharmGKBiPA33995.

Chemistry databases

ChEMBLiCHEMBL2889.

Polymorphism and mutation databases

BioMutaiPTPN22.
DMDMi20139861.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000947751 – 807Tyrosine-protein phosphatase non-receptor type 22Add BLAST807

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei35Phosphoserine; by PKC/PRKCD1 Publication1
Disulfide bondi129 ↔ 2271 Publication
Modified residuei449PhosphoserineCombined sources1
Modified residuei635PhosphoserineBy similarity1
Modified residuei684PhosphoserineBy similarity1
Modified residuei692PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation on Ser-35 by PKC/PRKCD abrogates its ability to dephosphorylate and inactivate the SRC family kinases.1 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

PaxDbiQ9Y2R2.
PeptideAtlasiQ9Y2R2.
PRIDEiQ9Y2R2.

PTM databases

DEPODiQ9Y2R2.
iPTMnetiQ9Y2R2.
PhosphoSitePlusiQ9Y2R2.

Expressioni

Tissue specificityi

Expressed in bone marrow, B and T-cells, PBMCs, natural killer cells, monocytes, dendritic cells and neutrophils (PubMed:15208781). Both isoform 1 and 4 are predominantly expressed in lymphoid tissues and cells. Isoform 1 is expressed in thymocytes and both mature B and T-cells.1 Publication

Inductioni

By muramyl-dipeptide and lipopolysaccharide.1 Publication

Gene expression databases

BgeeiENSG00000134242.
CleanExiHS_PTPN22.
ExpressionAtlasiQ9Y2R2. baseline and differential.
GenevisibleiQ9Y2R2. HS.

Organism-specific databases

HPAiCAB012209.
HPA004912.
HPA013350.

Interactioni

Subunit structurei

Interacts with CSK (PubMed:15208781). Interacts with LPXN (By similarity). Interacts with CBL (PubMed:10068674). Interacts with TRAF3 (via MATH domain); the interaction promotes TRAF3 polyubiquitination (PubMed:23871208).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD247P209634EBI-1211241,EBI-1165705
EGFRP005332EBI-1211241,EBI-297353
GRB2P629932EBI-1211241,EBI-401755
LCKP062396EBI-1211241,EBI-1348
PSTPIP1O435866EBI-1211241,EBI-1050964
SKAP2O755633EBI-1211241,EBI-2483161
Skap2Q3UND02EBI-1211241,EBI-642769From a different organism.
TRAF3Q131142EBI-1211241,EBI-357631
Traf3Q608035EBI-1211241,EBI-520135From a different organism.
ZAP70P434034EBI-1211241,EBI-1211276

GO - Molecular functioni

  • kinase binding Source: BHF-UCL
  • SH3 domain binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi117604. 14 interactors.
DIPiDIP-29953N.
IntActiQ9Y2R2. 23 interactors.
STRINGi9606.ENSP00000352833.

Chemistry databases

BindingDBiQ9Y2R2.

Structurei

Secondary structure

1807
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 16Combined sources14
Helixi21 – 40Combined sources20
Helixi47 – 50Combined sources4
Helixi52 – 55Combined sources4
Beta strandi59 – 62Combined sources4
Helixi67 – 69Combined sources3
Beta strandi70 – 72Combined sources3
Turni80 – 83Combined sources4
Beta strandi86 – 92Combined sources7
Beta strandi95 – 102Combined sources8
Helixi107 – 109Combined sources3
Helixi110 – 119Combined sources10
Beta strandi124 – 127Combined sources4
Beta strandi131 – 133Combined sources3
Beta strandi135 – 137Combined sources3
Beta strandi146 – 148Combined sources3
Beta strandi151 – 153Combined sources3
Beta strandi156 – 165Combined sources10
Beta strandi167 – 178Combined sources12
Beta strandi181 – 190Combined sources10
Beta strandi195 – 197Combined sources3
Helixi199 – 202Combined sources4
Helixi203 – 215Combined sources13
Beta strandi218 – 221Combined sources4
Beta strandi223 – 226Combined sources4
Beta strandi228 – 232Combined sources5
Helixi233 – 248Combined sources16
Helixi258 – 266Combined sources9
Helixi276 – 301Combined sources26

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ9Y2R2.
SMRiQ9Y2R2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y2R2.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 289Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST266

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni227 – 233Substrate binding7

Sequence similaritiesi

Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0789. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOVERGENiHBG103877.
InParanoidiQ9Y2R2.
KOiK18024.
PhylomeDBiQ9Y2R2.
TreeFamiTF351977.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR016276. PTPN22.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000930. PTPN8_PTPN22. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y2R2-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MDQREILQKF LDEAQSKKIT KEEFANEFLK LKRQSTKYKA DKTYPTTVAE
60 70 80 90 100
KPKNIKKNRY KDILPYDYSR VELSLITSDE DSSYINANFI KGVYGPKAYI
110 120 130 140 150
ATQGPLSTTL LDFWRMIWEY SVLIIVMACM EYEMGKKKCE RYWAEPGEMQ
160 170 180 190 200
LEFGPFSVSC EAEKRKSDYI IRTLKVKFNS ETRTIYQFHY KNWPDHDVPS
210 220 230 240 250
SIDPILELIW DVRCYQEDDS VPICIHCSAG CGRTGVICAI DYTWMLLKDG
260 270 280 290 300
IIPENFSVFS LIREMRTQRP SLVQTQEQYE LVYNAVLELF KRQMDVIRDK
310 320 330 340 350
HSGTESQAKH CIPEKNHTLQ ADSYSPNLPK STTKAAKMMN QQRTKMEIKE
360 370 380 390 400
SSSFDFRTSE ISAKEELVLH PAKSSTSFDF LELNYSFDKN ADTTMKWQTK
410 420 430 440 450
AFPIVGEPLQ KHQSLDLGSL LFEGCSNSKP VNAAGRYFNS KVPITRTKST
460 470 480 490 500
PFELIQQRET KEVDSKENFS YLESQPHDSC FVEMQAQKVM HVSSAELNYS
510 520 530 540 550
LPYDSKHQIR NASNVKHHDS SALGVYSYIP LVENPYFSSW PPSGTSSKMS
560 570 580 590 600
LDLPEKQDGT VFPSSLLPTS STSLFSYYNS HDSLSLNSPT NISSLLNQES
610 620 630 640 650
AVLATAPRID DEIPPPLPVR TPESFIVVEE AGEFSPNVPK SLSSAVKVKI
660 670 680 690 700
GTSLEWGGTS EPKKFDDSVI LRPSKSVKLR SPKSELHQDR SSPPPPLPER
710 720 730 740 750
TLESFFLADE DCMQAQSIET YSTSYPDTME NSTSSKQTLK TPGKSFTRSK
760 770 780 790 800
SLKILRNMKK SICNSCPPNK PAESVQSNNS SSFLNFGFAN RFSKPKGPRN

PPPTWNI
Length:807
Mass (Da):91,705
Last modified:March 27, 2002 - v2
Checksum:i1ABE8AE89C9D9FBF
GO
Isoform 2 (identifier: Q9Y2R2-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:691
Mass (Da):78,769
Checksum:iA85EF69FDFDE9D58
GO
Isoform 3 (identifier: Q9Y2R2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     251-305: Missing.

Note: No experimental confirmation available.
Show »
Length:752
Mass (Da):85,138
Checksum:i826CAD31B7C20983
GO
Isoform 4 (identifier: Q9Y2R2-4) [UniParc]FASTAAdd to basket
Also known as: LYP3

The sequence of this isoform differs from the canonical sequence as follows:
     647-674: Missing.

Show »
Length:779
Mass (Da):88,647
Checksum:iAEA60DFC0BB05C11
GO
Isoform 5 (identifier: Q9Y2R2-5) [UniParc]FASTAAdd to basket

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.
Show »
Length:179
Mass (Da):20,932
Checksum:iE5F9FFCC426C6E2C
GO
Isoform 6 (identifier: Q9Y2R2-6) [UniParc]FASTAAdd to basket
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.
Show »
Length:668
Mass (Da):75,488
Checksum:i93025ACF91033DAA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51 – 52KP → NA in AAD00904 (PubMed:10068674).Curated2
Sequence conflicti51 – 52KP → NA in AAD00905 (PubMed:10068674).Curated2
Sequence conflicti126V → G in AAD27764 (PubMed:21044313).Curated1
Sequence conflicti147G → V in AAD27764 (PubMed:21044313).Curated1
Sequence conflicti240I → IV in AAD00905 (PubMed:10068674).Curated1
Sequence conflicti372A → V in AK310570 (PubMed:14702039).Curated1
Sequence conflicti420L → P in AAD27764 (PubMed:21044313).Curated1
Sequence conflicti742P → S in AAD27764 (PubMed:21044313).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072629201S → F Polymorphism; moderately reduces phosphatase activity. 1 PublicationCorresponds to variant rs7416347dbSNPEnsembl.1
Natural variantiVAR_072630263R → Q Polymorphism; reduces risk of SLE and RA but not IDDM; associated with reduced risk of ulcerative colitis but not of Crohn disease; severely reduces phosphatase activity. 3 PublicationsCorresponds to variant rs33996649dbSNPEnsembl.1
Natural variantiVAR_072631266R → W Polymorphism; severely reduces phosphatase activity. 1 PublicationCorresponds to variant rs72650670dbSNPEnsembl.1
Natural variantiVAR_022605620R → W in IDDM, RA, SLE and VTLG; also found in patients with Graves disease, Hashimoto thyroiditis and Addison disease; associated with reduced risk of Crohn disease but not of ulcerative colitis; affects CSK kinase binding; alters B cell receptor signaling and memory B cell proliferation. 12 PublicationsCorresponds to variant rs2476601dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044428124 – 250Missing in isoform 6. 1 PublicationAdd BLAST127
Alternative sequenceiVSP_039725137 – 160Missing in isoform 5. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_039726181 – 203ETRTI…PSSID → VSVILAHQTSLQNLFSQITP AHF in isoform 5. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_039727204 – 807Missing in isoform 5. 1 PublicationAdd BLAST604
Alternative sequenceiVSP_039728251 – 305Missing in isoform 3. 1 PublicationAdd BLAST55
Alternative sequenceiVSP_039729647 – 674Missing in isoform 4. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_005134685 – 807ELHQD…PTWNI → GKNFSWL in isoform 2. 1 PublicationAdd BLAST123
Alternative sequenceiVSP_044429788 – 807FANRF…PTWNI → MCVILLKS in isoform 6. 1 PublicationAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF001846 mRNA. Translation: AAD00904.1.
AF001847 mRNA. Translation: AAD00905.1.
GU479452 mRNA. Translation: ADD59979.1.
AF077031 mRNA. Translation: AAD27764.1.
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.
CCDSiCCDS863.1. [Q9Y2R2-1]
CCDS864.2. [Q9Y2R2-3]
RefSeqiNP_001180360.1. NM_001193431.2. [Q9Y2R2-4]
NP_001295226.1. NM_001308297.1.
NP_036543.4. NM_012411.5. [Q9Y2R2-3]
NP_057051.3. NM_015967.6. [Q9Y2R2-1]
UniGeneiHs.535276.

Genome annotation databases

EnsembliENST00000460620; ENSP00000433141; ENSG00000134242. [Q9Y2R2-5]
GeneIDi26191.
KEGGihsa:26191.
UCSCiuc001edt.4. human. [Q9Y2R2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF001846 mRNA. Translation: AAD00904.1.
AF001847 mRNA. Translation: AAD00905.1.
GU479452 mRNA. Translation: ADD59979.1.
AF077031 mRNA. Translation: AAD27764.1.
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.
CCDSiCCDS863.1. [Q9Y2R2-1]
CCDS864.2. [Q9Y2R2-3]
RefSeqiNP_001180360.1. NM_001193431.2. [Q9Y2R2-4]
NP_001295226.1. NM_001308297.1.
NP_036543.4. NM_012411.5. [Q9Y2R2-3]
NP_057051.3. NM_015967.6. [Q9Y2R2-1]
UniGeneiHs.535276.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ9Y2R2.
SMRiQ9Y2R2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117604. 14 interactors.
DIPiDIP-29953N.
IntActiQ9Y2R2. 23 interactors.
STRINGi9606.ENSP00000352833.

Chemistry databases

BindingDBiQ9Y2R2.
ChEMBLiCHEMBL2889.

PTM databases

DEPODiQ9Y2R2.
iPTMnetiQ9Y2R2.
PhosphoSitePlusiQ9Y2R2.

Polymorphism and mutation databases

BioMutaiPTPN22.
DMDMi20139861.

Proteomic databases

PaxDbiQ9Y2R2.
PeptideAtlasiQ9Y2R2.
PRIDEiQ9Y2R2.

Protocols and materials databases

DNASUi26191.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000460620; ENSP00000433141; ENSG00000134242. [Q9Y2R2-5]
GeneIDi26191.
KEGGihsa:26191.
UCSCiuc001edt.4. human. [Q9Y2R2-1]

Organism-specific databases

CTDi26191.
DisGeNETi26191.
GeneCardsiPTPN22.
HGNCiHGNC:9652. PTPN22.
HPAiCAB012209.
HPA004912.
HPA013350.
MalaCardsiPTPN22.
MIMi152700. phenotype.
180300. phenotype.
193200. phenotype.
222100. phenotype.
600716. gene.
neXtProtiNX_Q9Y2R2.
OpenTargetsiENSG00000134242.
Orphaneti397. 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.
3437. Vogt-Koyanagi-Harada disease.
PharmGKBiPA33995.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0789. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOVERGENiHBG103877.
InParanoidiQ9Y2R2.
KOiK18024.
PhylomeDBiQ9Y2R2.
TreeFamiTF351977.

Enzyme and pathway databases

BioCyciZFISH:HS05837-MONOMER.
BRENDAi3.1.3.48. 2681.
ReactomeiR-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
R-HSA-202430. Translocation of ZAP-70 to Immunological synapse.
SignaLinkiQ9Y2R2.
SIGNORiQ9Y2R2.

Miscellaneous databases

ChiTaRSiPTPN22. human.
EvolutionaryTraceiQ9Y2R2.
GeneWikiiPTPN22.
GenomeRNAii26191.
PROiQ9Y2R2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134242.
CleanExiHS_PTPN22.
ExpressionAtlasiQ9Y2R2. baseline and differential.
GenevisibleiQ9Y2R2. HS.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR016276. PTPN22.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000930. PTPN8_PTPN22. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTN22_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2R2
Secondary accession number(s): A0N0K6
, B1ALC8, D4NZ71, E9PLD8, E9PPI1, O95063, O95064, Q6IPX8, Q8WVM1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: March 27, 2002
Last modified: November 30, 2016
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.