Q9Y2R2 (PTN22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	807 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Immunity
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Systemic lupus erythematosus
Molecular function	Hydrolase Protein phosphatase
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL T cell receptor signaling pathway Inferred from electronic annotation. Source: Compara 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 phosphoanandamide dephosphorylation Inferred from sequence or structural similarity. 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_component	internal 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_function	SH3 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD247	P20963	4	EBI-1211241,EBI-1165705
LCK	P06239	5	EBI-1211241,EBI-1348
ZAP70	P43403	4	EBI-1211241,EBI-1211276

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 807

807

Tyrosine-protein phosphatase non-receptor type 22

PRO_0000094775

Regions

Domain

24 – 289

266

Tyrosine-protein phosphatase

Region

227 – 233

7

Substrate binding

Sites

Active site

227

1

Phosphocysteine intermediate By similarity

Binding site

195

1

Substrate By similarity

Binding site

274

1

Substrate

Amino acid modifications

Modified residue

35

1

Phosphoserine; by PKC/PRKCD Ref.12

Modified residue

635

1

Phosphoserine By similarity

Modified residue

692

1

Phosphoserine By similarity

Disulfide bond

129 ↔ 227

Ref.13

Natural variations

Alternative sequence

124 – 250

127

Missing in isoform 6.

VSP_044428

Alternative sequence

137 – 160

24

Missing in isoform 5.

VSP_039725

Alternative sequence

181 – 203

23

ETRTI…PSSID → VSVILAHQTSLQNLFSQITP AHF in isoform 5.

VSP_039726

Alternative sequence

204 – 807

604

Missing in isoform 5.

VSP_039727

Alternative sequence

251 – 305

55

Missing in isoform 3.

VSP_039728

Alternative sequence

647 – 674

28

Missing in isoform 4.

VSP_039729

Alternative sequence

685 – 807

123

ELHQD…PTWNI → GKNFSWL in isoform 2.

VSP_005134

Alternative sequence

788 – 807

20

FANRF…PTWNI → MCVILLKS in isoform 6.

VSP_044429

Natural variant

620

1

R → 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

Mutagenesis

35

1

S → E: Loss of phosphorylation by PKC/PRKCD. Ref.12

Mutagenesis

36

1

T → E: No effect on phosphorylation by PKC/PRKCD. Ref.12

Mutagenesis

129

1

C → S: Decreases activity 2 fold. Ref.13

Mutagenesis

231

1

C → S: Decreases activity 7 fold. Ref.13

Sequence conflict

51 – 52

2

KP → NA in AAD00904. Ref.1

Sequence conflict

51 – 52

2

KP → NA in AAD00905. Ref.1

Sequence conflict

126

1

V → G in AAD27764. Ref.2

Sequence conflict

147

1

G → V in AAD27764. Ref.2

Sequence conflict

240

1

I → IV in AAD00905. Ref.1

Sequence conflict

372

1

A → V in AK310570. Ref.4

Sequence conflict

420

1

L → P in AAD27764. Ref.2

Sequence conflict

742

1

P → S in AAD27764. Ref.2

Secondary structure

1

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807

Helix Strand Turn

Details...

Helix

3 – 16

14

Helix

21 – 40

20

Helix

47 – 50

4

Helix

52 – 55

4

Beta strand

59 – 62

4

Helix

67 – 69

3

Beta strand

78 – 80

3

Beta strand

86 – 92

7

Beta strand

95 – 102

8

Helix

107 – 109

3

Helix

110 – 119

10

Beta strand

124 – 127

4

Beta strand

131 – 133

3

Beta strand

135 – 137

3

Beta strand

146 – 148

3

Beta strand

151 – 153

3

Beta strand

156 – 165

10

Beta strand

167 – 178

12

Beta strand

181 – 190

10

Beta strand

195 – 197

3

Helix

199 – 202

4

Helix

203 – 215

13

Beta strand

218 – 221

4

Beta strand

223 – 226

4

Beta strand

228 – 232

5

Helix

233 – 248

16

Helix

258 – 266

9

Helix

276 – 301

26

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (LyP1) [UniParc]. Last modified March 27, 2002. Version 2. Checksum: 1ABE8AE89C9D9FBF	FASTA	807	91,705
	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
	Isoform 2 (LyP2) [UniParc]. Checksum: A85EF69FDFDE9D58	FASTA	691	78,769
	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 EPKKFDDSVI LRPSKSVKLR SPKSGKNFSW L
	Isoform 3 [UniParc]. Checksum: 826CAD31B7C20983	FASTA	752	85,138
	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 SQAKHCIPEK NHTLQADSYS PNLPKSTTKA AKMMNQQRTK MEIKESSSFD 310 320 330 340 350 360 FRTSEISAKE ELVLHPAKSS TSFDFLELNY SFDKNADTTM KWQTKAFPIV GEPLQKHQSL 370 380 390 400 410 420 DLGSLLFEGC SNSKPVNAAG RYFNSKVPIT RTKSTPFELI QQRETKEVDS KENFSYLESQ 430 440 450 460 470 480 PHDSCFVEMQ AQKVMHVSSA ELNYSLPYDS KHQIRNASNV KHHDSSALGV YSYIPLVENP 490 500 510 520 530 540 YFSSWPPSGT SSKMSLDLPE KQDGTVFPSS LLPTSSTSLF SYYNSHDSLS LNSPTNISSL 550 560 570 580 590 600 LNQESAVLAT APRIDDEIPP PLPVRTPESF IVVEEAGEFS PNVPKSLSSA VKVKIGTSLE 610 620 630 640 650 660 WGGTSEPKKF DDSVILRPSK SVKLRSPKSE LHQDRSSPPP PLPERTLESF FLADEDCMQA 670 680 690 700 710 720 QSIETYSTSY PDTMENSTSS KQTLKTPGKS FTRSKSLKIL RNMKKSICNS CPPNKPAESV 730 740 750 QSNNSSSFLN FGFANRFSKP KGPRNPPPTW NI
	Isoform 4 (LYP3) [UniParc]. Checksum: AEA60DFC0BB05C11	FASTA	779	88,647
	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 SLSSAVKSVK LRSPKSELHQ 670 680 690 700 710 720 DRSSPPPPLP ERTLESFFLA DEDCMQAQSI ETYSTSYPDT MENSTSSKQT LKTPGKSFTR 730 740 750 760 770 SKSLKILRNM KKSICNSCPP NKPAESVQSN NSSSFLNFGF ANRFSKPKGP RNPPPTWNI
	Isoform 5 [UniParc]. Checksum: E5F9FFCC426C6E2C	FASTA	179	20,932
	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 SVLIIVMACM EYEMGKEAEK RKSDYIIRTL KVKFNSVSVI LAHQTSLQNL FSQITPAHF
	Isoform 6 (PTPN22.6) [UniParc]. Checksum: 93025ACF91033DAA	FASTA	668	75,488
	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 SVLIIPENFS VFSLIREMRT QRPSLVQTQE QYELVYNAVL ELFKRQMDVI RDKHSGTESQ 190 200 210 220 230 240 AKHCIPEKNH TLQADSYSPN LPKSTTKAAK MMNQQRTKME IKESSSFDFR TSEISAKEEL 250 260 270 280 290 300 VLHPAKSSTS FDFLELNYSF DKNADTTMKW QTKAFPIVGE PLQKHQSLDL GSLLFEGCSN 310 320 330 340 350 360 SKPVNAAGRY FNSKVPITRT KSTPFELIQQ RETKEVDSKE NFSYLESQPH DSCFVEMQAQ 370 380 390 400 410 420 KVMHVSSAEL NYSLPYDSKH QIRNASNVKH HDSSALGVYS YIPLVENPYF SSWPPSGTSS 430 440 450 460 470 480 KMSLDLPEKQ DGTVFPSSLL PTSSTSLFSY YNSHDSLSLN SPTNISSLLN QESAVLATAP 490 500 510 520 530 540 RIDDEIPPPL PVRTPESFIV VEEAGEFSPN VPKSLSSAVK VKIGTSLEWG GTSEPKKFDD 550 560 570 580 590 600 SVILRPSKSV KLRSPKSELH QDRSSPPPPL PERTLESFFL ADEDCMQAQS IETYSTSYPD 610 620 630 640 650 660 TMENSTSSKQ TLKTPGKSFT RSKSLKILRN MKKSICNSCP PNKPAESVQS NNSSSFLNFG MCVILLKS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.

IPI

IPI00103159.
IPI00219138.
IPI00298016.
IPI00970945.
IPI00970947.
IPI00985488.

RefSeq

NP_001180360.1. NM_001193431.1.
NP_036543.4. NM_012411.4.
NP_057051.3. NM_015967.5.

UniGene

Hs.535276.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2P6X	X-ray	1.90	A/B	1-302	[»]
2QCJ	X-ray	3.00	A/B	1-294	[»]
2QCT	X-ray	2.80	A/B	1-294	[»]
3BRH	X-ray	2.20	A/B	1-310	[»]
3H2X	X-ray	2.20	A	1-302	[»]
3OLR	X-ray	2.50	A/B/C/D	1-294	[»]
3OMH	X-ray	2.90	A/B/C/D	1-294	[»]

ProteinModelPortal

Q9Y2R2.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29953N.

IntAct

Q9Y2R2. 14 interactions.

STRING

9606.ENSP00000352833.

PTM databases

PhosphoSite

Q9Y2R2.

Polymorphism databases

DMDM

20139861.

Proteomic databases

PaxDb

Q9Y2R2.

PRIDE

Q9Y2R2.

Protocols and materials databases

DNASU

26191.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000359785; ENSP00000352833; ENSG00000134242.
ENST00000460620; ENSP00000433141; ENSG00000134242.

GeneID

26191.

KEGG

hsa:26191.

UCSC

uc001eds.3. human.
uc001edt.3. human.
uc009wgq.3. human.
uc021orx.1. human.

Organism-specific databases

CTD

26191.

GeneCards

GC01M114356.

HGNC

HGNC:9652. PTPN22.

HPA

CAB012209.
HPA004912.
HPA013350.

MIM

152700. phenotype.
600716. gene.

neXtProt

NX_Q9Y2R2.

PharmGKB

PA33995.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5599.

HOVERGEN

HBG103877.

InParanoid

Q9Y2R2.

KO

K01104.

OrthoDB

EOG4V1705.

Gene expression databases

ArrayExpress

Q9Y2R2.

Bgee

Q9Y2R2.

CleanEx

HS_PTPN22.

Genevestigator

Q9Y2R2.

GermOnline

ENSG00000134242. Homo sapiens.

Family and domain databases

InterPro

IPR016276. Non-rcpt_Tyr_Pase_8/22.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]

Pfam

PF00102. Y_phosphatase. 1 hit.
[Graphical view]

PIRSF

PIRSF000930. PTPN8_PTPN22. 1 hit.

PRINTS

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

Q9Y2R2.

ChEMBL

CHEMBL2889.

EvolutionaryTrace

Q9Y2R2.

GenomeRNAi

26191.

NextBio

35504118.

SOURCE

Search...

Entry information

Entry name

PTN22_HUMAN

Accession

Primary (citable) accession number: Q9Y2R2
Secondary accession number(s): A0N0K6 , 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:	May 1, 2013
This is version 116 of the entry and version 2 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.