UniProt functional annotation for Q01831



	UniProt functional annotation for Q01831

UniProt codes: Q01831, Q96AX0.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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}.

Subunit: Component of the XPC complex composed of XPC, RAD23B and CETN2 (PubMed:11279143, PubMed:12509233, PubMed:15964821, PubMed:17897675, PubMed:16627479, PubMed:16533048). Interacts with RAD23A; the interaction is suggesting the existence of a functional equivalent variant XPC complex (PubMed:9372924). Interacts with TDG; the interaction is demonstrated using the XPC:RAD23B dimer (PubMed:12505994, PubMed:20798892). Interacts with SMUG1; the interaction is demonstrated using the XPC:RAD23B dimer (PubMed:20798892). Interacts with DDB2 (PubMed:15882621). Interacts with CCNH, GTF2H1 and ERCC3 (PubMed:10734143, PubMed:12509233). Interacts with E2F1 and KAT2A; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (PubMed:29973595, PubMed:31527837). {ECO:0000269|PubMed:10734143, ECO:0000269|PubMed:11279143, ECO:0000269|PubMed:12505994, ECO:0000269|PubMed:12509233, ECO:0000269|PubMed:15882621, ECO:0000269|PubMed:15964821, ECO:0000269|PubMed:16533048, ECO:0000269|PubMed:16627479, ECO:0000269|PubMed:17897675, ECO:0000269|PubMed:20798892, ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837, ECO:0000269|PubMed:9372924}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11279143, ECO:0000269|PubMed:18682493, ECO:0000269|PubMed:8692695}. Chromosome {ECO:0000269|PubMed:29973595}. Cytoplasm {ECO:0000269|PubMed:18682493}. Note=Omnipresent in the nucleus and consistently associates with and dissociates from DNA in the absence of DNA damage (PubMed:18682493). Continuously shuttles between the cytoplasm and the nucleus, which is impeded by the presence of NER lesions (PubMed:18682493). {ECO:0000269|PubMed:18682493}.

Ptm: Ubiquitinated upon UV irradiation; the ubiquitination requires the UV-DDB complex, appears to be reversible and does not serve as a signal for degradation (PubMed:15882621, PubMed:23751493). Ubiquitinated by RNF11 via 'Lys-63'-linked ubiquitination (PubMed:23751493). Ubiquitination by RNF111 is polysumoylation-dependent and promotes nucleotide excision repair (PubMed:23751493). {ECO:0000269|PubMed:15882621, ECO:0000269|PubMed:23751493}.

Ptm: Sumoylated; sumoylation promotes ubiquitination by RNF111. {ECO:0000269|PubMed:23751493}.

Disease: Xeroderma pigmentosum complementation group C (XP-C) [MIM:278720]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. {ECO:0000269|PubMed:10447254, ECO:0000269|PubMed:10766188, ECO:0000269|PubMed:17355181, ECO:0000269|PubMed:17682058, ECO:0000269|PubMed:19609301, ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:8298653}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the XPC family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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}.


Subunit:		Component of the XPC complex composed of XPC, RAD23B and CETN2 (PubMed:11279143, PubMed:12509233, PubMed:15964821, PubMed:17897675, PubMed:16627479, PubMed:16533048). Interacts with RAD23A; the interaction is suggesting the existence of a functional equivalent variant XPC complex (PubMed:9372924). Interacts with TDG; the interaction is demonstrated using the XPC:RAD23B dimer (PubMed:12505994, PubMed:20798892). Interacts with SMUG1; the interaction is demonstrated using the XPC:RAD23B dimer (PubMed:20798892). Interacts with DDB2 (PubMed:15882621). Interacts with CCNH, GTF2H1 and ERCC3 (PubMed:10734143, PubMed:12509233). Interacts with E2F1 and KAT2A; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (PubMed:29973595, PubMed:31527837). {ECO:0000269\|PubMed:10734143, ECO:0000269\|PubMed:11279143, ECO:0000269\|PubMed:12505994, ECO:0000269\|PubMed:12509233, ECO:0000269\|PubMed:15882621, ECO:0000269\|PubMed:15964821, ECO:0000269\|PubMed:16533048, ECO:0000269\|PubMed:16627479, ECO:0000269\|PubMed:17897675, ECO:0000269\|PubMed:20798892, ECO:0000269\|PubMed:29973595, ECO:0000269\|PubMed:31527837, ECO:0000269\|PubMed:9372924}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11279143, ECO:0000269\|PubMed:18682493, ECO:0000269\|PubMed:8692695}. Chromosome {ECO:0000269\|PubMed:29973595}. Cytoplasm {ECO:0000269\|PubMed:18682493}. Note=Omnipresent in the nucleus and consistently associates with and dissociates from DNA in the absence of DNA damage (PubMed:18682493). Continuously shuttles between the cytoplasm and the nucleus, which is impeded by the presence of NER lesions (PubMed:18682493). {ECO:0000269\|PubMed:18682493}.
Ptm:		Ubiquitinated upon UV irradiation; the ubiquitination requires the UV-DDB complex, appears to be reversible and does not serve as a signal for degradation (PubMed:15882621, PubMed:23751493). Ubiquitinated by RNF11 via 'Lys-63'-linked ubiquitination (PubMed:23751493). Ubiquitination by RNF111 is polysumoylation-dependent and promotes nucleotide excision repair (PubMed:23751493). {ECO:0000269\|PubMed:15882621, ECO:0000269\|PubMed:23751493}.
Ptm:		Sumoylated; sumoylation promotes ubiquitination by RNF111. {ECO:0000269\|PubMed:23751493}.
Disease:		Xeroderma pigmentosum complementation group C (XP-C) [MIM:278720]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. {ECO:0000269\|PubMed:10447254, ECO:0000269\|PubMed:10766188, ECO:0000269\|PubMed:17355181, ECO:0000269\|PubMed:17682058, ECO:0000269\|PubMed:19609301, ECO:0000269\|PubMed:29973595, ECO:0000269\|PubMed:8298653}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the XPC family. {ECO:0000305}.