P52333

※ Protein Information

Tag	Content
UniProt Accession	JAK3_HUMAN; P52333;
Entrez ID	3718
GenBank Protein ID
GenBank Nucleotide ID
Protein Name	Tyrosine-protein kinase JAK3 (EC 2.7.10.2) (Janus kinase 3) (JAK-3) (Leukocyte janus kinase) (L-JAK)
Gene Name	JAK3
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	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 cytopla(view all) Functional Description 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.
Sequence (Fasta)	MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA EDLCVQAAKA 60 SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY RIRFYFPNWF GLEKCHRFGL 120 RKDLASAILD LPVLEHLFAQ HRSDLVSGRL PVGLSLKEQG ECLSLAVLDL ARMAREQAQR 180 PGELLKTVSY KACLPPSLRD LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM 240 DLERLDPAGA AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD 300 ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR LTTDSQHFFC 360 KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV LRRSPQDFDS FLLTVCVQNP 420 LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL RELLATCWDG GLHVDGVAVT LTSCCIPRPK 480 EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR 540 HEVVDGEARK TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ 600 EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA RKVLLAREGA 660 DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ TLSLEADKWG FGATVWEVFS 720 GVTMPISALD PAKKLQFYED RQQLPAPKWT ELALLIQQCM AYEPVQRPSF RAVIRDLNSL 780 ISSDYELLSD PTPGALAPRD GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR 840 YDPLGDNTGA LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL 900 VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL AARNILVESE 960 AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS DNIFSRQSDV WSFGVVLYEL 1020 FTYCDKSCSP SAEFLRMMGC ERDVPALCRL LELLEEGQRL PAPPACPAEV HELMKLCWAP 1080 SPQDRPSFSA LGPQLDMLWS GSRGCETHAF TAHPEGKHHS LSFS 1125 Fasta Sequence >P52333\|JAK3\|Homo sapiens (Human) MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKASGILPVYHSLFALATEDLSCWFPPSHIFSVEDASTQVLLYRIRFYFPNWFGLEKCHRFGLRKDLASAILDLPVLEHLFAQHRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQRPGELLKTVSYKACLPPSLRDLIQGLSFVTRRRIRRTVRRALRRVAACQADRHSLMAKYIMDLERLDPAGAAETFHVGLPGALGGHDGLGLLRVAGDGGIAWTQGEQEVLQPFCDFPEIVDISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFRLTTDSQHFFCKEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNPLGPDYKGCLIRRSPTGTFLLVGLSRPHSSLRELLATCWDGGLHVDGVAVTLTSCCIPRPKEKSNLIVVQRGHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCRHEVVDGEARKTEVLLKVMDAKHKNCMESFLEAASLMSQVSYRHLVLLHGVCMAGDSTMVQEFVHLGAIDMYLRKRGHLVPASWKLQVVKQLAYALNYLEDKGLPHGNVSARKVLLAREGADGSPPFIKLSDPGVSPAVLSLEMLTDRIPWVAPECLREAQTLSLEADKWGFGATVWEVFSGVTMPISALDPAKKLQFYEDRQQLPAPKWTELALLIQQCMAYEPVQRPSFRAVIRDLNSLISSDYELLSDPTPGALAPRDGLWNGAQLYACQDPTIFEERHLKYISQLGKGNFGSVELCRYDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGRQSLRLVMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDYYVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKSCSPSAEFLRMMGCERDVPALCRLLELLEEGQRLPAPPACPAEVHELMKLCWAPSPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHSLSFS

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Tyrosine Phosphorylation	Extranodal nasal-type natural killer cell lymphoma	NKCL cell line	U	Y980	23689514
1	[Reference]: Here, we demonstrate that STAT3 activation mostly results from constitutive Janus kinase (JAK)3 phosphorylation on tyrosine 980, as observed in three of the four tested NKCL cell lines and in 20 of the 23 NKCL tumor samples under study

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	acute megakaryocytic leukaemia, ETP ALL
CTD (Curated) (count: 7) (view all)	MESH:C531617 ; Amyotrophic lateral sclerosis 1 MESH:D054429 ; Leukemia, Myelomonocytic, Juvenile MESH:D016393 ; Lymphoma, B-Cell MESH:D054391 ; Lymphoma, Extranodal NK-T-Cell MESH:D008479 ; Mediastinal Neoplasms MESH:D016511 ; Severe Combined Immunodeficiency MESH:C563440 ; Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, NK Cell-Negative
DisGeNet (Curated) (count: 15) (view all)	C0011991; Diarrhea C0021843; Intestinal Obstruction C0025289; Meningitis C0032285; Pneumonia C0085110; Severe Combined Immunodeficiency C0149727; LYMPH NODE ABNORMALITY C0231246; Failure to gain weight C0349639; Juvenile Myelomonocytic Leukemia C0581381; Recurrent upper respiratory tract infection C1328587; Panhypogammaglobulinemia C1833275; Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, NK Cell-Negative C1855781; Lack of delayed skin hypersensitivity reaction C1862939; AMYOTROPHIC LATERAL SCLEROSIS 1 C2315100; Pediatric failure to thrive C4020899; Autosomal recessive predisposition
HGMD (count: 40) (view all)	CD040903; Immunodeficiency, severe combined; Small deletions CD014802; Immunodeficiency, severe combined; Small deletions CD013173; Immunodeficiency, severe combined; Small deletions CD087405; Immunodeficiency, severe combined; Small deletions CG005050; Immunodeficiency, severe combined; Gross deletions CG973485; Immunodeficiency, severe combined; Gross deletions CI951946; Immunodeficiency, severe combined; Small insertions CM012981; Immunodeficiency, severe combined; Missense/nonsense CM012982; Immunodeficiency, severe combined; Missense/nonsense CM950704; Immunodeficiency, severe combined; Missense/nonsense CM082906; Acute myeloid leukaemia, association with; Missense/nonsense CM000171; Immunodeficiency, severe combined; Missense/nonsense CM014863; Immunodeficiency, severe combined; Missense/nonsense CM970793; Immunodeficiency, severe combined; Missense/nonsense CM970794; Immunodeficiency, severe combined; Missense/nonsense CM056346; Immunodeficiency, severe combined; Missense/nonsense CM950705; Immunodeficiency, severe combined; Missense/nonsense CM981105; Immunodeficiency, severe combined; Missense/nonsense CM040755; Immunodeficiency, severe combined; Missense/nonsense CM012983; Immunodeficiency, severe combined; Missense/nonsense CM012984; Immunodeficiency, severe combined; Missense/nonsense CM012985; Immunodeficiency, severe combined; Missense/nonsense CM012986; Immunodeficiency, severe combined; Missense/nonsense CM055290; Immunodeficiency, severe combined; Missense/nonsense CM000172; Immunodeficiency, severe combined; Missense/nonsense CM970795; Immunodeficiency, severe combined; Missense/nonsense CM012987; Immunodeficiency, severe combined; Missense/nonsense CM012988; Immunodeficiency, severe combined; Missense/nonsense CM087404; Immunodeficiency, severe combined; Missense/nonsense CM000173; Immunodeficiency, severe combined; Missense/nonsense CM040756; Immunodeficiency, severe combined; Missense/nonsense CM000174; Immunodeficiency, severe combined; Missense/nonsense CS013096; Immunodeficiency, severe combined; Splicing CS971783; Immunodeficiency, severe combined; Splicing CS962410; Immunodeficiency, severe combined; Splicing CS013097; Immunodeficiency, severe combined; Splicing CS040844; Immunodeficiency, severe combined; Splicing CS000223; Immunodeficiency, severe combined; Splicing CS075167; Immunodeficiency, severe combined; Splicing CS971782; Immunodeficiency, severe combined; Splicing
GWASdb (count: 5)	rs3212799; Triglycerides; coronary artery disease\|lipid metabolism disorder\|arteriosclerosis rs3212756; Triglycerides; coronary artery disease\|lipid metabolism disorder\|arteriosclerosis rs867174; Nephrolithiasis; nephrolithiasis rs3212701; Cognitive decline; cognitive disorder rs13345965; Cognitive impairment induced by topiramate; cognitive disorder

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 26) (view all)	1120 HPEGKHHSLSFS* dbPAF 15 TPLIPQRSCSLLSTE dbPAF 17 LIPQRSCSLLSTEAG dbPAF 189 GELLKTVSYKACLPP dbPAF 190 ELLKTVSYKACLPPS dbPAF 197 YKACLPPSLRDLIQG dbPAF 20 QRSCSLLSTEAGALH dbPAF 21 RSCSLLSTEAGALHV dbPAF 391 FAINKLKTGGSRPGS dbPAF 398 TGGSRPGSYVLRRSP dbPAF 498 GHSPPTSSLVQPQSQ dbPAF 5 *MAPPSEETPLIP dbPAF 506 LVQPQSQYQLSQMTF dbPAF 536 HGSFTKIYRGCRHEV dbPAF 568 KHKNCMESFLEAASL dbPAF 663 AREGADGSPPFIKLS dbPAF 782 RDLNSLISSDYELLS dbPAF 783 DLNSLISSDYELLSD dbPAF 785 NSLISSDYELLSDPT dbPAF 8 MAPPSEETPLIPQRS dbPAF 904 SLRLVMEYLPSGCLR dbPAF 929 DASRLLLYSSQICKG dbPAF 931 SRLLLYSSQICKGME dbPAF 939 QICKGMEYLGSRRCV dbPAF 980 LLPLDKDYYVVREPG dbPAF 981 LPLDKDYYVVREPGQ dbPAF
Ubiquitination (count: 16) (view all)	1117 FTAHPEGKHHSLSFS PLMD 186 QRPGELLKTVSYKAC PLMD 237 DRHSLMAKYIMDLER PLMD 361 DSQHFFCKEVAPPRL PLMD 388 TLDFAINKLKTGGSR PLMD 390 DFAINKLKTGGSRPG PLMD 482 CIPRPKEKSNLIVVQ PLMD 652 HGNVSARKVLLAREG PLMD 734 SALDPAKKLQFYEDR PLMD 823 IFEERHLKYISQLGK PLMD 830 KYISQLGKGNFGSVE PLMD 855 TGALVAVKQLQHSGP PLMD 876 QREIQILKALHSDFI PLMD 935 LYSSQICKGMEYLGS PLMD 972 IADFGLAKLLPLDKD PLMD 978 AKLLPLDKDYYVVRE PLMD

PTM

Modification Sites

Phosphorylation
(count: 26)
(view all)

1120      HPEGKHHSLSFS***     dbPAF
15        TPLIPQRSCSLLSTE     dbPAF
17        LIPQRSCSLLSTEAG     dbPAF
189       GELLKTVSYKACLPP     dbPAF
190       ELLKTVSYKACLPPS     dbPAF
197       YKACLPPSLRDLIQG     dbPAF

Ubiquitination
(count: 16)
(view all)

1117      FTAHPEGKHHSLSFS     PLMD
186       QRPGELLKTVSYKAC     PLMD
237       DRHSLMAKYIMDLER     PLMD
361       DSQHFFCKEVAPPRL     PLMD
388       TLDFAINKLKTGGSR     PLMD
390       DFAINKLKTGGSRPG     PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

G3V0F8	P52333	HPRD
O14492	P52333	HPRD
O14543	P52333	HPRD
O14744	P52333	HPRD
O15524	P52333	HPRD
O60674	P52333	HPRD
O75886	P52333	HPRD
O95411	P52333	HPRD
P02647	P52333	IntAct
P06239	P52333	HPRD
P06493	P52333	IntAct
P07332	P52333	HPRD
P08575	P52333	HPRD
P09327	P52333	HPRD
P14784	P52333	HPRD
P16871	P52333	HPRD
P17706	P52333	HPRD
P20963	P52333	HPRD
P21860	P52333	MINT
P23458	P52333	HPRD
P24394	P52333	HPRD
P25942	P52333	HPRD
P27986	P52333	HPRD
P31785	P52333	HPRD; DIP
P35568	P52333	HPRD
P40763	P52333	HPRD
P42229	P52333	HPRD
P48357	P52333	IntAct
P52333	P52333	HPRD
P52333	P60033	IntAct
P52333	P61073	HPRD
P52333	Q00403	IntAct
P52333	Q07666	HPRD; IntAct
P52333	Q14289	HPRD
P52333	Q15464	HPRD
P52333	Q92783	HPRD
P52333	Q92835	HPRD
P52333	Q96PU4	IntAct
P52333	Q9UM73	HPRD
P52333	Q9Y4H2	HPRD
P52333	Q9Y6K9	IntAct

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction