Tyrosine-protein phosphatase non-receptor type 22

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

With

Entry

#Exp.

IntAct

Notes

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

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

Gene names

Name:	PTPN22
Synonyms:	PTPN8

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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Sequence length	807 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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Function	Seems to act on Cbl. May play a role in regulating the function of Cbl and its associated protein kinases.
Catalytic activity	Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate.
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.
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily. Contains 1 tyrosine-protein phosphatase domain.

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Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Systemic lupus erythematosus
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein amino acid dephosphorylation Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct protein tyrosine phosphatase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

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With	Entry	#Exp.	IntAct
CD247	P20963	2	EBI-1211241,EBI-1165705
CDH2	P19022	1	EBI-1211241,EBI-2256711
ERBB2	P04626	1	EBI-1211241,EBI-641062
GHR	P10912	1	EBI-1211241,EBI-286316
LCK	P06239	3	EBI-1211241,EBI-1348
NTRK1	P04629	1	EBI-1211241,EBI-1028226
PDGFRB	P09619	1	EBI-1211241,EBI-641237
PDPK1	O15530	1	EBI-1211241,EBI-717097
WAS	P42768	1	EBI-1211241,EBI-346375
ZAP70	P43403	2	EBI-1211241,EBI-1211276

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Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 807

807

Tyrosine-protein phosphatase non-receptor type 22

PRO_0000094775

Domain

24 – 289

266

Tyrosine-protein phosphatase

Active site

227

1

Phosphocysteine intermediate By similarity

Modified residue

635

1

Phosphoserine By similarity

Modified residue

692

1

Phosphoserine By similarity

Alternative sequence

685 – 807

123

ELHQD…PTWNI → GKNFSWL in isoform 2.

VSP_005134

Natural variant

620

1

R → W Confers susceptibility to systemic lupus erythematosus and type 1 diabetes mellitus; affects CSK kinase binding. dbSNP rs2476601. Ref.2 Ref.3 Ref.4

VAR_022605

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

420

1

L → P in AAD27764. Ref.2

Sequence conflict

742

1

P → S in AAD27764. Ref.2

1

.

807

Helix Strand Turn

Details...

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Sequence		Length	Mass (Da)
Isoform 1 (LyP1) [UniParc]. Last modified March 27, 2002. Version 2. Checksum: 1ABE8AE89C9D9FBF Show »	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 « Hide
Isoform 2 (LyP2). Checksum: A85EF69FDFDE9D58 Show »	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 « Hide

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[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: 10068674] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), CHARACTERIZATION.
[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]	"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. Behrens T.W. Am. J. Hum. Genet. 75:504-507(2004) [PubMed: 15273934] [Abstract] Cited for: VARIANT TRP-620.
[4]	"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: 15004560] [Abstract] Cited for: VARIANT TRP-620, CHARACTERIZATION OF VARIANT TRP-620.
+	Additional computationally mapped references.

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AF001846 mRNA. Translation: AAD00904.1.
AF001847 mRNA. Translation: AAD00905.1.
AF077031 mRNA. Translation: AAD27764.1.

IPI

IPI00219138.
IPI00298016.

RefSeq

NP_036543.3.
NP_057051.3.

UniGene

Hs.535276

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	[»]

ModBase

Search...

IntAct

Q9Y2R2. 13 interactions.

PhosphoSite

Q9Y2R2.

PRIDE

Q9Y2R2.

Ensembl

ENSG00000134242. Homo sapiens. [Contig view]

GeneID

26191.

KEGG

hsa:26191.

GeneCards

GC01M114157.

HGNC

HGNC:9652. PTPN22.

MIM

600716. gene.

PharmGKB

PA33995.

GenAtlas

Search...

HOGENOM

Q9Y2R2.

HOVERGEN

Q9Y2R2.

BRENDA

3.1.3.48. 247.

ArrayExpress

Q9Y2R2.

Bgee

Q9Y2R2.

CleanEx

HS_PTPN22.

GermOnline

ENSG00000134242. Homo sapiens.

InterPro

IPR016276. Non-rcpt_Tyr_Pase_8/22.
IPR000387. Tyr_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...

NextBio

48326.

SOURCE

Search...

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Entry name

PTN22_HUMAN

Accession

Primary (citable) accession number: Q9Y2R2
Secondary accession number(s): O95063, O95064

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	March 27, 2002
Last modified:	June 16, 2009
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Human chromosome 1

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

This entry describes 2 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