DegronMD - O94874(UFL1)

FUNCTION: E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress (PubMed:20018847, PubMed:20164180, PubMed:20228063, PubMed:25219498, PubMed:32160526). In response to endoplasmic reticulum stress, recruited to the endoplasmic reticulum membrane by DDRGK1, and mediates ufmylation of proteins such as RPN1 and RPL26/uL24, thereby promoting reticulophagy of endoplasmic reticulum sheets (PubMed:32160526). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) via ERN1/IRE1-alpha (PubMed:23152784, PubMed:32160526). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response (PubMed:32050156). Regulates inflammation in response to endoplasmic reticulum stress by promoting reticulophagy, leading to inhibit the activity of the NF-kappa-B transcription factor (By similarity). Mediates ufmylation of DDRGK1 and CDK5RAP3; the role of these modifications is however unclear: as both DDRGK1 and CDK5RAP3 act as substrate adapters for ufmylation, it is uncertain whether ufmylation of these proteins is a collateral effect or is required for ufmylation (PubMed:20531390, PubMed:20018847). Catalyzes ufmylation of various subunits of the ribosomal complex or associated components, such as RPS3/uS3, RPS20/uS10, RPL10/uL16, RPL26/uL24 and EIF6 (By similarity). Anchors CDK5RAP3 in the cytoplasm, preventing its translocation to the nucleus which allows expression of the CCND1 cyclin and progression of cells through the G1/S transition (PubMed:20531390). Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 (PubMed:30886146). Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear receptor-mediated transcription (PubMed:25219498). Required for hematopoietic stem cell function and hematopoiesis (By similarity). Required for cardiac homeostasis (By similarity). {ECO:0000250|UniProtKB:A1A4I9, ECO:0000250|UniProtKB:Q8CCJ3, ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:20164180, ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:20531390, ECO:0000269|PubMed:23152784, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:32050156, ECO:0000269|PubMed:32160526}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.T767N	TCGA-19-5956	GBM	TCGA	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.3056
p.T767N	DO13863	GBM	ICGC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.3056
p.R769H	TCGA-AX-A05S	UCEC	TCGA	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation altering degron motif	0.8244
p.R769H	DO43218	UCEC	ICGC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation altering degron motif	0.8244
p.R769H	SIDM02035	Colorectal Carcinoma	GDSC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation altering degron motif	0.8244
p.R769H	ACH-001356	Thyroid Cancer	CCLE	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation altering degron motif	0.8244
p.L784I	TCGA-AX-A05Z	UCEC	TCGA	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1111
p.L784I	DO40884	UCEC	ICGC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1111
p.A765T	TCGA-DF-A2KU	UCEC	TCGA	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.25
p.A765T	DO223286	UCEC	ICGC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.25
p.S778F	TCGA-EE-A2MS	SKCM	TCGA	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation blocking phosphorylation signal	0.7222
p.S778F	DO37567	SKCM	ICGC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation blocking phosphorylation signal	0.7222
p.A765S	TCGA-QS-A5YQ	UCEC	TCGA	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.25
p.A765S	DO49073	UCEC	ICGC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.25
p.S777L	DO222498	MELA	ICGC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation blocking phosphorylation signal	0.75
p.E762K	DO222653	MELA	ICGC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1667
p.D781V	SIDM00789	Colorectal Carcinoma	GDSC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1944
p.D781V	ACH-000997	Colon/Colorectal Cancer	CCLE	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1944
p.D781V	ACH-001061	Colon/Colorectal Cancer	CCLE	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1944
p.D781V	HCT-15	large intestine	COSMIC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1944
p.T768S	SIDM00633	Breast Carcinoma	GDSC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation altering degron motif	0.6005
p.T768S	ACH-000759	Breast Cancer	CCLE	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation altering degron motif	0.6005
p.T768S	MDA-MB-175-VII	breast	COSMIC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation altering degron motif	0.6005
p.E760K	SIDM00306	Non-Small Cell Lung Carcinoma	GDSC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1111
p.E760K	ACH-000672	Lung Cancer	CCLE	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1111
p.E760K	IA-LM	lung	COSMIC	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation rewiring degron network	0.1111
p.E771A	ACH-001577	Leukemia	CCLE	TRKELQELS	DEG_APCC_DBOX_1	768:776	Mutation altering degron motif	0.659

Kaplan plot for UFL1 in

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

UFL1

UniProt ID: O94874

Entrez ID: 23376

Protein name: E3 UFM1-protein ligase 1 (EC 2.3.2.-) (E3 UFM1-protein transferase 1) (Multiple alpha-helix protein located at ER) (Novel LZAP-binding protein) (Regulator of C53/LZAP and DDRGK1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for UFL1 in