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Reviewed, UniProtKB/Swiss-Prot P52333 (JAK3_HUMAN)

Last modified November 25, 2008. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1124 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

KHDRBS1Q076661EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11241124Tyrosine-protein kinase JAK3
PRO_0000088115

Regions

Domain24 – 356333FERM
Domain375 – 475101SH2; atypical
Domain521 – 781261Protein kinase 1
Domain822 – 1111290Protein kinase 2
Nucleotide binding828 – 8369ATP By similarity

Sites

Active site9491Proton acceptor By similarity
Binding site8551ATP By similarity

Amino acid modifications

Modified residue81Phosphothreonine By similarity
Modified residue7851Phosphotyrosine
Modified residue9801Phosphotyrosine; by autocatalysis By similarity
Modified residue10271Phosphoserine By similarity
Modified residue10311Phosphoserine By similarity

Natural variations

Alternative sequence1071 – 112454HELMK…SLSFS → SAAGLASVSQSVDWAGVSGK PAGA in isoform 1.
VSP_004989
Alternative sequence1071 – 112454HELMK…SLSFS → SCYSGWRDDICSMGWWPTVI SRWDLACSPCPRPLTITATT VQLPPTLHATAASVAVPNKT C in isoform 3.
VSP_004990
Natural variant121P → L
VAR_041722
Natural variant401R → H
VAR_041723
Natural variant581Missing in T(-)B(+)NK(-)SCID.
VAR_019337
Natural variant1001Y → C in T(-)B(+)NK(-)SCID.
VAR_006284
Natural variant1321P → T: dbSNP rs3212723.
VAR_019336
Natural variant1511P → R in T(-)B(+)NK(-)SCID.
VAR_010492
Natural variant1691D → E in T(-)B(+)NK(-)SCID.
VAR_019338
Natural variant4811E → G in T(-)B(+)NK(-)SCID.
VAR_010493
Natural variant5211L → V
VAR_041724
Natural variant5271L → P in a gastric adenocarcinoma sample; somatic mutation.
VAR_041725
Natural variant5821R → W in T(-)B(+)NK(-)SCID.
VAR_010494
Natural variant586 – 5927Missing in T(-)B(+)NK(-)SCID; lack of phosphorylation in response to cytokine stimulation.
VAR_010495
Natural variant5891G → S in T(-)B(+)NK(-)SCID.
VAR_019339
Natural variant6881I → F
VAR_041726
Natural variant7221V → I: dbSNP rs3213409.
VAR_010496
Natural variant7591C → R in T(-)B(+)NK(-)SCID; constitutive phosphorylation.
VAR_010497
Natural variant9101L → S in T(-)B(+)NK(-)SCID.
VAR_010498

Experimental info

Sequence conflict341G → A in AAA19626. Ref.1
Sequence conflict1471Missing in AAC50542. Ref.5
Sequence conflict1871T → A in AAC50542. Ref.5
Sequence conflict2121R → A in AAA19626. Ref.1
Sequence conflict2221R → P in AAA19626. Ref.1
Sequence conflict6101M → I in AAC50226. Ref.2
Sequence conflict845 – 8462GD → AH in AAA19626. Ref.1
Sequence conflict896 – 8972QS → PE in AAA19626. Ref.1

Secondary structure

.................................................. 1124
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (JAK3S) (Spleen-JAK3) [UniParc].

Last modified July 19, 2004. Version 2.
Checksum: 895D8563439B2B7C

FASTA1,124125,099
        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 

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Isoform 1 (JAK3B) (Breast-JAK3) [UniParc].

Checksum: D491FADB3D772693
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1,094121,268
Isoform 3 (JAK3M) (Activated monocytes-JAK3) [UniParc].