UniProtKB - Q75R65 (JAK2_CHICK)
Protein
Tyrosine-protein kinase JAK2
Gene
JAK2
Organism
Gallus gallus (Chicken)
Status
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
- EC:2.7.10.2PROSITE-ProRule annotation
Activity 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 879 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 973 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 852 – 860 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- heme binding Source: UniProtKB
- histone binding Source: UniProtKB
- histone kinase activity (H3-Y41 specific) Source: UniProtKB
- protein tyrosine kinase activity Source: UniProtKB
GO - Biological processi
- activation of Janus kinase activity Source: UniProtKB
- cytokine-mediated signaling pathway Source: UniProtKB
- erythrocyte differentiation Source: UniProtKB
- growth hormone receptor signaling pathway via JAK-STAT Source: UniProtKB
- histone H3-Y41 phosphorylation Source: UniProtKB
- intracellular signal transduction Source: InterPro
- protein autophosphorylation Source: UniProtKB
- regulation of apoptotic process Source: GO_Central
- signal transduction Source: UniProtKB
- tyrosine phosphorylation of STAT protein Source: GO_Central
Keywordsi
Molecular function | Chromatin regulator, Kinase, Transferase, Tyrosine-protein kinase |
Ligand | ATP-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 |
Organismi | Gallus gallus (Chicken) |
Taxonomic identifieri | 9031 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Archelosauria › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galloanserae › Galliformes › Phasianidae › Phasianinae › Gallus |
Proteomesi |
|
Subcellular locationi
Nucleus
- Nucleus By similarity
Other locations
- Endomembrane system By similarity; Peripheral membrane protein By similarity
Cytoskeleton
- cytoskeleton Source: InterPro
Nucleus
- nucleus Source: UniProtKB
Other locations
- endomembrane system Source: UniProtKB-SubCell
- membrane Source: UniProtKB-KW
Keywords - Cellular componenti
Membrane, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000324095 | 1 – 1129 | Tyrosine-protein kinase JAK2Add BLAST | 1129 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 117 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 865 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 963 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 969 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 1004 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 1005 | Phosphotyrosine; by autocatalysisBy similarity | 1 |
Post-translational modificationi
Autophosphorylated, leading to regulate its activity.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q75R65 |
Interactioni
GO - Molecular functioni
- histone binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 9031.ENSGALP00000037587 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 35 – 378 | FERMPROSITE-ProRule annotationAdd BLAST | 344 | |
Domaini | 399 – 480 | SH2; atypicalPROSITE-ProRule annotationAdd BLAST | 82 | |
Domaini | 542 – 806 | Protein kinase 1PROSITE-ProRule annotationAdd BLAST | 265 | |
Domaini | 846 – 1118 | Protein kinase 2PROSITE-ProRule annotationAdd BLAST | 273 |
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 domainPhylogenomic databases
eggNOGi | KOG0197, Eukaryota |
InParanoidi | Q75R65 |
PhylomeDBi | Q75R65 |
Family and domain databases
CDDi | cd14473, 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 |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR019749, Band_41_domain IPR035963, FERM_2 IPR019748, FERM_central IPR000299, FERM_domain IPR041155, FERM_F1 IPR041046, FERM_F2 IPR041381, Jak1_PHL_dom 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 |
Pfami | View protein in Pfam PF18379, FERM_F1, 1 hit PF18377, FERM_F2, 1 hit PF17887, Jak1_Phl, 1 hit PF07714, PK_Tyr_Ser-Thr, 2 hits |
PIRSFi | PIRSF000636, TyrPK_Jak, 1 hit |
PRINTSi | PR01823, JANUSKINASE PR01825, JANUSKINASE2 PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00295, B41, 1 hit SM00252, SH2, 1 hit SM00219, TyrKc, 2 hits |
SUPFAMi | SSF47031, SSF47031, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 2 hits |
PROSITEi | View 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 |
i Sequence
Sequence statusi: Complete.
Q75R65-1 [UniParc]FASTAAdd to basket
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
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB159042 mRNA Translation: BAD07298.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB159042 mRNA Translation: BAD07298.1 |
3D structure databases
SMRi | Q75R65 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9031.ENSGALP00000037587 |
Proteomic databases
PaxDbi | Q75R65 |
Phylogenomic databases
eggNOGi | KOG0197, Eukaryota |
InParanoidi | Q75R65 |
PhylomeDBi | Q75R65 |
Family and domain databases
CDDi | cd14473, 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 |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR019749, Band_41_domain IPR035963, FERM_2 IPR019748, FERM_central IPR000299, FERM_domain IPR041155, FERM_F1 IPR041046, FERM_F2 IPR041381, Jak1_PHL_dom 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 |
Pfami | View protein in Pfam PF18379, FERM_F1, 1 hit PF18377, FERM_F2, 1 hit PF17887, Jak1_Phl, 1 hit PF07714, PK_Tyr_Ser-Thr, 2 hits |
PIRSFi | PIRSF000636, TyrPK_Jak, 1 hit |
PRINTSi | PR01823, JANUSKINASE PR01825, JANUSKINASE2 PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00295, B41, 1 hit SM00252, SH2, 1 hit SM00219, TyrKc, 2 hits |
SUPFAMi | SSF47031, SSF47031, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 2 hits |
PROSITEi | View 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | JAK2_CHICK | |
Accessioni | Q75R65Primary (citable) accession number: Q75R65 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 18, 2008 |
Last sequence update: | July 5, 2004 | |
Last modified: | October 7, 2020 | |
This is version 120 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families