JAK2_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: JAK2_RAT
• UniProt AC: Q62689
• Protein Name: Tyrosine-protein kinase JAK2
• Gene Name: Jak2
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 1132
• Subcellular Localization: Endomembrane system; Peripheral membrane protein. Cytoplasm. Nucleus.
• Protein Description: 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 type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. 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 addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. 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..
• Protein Sequence: MGMACLTMTEMEGTSTSPAHQNGDIPGNANSVKQTEPVLQVYLYHSLGQAEGDYLKFPNGEYVAEEICVAASKACGITPVYHNMFALMSETERIWYPPNHVFHIDESTRHNILYRIRFYFPHWYCSGSNRTYRYGVSRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLGMAVLDMMRIAKEKDQTPLAVYNSISYKTFLPKCVRAKIQDYHILTRKRIRYRFRRFIQQFSQCKATARNLKLKYLINLETLQSAFYTEQFEVKESARGPSGEEIFATIIITGNGGIQWSRGKHKESETLTEQDLQLYCDFPDIIDVSIKQANQECSTESRVVTVHKQDGKVLEIELSSLKEALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIHSNCHGPISMDFAISKLKKAGNQTGLYVLRCSPKDFNKYFLTFAVERENVIEYKHCLITKNENGEYNLSGTKRNFSSLKDLLNCYQMETVRSDSIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVQLSPTLQRHNNVNQMVFHKIRNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASMMSQLSHKHLVLNYGVCVCGEENILVQEFVKFGSLDTYLKKNKNSINILWKLGVAKQLAWAMHFLEEKSLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVPPECIENPKNLTLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDKHQLPAPKWTELANLINTCMDYEPDFRPAFRAVIRDLNSLFTPDYELLTENDMLPNMRIGALGFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAGRRNLRLIMEYLPYGSLRDYLQKHKERIDHKKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPVEFMRMIGNDKQGQMIVFHLIELLKNNGRLPRPEGCPDEIYVIMTECWNNNVNQRPSFRDLSLRVDQIRDSMAA

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
119	Phosphorylation	ILYRIRFYFPHWYCS HHHEEEEECCCCEEC	13.32	-
372	Phosphorylation	FVSLIDGYYRLTADA HHHHHHCEEHHCHHH	5.01	-
373	Phosphorylation	VSLIDGYYRLTADAH HHHHHCEEHHCHHHH	12.50	-
514	Phosphorylation	SNLLVFRTNGVSDVQ CCEEEEECCCCCCCC	25.51	28689409
523	Phosphorylation	GVSDVQLSPTLQRHN CCCCCCCCHHHHHCC	9.96	27097102
525	Phosphorylation	SDVQLSPTLQRHNNV CCCCCCHHHHHCCCC	31.95	27097102
570	Phosphorylation	VRREVGDYGQLHETE HHCCCCCCCCEEHHH	10.80	30181290
813	Phosphorylation	NSLFTPDYELLTEND HHHCCCCHHHCCCCC	15.07	-
868	Phosphorylation	GSVEMCRYDPLQDNT CCEEEEECCCCCCCC	19.58	-
904	Phosphorylation	REIEILKSLQHDNIV HHHHHHHHCCCCCCC	29.80	22673903
966	Phosphorylation	QICKGMEYLGTKRYI HHHHHHHHHCCCCCC	11.09	-
972	Phosphorylation	EYLGTKRYIHRDLAT HHHCCCCCCCCCHHH	11.57	-
1007	Phosphorylation	VLPQDKEYYKVKEPG ECCCCCCEEECCCCC	17.83	18230613
1008	Phosphorylation	LPQDKEYYKVKEPGE CCCCCCEEECCCCCC	15.47	18230613

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
1007	Y	Phosphorylation	Kinase	PTK2B	P70600	GPS
1008	Y	Phosphorylation	Kinase	PTK2B	P70600	GPS

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of JAK2_RAT !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of JAK2_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
STA5A_RAT	Stat5a	physical	12538627
JAK2_RAT	Jak2	physical	12960006
IRS1_RAT	Irs1	physical	12960006
IKBA_RAT	Nfkbia	physical	11493922

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.