DegronMD - P57059(SIK1)

FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348). Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:16306228, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:19622832, ECO:0000269|PubMed:29211348}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A486V	TCGA-B5-A3FC	UCEC	TCGA	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation rewiring degron network	0.1111
p.A486V	DO230326	COCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation rewiring degron network	0.1111
p.A486V	DO41871	UCEC	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation rewiring degron network	0.1111
p.R470Q	TCGA-VS-A9U6	CESC	TCGA	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation altering degron motif	0.6218
p.R470Q	DO219728	CESC	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation altering degron motif	0.6218
p.T479P	DO222499	BTCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation blocking phosphorylation signal	0.75
p.T479P	DO229188	THCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation blocking phosphorylation signal	0.75
p.T479P	DO229103	THCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation blocking phosphorylation signal	0.75
p.T479P	DO229084	THCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation blocking phosphorylation signal	0.75
p.R480H	DO50437	ESAD	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation rewiring degron network	0.2778
p.R480H	DO231997	ORCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation rewiring degron network	0.2778
p.L484I	DO220873	MELA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation rewiring degron network	0.1667
p.T460M	DO232761	PBCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation blocking phosphorylation signal	0.5
p.T460S	DO229221	THCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation blocking phosphorylation signal	0.5
p.S467G	DO229234	THCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation rewiring degron network	0.25
p.C488F	DO229245	THCA	ICGC	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation rewiring degron network	0.0556
p.G469C	ACH-000997	Colon/Colorectal Cancer	CCLE	RRHTLAEVS	DEG_APCC_DBOX_1	470:478	Mutation rewiring degron network	0.3056

Kaplan plot for SIK1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

SIK1

UniProt ID: P57059

Entrez ID: 102724428

Protein name: Serine/threonine-protein kinase SIK1 (EC 2.7.11.1) (Salt-inducible kinase 1) (SIK-1) (Serine/threonine-protein kinase SNF1-like kinase 1) (Serine/threonine-protein kinase SNF1LK)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SIK1 in