Protein detail
JAK3
Tyrosine-protein kinase JAK3 (EC 2.7.10.2) (Janus kinase 3) (JAK-3) (Leukocyte janus kinase) (L-JAK)
Entry name JAK3 | UniProt ID | EVMP confidence score 0.50 |
Supporting publications (n) 3 | Transmembrane count | Protein classification Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteins |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic Information11
Protein Names
Tyrosine-protein kinase JAK3 (EC 2.7.10.2) (Janus kinase 3) (JAK-3) (Leukocyte janus kinase) (L-JAK)
Protein Class (6)
Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteins
Protein Function (8)
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Human disease related genes:Immune system diseases:Primary immunodeficiency
- Enzymes
- Cancer-related genes
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Ensembl
Entrez Gene Symbol
Gene Synonym (5)
JAK-3JAK3_HUMANJAKLL-JAKLJAK
Gene Description
Janus kinase 3
Chromosome
19
Position
17824780-17848071
Supporting publications (n)
3
EVMP confidence score
0.50
Fluorescence & Localization5
Tissue Specificfallopian tubeCell SpecificAstrocytesSingle-Nuclei Brain Specificependymal cellBlood Cell Specificbasophil
Function & Pathway8
Protein Function (8)
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Human disease related genes:Immune system diseases:Primary immunodeficiency
- Enzymes
- Cancer-related genes
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component (7)
Molecular Function (6)
Biological Process (3)
KEGG (15)
- hsa04062 Chemokine signaling pathway
- KEGG:hsa04151 PI3K-Akt signaling pathway
- KEGG:hsa04217 Necroptosis
- KEGG:hsa04550 Signaling pathways regulating pluripotency of stem cells
- KEGG:hsa04630 JAK-STAT signaling pathway
- KEGG:hsa04658 Th1 and Th2 cell differentiation
- KEGG:hsa04659 Th17 cell differentiation
- KEGG:hsa05161 Hepatitis B
- KEGG:hsa05162 Measles
- KEGG:hsa05166 Human T-cell leukemia virus 1 infection
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Reactome (20)
- R-hsa-1280215 cytokine signaling in immune system
- R-hsa-5663205 infectious disease
- R-hsa-8983432 interleukin 15 signaling
- R-hsa-8854691 interleukin 20 family signaling
- R-hsa-9020958 interleukin 21 signaling
- R-hsa-451927 interleukin 2 family signaling
- R-hsa-9020558 interleukin 2 signaling
- R-hsa-512988 interleukin 3 interleukin 5 and gm csf signaling
- R-hsa-6785807 interleukin 4 and interleukin 13 signaling
- R-hsa-1266695 interleukin 7 signaling
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Canonical Pathways
M232 Pid ecadherin stabilization pathway
Mediation Categories (4)
Adhesion and uptake mediationClinical-translation mediationImmune mediationReceptor-signaling mediation
Relations & Evidence46
Enzyme-Mediated Modification (5)
5 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| JAK3 | PTPN2 | P17706 | Y | 980 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:11909529 |
| JAK3 | PTPN2 | P17706 | Y | 981 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:11909529 |
| JAK3 | CDKL2 | Q92772 | Y | 506 | phosphorylation | RLIMS-P_ProtMapperProtMapper | ProtMapper:10889465 |
| JAK3 | IGF1R | P08069 | Y | 981 | phosphorylation | KEA | KEA:17570479 |
| JAK3 | LCK | P06239 | Y | 981 | phosphorylation | KEA | KEA:17570479 |
Ligand-Receptor Signaling (6)
6 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | OmniPath | No | Yes | No | No | No |
| intracellular | intracellular | ComPPI | No | No | No | No | No |
| intracellular | intracellular | GO_Intercell | No | No | No | No | No |
| intracellular | intracellular | UniProt_location | No | No | No | No | No |
| intracellular | intracellular | OmniPath | No | No | No | No | No |
| receptor | receptor | scConnect | No | Yes | No | No | No |
Regulatory Interaction Network (30)
30 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| CXCR4 | P61073 | JAK3 | P52333 | Yes | Yes | No | WangHPRDSignaLink3InnateDBSPIKE_LCTCRcuration_SignaLink3 | SignaLink3:23109003SignaLink3:11406370SignaLink3:12495636HPRD:10506573InnateDB:10506573SignaLink3:17169327SPIKE_LC:16189514 |
| JAK3 | P52333 | CTNB1 | P35222 | Yes | Yes | No | Sparser_ProtMapperPhosphoSite_norefSIGNORProtMapperRLIMS-P_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:33814980ProtMapper:28821617SIGNOR:28821617PhosphoSite:28821617 |
| I15RA | Q13261 | JAK3 | P52333 | Yes | Yes | No | WangSIGNOR | SIGNOR:30029643 |
| SOCS1 | O15524 | JAK3 | P52333 | Yes | No | Yes | NCI-PID_ProtMapperSIGNORProtMapperHPRDBioGRIDWang | ProtMapper:8458387ProtMapper:10950967ProtMapper:7822337ProtMapper:1948049ProtMapper:12459556ProtMapper:7973658HPRD:11133764ProtMapper:9799097SIGNOR:21508344ProtMapper:8624802ProtMapper:9380721ProtMapper:10201892BioGRID:27144517ProtMapper:8134361 |
| JAK3 | P52333 | SIG10 | Q96LC7 | Yes | Yes | No | WangphosphoELM_MIMPPhosphoSite_MIMPMIMPiPTMnetSIGNORProtMapperPhosphoSite_KEAKEAphosphoELM_KEAphosphoELMSIGNOR_ProtMapperPhosphoSite_ProtMapper | SIGNOR:11733002phosphoELM:11733002KEA:11733002ProtMapper:11733002 |
| JAK3 | P52333 | EZH2 | Q15910 | Yes | Yes | No | Sparser_ProtMapperSIGNORProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | PhosphoSite:27297789PhosphoSite:32631994ProtMapper:33327550ProtMapper:29556394SIGNOR:28868240ProtMapper:28868240 |
| JAK3 | P52333 | PLD2 | O14939 | Yes | Yes | No | Sparser_ProtMapperPhosphoSite_MIMPMIMPiPTMnetSIGNORProtMapperRLIMS-P_ProtMapperSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:20176813ProtMapper:21414324PhosphoSite:21414324ProtMapper:33368247PhosphoSite:23378025SIGNOR:20176813 |
| JAK3 | P52333 | NFAC1 | O95644 | Yes | Yes | No | iPTMnetSIGNORProtMapperPhosphoSitePhosphoSite_ProtMapper | SIGNOR:23263556PhosphoSite:23263556PhosphoSite:24465763 |
| JAK3 | P52333 | SHC1 | P29353 | Yes | Yes | No | WangPhosphoSite_norefPhosphoSiteiPTMnet | PhosphoSite:24795043 |
| JAK3 | P52333 | ELAV1 | Q15717 | Yes | No | No | Sparser_ProtMapperPhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefiPTMnetProtMapperRLIMS-P_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | PhosphoSite:24106086ProtMapper:24106086 |
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Protein Complex Composition (4)
4 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| HT_DM_Cluster67 | ALDH16A1DERAINSL3JAK1JAK2JAK3NAA20NAA25TYK2YJU2B | O60674P13994P23458P29597P51460P52333P61599Q14CX7Q8IZ83Q9Y315 | 1:1:1:1:1:1:1:1:1:1 | Compleat | Compleat:HC2854 | 22036573 |
| JAK3PTPN1 | P18031P52333 | 1:1 | PDB | PDB:8exm | ||
| JAK1JAK3 | P23458P52333 | 0:0 | KEGG-MEDICUS | |||
| JAK3 | P52333 | 4 | PDB | PDB:6aakPDB:6gl9PDB:4qpsPDB:6glaPDB:7apgPDB:5w86PDB:3zc6PDB:4v0gPDB:6glbPDB:4z16PDB:7uyvPDB:3zepPDB:7apfPDB:6hzv |
Isolation & Detection Technology (1)
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| PRotein Organic Solvent Precipitation；Differential Ultracentrifugation | Mass spectrometry | 1 | 32384937 |
Sequence, Structure & Domains14
Sequences
Length
1,124
Mass
125,099
Sequence
MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKASGILPVYHSLFALATEDLSCWFPPSHIFSVEDASTQVLLYRIRFYFPNWFGLEKCHRFGLRKDLASAILDLPVLEHLFAQHRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQRPGELLKTVSYKACLPPSLRDLIQGLSFVTRRRIRRTVRRALRRVAACQADRHSLMAKYIMDLERLDPAGAAETFHVGLPGALGGHDGLGLLRVAGDGGIAWTQGEQEVLQPFCDFPEIVDISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFRLTTDSQHFFCKEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNPLGPDYKGCLIRRSPTGTFLLVGLSRPHSSLRELLATCWDGGLHVDGVAVTLTSCCIPRPKEKSNLIVVQRGHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCRHEVVDGEARKTEVLLKVMDAKHKNCMESFLEAASLMSQVSYRHLVLLHGVCMAGDSTMVQEFVHLGAIDMYLRKRGHLVPASWKLQVVKQLAYALNYLEDKGLPHGNVSARKVLLAREGADGSPPFIKLSDPGVSPAVLSLEMLTDRIPWVAPECLREAQTLSLEADKWGFGATVWEVFSGVTMPISALDPAKKLQFYEDRQQLPAPKWTELALLIQQCMAYEPVQRPSFRAVIRDLNSLISSDYELLSDPTPGALAPRDGLWNGAQLYACQDPTIFEERHLKYISQLGKGNFGSVELCRYDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGRQSLRLVMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDYYVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKSCSPSAEFLRMMGCERDVPALCRLLELLEEGQRLPAPPACPAEVHELMKLCWAPSPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHSLSFS
Alternative Products
Event=Alternative splicing; Named isoforms=3; Name=2; Synonyms=JAK3S, Spleen-JAK3; IsoId=P52333-1; Sequence=Displayed; Name=1; Synonyms=JAK3B, Breast-JAK3; IsoId=P52333-2; Sequence=VSP_004989; Name=3; IsoId=P52333-4; Sequence=VSP_054165, VSP_054166
Alternative Sequence
597..619; TMVQEFVHLGAIDMYLRKRGHLV -> ESPPPTHPTPASPKSRLFFPPLF (in isoform 3); 620..1124; Missing (in isoform 3); 1071..1124; HELMKLCWAPSPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHSLSFS -> SAAGLASVSQSVDWAGVSGKPAGA (in isoform 1)
3D Structural Models
Turn
1022..1024
Helix
819..821; 862..877; 910..917; 918..920; 923..942; 952..954; 968..970; 991..993; 996..1001; 1006..1021; 1026..1028; 1030..1037; 1046..1055; 1068..1077; 1082..1084; 1088..1102
Beta Strand
816..818; 822..830; 832..841; 845..847; 849..859; 886..891; 893..896; 898..903; 955..959; 962..965; 979..982; 1003..1005; 1042..1044
3D Structure
X-ray crystallography (42)
Domain & Motif Annotations
Domain (CC)
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..
Domain (FT)
24..356; FERM; 375..475; SH2; atypical; 521..781; Protein kinase 1; 822..1111; Protein kinase 2
Region
1..223; Interaction with cytokine/interferon/growth hormone receptors
Protein Families (3)
- Protein kinase superfamily
- Tyr protein kinase family
- JAK subfamily
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.
Clinical Relevance7
Disease Involvement (4)
Cancer-related genesDisease variantFDA approved drug targetsSCID
Drug Targets
FDA approved drug targets
Drugs (46)
PACRITINIBQUIZARTINIBUPADACITINIBPHA-767491NEZULCITINIBPF-06651600GO-6976MIDOSTAURINWHI-P131CHEMBL:CHEMBL379975TOFACITINIBDECERNOTINIBGUSACITINIBSOTRASTAURINLAUROGUADINECERDULATINIBGILTERITINIBATEZOLIZUMABSELUMETINIBILGINATINIBR-333DELGOCITINIBPD-0166285PEFICITINIBSORAFENIBPF-562271NVP-TAE684RITLECITINIBADAVOSERTIBTASOCITINIBIZENCITINIBENTRECTINIBTAMATINIBTRICETAMIDERUXOLITINIBDEXAMETHASONEAT-9283R-348BARICITINIBRG-1530CENISERTIBCHEMBL:CHEMBL1997335CYC-116JNJ-7706621GW843682XAT9283
Antibody
Interaction Protein (2)
ENSG00000102316ENSG00000187109
Interaction Count
2
Interaction Dataset
intact_biogrid
Supporting Publications3
| PMID | Title | Abstract |
|---|---|---|
| 18802920 | Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes. | The exosomes were able to activate pro-MMP-2 and degrade type 1 collagen and gelatin, suggesting that the exosomal MT1-MMP was functionally active. The isolated exosomes were identified by their vesicular structure in electron microscopy and by exosomal marker proteins CD9 and tumor susceptibility gene (TSG101). The targeting of MT1-MMP in exosomes represents a novel mechanism for cancer cells to secrete membrane type metalloproteolytic activity into the extracellular space. Using cultured human fibrosarcoma (HT-1080) and melanoma (G361) cells we provide evidence that both the full-length 60 kDa and the proteolytically processed 43 kDa forms of MT1-MMP are secreted in exosomes. We hypothesized that some of the endosomal MT1-MMP could be directed to exosomes for extracellular release. |
| 38612385 | Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells. | Of the 31 exosome surface markers analyzed, a subset of biomarkers were significantly enriched in astrocytes (CD29, CD44, and CD49e), microglia-like cells (CD44), and neural stem cells (SSEA4). |
| 39166055 | Dental pulp stem cells regenerate neural tissue in degenerative disorders and stroke rehabilitation: A scope systematic review. | DPSC-derived exosomes suppressed the expression of IL-6, IL-1β, TNF-α, and TGF, key mediators of nerve tissue inflammation. |