Protein:JAK3 |
Protein Summary |
 Gene summary |
| Gene name: JAK3 | ASpdb.0 ID: 3718 | Gene | Gene symbol | JAK3 | Gene ID | 3718 |
| Gene name | Janus kinase 3 |
| Synonyms | JAK-3|JAK3_HUMAN|JAKL|L-JAK|LJAK |
| Cytomap | 19p13.11 |
| Type of gene | protein-coding |
| Description | tyrosine-protein kinase JAK3Janus kinase 3 (a protein tyrosine kinase, leukocyte)leukocyte Janus kinase |
| Modification date | 20240411 |
| UniProtAcc | P52333 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | JAK3 | GO:0004713 | protein tyrosine kinase activity | 7973658|18829468 |
| Gene | JAK3 | GO:0031234 | extrinsic component of cytoplasmic side of plasma membrane | 7568001 |
| Gene | JAK3 | GO:0035723 | interleukin-15-mediated signaling pathway | 7568001 |
| Gene | JAK3 | GO:0035771 | interleukin-4-mediated signaling pathway | 7538655 |
| Gene | JAK3 | GO:0038110 | interleukin-2-mediated signaling pathway | 7973659 |
| Gene | JAK3 | GO:0038113 | interleukin-9-mediated signaling pathway | 18829468 |
| Gene | JAK3 | GO:0070670 | response to interleukin-4 | 7538655|7594533 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P52333-1 | P52333-1_6gl9_A.pdb | 6GL9 | X-ray | 1.7 | A | 812 | 1103 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P52333 | JAK3 | P52333-1 | P52333-2 | 1124 | 1094 | 1071 | 1124 | Substitution | HELMKLCWAPSPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHSLSFS | SAAGLASVSQSVDWAGVSGKPAGA | 1071 | 1094 |
| P52333 | JAK3 | P52333-1 | P52333-4 | 1124 | 619 | 597 | 619 | Substitution | TMVQEFVHLGAIDMYLRKRGHLV | ESPPPTHPTPASPKSRLFFPPLF | 597 | 619 |
| P52333 | JAK3 | P52333-1 | P52333-4 | 1124 | 619 | 620 | 1124 | Deletion | none | none | 619 | 619 |
| Multiple sequence alignment of our canonical and alternatively spliced JAK3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of JAK3 |
| UniProt-id | ENSG | ENST | ENSP |
| P52333-1 | ENSG00000105639.21 | ENST00000458235.7 | ENSP00000391676.1 |
| P52333-1 | ENSG00000105639.21 | ENST00000527670.5 | ENSP00000432511.1 |
| P52333-2 | ENSG00000105639.21 | ENST00000534444.1 | ENSP00000436421.1 |
| UniProt-id | NM ID | NP ID |
| P52333-1 | NM_000215.3 | NP_000206.2 |
| Amino acid sequences of our canonical and alternatively spliced JAK3 |
| accession_id | Protein sequence |
| P52333-1 | MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKASGILPVYHSLFALATEDLSCWFPPSHIFSV EDASTQVLLYRIRFYFPNWFGLEKCHRFGLRKDLASAILDLPVLEHLFAQHRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQR PGELLKTVSYKACLPPSLRDLIQGLSFVTRRRIRRTVRRALRRVAACQADRHSLMAKYIMDLERLDPAGAAETFHVGLPGALGGHDGLGL LRVAGDGGIAWTQGEQEVLQPFCDFPEIVDISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFRLTTDSQHFFC KEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNPLGPDYKGCLIRRSPTGTFLLVGLSRPHSSL RELLATCWDGGLHVDGVAVTLTSCCIPRPKEKSNLIVVQRGHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCR HEVVDGEARKTEVLLKVMDAKHKNCMESFLEAASLMSQVSYRHLVLLHGVCMAGDSTMVQEFVHLGAIDMYLRKRGHLVPASWKLQVVKQ LAYALNYLEDKGLPHGNVSARKVLLAREGADGSPPFIKLSDPGVSPAVLSLEMLTDRIPWVAPECLREAQTLSLEADKWGFGATVWEVFS GVTMPISALDPAKKLQFYEDRQQLPAPKWTELALLIQQCMAYEPVQRPSFRAVIRDLNSLISSDYELLSDPTPGALAPRDGLWNGAQLYA CQDPTIFEERHLKYISQLGKGNFGSVELCRYDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGRQSLRL VMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDYYVVREPGQSP IFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKSCSPSAEFLRMMGCERDVPALCRLLELLEEGQRLPAPPACPAEVHELMKLCWAP |
| P52333-2 | MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKASGILPVYHSLFALATEDLSCWFPPSHIFSV EDASTQVLLYRIRFYFPNWFGLEKCHRFGLRKDLASAILDLPVLEHLFAQHRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQR PGELLKTVSYKACLPPSLRDLIQGLSFVTRRRIRRTVRRALRRVAACQADRHSLMAKYIMDLERLDPAGAAETFHVGLPGALGGHDGLGL LRVAGDGGIAWTQGEQEVLQPFCDFPEIVDISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFRLTTDSQHFFC KEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNPLGPDYKGCLIRRSPTGTFLLVGLSRPHSSL RELLATCWDGGLHVDGVAVTLTSCCIPRPKEKSNLIVVQRGHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCR HEVVDGEARKTEVLLKVMDAKHKNCMESFLEAASLMSQVSYRHLVLLHGVCMAGDSTMVQEFVHLGAIDMYLRKRGHLVPASWKLQVVKQ LAYALNYLEDKGLPHGNVSARKVLLAREGADGSPPFIKLSDPGVSPAVLSLEMLTDRIPWVAPECLREAQTLSLEADKWGFGATVWEVFS GVTMPISALDPAKKLQFYEDRQQLPAPKWTELALLIQQCMAYEPVQRPSFRAVIRDLNSLISSDYELLSDPTPGALAPRDGLWNGAQLYA CQDPTIFEERHLKYISQLGKGNFGSVELCRYDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGRQSLRL VMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDYYVVREPGQSP IFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKSCSPSAEFLRMMGCERDVPALCRLLELLEEGQRLPAPPACPAEVSAAGLASVSQ |
| P52333-4 | MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKASGILPVYHSLFALATEDLSCWFPPSHIFSV EDASTQVLLYRIRFYFPNWFGLEKCHRFGLRKDLASAILDLPVLEHLFAQHRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQR PGELLKTVSYKACLPPSLRDLIQGLSFVTRRRIRRTVRRALRRVAACQADRHSLMAKYIMDLERLDPAGAAETFHVGLPGALGGHDGLGL LRVAGDGGIAWTQGEQEVLQPFCDFPEIVDISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFRLTTDSQHFFC KEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNPLGPDYKGCLIRRSPTGTFLLVGLSRPHSSL RELLATCWDGGLHVDGVAVTLTSCCIPRPKEKSNLIVVQRGHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCR |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| JAK3 (go to UniProt):P52333 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P52333 | Domain | 521 | 781 | Note=Protein kinase 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Substitution;Start=597;End=619 |
| P52333 | Domain | 521 | 781 | Note=Protein kinase 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=620;End=1124 |
| P52333 | Domain | 822 | 1111 | Note=Protein kinase 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Substitution;Start=1071;End=1124 |
| P52333 | Domain | 822 | 1111 | Note=Protein kinase 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=620;End=1124 |
Gene Isoform Structures and Expression Levels for JAK3 |
| Gene structures of our canonical and alternative spliced genes of JAK3 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P52333-1 |
| 3D view using mol* of P52333-2 |
| 3D view using mol* of P52333-4 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P52333-1 |
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| pLDDT distribution across the protein length of P52333-2 |
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| pLDDT distribution across the protein length of P52333-4 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P52333-1 |
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| Ramachandran plot of P52333-4 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P52333-1 | 1.18 | 174 | 1.019 | 253.82 | 0.293 | 0.966 | 1.25 | 0.861 | 1.535 | 0.561 | 0.63 | 50,51,54,65,66,68,69,71,72,73,81,82,83,84,103,104, 117,343,347,350,351,355,356,365,367,368,371,377,37 8,379,403,404,407,408,410,485 |
| P52333-2 | 1.049 | 609 | 1.016 | 1612.443 | 0.476 | 0.771 | 1.005 | 0.462 | 1.185 | 0.389 | 0.717 | 527,528,529,530,531,532,533,535,554,556,569,600,60 2,603,604,605,606,607,609,610,611,612,613,614,615, 616,617,619,620,621,624,646,647,648,649,650,651,65 2,654,658,670,671,673,674,679,683,686,687,688,690, 691,692,706,707,710,717,718,721,722,723,724,725,72 7,728,729,730,731,734,786,789,790,791,792,793,808, 809,811,812,813,814,816,817,818,819,820,821,823,84 1,843,844,845,846,847,890,891,892,893,894,895 |
| P52333-4 | 1.182 | 169 | 1.064 | 232.211 | 0.228 | 0.97 | 1.3 | 0.99 | 1.403 | 0.706 | 0.977 | 50,51,54,65,66,68,69,71,72,73,82,83,84,103,104,343 ,346,347,350,351,355,356,363,365,367,368,371,377,3 78,379,380,403,408,485 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P52333-1_P52333-1_6gl9_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P52333-1_6gl9_A_P52333-2.pdb |
| 3D view using mol* of P52333-1_6gl9_A_P52333-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P52333-1_P52333-2.pdb |
| 3D view using mol* of P52333-1_P52333-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P52333-1_vs_P52333-2.png |
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| ./stats/secondary_structure/figure/P52333-1_vs_P52333-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P52333-1_vs_P52333-2.png |
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| ./stats/relative_asa/P52333-1_vs_P52333-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to JAK3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P52333 | JAK3 | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P52333 | JAK3 | DB08877 | Ruxolitinib | approved | inhibitor |
| P52333 | JAK3 | DB04716 | 2-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-one | experimental | |
| P52333 | JAK3 | DB14973 | Abrocitinib | approved, investigational | inhibitor |
| P52333 | JAK3 | DB15035 | Zanubrutinib | approved, investigational | inhibitor |
| P52333 | JAK3 | DB11817 | Baricitinib | approved, investigational | inhibitor |
| P52333 | JAK3 | DB08895 | Tofacitinib | approved, investigational | inhibitor |
| P52333 | JAK3 | DB11763 | Momelotinib | approved, investigational | inhibitor |
| P52333 | JAK3 | DB14924 | Ritlecitinib | approved, investigational | inhibitor |
| P52333 | JAK3 | DB06321 | R-348 | investigational |
Related Diseases to JAK3 |
| Previous studies relating to the alternative splicing of JAK3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| JAK3 | 15385932 | Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma. | Using a cDNA microarray, we found that suppressor of cytokine signaling 3 (SOCS3) is highly expressed in anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma (ALCL) cell lines. As SOCS3 is induced by activated signal transducer and activator of transcription 3 (STAT3), and ALK activates STAT3, we hypothesized that SOCS3 may play a role in ALK+ ALCL pathogenesis via the Janus kinase 3 (JAK3)-STAT3 pathway. Using ALCL cell lines, we show by coimmunoprecipitation experiments that SOCS3 physically binds with JAK3 in vitro, and that JAK3 inhibition by WHI-P154 downregulates SOCS3 expression. Western blot analysis confirmed expression of SOCS3 and also showed coexpression of phosphorylated (activated) STAT3 (pSTAT3). Direct sequencing of the SOCS3 gene showed no mutations or alternative splicing. In ALCL tumors that were assessed by immunohistochemistry, nine of 12 (75%) ALK+ tumors were SOCS3 positive and eight (67%) coexpressed pSTAT3. In comparison, 18 of 25 (72%) ALK-- tumors were SOCS3 positive and seven (28%) coexpressed pSTAT3. These results show that SOCS3 is overexpressed in ALCL, attributable to JAK3-STAT3 activation and likely related to ALK in ALK+ tumors. However, SOCS3 is also expressed in tumors that lack STAT3 and ALK suggesting alternative mechanisms of upregulation. | D017728 | Lymphoma, Large-Cell, Anaplastic |
Clinically important variants in JAK3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
| P52333 | P52333-1 | JAK3 | Indel | p.Leu521_Glu522delinsTer | Pathogenic |
| P52333 | P52333-1 | JAK3 | Indel | p.Leu521_Glu522delinsTer | Pathogenic |
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