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Protein

Tyrosine-protein kinase JAK1

Gene

JAK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:7615558). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529).2 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation2 Publications

Cofactori

Mg2+1 PublicationNote: Mn2+ was used in the in vitro kinase assay but Mg2+ is likely to be the in vivo cofactor.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei908ATPPROSITE-ProRule annotation1
Active sitei1003Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi881 – 889ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-1059683 Interleukin-6 signaling
R-HSA-110056 MAPK3 (ERK1) activation
R-HSA-112411 MAPK1 (ERK2) activation
R-HSA-1169408 ISG15 antiviral mechanism
R-HSA-1266695 Interleukin-7 signaling
R-HSA-449836 Other interleukin signaling
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-6788467 IL-6-type cytokine receptor ligand interactions
R-HSA-877300 Interferon gamma signaling
R-HSA-877312 Regulation of IFNG signaling
R-HSA-8854691 Interleukin-20 family signaling
R-HSA-8983432 Interleukin-15 signaling
R-HSA-8984722 Interleukin-35 Signalling
R-HSA-8985947 Interleukin-9 signaling
R-HSA-9020558 Interleukin-2 signaling
R-HSA-9020591 Interleukin-12 signaling
R-HSA-9020956 Interleukin-27 signaling
R-HSA-9020958 Interleukin-21 signaling
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912694 Regulation of IFNA signaling
SignaLinkiP23458
SIGNORiP23458

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase JAK1 (EC:2.7.10.22 Publications)
Alternative name(s):
Janus kinase 1
Short name:
JAK-1
Gene namesi
Name:JAK1
Synonyms:JAK1A, JAK1B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000162434.11
HGNCiHGNC:6190 JAK1
MIMi147795 gene
neXtProtiNX_P23458

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi3716
OpenTargetsiENSG00000162434
PharmGKBiPA29988

Chemistry databases

ChEMBLiCHEMBL2835
DrugBankiDB08877 Ruxolitinib
DB08895 Tofacitinib
GuidetoPHARMACOLOGYi2047

Polymorphism and mutation databases

BioMutaiJAK1
DMDMi215274013

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881081 – 1154Tyrosine-protein kinase JAK1Add BLAST1154

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei3PhosphotyrosineCombined sources1
Modified residuei228PhosphoserineCombined sources1
Modified residuei1034Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1035Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylated (PubMed:7615558). 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).2 Publications
Ubiquitinated by RNF125; leading to its degradation by the proteasome.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP23458
MaxQBiP23458
PaxDbiP23458
PeptideAtlasiP23458
PRIDEiP23458
ProteomicsDBi54097

PTM databases

CarbonylDBiP23458
GlyConnecti1869
iPTMnetiP23458
PhosphoSitePlusiP23458
SwissPalmiP23458

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSG00000162434 Expressed in 235 organ(s), highest expression level in blood
CleanExiHS_JAK1
GenevisibleiP23458 HS

Organism-specific databases

HPAiCAB013088

Interactioni

Subunit structurei

Interacts with IL31RA (PubMed:15194700). Interacts with IFNAR2 (PubMed:7759950). Interacts with IFNGR1 (PubMed:7615558). Interacts with JAKMIP1 (PubMed:15277531). Interacts with SHB (PubMed:12200137). Interacts with FER (By similarity).By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109919, 106 interactors
CORUMiP23458
DIPiDIP-133N
IntActiP23458, 51 interactors
MINTiP23458
STRINGi9606.ENSP00000343204

Chemistry databases

BindingDBiP23458

Structurei

Secondary structure

11154
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP23458
SMRiP23458
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23458

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 420FERMPROSITE-ProRule annotationAdd BLAST387
Domaini439 – 544SH2PROSITE-ProRule annotationAdd BLAST106
Domaini583 – 855Protein kinase 1PROSITE-ProRule annotationAdd BLAST273
Domaini875 – 1153Protein kinase 2PROSITE-ProRule annotationAdd BLAST279

Domaini

Possesses two phosphotransferase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for domain 1.By similarity
The FERM domain mediates interaction with JAKMIP1.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00900000140909
HOGENOMiHOG000049158
HOVERGENiHBG006195
InParanoidiP23458
KOiK11217
OMAiCFEKSEQ
OrthoDBiEOG091G01IS
PhylomeDBiP23458
TreeFamiTF327041

Family and domain databases

CDDicd14473 FERM_B-lobe, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR035963 FERM_2
IPR019748 FERM_central
IPR000299 FERM_domain
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016251 Tyr_kinase_non-rcpt_Jak/Tyk2
IPR020776 Tyr_kinase_non-rcpt_Jak1
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 2 hits
PIRSFiPIRSF000636 TyrPK_Jak, 1 hit
PRINTSiPR01823 JANUSKINASE
PR01824 JANUSKINASE1
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM00252 SH2, 1 hit
SM00219 TyrKc, 2 hits
SUPFAMiSSF47031 SSF47031, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS50057 FERM_3, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 2 hits
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS50001 SH2, 1 hit

Sequencei

Sequence statusi: Complete.

P23458-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MQYLNIKEDC NAMAFCAKMR SSKKTEVNLE APEPGVEVIF YLSDREPLRL
60 70 80 90 100
GSGEYTAEEL CIRAAQACRI SPLCHNLFAL YDENTKLWYA PNRTITVDDK
110 120 130 140 150
MSLRLHYRMR FYFTNWHGTN DNEQSVWRHS PKKQKNGYEK KKIPDATPLL
160 170 180 190 200
DASSLEYLFA QGQYDLVKCL APIRDPKTEQ DGHDIENECL GMAVLAISHY
210 220 230 240 250
AMMKKMQLPE LPKDISYKRY IPETLNKSIR QRNLLTRMRI NNVFKDFLKE
260 270 280 290 300
FNNKTICDSS VSTHDLKVKY LATLETLTKH YGAEIFETSM LLISSENEMN
310 320 330 340 350
WFHSNDGGNV LYYEVMVTGN LGIQWRHKPN VVSVEKEKNK LKRKKLENKH
360 370 380 390 400
KKDEEKNKIR EEWNNFSYFP EITHIVIKES VVSINKQDNK KMELKLSSHE
410 420 430 440 450
EALSFVSLVD GYFRLTADAH HYLCTDVAPP LIVHNIQNGC HGPICTEYAI
460 470 480 490 500
NKLRQEGSEE GMYVLRWSCT DFDNILMTVT CFEKSEQVQG AQKQFKNFQI
510 520 530 540 550
EVQKGRYSLH GSDRSFPSLG DLMSHLKKQI LRTDNISFML KRCCQPKPRE
560 570 580 590 600
ISNLLVATKK AQEWQPVYPM SQLSFDRILK KDLVQGEHLG RGTRTHIYSG
610 620 630 640 650
TLMDYKDDEG TSEEKKIKVI LKVLDPSHRD ISLAFFEAAS MMRQVSHKHI
660 670 680 690 700
VYLYGVCVRD VENIMVEEFV EGGPLDLFMH RKSDVLTTPW KFKVAKQLAS
710 720 730 740 750
ALSYLEDKDL VHGNVCTKNL LLAREGIDSE CGPFIKLSDP GIPITVLSRQ
760 770 780 790 800
ECIERIPWIA PECVEDSKNL SVAADKWSFG TTLWEICYNG EIPLKDKTLI
810 820 830 840 850
EKERFYESRC RPVTPSCKEL ADLMTRCMNY DPNQRPFFRA IMRDINKLEE
860 870 880 890 900
QNPDIVSEKK PATEVDPTHF EKRFLKRIRD LGEGHFGKVE LCRYDPEGDN
910 920 930 940 950
TGEQVAVKSL KPESGGNHIA DLKKEIEILR NLYHENIVKY KGICTEDGGN
960 970 980 990 1000
GIKLIMEFLP SGSLKEYLPK NKNKINLKQQ LKYAVQICKG MDYLGSRQYV
1010 1020 1030 1040 1050
HRDLAARNVL VESEHQVKIG DFGLTKAIET DKEYYTVKDD RDSPVFWYAP
1060 1070 1080 1090 1100
ECLMQSKFYI ASDVWSFGVT LHELLTYCDS DSSPMALFLK MIGPTHGQMT
1110 1120 1130 1140 1150
VTRLVNTLKE GKRLPCPPNC PDEVYQLMRK CWEFQPSNRT SFQNLIEGFE

ALLK
Length:1,154
Mass (Da):133,277
Last modified:November 25, 2008 - v2
Checksum:iA2C4BE27851ACABB
GO

Sequence cautioni

The sequence AAA36527 differs from that shown. Reason: Frameshift at positions 858 and 862.Curated
The sequence AAA36527 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti350H → D in AAA36527 (PubMed:1848670).Curated1
Sequence conflicti368Y → F in AAA36527 (PubMed:1848670).Curated1
Sequence conflicti898Missing in AAA36527 (PubMed:1848670).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041715973N → K1 PublicationCorresponds to variant dbSNP:rs34680086Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64174 mRNA Translation: AAA36527.1 Sequence problems.
AB209057 mRNA Translation: BAD92294.1
AC093427 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX06547.1
BC132729 mRNA Translation: AAI32730.1
CCDSiCCDS41346.1
PIRiA39577
RefSeqiNP_001307852.1, NM_001320923.1
NP_001308781.1, NM_001321852.1
NP_001308782.1, NM_001321853.1
NP_001308783.1, NM_001321854.1
NP_001308784.1, NM_001321855.1
NP_001308785.1, NM_001321856.1
NP_002218.2, NM_002227.3
UniGeneiHs.207538

Genome annotation databases

EnsembliENST00000342505; ENSP00000343204; ENSG00000162434
GeneIDi3716
KEGGihsa:3716
UCSCiuc001dbu.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64174 mRNA Translation: AAA36527.1 Sequence problems.
AB209057 mRNA Translation: BAD92294.1
AC093427 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX06547.1
BC132729 mRNA Translation: AAI32730.1
CCDSiCCDS41346.1
PIRiA39577
RefSeqiNP_001307852.1, NM_001320923.1
NP_001308781.1, NM_001321852.1
NP_001308782.1, NM_001321853.1
NP_001308783.1, NM_001321854.1
NP_001308784.1, NM_001321855.1
NP_001308785.1, NM_001321856.1
NP_002218.2, NM_002227.3
UniGeneiHs.207538

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3EYGX-ray1.90A865-1154[»]
3EYHX-ray2.00A865-1154[»]
4E4LX-ray2.00A/B/D/E854-1154[»]
4E4NX-ray1.90A/B854-1154[»]
4E5WX-ray1.86A/B854-1154[»]
4EHZX-ray2.17A/B/C/D854-1154[»]
4EI4X-ray2.22A/B854-1154[»]
4FK6X-ray2.20A/B854-1154[»]
4GS0X-ray1.80C1033-1036[»]
4I5CX-ray2.10A/B854-1154[»]
4IVBX-ray1.90A/B854-1154[»]
4IVCX-ray2.35A/B854-1154[»]
4IVDX-ray1.93A/B854-1154[»]
4K6ZX-ray2.73A854-1154[»]
4K77X-ray2.40A/B854-1154[»]
4L00X-ray1.80A/B561-860[»]
4L01X-ray1.90A/B561-860[»]
5E1EX-ray2.30A/B865-1154[»]
5HX8X-ray2.20A/B854-1154[»]
5IXDX-ray2.85A35-559[»]
5IXIX-ray2.57A35-559[»]
5KHWX-ray2.47A/B841-1154[»]
5KHXX-ray2.40A841-1154[»]
5L04X-ray2.10A31-577[»]
5WO4X-ray1.84A/B854-1154[»]
6AAHX-ray1.83A/B865-1154[»]
6BBUX-ray2.08A841-1154[»]
6C7YX-ray2.50A869-1153[»]
6DBNX-ray2.48A841-1154[»]
ProteinModelPortaliP23458
SMRiP23458
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109919, 106 interactors
CORUMiP23458
DIPiDIP-133N
IntActiP23458, 51 interactors
MINTiP23458
STRINGi9606.ENSP00000343204

Chemistry databases

BindingDBiP23458
ChEMBLiCHEMBL2835
DrugBankiDB08877 Ruxolitinib
DB08895 Tofacitinib
GuidetoPHARMACOLOGYi2047

PTM databases

CarbonylDBiP23458
GlyConnecti1869
iPTMnetiP23458
PhosphoSitePlusiP23458
SwissPalmiP23458

Polymorphism and mutation databases

BioMutaiJAK1
DMDMi215274013

Proteomic databases

EPDiP23458
MaxQBiP23458
PaxDbiP23458
PeptideAtlasiP23458
PRIDEiP23458
ProteomicsDBi54097

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342505; ENSP00000343204; ENSG00000162434
GeneIDi3716
KEGGihsa:3716
UCSCiuc001dbu.2 human

Organism-specific databases

CTDi3716
DisGeNETi3716
EuPathDBiHostDB:ENSG00000162434.11
GeneCardsiJAK1
HGNCiHGNC:6190 JAK1
HPAiCAB013088
MIMi147795 gene
neXtProtiNX_P23458
OpenTargetsiENSG00000162434
PharmGKBiPA29988
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00900000140909
HOGENOMiHOG000049158
HOVERGENiHBG006195
InParanoidiP23458
KOiK11217
OMAiCFEKSEQ
OrthoDBiEOG091G01IS
PhylomeDBiP23458
TreeFamiTF327041

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-1059683 Interleukin-6 signaling
R-HSA-110056 MAPK3 (ERK1) activation
R-HSA-112411 MAPK1 (ERK2) activation
R-HSA-1169408 ISG15 antiviral mechanism
R-HSA-1266695 Interleukin-7 signaling
R-HSA-449836 Other interleukin signaling
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-6788467 IL-6-type cytokine receptor ligand interactions
R-HSA-877300 Interferon gamma signaling
R-HSA-877312 Regulation of IFNG signaling
R-HSA-8854691 Interleukin-20 family signaling
R-HSA-8983432 Interleukin-15 signaling
R-HSA-8984722 Interleukin-35 Signalling
R-HSA-8985947 Interleukin-9 signaling
R-HSA-9020558 Interleukin-2 signaling
R-HSA-9020591 Interleukin-12 signaling
R-HSA-9020956 Interleukin-27 signaling
R-HSA-9020958 Interleukin-21 signaling
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912694 Regulation of IFNA signaling
SignaLinkiP23458
SIGNORiP23458

Miscellaneous databases

ChiTaRSiJAK1 human
EvolutionaryTraceiP23458
GeneWikiiJanus_kinase_1
GenomeRNAii3716
PROiPR:P23458
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162434 Expressed in 235 organ(s), highest expression level in blood
CleanExiHS_JAK1
GenevisibleiP23458 HS

Family and domain databases

CDDicd14473 FERM_B-lobe, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR035963 FERM_2
IPR019748 FERM_central
IPR000299 FERM_domain
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016251 Tyr_kinase_non-rcpt_Jak/Tyk2
IPR020776 Tyr_kinase_non-rcpt_Jak1
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 2 hits
PIRSFiPIRSF000636 TyrPK_Jak, 1 hit
PRINTSiPR01823 JANUSKINASE
PR01824 JANUSKINASE1
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM00252 SH2, 1 hit
SM00219 TyrKc, 2 hits
SUPFAMiSSF47031 SSF47031, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS50057 FERM_3, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 2 hits
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS50001 SH2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiJAK1_HUMAN
AccessioniPrimary (citable) accession number: P23458
Secondary accession number(s): Q59GQ2, Q9UD26
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 25, 2008
Last modified: November 7, 2018
This is version 206 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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