P23458 · JAK1_HUMAN
- ProteinTyrosine-protein kinase JAK1
- GeneJAK1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1154 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552).
Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952).
Kinase partner for the type I interferon receptor IFNAR2 (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552).
In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950).
Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552).
Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952).
Kinase partner for the type I interferon receptor IFNAR2 (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552).
In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950).
Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552).
Catalytic activity
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
Cofactor
Note: Mn2+ was used in the in vitro kinase assay but Mg2+ is likely to be the in vivo cofactor.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosine-protein kinase JAK1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP23458
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endomembrane system ; Peripheral membrane protein
Note: Wholly intracellular, possibly membrane associated.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Autoinflammation, immune dysregulation, and eosinophilia (AIIDE)
- Note
- DescriptionAn autosomal dominant disorder characterized by immune dysregulation, severe atopic dermatitis, and chronic gastrointestinal inflammation. Additional features include asthma, food or environmental allergies, as well as poor overall growth with short stature.
- See alsoMIM:618999
Natural variants in AIIDE
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_084991 | 634 | A>D | in AIIDE; constitutive gain of function resulting in increased receptor signaling pathway via JAK-STAT; no effect on protein abundance | |
VAR_084992 | 703 | S>I | in AIIDE; increased activation of protein kinase activity; constitutive gain of function through the transactivation of associated JAK kinases; increased receptor signaling pathway via JAK-STAT |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_084991 | 634 | in AIIDE; constitutive gain of function resulting in increased receptor signaling pathway via JAK-STAT; no effect on protein abundance | |||
Sequence: A → D | ||||||
Mutagenesis | 658 | Constitutively active. Increased receptor signaling pathway via JAK-STAT. | ||||
Sequence: V → F | ||||||
Natural variant | VAR_084992 | 703 | in AIIDE; increased activation of protein kinase activity; constitutive gain of function through the transactivation of associated JAK kinases; increased receptor signaling pathway via JAK-STAT | |||
Sequence: S → I | ||||||
Mutagenesis | 908 | Loss of protein tyrosine kinase activity. | ||||
Sequence: K → A | ||||||
Natural variant | VAR_041715 | 973 | in dbSNP:rs34680086 | |||
Sequence: N → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 2,081 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000088108 | 1-1154 | UniProt | Tyrosine-protein kinase JAK1 | |||
Sequence: MQYLNIKEDCNAMAFCAKMRSSKKTEVNLEAPEPGVEVIFYLSDREPLRLGSGEYTAEELCIRAAQACRISPLCHNLFALYDENTKLWYAPNRTITVDDKMSLRLHYRMRFYFTNWHGTNDNEQSVWRHSPKKQKNGYEKKKIPDATPLLDASSLEYLFAQGQYDLVKCLAPIRDPKTEQDGHDIENECLGMAVLAISHYAMMKKMQLPELPKDISYKRYIPETLNKSIRQRNLLTRMRINNVFKDFLKEFNNKTICDSSVSTHDLKVKYLATLETLTKHYGAEIFETSMLLISSENEMNWFHSNDGGNVLYYEVMVTGNLGIQWRHKPNVVSVEKEKNKLKRKKLENKHKKDEEKNKIREEWNNFSYFPEITHIVIKESVVSINKQDNKKMELKLSSHEEALSFVSLVDGYFRLTADAHHYLCTDVAPPLIVHNIQNGCHGPICTEYAINKLRQEGSEEGMYVLRWSCTDFDNILMTVTCFEKSEQVQGAQKQFKNFQIEVQKGRYSLHGSDRSFPSLGDLMSHLKKQILRTDNISFMLKRCCQPKPREISNLLVATKKAQEWQPVYPMSQLSFDRILKKDLVQGEHLGRGTRTHIYSGTLMDYKDDEGTSEEKKIKVILKVLDPSHRDISLAFFEAASMMRQVSHKHIVYLYGVCVRDVENIMVEEFVEGGPLDLFMHRKSDVLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNLLLAREGIDSECGPFIKLSDPGIPITVLSRQECIERIPWIAPECVEDSKNLSVAADKWSFGTTLWEICYNGEIPLKDKTLIEKERFYESRCRPVTPSCKELADLMTRCMNYDPNQRPFFRAIMRDINKLEEQNPDIVSEKKPATEVDPTHFEKRFLKRIRDLGEGHFGKVELCRYDPEGDNTGEQVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEDGGNGIKLIMEFLPSGSLKEYLPKNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKEYYTVKDDRDSPVFWYAPECLMQSKFYIASDVWSFGVTLHELLTYCDSDSSPMALFLKMIGPTHGQMTVTRLVNTLKEGKRLPCPPNCPDEVYQLMRKCWEFQPSNRTSFQNLIEGFEALLK | |||||||
Modified residue | 3 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 228 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 228 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 537 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 857 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 963 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1034 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 1034 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 1035 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 1125 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Autophosphorylated (PubMed:7615558).
Phosphorylated by TYK2 on tyrosine residues in response to type-I interferon signaling, leading to its activation (PubMed:8232552).
Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558).
Dephosphorylation of Tyr-1034 and Tyr-1035 by PTPN2 negatively regulates cytokine-mediated signaling (PubMed:11909529).
Phosphorylated by TYK2 on tyrosine residues in response to type-I interferon signaling, leading to its activation (PubMed:8232552).
Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558).
Dephosphorylation of Tyr-1034 and Tyr-1035 by PTPN2 negatively regulates cytokine-mediated signaling (PubMed:11909529).
Ubiquitinated by RNF125; leading to its degradation by the proteasome.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed at higher levels in primary colon tumors than in normal colon tissue. The expression level in metastatic colon tumors is comparable to the expression level in normal colon tissue.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with IL31RA (PubMed:15194700).
Interacts with IFNGR1 (PubMed:7615558).
Interacts with JAKMIP1 (PubMed:15277531).
Interacts with SHB (PubMed:12200137).
Interacts (via N-terminus) with IL2RB and IL10RA (via its cytoplasmic domain) (PubMed:12133952).
Interacts with FER (By similarity).
Interacts with IFNGR1 (PubMed:7615558).
Interacts with JAKMIP1 (PubMed:15277531).
Interacts with SHB (PubMed:12200137).
Interacts (via N-terminus) with IL2RB and IL10RA (via its cytoplasmic domain) (PubMed:12133952).
Interacts with FER (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P23458 | ERBB2 P04626 | 2 | EBI-1383438, EBI-641062 | |
BINARY | P23458 | IFNAR2 P48551 | 3 | EBI-1383438, EBI-958408 | |
BINARY | P23458 | IL6ST P40189-1 | 3 | EBI-1383438, EBI-15742214 | |
BINARY | P23458 | JAK2 O60674 | 4 | EBI-1383438, EBI-518647 | |
BINARY | P23458 | OSMR Q99650 | 2 | EBI-1383438, EBI-2804080 | |
BINARY | P23458 | STAT1 P42224 | 6 | EBI-1383438, EBI-1057697 | |
BINARY | P23458 | STAT3 P40763 | 2 | EBI-1383438, EBI-518675 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 34-420 | FERM | ||||
Sequence: PGVEVIFYLSDREPLRLGSGEYTAEELCIRAAQACRISPLCHNLFALYDENTKLWYAPNRTITVDDKMSLRLHYRMRFYFTNWHGTNDNEQSVWRHSPKKQKNGYEKKKIPDATPLLDASSLEYLFAQGQYDLVKCLAPIRDPKTEQDGHDIENECLGMAVLAISHYAMMKKMQLPELPKDISYKRYIPETLNKSIRQRNLLTRMRINNVFKDFLKEFNNKTICDSSVSTHDLKVKYLATLETLTKHYGAEIFETSMLLISSENEMNWFHSNDGGNVLYYEVMVTGNLGIQWRHKPNVVSVEKEKNKLKRKKLENKHKKDEEKNKIREEWNNFSYFPEITHIVIKESVVSINKQDNKKMELKLSSHEEALSFVSLVDGYFRLTADAH | ||||||
Domain | 439-544 | SH2 | ||||
Sequence: GCHGPICTEYAINKLRQEGSEEGMYVLRWSCTDFDNILMTVTCFEKSEQVQGAQKQFKNFQIEVQKGRYSLHGSDRSFPSLGDLMSHLKKQILRTDNISFMLKRCC | ||||||
Domain | 583-855 | Protein kinase 1 | ||||
Sequence: LVQGEHLGRGTRTHIYSGTLMDYKDDEGTSEEKKIKVILKVLDPSHRDISLAFFEAASMMRQVSHKHIVYLYGVCVRDVENIMVEEFVEGGPLDLFMHRKSDVLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNLLLAREGIDSECGPFIKLSDPGIPITVLSRQECIERIPWIAPECVEDSKNLSVAADKWSFGTTLWEICYNGEIPLKDKTLIEKERFYESRCRPVTPSCKELADLMTRCMNYDPNQRPFFRAIMRDINKLEEQNPDI | ||||||
Domain | 875-1153 | Protein kinase 2 | ||||
Sequence: LKRIRDLGEGHFGKVELCRYDPEGDNTGEQVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEDGGNGIKLIMEFLPSGSLKEYLPKNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKEYYTVKDDRDSPVFWYAPECLMQSKFYIASDVWSFGVTLHELLTYCDSDSSPMALFLKMIGPTHGQMTVTRLVNTLKEGKRLPCPPNCPDEVYQLMRKCWEFQPSNRTSFQNLIEGFEALL |
Domain
The protein kinase 1 domain is also called the pseudokinase domain and has a regulatory role through the transactivation of other JAK kinases associated with signaling receptors.
The protein kinase 2 domain is the catalytically active domain.
The FERM domain mediates interaction with JAKMIP1.
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,154
- Mass (Da)133,277
- Last updated2008-11-25 v2
- ChecksumA2C4BE27851ACABB
Computationally mapped potential isoform sequences
There are 14 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A5F9ZH07 | A0A5F9ZH07_HUMAN | JAK1 | 1111 | ||
A0A5F9ZH73 | A0A5F9ZH73_HUMAN | JAK1 | 87 | ||
A0A5F9ZHI1 | A0A5F9ZHI1_HUMAN | JAK1 | 131 | ||
A0A5F9ZHK2 | A0A5F9ZHK2_HUMAN | JAK1 | 129 | ||
A0A5F9ZHN8 | A0A5F9ZHN8_HUMAN | JAK1 | 1110 | ||
A0A5F9ZI01 | A0A5F9ZI01_HUMAN | JAK1 | 345 | ||
A0A5F9ZI39 | A0A5F9ZI39_HUMAN | JAK1 | 1152 | ||
A0A5F9ZHW0 | A0A5F9ZHW0_HUMAN | JAK1 | 1119 | ||
A0A0A0N0M2 | A0A0A0N0M2_HUMAN | JAK1 | 1152 | ||
A0A8V8TPG3 | A0A8V8TPG3_HUMAN | JAK1 | 141 | ||
A0A8V8TPQ9 | A0A8V8TPQ9_HUMAN | JAK1 | 1153 | ||
A0A8V8TN56 | A0A8V8TN56_HUMAN | JAK1 | 444 | ||
A0A8V8TMY8 | A0A8V8TMY8_HUMAN | JAK1 | 823 | ||
A0A8V8TN11 | A0A8V8TN11_HUMAN | JAK1 | 183 |
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 350 | in Ref. 1; AAA36527 | ||||
Sequence: H → D | ||||||
Sequence conflict | 368 | in Ref. 1; AAA36527 | ||||
Sequence: Y → F | ||||||
Sequence conflict | 898 | in Ref. 1; AAA36527 | ||||
Sequence: Missing |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M64174 EMBL· GenBank· DDBJ | AAA36527.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AB209057 EMBL· GenBank· DDBJ | BAD92294.1 EMBL· GenBank· DDBJ | mRNA | ||
AC093427 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471059 EMBL· GenBank· DDBJ | EAX06547.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC132729 EMBL· GenBank· DDBJ | AAI32730.1 EMBL· GenBank· DDBJ | mRNA |