DegronMD - Q96KS0(EGLN2)

FUNCTION: Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as ATF4, IKBKB, CEP192 and HIF1A (PubMed:11595184, PubMed:12039559, PubMed:15925519, PubMed:16509823, PubMed:17114296, PubMed:23932902). Target proteins are preferentially recognized via a LXXLAP motif (PubMed:11595184, PubMed:12039559, PubMed:15925519). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519, PubMed:19339211). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519). Also hydroxylates HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519). Has a preference for the CODD site for both HIF1A and HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:11595184, PubMed:12039559, PubMed:15925519). Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes (PubMed:11595184, PubMed:12039559, PubMed:15925519). EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle (PubMed:11595184, PubMed:12039559, PubMed:15925519). Also regulates susceptibility to normoxic oxidative neuronal death (PubMed:11595184, PubMed:12039559, PubMed:15925519). Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation (PubMed:23932902). Hydroxylates IKBKB, mediating NF-kappa-B activation in hypoxic conditions (PubMed:17114296). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (By similarity). {ECO:0000250|UniProtKB:Q91YE2, ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12039559, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:15925519, ECO:0000269|PubMed:16509823, ECO:0000269|PubMed:17114296, ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:23932902}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R77W	TCGA-37-4133	LUSC	TCGA	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1944
p.R77W	TCGA-AP-A1DV	UCEC	TCGA	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1944
p.R77W	DO26465	LUSC	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1944
p.R77W	DO43186	UCEC	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1944
p.R77L	TCGA-66-2734	LUSC	TCGA	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1944
p.R77L	DO26430	LUSC	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1944
p.A68T	TCGA-B5-A3FC	UCEC	TCGA	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation altering degron motif	0.7139
p.A68T	DO41871	UCEC	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation altering degron motif	0.7139
p.P15H	TCGA-BQ-7053	KIRP	TCGA	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.25
p.P15H	DO20946	KIRP	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.25
p.G19W	TCGA-EE-A2MM	SKCM	TCGA	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation altering degron motif	0.6714
p.G19W	DO37770	SKCM	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation altering degron motif	0.6714
p.R77Q	TCGA-FD-A5C0	BLCA	TCGA	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1944
p.R77Q	DO44046	BLCA	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1944
p.G21V	DO1142	BRCA	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation altering degron motif	0.7532
p.R73W	DO12256	GBM	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.3056
p.P19T	DO52078	HNSC	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation altering degron motif	0.7031
p.R73Q	DO229055	LICA	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.3056
p.V78L	DO229009	LICA	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1667
p.Y82C	DO52187	LIHC	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.0556
p.C25F	DO23907	LUAD	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.25
p.P19L	DO222868	MELA	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation altering degron motif	0.7582
p.G11R	DO32449	OV	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.1389
p.R64L	DO28923	OV	ICGC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.2222
p.G9W	DO37961	SKCM	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.0833
p.G11W	DO37961	SKCM	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.1389
p.G9R	DO43306	UCEC	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.0833
p.G9R	DO42312	UCEC	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.0833
p.G21S	DO41791	UCEC	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation altering degron motif	0.6993
p.G9V	DO42568	UCEC	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.0833
p.D17Y	DO41488	UCEC	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.3056
p.C28Y	DO41361	UCEC	ICGC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.1667
p.T72N	SIDM00334	Endometrial Carcinoma	GDSC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation altering degron motif	0.7055
p.T72N	ACH-000879	Endometrial/Uterine Cancer	CCLE	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation altering degron motif	0.7055
p.T72N	MFE-296	endometrium	COSMIC	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation altering degron motif	0.7055
p.R31L	SIDM01387	Small Cell Lung Carcinoma	GDSC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.0833
p.R31L	ACH-000921	Lung Cancer	CCLE	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.0833
p.G79S	ACH-001061	Colon/Colorectal Cancer	CCLE	ATSTT	DEG_SPOP_SBC_1	68:72	Mutation rewiring degron network	0.1389
p.V13I	KNS-81-FD	central nervous system	COSMIC	PGSSS	DEG_SPOP_SBC_1	18:22	Mutation rewiring degron network	0.1944

Kaplan plot for EGLN2 in

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

EGLN2

UniProt ID: Q96KS0

Entrez ID: 112398

Protein name: Prolyl hydroxylase EGLN2 (EC 1.14.11.-) (Egl nine homolog 2) (EC 1.14.11.29) (Estrogen-induced tag 6) (EIT-6) (HPH-3) (Hypoxia-inducible factor prolyl hydroxylase 1) (HIF-PH1) (HIF-prolyl hydroxylase 1) (HPH-1) (Prolyl hydroxylase domain-containing protein 1) (PHD1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for EGLN2 in