DegronMD - Q01831(XPC)

FUNCTION: Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex (PubMed:10734143, PubMed:19609301, PubMed:20649465, PubMed:9734359, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892). Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides (PubMed:10734143, PubMed:19609301, PubMed:20649465). This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity (PubMed:10734143, PubMed:19609301, PubMed:20649465). The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex (PubMed:9734359, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892). The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs (PubMed:9734359, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892). The orientation of XPC complex binding appears to be crucial for inducing a productive NER (PubMed:9734359, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892). XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery (PubMed:9734359, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892). Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair (PubMed:9734359, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892). In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts (PubMed:20028083). XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1 (PubMed:20028083). {ECO:0000269|PubMed:10734143, ECO:0000269|PubMed:10873465, ECO:0000269|PubMed:12509299, ECO:0000269|PubMed:12547395, ECO:0000269|PubMed:19609301, ECO:0000269|PubMed:19941824, ECO:0000269|PubMed:20028083, ECO:0000269|PubMed:20649465, ECO:0000269|PubMed:20798892, ECO:0000269|PubMed:9734359}.; FUNCTION: In absence of DNA repair, the XPC complex also acts as a transcription coactivator: XPC interacts with the DNA-binding transcription factor E2F1 at a subset of promoters to recruit KAT2A and histone acetyltransferase complexes (HAT) (PubMed:29973595, PubMed:31527837). KAT2A recruitment specifically promotes acetylation of histone variant H2A.Z.1/H2A.Z, but not H2A.Z.2/H2A.V, thereby promoting expression of target genes (PubMed:31527837). {ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A500P	TCGA-55-8620	LUAD	TCGA	AASSS	DEG_SPOP_SBC_1	499:503	Mutation altering degron motif	0.6392
p.A500P	DO24547	LUAD	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation altering degron motif	0.6392
p.K508T	TCGA-AX-A2HC	UCEC	TCGA	AASSS	DEG_SPOP_SBC_1	499:503	Mutation blocking ubiquitination signal	0.6389
p.K508T	DO41572	UCEC	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation blocking ubiquitination signal	0.6389
p.A499V	DO229010	COCA	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation altering degron motif	0.5825
p.A499V	DO229013	COCA	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation altering degron motif	0.5825
p.A499V	DO229016	COCA	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation altering degron motif	0.5825
p.A499V	DO229003	COCA	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation altering degron motif	0.5825
p.A499V	DO228947	LICA	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation altering degron motif	0.5825
p.A499V	DO231124	LUSC	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation altering degron motif	0.5825
p.S501A	DO233882	GACA	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation altering degron motif	0.87
p.R492H	DO231049	LUSC	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation rewiring degron network	0.1389
p.S505L	DO222413	MELA	ICGC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation rewiring degron network	0.2778
p.M513I	SIDM00040	Gastric Carcinoma	GDSC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation rewiring degron network	0.0556
p.M513I	SIDM00410	Other Blood Cancers	GDSC	AASSS	DEG_SPOP_SBC_1	499:503	Mutation rewiring degron network	0.0556
p.P495L	ACH-001566	Skin Cancer	CCLE	AASSS	DEG_SPOP_SBC_1	499:503	Mutation rewiring degron network	0.2222

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

XPC

UniProt ID: Q01831

Entrez ID: 7508

Protein name: DNA repair protein complementing XP-C cells (Xeroderma pigmentosum group C-complementing protein) (p125)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for XPC in