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Protein

Tyrosine-protein kinase JAK2

Gene

JAK2

Organism
Gallus gallus (Chicken)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with cytokine receptors. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B). In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.By similarity

Catalytic activityi

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

Enzyme regulationi

Regulated by autophosphorylation, can both activate or decrease activity. Heme regulates its activity by enhancing the phosphorylation on Tyr-1004 and Tyr-1005.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei879ATPPROSITE-ProRule annotation1
Active sitei973Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi852 – 860ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Kinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase JAK2 (EC:2.7.10.2)
Alternative name(s):
Janus kinase 2
Short name:
JAK-2
Gene namesi
Name:JAK2
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiArchelosauriaArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalloanseraeGalliformesPhasianidaePhasianinaeGallus
Proteomesi
  • UP000000539 Componenti: Unplaced

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, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003240951 – 1129Tyrosine-protein kinase JAK2Add BLAST1129

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei117Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei865Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei963Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei969Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1004Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1005Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylated, leading to regulate its activity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ75R65

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9031.ENSGALP00000037587

Structurei

3D structure databases

ProteinModelPortaliQ75R65
SMRiQ75R65
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 378FERMPROSITE-ProRule annotationAdd BLAST344
Domaini399 – 480SH2; atypicalPROSITE-ProRule annotationAdd BLAST82
Domaini542 – 806Protein kinase 1PROSITE-ProRule annotationAdd BLAST265
Domaini846 – 1118Protein kinase 2PROSITE-ProRule annotationAdd BLAST273

Domaini

Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1 (By similarity).By similarity

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
HOGENOMiHOG000049158
HOVERGENiHBG006195
InParanoidiQ75R65
PhylomeDBiQ75R65

Family and domain databases

CDDicd14473 FERM_B-lobe, 1 hit
cd13333 FERM_C_JAK2, 1 hit
cd05078 PTK_Jak2_rpt1, 1 hit
cd14205 PTKc_Jak2_rpt2, 1 hit
cd10379 SH2_Jak2, 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
IPR037838 JAK2_FERM_C-lobe
IPR035860 JAK2_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR035588 PTK_Jak2_rpt1
IPR035589 PTKc_Jak2_rpt2
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
IPR020693 Tyr_kinase_non-rcpt_Jak2
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 2 hits
PIRSFiPIRSF000636 TyrPK_Jak, 1 hit
PRINTSiPR01823 JANUSKINASE
PR01825 JANUSKINASE2
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM00252 SH2, 1 hit
SM00219 TyrKc, 2 hits
SUPFAMiSSF47031 SSF47031, 1 hit
SSF55550 SSF55550, 2 hits
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.

Q75R65-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MACLTMANIE GSATATVHQN GDILGNTSAP KQTEPLLQVY LYYSPGKTGG
60 70 80 90 100
DYLQFPAGEY VAEEICIVAC KACGIMPVYH NMFALMSETE RVWYPPNHIF
110 120 130 140 150
HVDEATRLKL LYRIRFYFPH WYCNGTSRAC RYGIIRGSES PVLDDLVMSY
160 170 180 190 200
LFAQWRKDFL DGWIQMPVTH ETQEECLGMA VLDMMRVAKE KDQTPLAVYN
210 220 230 240 250
SVSYKMFLPK CVRAKIQEYH ILTRKRIRYR FRKFIQQFGQ CKATARNLKL
260 270 280 290 300
KYLINLETLQ SAFYSEVFEV KEPGGDPSGE ESFATIVITG NGGIQCSRGK
310 320 330 340 350
LKNCETLAEQ DLQTYCDFPD IIDVSIKQAS QEGSSERRIV TIHKQDSKNL
360 370 380 390 400
EAEFQSLREA LSFVSLIDGY YRLTADAHHY LCKEVAPPSV LENIQSNCHG
410 420 430 440 450
PIFMDFAINK LKKAGNQTGF YVLRCSPKDF KKYFLTFAIE RENATDYKHC
460 470 480 490 500
LITKNENGEY NLSGTKRSFG NLKDLLTCYQ TETVRSDSII FQFIKCCPPK
510 520 530 540 550
PKDKSNLLVF RSNSVSDVPS SPTLQRHNVS QMVFHKIRNE DLIFEESLGQ
560 570 580 590 600
GTFTKIFKGI RKEVGDYGQL HQTEVLLKVL DKVHRNYSES FFEAASMMSQ
610 620 630 640 650
LSYKHLVLNY GVCVCGEENI LVQEYVKFGS LDTYLKKNKN VINILWKLEV
660 670 680 690 700
AKQLALAMHF LEDKGLVHGN VCAKNILLIR EEDRKSGNLP FIKLSDPGIS
710 720 730 740 750
ITVLPRDILL ERIPWVPPEC IENPRQLSLA TDKWSFGTTL WEICSGGDKP
760 770 780 790 800
LSALDSSRKL QFYEDRHQLP APNWTELANL INNCMDYEPD FRPSFRAIIR
810 820 830 840 850
DLNSLFTPDY ELLTENDMLP NIRTGALGFS GAFEDRDPTQ FEERHLKFLQ
860 870 880 890 900
QLGKGNFGSV EMCRYDPLQD NTGEVVAVKK LQHSTEEHLR DFEREIEILK
910 920 930 940 950
SLQHDNIVKY KGVCYSAGRR NLRLIMEYLP YGSLRDYLQK HKERLDHKKL
960 970 980 990 1000
LLYASQICKG MEYLGTKRYV HRDLATRNIL VENENRVKIG DFGLTKVLPQ
1010 1020 1030 1040 1050
DKEYYKVKEP GESPIFWYAP ESLTESKFSV ASDVWSFGVV LYELFTYIEK
1060 1070 1080 1090 1100
SKSPPAEFMR MIGNDKQGQM IVFHLIELLK NNGRLPRPDG CPDEIYAIMK
1110 1120
ECWNNNVAQR PTFRDLAQRV DQIRDNMGG
Length:1,129
Mass (Da):129,847
Last modified:July 5, 2004 - v1
Checksum:i1631EE82D331B9BE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB159042 mRNA Translation: BAD07298.1
UniGeneiGga.954

Similar proteinsi

Entry informationi

Entry nameiJAK2_CHICK
AccessioniPrimary (citable) accession number: Q75R65
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: July 5, 2004
Last modified: May 23, 2018
This is version 111 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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