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	Intracytoplasmic membrane; Peripheral membrane proteinBy 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.
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.
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)
Biological process	protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc
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: InterPro Janus kinase activity Inferred from electronic annotation. Source: InterPro 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

Notes: 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

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

VAR_041722

Natural variant

40

1

R → H

VAR_041723

Natural variant

58

1

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

VAR_019337

Natural variant

100

1

Y → C in T(-)B(+)NK(-)SCID.

VAR_006284

Natural variant

132

1

P → T: dbSNP rs3212723.

VAR_019336

Natural variant

151

1

P → R in T(-)B(+)NK(-)SCID.

VAR_010492

Natural variant

169

1

D → E in T(-)B(+)NK(-)SCID.

VAR_019338

Natural variant

481

1

E → G in T(-)B(+)NK(-)SCID.

VAR_010493

Natural variant

521

1

L → V

VAR_041724

Natural variant

527

1

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

VAR_041725

Natural variant

582

1

R → W in T(-)B(+)NK(-)SCID.

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.

VAR_019339

Natural variant

688

1

I → F

VAR_041726

Natural variant

722

1

V → I: dbSNP rs3213409.

VAR_010496

Natural variant

759

1

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

VAR_010497

Natural variant

910

1

L → S in T(-)B(+)NK(-)SCID.

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) [UniParc]. Checksum: D491FADB3D772693		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) [UniParc].