DegronMD - P54646(PRKAA2)

FUNCTION: Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (PubMed:7959015). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). Involved in insulin receptor/INSR internalization (PubMed:25687571). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11554766, PubMed:11518699, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:20160076, PubMed:21205641). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation (By similarity). Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). {ECO:0000250|UniProtKB:Q09137, ECO:0000250|UniProtKB:Q8BRK8, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:7959015, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.T389M	TCGA-06-5416	GBM	TCGA	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.3056
p.T389M	DO10880	GBM	ICGC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.3056
p.T389M	SIDM01293	Colorectal Carcinoma	GDSC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.3056
p.D354Y	TCGA-55-8208	LUAD	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.0833
p.D354Y	DO51192	LUAD	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.0833
p.R369M	TCGA-AA-3858	COAD	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.3056
p.R369M	DO10308	COAD	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.3056
p.S377I	TCGA-AP-A051	UCEC	TCGA	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation blocking phosphorylation signal	0.6944
p.S377I	TCGA-AP-A051	UCEC	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation blocking phosphorylation signal	0.5278
p.S377I	DO42673	UCEC	ICGC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation blocking phosphorylation signal	0.6944
p.S377I	DO42673	UCEC	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation blocking phosphorylation signal	0.5278
p.P361T	TCGA-BR-4361	STAD	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.2778
p.P361T	DO38887	STAD	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.2778
p.H358Y	TCGA-BR-8680	STAD	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.1944
p.H358Y	DO47769	STAD	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.1944
p.S377N	TCGA-DA-A1I1	SKCM	TCGA	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation blocking phosphorylation signal	0.6944
p.S377N	TCGA-DA-A1I1	SKCM	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation blocking phosphorylation signal	0.5278
p.S377N	DO37966	SKCM	ICGC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation blocking phosphorylation signal	0.6944
p.S377N	DO37966	SKCM	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation blocking phosphorylation signal	0.5278
p.P367T	TCGA-DK-A3IL	BLCA	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.5919
p.P367T	DO555	BLCA	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.5919
p.H366Y	TCGA-EB-A5SG	SKCM	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.6118
p.H366Y	DO48726	SKCM	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.6118
p.P367L	TCGA-EB-A5UL	SKCM	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.6471
p.P367L	DO47601	SKCM	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.6471
p.E368Q	TCGA-FD-A43X	BLCA	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.6744
p.E368Q	DO44067	BLCA	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.6744
p.P378H	TCGA-FS-A1ZP	SKCM	TCGA	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.2778
p.P378H	TCGA-FS-A1ZP	SKCM	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.0556
p.P378H	DO37703	SKCM	ICGC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.2778
p.P378H	DO37703	SKCM	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.0556
p.P392L	TCGA-GN-A4U8	SKCM	TCGA	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.2222
p.P392L	DO47320	SKCM	ICGC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.2222
p.K391R	TCGA-RD-A8MW	STAD	TCGA	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation blocking ubiquitination signal	0.6944
p.K391R	DO50134	STAD	ICGC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation blocking ubiquitination signal	0.6944
p.L363P	TCGA-VQ-A92D	STAD	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.7582
p.L363P	DO222366	STAD	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation altering degron motif	0.7582
p.A356V	TCGA-XK-AAIW	PRAD	TCGA	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.1389
p.A356V	DO51407	PRAD	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.1389
p.S394F	DO222908	MELA	ICGC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.1667
p.D354N	DO229491	SKCA	ICGC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.0833
p.P371T	SIDM00885	Breast Carcinoma	GDSC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.0833
p.P371T	SIDM00885	Breast Carcinoma	GDSC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.25
p.P371T	ACH-000111	Breast Cancer	CCLE	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.0833
p.P371T	ACH-000111	Breast Cancer	CCLE	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.25
p.P371T	HCC1187	breast	COSMIC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.0833
p.P371T	HCC1187	breast	COSMIC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.25
p.V397M	SIDM00282	Colorectal Carcinoma	GDSC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.0833
p.V397M	ACH-000998	Colon/Colorectal Cancer	CCLE	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.0833
p.V397M	CW-2	large intestine	COSMIC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.0833
p.R369S	SIDM00138	Non-Small Cell Lung Carcinoma	GDSC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.3056
p.R369S	ACH-000900	Lung Cancer	CCLE	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.3056
p.R369S	NCI-H23	lung	COSMIC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.3056
p.P378L	ACH-002396	Bone Cancer	CCLE	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.2778
p.P378L	ACH-002396	Bone Cancer	CCLE	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.0556
p.P378L	Sarc9371	bone	COSMIC	ARCPLDALN	DEG_APCC_DBOX_1	380:388	Mutation rewiring degron network	0.2778
p.P378L	Sarc9371	bone	COSMIC	LKPHPE	LIG_APCC_ABBA_1	363:368	Mutation rewiring degron network	0.0556

Kaplan plot for PRKAA2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

PRKAA2

UniProt ID: P54646

Entrez ID: 5563

Protein name: 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK subunit alpha-2) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (EC 2.7.11.27) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PRKAA2 in