Reviewed, UniProtKB/Swiss-Prot P52333 (JAK3_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1124 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Tyrosine kinase of the non-receptor type, involved in the interleukin-2 and interleukin-4 signaling pathway. Phosphorylates STAT6, IRS1, IRS2 and PI3K.
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.
Subcellular location	Endomembrane system; Peripheral membrane protein By similarity. Note: Wholly intracellular, possibly membrane associated 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- and M-forms are detected in cells both of hematopoietic and epithelial origins.
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.
Post-translational modification	Tyrosine phosphorylated in response to IL-2 and IL-4. Ref.8
Involvement in disease	Defects in JAK3 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T-B+NK-SCID) [MIM:600802]. SCID refers to 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 with SCID present in infancy with 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. Ref.8 Ref.3 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. Contains 1 FERM domain. Contains 1 protein kinase domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	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
Gene Ontology (GO)
Cellular component	cytoskeleton Inferred from electronic annotation. Source: InterPro 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 binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KHDRBS1	Q07666	1	EBI-518246,EBI-1364

Alternative products

This entry describes 3 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.

Isoform 3 (identifier: P52333-3)

Also known as: JAK3M; Activated monocytes-JAK3;

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

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

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 Ref.8

Modified residue

980

1

Phosphotyrosine; by autocatalysis By similarity

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

Alternative sequence

1071 – 1124

54

HELMK…SLSFS → SCYSGWRDDICSMGWWPTVI SRWDLACSPCPRPLTITATT VQLPPTLHATAASVAVPNKT C in isoform 3.

VSP_004990

Natural variant

12

1

P → L Ref.14

VAR_041722

Natural variant

40

1

R → H Ref.14

VAR_041723

Natural variant

58

1

Missing in T(-)B(+)NK(-)SCID. Ref.13

VAR_019337

Natural variant

100

1

Y → C in T(-)B(+)NK(-)SCID. Ref.9

VAR_006284

Natural variant

132

1

P → T: dbSNP rs3212723. Ref.3 Ref.14

VAR_019336

Natural variant

151

1

P → R in T(-)B(+)NK(-)SCID. Ref.12

VAR_010492

Natural variant

169

1

D → E in T(-)B(+)NK(-)SCID. Ref.13

VAR_019338

Natural variant

481

1

E → G in T(-)B(+)NK(-)SCID. Ref.10

VAR_010493

Natural variant

521

1

L → V Ref.14

VAR_041724

Natural variant

527

1

L → P in a gastric adenocarcinoma sample; somatic mutation. Ref.14

VAR_041725

Natural variant

582

1

R → W in T(-)B(+)NK(-)SCID. Ref.11

VAR_010494

Natural variant

586 – 592

7

Missing in T(-)B(+)NK(-)SCID; lack of phosphorylation in response to cytokine stimulation. Ref.10

VAR_010495

Natural variant

589

1

G → S in T(-)B(+)NK(-)SCID. Ref.13

VAR_019339

Natural variant

688

1

I → F: dbSNP rs35785705. Ref.14

VAR_041726

Natural variant

722

1

V → I: dbSNP rs3213409. Ref.3 Ref.12 Ref.13 Ref.14

VAR_010496

Natural variant

759

1

C → R in T(-)B(+)NK(-)SCID; constitutive phosphorylation. Ref.10

VAR_010497

Natural variant

910

1

L → S in T(-)B(+)NK(-)SCID. Ref.12

VAR_010498

Experimental info

Sequence conflict

34

1

G → A in AAA19626. Ref.1

Sequence conflict

147

1

Missing in AAC50542. Ref.5

Sequence conflict

187

1

T → A in AAC50542. Ref.5

Sequence conflict

212

1

R → A in AAA19626. Ref.1

Sequence conflict

222

1

R → P in AAA19626. Ref.1

Sequence conflict

610

1

M → I in AAC50226. Ref.2

Sequence conflict

845 – 846

2

GD → AH in AAA19626. Ref.1

Sequence conflict

896 – 897

2

QS → PE in AAA19626. Ref.1

Secondary structure

1

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1124

Helix Strand Turn

Details...

Helix

819 – 821

3

Beta strand

822 – 830

9

Beta strand

835 – 841

7

Beta strand

843 – 847

5

Beta strand

851 – 856

6

Helix

864 – 877

14

Beta strand

886 – 889

4

Beta strand

893 – 896

4

Beta strand

899 – 902

4

Helix

910 – 916

7

Turn

917 – 920

4

Helix

923 – 942

20

Helix

952 – 954

3

Beta strand

955 – 959

5

Beta strand

962 – 965

4

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

1030 – 1038

9

Beta strand

1041 – 1043

3

Helix

1046 – 1055

10

Helix

1068 – 1077

10

Helix

1082 – 1084

3

Helix

1088 – 1100

13

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). 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
	Isoform 3 (JAK3M) (Activated monocytes-JAK3). Checksum: B6CFA497BD549C19	FASTA	1,131	125,729
	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 SCYSGWRDDI 1090 1100 1110 1120 1130 CSMGWWPTVI SRWDLACSPC PRPLTITATT VQLPPTLHAT AASVAVPNKT C

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: 8022790] [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: 7559633] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
[3]	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.
[4]	"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: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 8662778] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 36-191.
[6]	"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: 10899310] [Abstract] Cited for: INTERACTION WITH STAM2. Tissue: Fetal brain.
[7]	"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: 12200137] [Abstract] Cited for: INTERACTION WITH SHB.
[8]	"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: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-785, MASS SPECTROMETRY.
[9]	"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: 7659163] [Abstract] Cited for: VARIANT T(-)B(+)NK(-)SCID CYS-100.
[10]	"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: 9354668] [Abstract] Cited for: VARIANTS T(-)B(+)NK(-)SCID GLY-481; 586-LEU--MET-592 DEL AND ARG-759.
[11]	"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: 9753072] [Abstract] Cited for: VARIANT T(-)B(+)NK(-)SCID TRP-582.
[12]	"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: 10982185] [Abstract] Cited for: VARIANTS T(-)B(+)NK(-)SCID ARG-151 AND SER-910, VARIANT ILE-722.
[13]	"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: 14615376] [Abstract] Cited for: VARIANTS T(-)B(+)NK(-)SCID ALA-58 DEL; GLU-169 AND SER-589, VARIANT ILE-722.
[14]	"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: 17344846] [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

EMBLGenBankDDBJ

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

IPI

IPI00002773.
IPI00219417.
IPI00219418.

PIR

A55747.

RefSeq

NP_000206.2.

UniGene

Hs.515247

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YVJ	X-ray	2.55	A	814-1103	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:274N.

IntAct

P52333. 3 interactions.

PTM databases

PhosphoSite

P52333.

Proteomic databases

PRIDE

P52333.

Genome annotation databases

Ensembl

ENSG00000105639. Homo sapiens. [Contig view]

GeneID

3718.

KEGG

hsa:3718.

Organism-specific databases

GeneCards

GC19M017790.

HGNC

HGNC:6193. JAK3.

MIM

600173. gene.
600802. phenotype.

Orphanet

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

PharmGKB

PA29990.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P52333.

OMA

P52333. NCMESFL.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.

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.

Gene expression databases

ArrayExpress

P52333.

Bgee

P52333.

CleanEx

HS_JAK3.

GermOnline

ENSG00000105639. Homo sapiens.

Family and domain databases

InterPro

IPR019749. Band_41_domain.
IPR019747. FERM_CS.
IPR000299. FERM_domain.
IPR009127. JAK.
IPR009130. JAK3.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR016251. TyrPK_Jak.
[Graphical view]

Pfam

PF07714. Pkinase_Tyr. 2 hits.
[Graphical view]

PIRSF

PIRSF000636. TyrPK_Jak. 1 hit.

PRINTS

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

ProDom

PD000001. Prot_kinase. 2 hits.
PD000093. SH2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

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

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 Resources

NextBio

14571.

SOURCE

Search...

Entry information

Entry name

JAK3_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 19, 2004
Last modified:	June 16, 2009
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)