P52333 (JAK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase JAK3
EC=2.7.10.2

Alternative name(s):
Janus kinase 3
Short name=JAK-3
Leukocyte janus kinase
Short name=L-JAK

Gene names

Name:

JAK3

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	1124 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion. Ref.7 Ref.8 Ref.19
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with STAM2 and MYO18A By similarity. Interacts with SHB. Ref.10 Ref.11
Subcellular location	Endomembrane system; Peripheral membrane protein By similarity. Cytoplasm By similarity.
Tissue specificity	In NK cells and an NK-like cell line but not in resting T-cells or in other tissues. The S-form is more commonly seen in hematopoietic lines, whereas the B-form is detected in cells both of hematopoietic and epithelial origins. Ref.9
Domain	Possesses two phosphotransferase domains. The second one probably contains the catalytic domain By similarity, while the presence of slight differences suggest a different role for domain 1. Ref.12
Post-translational modification	Tyrosine phosphorylated in response to IL-2 and IL-4. Ref.13 Ref.15 Ref.20
Involvement in disease	Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:600802]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.13 Ref.15 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. Contains 1 FERM domain. Contains 2 protein kinase domains. Contains 1 SH2 domain.
Sequence caution	The sequence AAC50227.1 differs from that shown. Reason: Wrong choice of CDS. Was erroneously described as an isoform JAK3M while it is a fragmentary mRNA of INSL3.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity Innate immunity
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation SCID
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL JAK-STAT cascade involved in growth hormone signaling pathway Traceable author statement Ref.16. Source: UniProtKB STAT protein import into nucleus Traceable author statement Ref.16. Source: UniProtKB T cell homeostasis Traceable author statement Ref.16. Source: UniProtKB innate immune response Inferred from electronic annotation. Source: UniProtKB-KW interleukin-4-mediated signaling pathway Inferred from direct assay PubMed 7538655. Source: BHF-UCL negative regulation of FasL biosynthetic process Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of T-helper 1 cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of dendritic cell cytokine production Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of interleukin-10 production Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of interleukin-12 production Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of thymocyte apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara response to interleukin-15 Traceable author statement PubMed 7594533. Source: BHF-UCL response to interleukin-2 Traceable author statement PubMed 9973401. Source: BHF-UCL response to interleukin-9 Traceable author statement PubMed 7594533. Source: BHF-UCL tyrosine phosphorylation of STAT protein Traceable author statement Ref.16. Source: UniProtKB
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: InterPro cytosol Traceable author statement. Source: Reactome endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KHDRBS1	Q07666	2	EBI-518246,EBI-1364

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: P52333-1)

Also known as: JAK3S; Spleen-JAK3;

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 1 (identifier: P52333-2)

Also known as: JAK3B; Breast-JAK3;

The sequence of this isoform differs from the canonical sequence as follows:
     1071-1124: HELMKLCWAP...EGKHHSLSFS → SAAGLASVSQSVDWAGVSGKPAGA

Note: May be inactive as it lacks some part of the kinase domain.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1124

1124

Tyrosine-protein kinase JAK3

PRO_0000088115

Regions

Domain

24 – 356

333

FERM

Domain

375 – 475

101

SH2; atypical

Domain

521 – 781

261

Protein kinase 1

Domain

822 – 1111

290

Protein kinase 2

Nucleotide binding

828 – 836

9

ATP By similarity

Region

1 – 223

223

Interaction with cytokine/interferon/growth hormone receptors By similarity

Sites

Active site

949

1

Proton acceptor By similarity

Binding site

855

1

ATP By similarity

Amino acid modifications

Modified residue

8

1

Phosphothreonine By similarity

Modified residue

785

1

Phosphotyrosine; by autocatalysis Ref.13

Modified residue

904

1

Phosphotyrosine Ref.15

Modified residue

939

1

Phosphotyrosine Ref.15

Modified residue

980

1

Phosphotyrosine; by autocatalysis Ref.20

Modified residue

981

1

Phosphotyrosine; by autocatalysis Ref.20

Modified residue

1027

1

Phosphoserine By similarity

Modified residue

1031

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1071 – 1124

54

HELMK…SLSFS → SAAGLASVSQSVDWAGVSGK PAGA in isoform 1.

VSP_004989

Natural variant

12

1

P → L. Ref.26
Corresponds to variant rs56061056 [ dbSNP | Ensembl ].

VAR_041722

Natural variant

40

1

R → H. Ref.26
Corresponds to variant rs56384680 [ dbSNP | Ensembl ].

VAR_041723

Natural variant

58

1

Missing in T(-)B(+)NK(-) SCID. Ref.25

VAR_019337

Natural variant

100

1

Y → C in T(-)B(+)NK(-) SCID. Ref.21

VAR_006284

Natural variant

132

1

P → T. Ref.4 Ref.26
Corresponds to variant rs3212723 [ dbSNP | Ensembl ].

VAR_019336

Natural variant

151

1

P → R in T(-)B(+)NK(-) SCID. Ref.24 Ref.26
Corresponds to variant rs55778349 [ dbSNP | Ensembl ].

VAR_010492

Natural variant

169

1

D → E in T(-)B(+)NK(-) SCID. Ref.25

VAR_019338

Natural variant

481

1

E → G in T(-)B(+)NK(-) SCID. Ref.22

VAR_010493

Natural variant

521

1

L → V. Ref.26
Corresponds to variant rs55666418 [ dbSNP | Ensembl ].

VAR_041724

Natural variant

527

1

L → P in a gastric adenocarcinoma sample; somatic mutation. Ref.26

VAR_041725

Natural variant

582

1

R → W in T(-)B(+)NK(-) SCID. Ref.23

VAR_010494

Natural variant

586 – 592

7

Missing in T(-)B(+)NK(-) SCID; lack of phosphorylation in response to cytokine stimulation.

VAR_010495

Natural variant

589

1

G → S in T(-)B(+)NK(-) SCID. Ref.25

VAR_019339

Natural variant

688

1

I → F. Ref.26
Corresponds to variant rs35785705 [ dbSNP | Ensembl ].

VAR_041726

Natural variant

722

1

V → I. Ref.4 Ref.24 Ref.25 Ref.26
Corresponds to variant rs3213409 [ dbSNP | Ensembl ].

VAR_010496

Natural variant

759

1

C → R in T(-)B(+)NK(-) SCID; constitutive phosphorylation. Ref.22

VAR_010497

Natural variant

910

1

L → S in T(-)B(+)NK(-) SCID. Ref.24

VAR_010498

Experimental info

Mutagenesis

785

1

Y → F: Strong decrease of JAK3 phosphorylation. Ref.13

Mutagenesis

855

1

K → A: More than 90% loss of STAT5a activation. Ref.15

Mutagenesis

904

1

Y → F: About 40% loss of STAT5a activation. Ref.15

Mutagenesis

939

1

Y → F: About 80% loss of STAT5a activation. Ref.15

Sequence conflict

34

1

G → A in AAA19626. Ref.1

Sequence conflict

45

1

F → S in AAC50950. Ref.3

Sequence conflict

103

1

R → RS in AAC50950. Ref.3

Sequence conflict

147

1

Missing in AAC50542. Ref.6

Sequence conflict

187

1

T → A in AAC50542. Ref.6

Sequence conflict

212

1

R → A in AAA19626. Ref.1

Sequence conflict

212

1

R → A in AAC50950. Ref.3

Sequence conflict

222

1

R → P in AAA19626. Ref.1

Sequence conflict

222

1

R → P in AAC50950. Ref.3

Sequence conflict

271

1

L → F in AAC50950. Ref.3

Sequence conflict

287

1

Missing in AAC50950. Ref.3

Sequence conflict

610

1

M → I in AAC50226. Ref.2

Sequence conflict

845 – 846

2

GD → AH in AAA19626. Ref.1

Sequence conflict

895 – 897

3

RQS → EPE in AAC50950. Ref.3

Sequence conflict

896 – 897

2

QS → PE in AAA19626. Ref.1

Secondary structure

1

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1124

Helix Strand Turn

Details...

Beta strand

816 – 818

3

Helix

819 – 821

3

Beta strand

822 – 831

10

Beta strand

834 – 841

8

Beta strand

845 – 847

3

Beta strand

849 – 859

11

Helix

862 – 876

15

Beta strand

886 – 891

6

Beta strand

893 – 895

3

Beta strand

897 – 903

7

Helix

910 – 917

8

Helix

918 – 920

3

Helix

923 – 942

20

Helix

952 – 954

3

Beta strand

955 – 959

5

Beta strand

962 – 965

4

Helix

968 – 970

3

Beta strand

979 – 982

4

Helix

991 – 993

3

Helix

996 – 1001

6

Beta strand

1003 – 1005

3

Helix

1006 – 1021

16

Turn

1022 – 1024

3

Helix

1026 – 1028

3

Helix

1030 – 1037

8

Beta strand

1041 – 1043

3

Helix

1046 – 1055

10

Helix

1068 – 1077

10

Helix

1082 – 1084

3

Helix

1088 – 1097

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (JAK3S) (Spleen-JAK3) [UniParc]. Last modified July 19, 2004. Version 2. Checksum: 895D8563439B2B7C	FASTA	1,124	125,099
	10 20 30 40 50 60 MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA EDLCVQAAKA 70 80 90 100 110 120 SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY RIRFYFPNWF GLEKCHRFGL 130 140 150 160 170 180 RKDLASAILD LPVLEHLFAQ HRSDLVSGRL PVGLSLKEQG ECLSLAVLDL ARMAREQAQR 190 200 210 220 230 240 PGELLKTVSY KACLPPSLRD LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM 250 260 270 280 290 300 DLERLDPAGA AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD 310 320 330 340 350 360 ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR LTTDSQHFFC 370 380 390 400 410 420 KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV LRRSPQDFDS FLLTVCVQNP 430 440 450 460 470 480 LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL RELLATCWDG GLHVDGVAVT LTSCCIPRPK 490 500 510 520 530 540 EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR 550 560 570 580 590 600 HEVVDGEARK TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ 610 620 630 640 650 660 EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA RKVLLAREGA 670 680 690 700 710 720 DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ TLSLEADKWG FGATVWEVFS 730 740 750 760 770 780 GVTMPISALD PAKKLQFYED RQQLPAPKWT ELALLIQQCM AYEPVQRPSF RAVIRDLNSL 790 800 810 820 830 840 ISSDYELLSD PTPGALAPRD GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR 850 860 870 880 890 900 YDPLGDNTGA LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL 910 920 930 940 950 960 VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL AARNILVESE 970 980 990 1000 1010 1020 AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS DNIFSRQSDV WSFGVVLYEL 1030 1040 1050 1060 1070 1080 FTYCDKSCSP SAEFLRMMGC ERDVPALCRL LELLEEGQRL PAPPACPAEV HELMKLCWAP 1090 1100 1110 1120 SPQDRPSFSA LGPQLDMLWS GSRGCETHAF TAHPEGKHHS LSFS
	Isoform 1 (JAK3B) (Breast-JAK3) [UniParc]. Checksum: D491FADB3D772693	FASTA	1,094	121,268
	10 20 30 40 50 60 MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA EDLCVQAAKA 70 80 90 100 110 120 SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY RIRFYFPNWF GLEKCHRFGL 130 140 150 160 170 180 RKDLASAILD LPVLEHLFAQ HRSDLVSGRL PVGLSLKEQG ECLSLAVLDL ARMAREQAQR 190 200 210 220 230 240 PGELLKTVSY KACLPPSLRD LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM 250 260 270 280 290 300 DLERLDPAGA AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD 310 320 330 340 350 360 ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR LTTDSQHFFC 370 380 390 400 410 420 KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV LRRSPQDFDS FLLTVCVQNP 430 440 450 460 470 480 LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL RELLATCWDG GLHVDGVAVT LTSCCIPRPK 490 500 510 520 530 540 EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR 550 560 570 580 590 600 HEVVDGEARK TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ 610 620 630 640 650 660 EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA RKVLLAREGA 670 680 690 700 710 720 DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ TLSLEADKWG FGATVWEVFS 730 740 750 760 770 780 GVTMPISALD PAKKLQFYED RQQLPAPKWT ELALLIQQCM AYEPVQRPSF RAVIRDLNSL 790 800 810 820 830 840 ISSDYELLSD PTPGALAPRD GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR 850 860 870 880 890 900 YDPLGDNTGA LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL 910 920 930 940 950 960 VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL AARNILVESE 970 980 990 1000 1010 1020 AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS DNIFSRQSDV WSFGVVLYEL 1030 1040 1050 1060 1070 1080 FTYCDKSCSP SAEFLRMMGC ERDVPALCRL LELLEEGQRL PAPPACPAEV SAAGLASVSQ 1090 SVDWAGVSGK PAGA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes." Kawamura M., McVicar D.W., Johnston J.A., Blake T.B., Chen Y.-Q., Lal B.K., Lloyd A.R., Kelvin D.J., Staples J.E., Ortaldo J.R., O'Shea J.J. Proc. Natl. Acad. Sci. U.S.A. 91:6374-6378(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells." Lai K.S., Jin Y., Graham D.K., Witthuhn B.A., Ihle J.N., Liu E.T. J. Biol. Chem. 270:25028-25036(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORM 2).
[3]	"Genomic sequence, organization, and chromosomal localization of human JAK3." Riedy M.C., Dutra A.S., Blake T.B., Modi W., Lal B.K., Davis J., Bosse A., O'Shea J.J., Johnston J.A. Genomics 37:57-61(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	SeattleSNPs variation discovery resource Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-132 AND ILE-722.
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells." Verbsky J.W., Bach E.A., Fang Y.F., Yang L., Randolph D.A., Fields L.E. J. Biol. Chem. 271:13976-13980(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 36-191.
[7]	"Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2." Johnston J.A., Kawamura M., Kirken R.A., Chen Y.Q., Blake T.B., Shibuya K., Ortaldo J.R., McVicar D.W., O'Shea J.J. Nature 370:151-153(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN IL2 SIGNALING PATHWAY.
[8]	"JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of phosphatidylinositol-3' kinase." Sharfe N., Dadi H.K., Roifman C.M. Blood 86:2077-2085(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN IL7 SIGNALING PATHWAY.
[9]	"Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7." Musso T., Johnston J.A., Linnekin D., Varesio L., Rowe T.K., O'Shea J.J., McVicar D.W. J. Exp. Med. 181:1425-1431(1995) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"STAM2, a new member of the STAM family, binding to the Janus kinases." Endo K., Takeshita T., Kasai H., Sasaki Y., Tanaka N., Asao H., Kikuchi K., Yamada M., Chenb M., O'Shea J.J., Sugamura K. FEBS Lett. 477:55-61(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STAM2. Tissue: Fetal brain.
[11]	"IL-2 receptor signaling through the Shb adapter protein in T and NK cells." Lindholm C.K. Biochem. Biophys. Res. Commun. 296:929-936(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SHB.
[12]	"The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction." Saharinen P., Silvennoinen O. J. Biol. Chem. 277:47954-47963(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN.
[13]	"Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation of JAK2 by SH2-B beta." Kurzer J.H., Argetsinger L.S., Zhou Y.J., Kouadio J.L., O'Shea J.J., Carter-Su C. Mol. Cell. Biol. 24:4557-4570(2004) [PubMed] [Europe PMC] [Abstract] Cited for: AUTOPHOSPHORYLATION AT TYR-785, MUTAGENESIS OF TYR-785.
[14]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Phosphorylation of human Jak3 at tyrosines 904 and 939 positively regulates its activity." Cheng H., Ross J.A., Frost J.A., Kirken R.A. Mol. Cell. Biol. 28:2271-2282(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-904 AND TYR-939, MUTAGENESIS OF LYS-855; TYR-904 AND TYR-939.
[16]	"Janus kinases in immune cell signaling." Ghoreschi K., Laurence A., O'Shea J.J. Immunol. Rev. 228:273-287(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[17]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[19]	"IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis." Malamut G., El Machhour R., Montcuquet N., Martin-Lanneree S., Dusanter-Fourt I., Verkarre V., Mention J.J., Rahmi G., Kiyono H., Butz E.A., Brousse N., Cellier C., Cerf-Bensussan N., Meresse B. J. Clin. Invest. 120:2131-2143(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN IL15 SIGNALING PATHWAY.
[20]	"Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog." Boggon T.J., Li Y., Manley P.W., Eck M.J. Blood 106:996-1002(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 814-1103 IN COMPLEX WITH STAUROSPORINE ANALOG AFN941, PHOSPHORYLATION AT TYR-980 AND TYR-981.
[21]	"Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)." Macchi P., Villa A., Giliani S., Sacco M.G., Frattini A., Porta F., Ugazio A.G., Johnston J.A., Candotti F., O'Shea J.J., Vezzoni P., Notarangelo L.D. Nature 377:65-68(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT T(-)B(+)NK(-) SCID CYS-100.
[22]	"Structural and functional basis for JAK3-deficient severe combined immunodeficiency." Candotti F., Oakes S.A., Johnston J.A., Giliani S., Schumacher R.F., Mella P., Fiorini M., Ugazio A.G., Badolato R., Notarangelo L.D., Bozzi F., Macchi P., Strina D., Vezzoni P., Blaese R.M., O'Shea J.J., Villa A. Blood 90:3996-4003(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS T(-)B(+)NK(-) SCID GLY-481; 586-LEU--MET-592 DEL AND ARG-759.
[23]	"Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment." Bozzi F., Lefranc G., Villa A., Badolato R., Schumacher R.F., Khalil G., Loiselet J., Bresciani S., O'Shea J.J., Vezzoni P., Notarangelo L.D., Candotti F. Br. J. Haematol. 102:1363-1366(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT T(-)B(+)NK(-) SCID TRP-582.
[24]	"Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism." Schumacher R.F., Mella P., Badolato R., Fiorini M., Savoldi G., Giliani S., Villa A., Candotti F., Tampalini A., O'Shea J.J., Notarangelo L.D. Hum. Genet. 106:73-79(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS T(-)B(+)NK(-) SCID ARG-151 AND SER-910, VARIANT ILE-722.
[25]	"Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation." Roberts J.L., Lengi A., Brown S.M., Chen M., Zhou Y.-J., O'Shea J.J., Buckley R.H. Blood 103:2009-2018(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS T(-)B(+)NK(-) SCID ALA-58 DEL; GLU-169 AND SER-589, VARIANT ILE-722.
[26]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-12; HIS-40; THR-132; ARG-151; VAL-521; PRO-527; PHE-688 AND ILE-722.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

JAK3base

JAK3 mutation db

GeneReviews

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U09607 mRNA. Translation: AAA19626.1.
U31601 mRNA. Translation: AAC50226.1.
U31602 mRNA. Translation: AAC50227.1. Sequence problems.
U70065 Genomic DNA. Translation: AAC50950.1.
AF513860 Genomic DNA. Translation: AAM44860.1.
AC007201 Genomic DNA. Translation: AAD22741.1.
U57096 mRNA. Translation: AAC50542.1.

IPI

IPI00002773.
IPI00219418.

PIR

A55747.

RefSeq

NP_000206.2. NM_000215.3.

UniGene

Hs.515247.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YVJ	X-ray	2.55	A	814-1103	[»]
3LXK	X-ray	2.00	A	806-1124	[»]
3LXL	X-ray	1.74	A	806-1124	[»]
3PJC	X-ray	2.20	A	812-1124	[»]
4HVD	X-ray	1.85	A	811-1124	[»]
4HVG	X-ray	2.75	A	811-1124	[»]
4HVH	X-ray	2.30	A	811-1124	[»]
4HVI	X-ray	2.40	A	811-1124	[»]

ProteinModelPortal

P52333.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-274N.

IntAct

P52333. 8 interactions.

MINT

MINT-1497014.

STRING

9606.ENSP00000391676.

PTM databases

PhosphoSite

P52333.

Polymorphism databases

DMDM

50403745.

Proteomic databases

PaxDb

P52333.

PRIDE

P52333.

Protocols and materials databases

DNASU

3718.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000458235; ENSP00000391676; ENSG00000105639.
ENST00000527670; ENSP00000432511; ENSG00000105639.
ENST00000534444; ENSP00000436421; ENSG00000105639.

GeneID

3718.

KEGG

hsa:3718.

UCSC

uc002nhn.4. human.
uc002nho.2. human.

Organism-specific databases

CTD

3718.

GeneCards

GC19M017935.

HGNC

HGNC:6193. JAK3.

MIM

600173. gene.
600802. phenotype.

neXtProt

NX_P52333.

Orphanet

35078. Severe combined immunodeficiency T- B+ due to JAK3 deficiency.

PharmGKB

PA29990.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000049158.

HOVERGEN

HBG006195.

InParanoid

P52333.

KO

K11218.

OMA

DFLQRHR.

OrthoDB

EOG4001HH.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.
il4_2pathway. IL4-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P52333.

Bgee

P52333.

CleanEx

HS_JAK3.

Genevestigator

P52333.

GermOnline

ENSG00000105639. Homo sapiens.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR019749. Band_41_domain.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016251. Tyr_kinase_non-rcpt_Jak/Tyk2.
IPR020775. Tyr_kinase_non-rcpt_Jak3.
[Graphical view]

Pfam

PF07714. Pkinase_Tyr. 2 hits.
[Graphical view]

PIRSF

PIRSF000636. TyrPK_Jak. 1 hit.

PRINTS

PR01823. JANUSKINASE.
PR01826. JANUSKINASE3.
PR00109. TYRKINASE.

SMART

SM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 2 hits.

PROSITE

PS00660. FERM_1. False negative.
PS00661. FERM_2. False negative.
PS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P52333.

ChEMBL

CHEMBL2148.

EvolutionaryTrace

P52333.

GenomeRNAi

3718.

NextBio

14571.

SOURCE

Search...

Entry information

Entry name

JAK3_HUMAN

Accession

Primary (citable) accession number: P52333
Secondary accession number(s): Q13259 , Q13260, Q13611, Q99699, Q9Y6S2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 19, 2004
Last modified:	May 1, 2013
This is version 149 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.