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UniProtKB - P23458 (JAK1_HUMAN)

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Protein

Tyrosine-protein kinase JAK1

Gene

JAK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

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-110056. MAPK3 (ERK1) activation.
R-HSA-112411. MAPK1 (ERK2) activation.
R-HSA-114604. GPVI-mediated activation cascade.
R-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-1266695. Interleukin-7 signaling.
R-HSA-392451. G beta:gamma signalling through PI3Kgamma.
R-HSA-447115. Interleukin-12 family signaling.
R-HSA-451927. Interleukin-2 signaling.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6783589. Interleukin-6 family signaling.
R-HSA-6783783. Interleukin-10 signaling.
R-HSA-6785807. Interleukin-4 and 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-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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6190. JAK1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • cytoskeleton Source: InterPro
  • cytosol Source: Reactome
  • endomembrane system Source: UniProtKB-SubCell
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • focal adhesion Source: UniProtKB
  • nucleus Source: BHF-UCL
Complete GO annotation...

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.

PTM databases

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.
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

Show more details

GO - Molecular functioni

  • CCR5 chemokine receptor binding Source: Ensembl
  • growth hormone receptor binding Source: BHF-UCL
  • protein phosphatase binding Source: UniProtKB
  • receptor binding Source: GO_Central
  • ubiquitin protein ligase binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi109919. 97 interactors.
DIPiDIP-133N.
IntActiP23458. 49 interactors.
MINTiMINT-145830.
STRINGi9606.ENSP00000343204.

Chemistry databases

BindingDBiP23458.

Structurei

Secondary structure

11154
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi36 – 39Combined sources4
Beta strandi43 – 45Combined sources3
Beta strandi48 – 50Combined sources3
Beta strandi52 – 56Combined sources5
Helixi57 – 67Combined sources11
Turni72 – 74Combined sources3
Helixi75 – 77Combined sources3
Beta strandi78 – 82Combined sources5
Turni83 – 86Combined sources4
Beta strandi94 – 97Combined sources4
Beta strandi103 – 109Combined sources7
Turni114 – 117Combined sources4
Beta strandi121 – 123Combined sources3
Beta strandi149 – 151Combined sources3
Helixi152 – 167Combined sources16
Helixi179 – 204Combined sources26
Turni208 – 210Combined sources3
Helixi217 – 220Combined sources4
Helixi223 – 230Combined sources8
Helixi234 – 252Combined sources19
Helixi254 – 259Combined sources6
Helixi263 – 277Combined sources15
Beta strandi278 – 280Combined sources3
Beta strandi284 – 289Combined sources6
Beta strandi291 – 293Combined sources3
Beta strandi299 – 304Combined sources6
Beta strandi313 – 318Combined sources6
Turni319 – 321Combined sources3
Beta strandi322 – 327Combined sources6
Beta strandi364 – 367Combined sources4
Helixi369 – 371Combined sources3
Beta strandi372 – 378Combined sources7
Beta strandi381 – 386Combined sources6
Beta strandi391 – 395Combined sources5
Helixi399 – 416Combined sources18
Helixi425 – 427Combined sources3
Helixi430 – 437Combined sources8
Helixi446 – 456Combined sources11
Beta strandi463 – 467Combined sources5
Beta strandi472 – 482Combined sources11
Beta strandi493 – 503Combined sources11
Beta strandi506 – 509Combined sources4
Beta strandi516 – 518Combined sources3
Helixi519 – 527Combined sources9
Beta strandi529 – 533Combined sources5
Beta strandi536 – 538Combined sources3
Beta strandi555 – 557Combined sources3
Helixi559 – 562Combined sources4
Helixi569 – 572Combined sources4
Beta strandi575 – 578Combined sources4
Helixi580 – 582Combined sources3
Beta strandi583 – 592Combined sources10
Beta strandi595 – 603Combined sources9
Beta strandi616 – 624Combined sources9
Helixi629 – 644Combined sources16
Beta strandi653 – 659Combined sources7
Beta strandi662 – 668Combined sources7
Helixi675 – 682Combined sources8
Turni683 – 685Combined sources3
Helixi688 – 707Combined sources20
Helixi717 – 719Combined sources3
Beta strandi720 – 724Combined sources5
Beta strandi727 – 731Combined sources5
Beta strandi734 – 737Combined sources4
Helixi744 – 746Combined sources3
Helixi749 – 754Combined sources6
Turni755 – 758Combined sources4
Helixi761 – 765Combined sources5
Helixi767 – 769Combined sources3
Helixi774 – 787Combined sources14
Turni788 – 790Combined sources3
Turni793 – 796Combined sources4
Helixi799 – 807Combined sources9
Helixi818 – 827Combined sources10
Helixi832 – 834Combined sources3
Helixi838 – 848Combined sources11
Helixi872 – 874Combined sources3
Beta strandi875 – 883Combined sources9
Beta strandi885 – 894Combined sources10
Beta strandi898 – 900Combined sources3
Beta strandi902 – 910Combined sources9
Helixi919 – 930Combined sources12
Beta strandi940 – 945Combined sources6
Turni947 – 950Combined sources4
Beta strandi952 – 957Combined sources6
Helixi964 – 971Combined sources8
Turni972 – 974Combined sources3
Helixi977 – 996Combined sources20
Beta strandi998 – 1000Combined sources3
Helixi1006 – 1008Combined sources3
Beta strandi1009 – 1013Combined sources5
Beta strandi1016 – 1019Combined sources4
Beta strandi1034 – 1036Combined sources3
Beta strandi1039 – 1041Combined sources3
Helixi1045 – 1047Combined sources3
Helixi1050 – 1055Combined sources6
Beta strandi1057 – 1059Combined sources3
Helixi1060 – 1075Combined sources16
Turni1076 – 1078Combined sources3
Helixi1080 – 1082Combined sources3
Helixi1084 – 1092Combined sources9
Helixi1097 – 1099Combined sources3
Helixi1100 – 1109Combined sources10
Helixi1122 – 1130Combined sources9
Helixi1136 – 1138Combined sources3
Helixi1142 – 1153Combined sources12

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[»]
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.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.
InParanoidiP23458.
KOiK11217.
OMAiPLDLFMH.
OrthoDBiEOG091G01IS.
PhylomeDBiP23458.
TreeFamiTF327041.

Family and domain databases

CDDicd14473. FERM_B-lobe. 1 hit.
Gene3Di1.20.80.10. 1 hit.
3.30.505.10. 1 hit.
InterProiView protein in InterPro
IPR019749. Band_41_domain.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
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.
SSF50729. SSF50729. 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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: June 7, 2017
This is version 192 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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families