dbPTM

CLK2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	CLK2_MOUSE
UniProt AC	O35491
Protein Name	Dual specificity protein kinase CLK2
Gene Name	Clk2
Organism	Mus musculus (Mouse).
Sequence Length	499
Subcellular Localization	Nucleus. Nucleus speckle. Inhibition of phosphorylation at Ser-141 results in accumulation in the nuclear speckle.
Protein Description	Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells..
Protein Sequence	MPHPRRYHSSERGSRGSYHEHYQSRKHKRRRSRSWSSSSDRTRRRRREDSYHVRSRSSYDDHSSDRRLYDRRYCGSYRRNDYSRDRGEAYYDTDFRQSYEYHRENSSYRSQRSSRRKHRRRRRRSRTFSRSSSHSSRRAKSVEDDAEGHLIYHVGDWLQERYEIVSTLGEGTFGRVVQCVDHRRGGTQVALKIIKNVEKYKEAARLEINVLEKINEKDPDNKNLCVQMFDWFDYHGHMCISFELLGLSTFDFLKDNNYLPYPIHQVRHMAFQLCQAVKFLHDNKLTHTDLKPENILFVNSDYELTYNLEKKRDERSVKSTAVRVVDFGSATFDHEHHSTIVSTRHYRAPEVILELGWSQPCDVWSIGCIIFEYYVGFTLFQTHDNREHLAMMERILGPVPSRMIRKTRKQKYFYRGRLDWDENTSAGRYVRENCKPLRRYLTSEAEDHHQLFDLIENMLEYEPAKRLTLGEALQHPFFACLRTEPPNTKLWDSSRDISR

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
9	Phosphorylation	PHPRRYHSSERGSRG CCCCCCCCCCCCCCC	25.59	23684622
10	Phosphorylation	HPRRYHSSERGSRGS CCCCCCCCCCCCCCC	20.28	23684622
14	Phosphorylation	YHSSERGSRGSYHEH CCCCCCCCCCCHHHH	39.42	23684622
17	Phosphorylation	SERGSRGSYHEHYQS CCCCCCCCHHHHHHC	23.39	25266776
18	Phosphorylation	ERGSRGSYHEHYQSR CCCCCCCHHHHHHCH	17.66	-
22	Phosphorylation	RGSYHEHYQSRKHKR CCCHHHHHHCHHHHH	12.75	-
24	Phosphorylation	SYHEHYQSRKHKRRR CHHHHHHCHHHHHHH	35.81	-
34	Phosphorylation	HKRRRSRSWSSSSDR HHHHHCCCCCCCCHH	32.34	-
50	Phosphorylation	RRRRREDSYHVRSRS HHHHHHCCCCCCCCC	16.63	22322096
51	Phosphorylation	RRRREDSYHVRSRSS HHHHHCCCCCCCCCC	19.36	28507225
55	Phosphorylation	EDSYHVRSRSSYDDH HCCCCCCCCCCCCCC	35.11	23684622
57	Phosphorylation	SYHVRSRSSYDDHSS CCCCCCCCCCCCCCC	34.20	25266776
58	Phosphorylation	YHVRSRSSYDDHSSD CCCCCCCCCCCCCCC	31.32	23684622
59	Phosphorylation	HVRSRSSYDDHSSDR CCCCCCCCCCCCCCC	27.00	-
63	Phosphorylation	RSSYDDHSSDRRLYD CCCCCCCCCCCCCCC	40.71	29514104
64	Phosphorylation	SSYDDHSSDRRLYDR CCCCCCCCCCCCCCC	31.55	29514104
76	Phosphorylation	YDRRYCGSYRRNDYS CCCCCCCCCCCCCCC	16.35	21183079
98	Phosphorylation	YDTDFRQSYEYHREN CCCCHHHHHHHHHCC	18.71	21183079
99	Phosphorylation	DTDFRQSYEYHRENS CCCHHHHHHHHHCCC	16.51	20074525
127	Phosphorylation	RRRRRSRTFSRSSSH HHHHHHHHHCCCCCC	27.49	-
141	Phosphorylation	HSSRRAKSVEDDAEG CCCCCCCCCCCCCCC	29.74	9852100
152	Phosphorylation	DAEGHLIYHVGDWLQ CCCCCEEEECHHHHH	9.23	-
342	Phosphorylation	EHHSTIVSTRHYRAP CCCCEEEEECCCCCC	18.84	-
343	Phosphorylation	HHSTIVSTRHYRAPE CCCEEEEECCCCCCH	15.57	20074525
498	Phosphorylation	WDSSRDISR------ CCCCCCCCC------	35.91	25338131

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
34	S	Phosphorylation	Kinase	AKT1	P31750	Uniprot
98	S	Phosphorylation	Kinase	CLK2	O35491	GPS
99	Y	Phosphorylation	Kinase	CLK2	O35491	GPS
127	T	Phosphorylation	Kinase	AKT1	P31750	Uniprot
141	S	Phosphorylation	Kinase	CLK2	O35491	GPS
343	T	Phosphorylation	Kinase	AKT2	P31751	PSP
343	T	Phosphorylation	Kinase	AKT2	Q60823	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
34	S	Phosphorylation	9852100
Phosphorylation on Ser-34 and Thr-127 by AKT1 is induced by ionizing radiation or insulin.
127	T	Phosphorylation	9852100
Phosphorylation on Ser-34 and Thr-127 by AKT1 is induced by ionizing radiation or insulin.
141	S	Phosphorylation	9852100
The phosphorylation status at Ser-141 influences its subnuclear localization; inhibition of phosphorylation at Ser-141 results in accumulation in the nuclear speckle.
343	T	Phosphorylation	9852100
Phosphorylation at Thr-343 by PKB/AKT2 induces its kinase activity which is required for its stability.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of CLK2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
SAFB1_RAT	Safb	physical	9671816

Drug and Disease Associations

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

Regulatory Network of CLK2_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Cdc2-like kinase 2 is an insulin-regulated suppressor of hepaticgluconeogenesis."; Rodgers J.T., Haas W., Gygi S.P., Puigserver P.; Cell Metab. 11:23-34(2010). Cited for: FUNCTION, PHOSPHORYLATION AT SER-98; TYR-99 AND THR-343, INDUCTION,AND INTERACTION WITH AKT1.	20074525 [Abstract]
"The cellular localization of the murine serine/arginine-rich proteinkinase CLK2 is regulated by serine 141 autophosphorylation."; Nayler O., Schnorrer F., Stamm S., Ullrich A.; J. Biol. Chem. 273:34341-34348(1998). Cited for: PHOSPHORYLATION AT SER-141, SUBCELLULAR LOCATION, ENZYME REGULATION,AND MUTAGENESIS OF SER-141.	9852100 [Abstract]

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