JAK3_HUMAN - dbPTM
JAK3_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID JAK3_HUMAN
UniProt AC P52333
Protein Name Tyrosine-protein kinase JAK3
Gene Name JAK3
Organism Homo sapiens (Human).
Sequence Length 1124
Subcellular Localization Endomembrane system
Peripheral membrane protein. Cytoplasm.
Protein 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..
Protein Sequence MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKASGILPVYHSLFALATEDLSCWFPPSHIFSVEDASTQVLLYRIRFYFPNWFGLEKCHRFGLRKDLASAILDLPVLEHLFAQHRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQRPGELLKTVSYKACLPPSLRDLIQGLSFVTRRRIRRTVRRALRRVAACQADRHSLMAKYIMDLERLDPAGAAETFHVGLPGALGGHDGLGLLRVAGDGGIAWTQGEQEVLQPFCDFPEIVDISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFRLTTDSQHFFCKEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNPLGPDYKGCLIRRSPTGTFLLVGLSRPHSSLRELLATCWDGGLHVDGVAVTLTSCCIPRPKEKSNLIVVQRGHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCRHEVVDGEARKTEVLLKVMDAKHKNCMESFLEAASLMSQVSYRHLVLLHGVCMAGDSTMVQEFVHLGAIDMYLRKRGHLVPASWKLQVVKQLAYALNYLEDKGLPHGNVSARKVLLAREGADGSPPFIKLSDPGVSPAVLSLEMLTDRIPWVAPECLREAQTLSLEADKWGFGATVWEVFSGVTMPISALDPAKKLQFYEDRQQLPAPKWTELALLIQQCMAYEPVQRPSFRAVIRDLNSLISSDYELLSDPTPGALAPRDGLWNGAQLYACQDPTIFEERHLKYISQLGKGNFGSVELCRYDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGRQSLRLVMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDYYVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKSCSPSAEFLRMMGCERDVPALCRLLELLEEGQRLPAPPACPAEVHELMKLCWAPSPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHSLSFS
Overview of Protein Modification Sites with Functional and Structural Information
Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations Modification Substrate Peptides
&
Secondary Structure		 ASA (%) Reference Orthologous
Protein Cluster
5Phosphorylation---MAPPSEETPLIP
---CCCCCCCCCCCC		47.1821722762
8PhosphorylationMAPPSEETPLIPQRS
CCCCCCCCCCCCHHH		21.2421722762
15PhosphorylationTPLIPQRSCSLLSTE
CCCCCHHHCCEEECC		11.6530108239
17PhosphorylationLIPQRSCSLLSTEAG
CCCHHHCCEEECCCC		33.3228348404
20PhosphorylationQRSCSLLSTEAGALH
HHHCCEEECCCCEEE		29.5126657352
21PhosphorylationRSCSLLSTEAGALHV
HHCCEEECCCCEEEE		29.8030108239
122UbiquitinationCHRFGLRKDLASAIL
HHHHCCCHHHHHHHH		63.24-
155PhosphorylationGRLPVGLSLKEQGEC
CCCCCCCCHHHHCHH		31.3124719451
157UbiquitinationLPVGLSLKEQGECLS
CCCCCCHHHHCHHHH		44.61-
186UbiquitinationQRPGELLKTVSYKAC
CCCCHHHHEEEHHHC		60.55-
189PhosphorylationGELLKTVSYKACLPP
CHHHHEEEHHHCCCH		26.5824260401
190PhosphorylationELLKTVSYKACLPPS
HHHHEEEHHHCCCHH		9.7724260401
197PhosphorylationYKACLPPSLRDLIQG
HHHCCCHHHHHHHHH		33.8124260401
209PhosphorylationIQGLSFVTRRRIRRT
HHHHHHHHHHHHHHH		19.2224719451
233PhosphorylationACQADRHSLMAKYIM
HHHCCHHHHHHHHHH		22.2722210691
237UbiquitinationDRHSLMAKYIMDLER
CHHHHHHHHHHCHHH		22.73-
361UbiquitinationDSQHFFCKEVAPPRL
CCCCCEECCCCCHHH		50.4921906983
361 (in isoform 1)Ubiquitination-50.4921906983
361 (in isoform 2)Ubiquitination-50.4921906983
361UbiquitinationDSQHFFCKEVAPPRL
CCCCCEECCCCCHHH		50.4921906983
388UbiquitinationTLDFAINKLKTGGSR
EHHHHHHHCCCCCCC		45.29-
390UbiquitinationDFAINKLKTGGSRPG
HHHHHHCCCCCCCCC		46.89-
391PhosphorylationFAINKLKTGGSRPGS
HHHHHCCCCCCCCCC		58.15-
398PhosphorylationTGGSRPGSYVLRRSP
CCCCCCCCEEEECCC		18.10-
482UbiquitinationCIPRPKEKSNLIVVQ
CCCCCCCCCCEEEEE		51.26-
483PhosphorylationIPRPKEKSNLIVVQR
CCCCCCCCCEEEEEC		37.6522985185
493PhosphorylationIVVQRGHSPPTSSLV
EEEECCCCCCCHHCC		35.0827080861
496PhosphorylationQRGHSPPTSSLVQPQ
ECCCCCCCHHCCCCC		34.0427080861
497PhosphorylationRGHSPPTSSLVQPQS
CCCCCCCHHCCCCCH		27.7027080861
498PhosphorylationGHSPPTSSLVQPQSQ
CCCCCCHHCCCCCHH		34.7328270605
506PhosphorylationLVQPQSQYQLSQMTF
CCCCCHHHHHHHCCC		19.37-
531PhosphorylationHENLGHGSFTKIYRG
HHHCCCCHHHHHHCC		24.8624719451
534UbiquitinationLGHGSFTKIYRGCRH
CCCCHHHHHHCCCCC		35.41-
536PhosphorylationHGSFTKIYRGCRHEV
CCHHHHHHCCCCCEE		11.51-
568PhosphorylationKHKNCMESFLEAASL
CCCCHHHHHHHHHHH		14.30-
577PhosphorylationLEAASLMSQVSYRHL
HHHHHHHHHHHHHHH		32.4929083192
580PhosphorylationASLMSQVSYRHLVLL
HHHHHHHHHHHHHHH		14.6029083192
581PhosphorylationSLMSQVSYRHLVLLH
HHHHHHHHHHHHHHH		11.8229083192
622PhosphorylationRGHLVPASWKLQVVK
CCCCCCCHHHHHHHH		20.7624719451
624UbiquitinationHLVPASWKLQVVKQL
CCCCCHHHHHHHHHH		26.92-
637 (in isoform 2)Phosphorylation-16.5925147952
652UbiquitinationHGNVSARKVLLAREG
CCCCCHHHHHHHHCC		36.63-
663PhosphorylationAREGADGSPPFIKLS
HHCCCCCCCCCEECC		29.9121722762
734UbiquitinationSALDPAKKLQFYEDR
HHCCHHHHHCCHHCH		50.02-
748AcetylationRQQLPAPKWTELALL
HHCCCCCHHHHHHHH		69.707662939
779PhosphorylationAVIRDLNSLISSDYE
HHHHHHHHHHHCCHH		34.0821722762
782PhosphorylationRDLNSLISSDYELLS
HHHHHHHHCCHHHHC		23.5821722762
783PhosphorylationDLNSLISSDYELLSD
HHHHHHHCCHHHHCC		36.9021722762
785PhosphorylationNSLISSDYELLSDPT
HHHHHCCHHHHCCCC		15.4915121872
789PhosphorylationSSDYELLSDPTPGAL
HCCHHHHCCCCCCCC		54.9226356563
823 (in isoform 2)Ubiquitination-34.1221906983
823UbiquitinationIFEERHLKYISQLGK
HHHHHHHHHHHHHCC		34.1221906983
823 (in isoform 1)Ubiquitination-34.1221906983
830 (in isoform 2)Ubiquitination-60.31-
830UbiquitinationKYISQLGKGNFGSVE
HHHHHHCCCCCCCEE		60.31-
855UbiquitinationTGALVAVKQLQHSGP
CCCEEEEEEHHHCCC		35.24-
876UbiquitinationQREIQILKALHSDFI
HHHHHHHHHHCCCEE		51.00-
880PhosphorylationQILKALHSDFIVKYR
HHHHHHCCCEEEEEC		34.7624719451
886PhosphorylationHSDFIVKYRGVSYGP
CCCEEEEECCCCCCC		11.1624719451
904PhosphorylationSLRLVMEYLPSGCLR
HHHHHHHHCCCCHHH		13.0518250158
929PhosphorylationDASRLLLYSSQICKG
CHHHHHHHHHHHHCC		13.2722461510
931PhosphorylationSRLLLYSSQICKGME
HHHHHHHHHHHCCCH		15.2622461510
935UbiquitinationLYSSQICKGMEYLGS
HHHHHHHCCCHHHCC		64.02-
939PhosphorylationQICKGMEYLGSRRCV
HHHCCCHHHCCCCCH		13.8918250158
959PhosphorylationARNILVESEAHVKIA
HHCCEEEECCCEEEH		32.3827251275
972 (in isoform 1)Ubiquitination-56.4521906983
972UbiquitinationIADFGLAKLLPLDKD
EHHCCHHHHCCCCCC		56.452190698
972 (in isoform 2)Ubiquitination-56.4521906983
978UbiquitinationAKLLPLDKDYYVVRE
HHHCCCCCCEEEEEC		56.14-
980PhosphorylationLLPLDKDYYVVREPG
HCCCCCCEEEEECCC		12.1420090780
981PhosphorylationLPLDKDYYVVREPGQ
CCCCCCEEEEECCCC		11.557559633
1117UbiquitinationFTAHPEGKHHSLSFS
EECCCCCCCCCCCCC		36.16-
1120PhosphorylationHPEGKHHSLSFS---
CCCCCCCCCCCC---		25.9830108239
1122PhosphorylationEGKHHSLSFS-----
CCCCCCCCCC-----		26.8523401153
1124PhosphorylationKHHSLSFS-------
CCCCCCCC-------		35.6221722762
Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)
Modified Location Modified Residue Modification Type of Upstream Proteins Gene Name of Upstream Proteins UniProt AC of Upstream Proteins Sources
785YPhosphorylationKinaseJAK3P52333
PSP
904YPhosphorylationKinaseJAK3P52333
PSP
939YPhosphorylationKinaseJAK3P52333
PSP
980YPhosphorylationKinaseJAK3P52333
PSP
981YPhosphorylationKinaseJAK3P52333
PSP
-KUbiquitinationE3 ubiquitin ligaseSKP2Q13309
PMID:24658274
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference

Oops, there are no descriptions of PTM sites of JAK3_HUMAN !!
Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location Modification Variant Position
(Distance <= 10) 		Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of JAK3_HUMAN !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
TIAF1_HUMANTIAF1physical
10733938
STA5A_HUMANSTAT5Aphysical
9047382
IL2RG_HUMANIL2RGphysical
7973659
STA5B_HUMANSTAT5Bphysical
9047382
IL2RG_HUMANIL2RGphysical
7973658
STA5A_HUMANSTAT5Aphysical
18250158
SOCS3_HUMANSOCS3physical
15385932
JAK1_HUMANJAK1physical
12207328
JAK2_HUMANJAK2physical
12207328
TYK2_HUMANTYK2physical
12207328
STAT3_HUMANSTAT3physical
12207328
STAT6_HUMANSTAT6physical
12207328
BAG2_HUMANBAG2physical
25852190
TCPB_HUMANCCT2physical
25852190
TCPG_HUMANCCT3physical
25852190
TCPD_HUMANCCT4physical
25852190
TCPZ_HUMANCCT6Aphysical
25852190
TCPQ_HUMANCCT8physical
25852190
GNAS3_HUMANGNASphysical
25852190
GNAS2_HUMANGNASphysical
25852190
ALEX_HUMANGNASphysical
25852190
GNAS1_HUMANGNASphysical
25852190
GPTC8_HUMANGPATCH8physical
25852190
MAGD2_HUMANMAGED2physical
25852190
NP1L1_HUMANNAP1L1physical
25852190
NP1L4_HUMANNAP1L4physical
25852190
RNPS1_HUMANRNPS1physical
25852190
SRRM2_HUMANSRRM2physical
25852190
TCPA_HUMANTCP1physical
25852190
TBB1_HUMANTUBB1physical
25852190
LNX1_HUMANLNX1physical
25814554
ARAF_HUMANARAFphysical
26496610
CAN2_HUMANCAPN2physical
26496610
TCPZ_HUMANCCT6Aphysical
26496610
CENPC_HUMANCENPCphysical
26496610
COX41_HUMANCOX4I1physical
26496610
CRY1_HUMANCRY1physical
26496610
KC1E_HUMANCSNK1Ephysical
26496610
DECR_HUMANDECR1physical
26496610
I5P2_HUMANINPP5Bphysical
26496610
RM23_HUMANMRPL23physical
26496610
TAF1_HUMANTAF1physical
26496610
TCPA_HUMANTCP1physical
26496610
TBA4A_HUMANTUBA4Aphysical
26496610
DHX16_HUMANDHX16physical
26496610
RB11A_HUMANRAB11Aphysical
26496610
NMI_HUMANNMIphysical
26496610
WDR46_HUMANWDR46physical
26496610
CHIP_HUMANSTUB1physical
26496610
SPTC1_HUMANSPTLC1physical
26496610
TCPD_HUMANCCT4physical
26496610
TCPQ_HUMANCCT8physical
26496610
MTF2_HUMANMTF2physical
26496610
RFIP2_HUMANRAB11FIP2physical
26496610
TNPO3_HUMANTNPO3physical
26496610
UBR5_HUMANUBR5physical
26496610
GEMI6_HUMANGEMIN6physical
26496610
CCNL2_HUMANCCNL2physical
26496610
LYSM2_HUMANLYSMD2physical
26496610
Drug and Disease Associations
Kegg Disease
H00091 T-B+Severe combined immunodeficiencies (SCIDs), including the following eight diseases: X-linked SCI
OMIM Disease
600802Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID)
Kegg Drug
D09783 Tofacitinib citrate (JAN/USAN); Tasocitinib citrate; Xeljanz (TN)
D09970 Tofacitinib (USAN); Tasocitinib
DrugBank
DB08895Tofacitinib
Regulatory Network of JAK3_HUMAN

loading...

Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783 AND TYR-785, ANDMASS SPECTROMETRY.
"Crystal structure of the Jak3 kinase domain in complex with astaurosporine analog.";
Boggon T.J., Li Y., Manley P.W., Eck M.J.;
Blood 106:996-1002(2005).
Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 814-1103 IN COMPLEX WITHSTAUROSPORINE ANALOG AFN941, AND PHOSPHORYLATION AT TYR-980 ANDTYR-981.
"Phosphorylation of human Jak3 at tyrosines 904 and 939 positivelyregulates its activity.";
Cheng H., Ross J.A., Frost J.A., Kirken R.A.;
Mol. Cell. Biol. 28:2271-2282(2008).
Cited for: PHOSPHORYLATION AT TYR-904 AND TYR-939, AND MUTAGENESIS OF LYS-855;TYR-904 AND TYR-939.
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells.";
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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-785, AND MASSSPECTROMETRY.
"Tyrosine 813 is a site of JAK2 autophosphorylation critical foractivation 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).
Cited for: AUTOPHOSPHORYLATION AT TYR-785, AND MUTAGENESIS OF TYR-785.

TOP
© 2024 Institute of Bioinformatics and Systems Biology, NYCU | Designed by : BiOmics Laboratory