UniProt functional annotation for Q13216



	UniProt functional annotation for Q13216

UniProt code: Q13216.

Organism: Homo sapiens (Human).

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

Function: Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair. The CSA complex (DCX(ERCC8) complex) promotes the ubiquitination and subsequent proteasomal degradation of ERCC6 in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair. It is required for the recruitment of XAB2, HMGN1 and TCEA1/TFIIS to a transcription-coupled repair complex which removes RNA polymerase II-blocking lesions from the transcribed strand of active genes. Plays a role in DNA single-strand and double- strand breaks (DSSBs) repair; involved in repair of DSSBs by non- homologous end joining (NHEJ) (PubMed:29545921). {ECO:0000269|PubMed:16751180, ECO:0000269|PubMed:16916636, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:29545921}.

Pathway: Protein modification; protein ubiquitination.

Subunit: Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Interacts with ERCC6 and KIAA1530/UVSSA. Interacts with a subunit of RNA polymerase II TFIIH. Interacts directly with DDB1 (PubMed:22118460). {ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:16751180, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:22466612}.

Subcellular location: Nucleus {ECO:0000305}. Nucleus matrix {ECO:0000269|PubMed:26620705}. Note=UV-induced translocation to the nuclear matrix is dependent on ERCC6. {ECO:0000269|PubMed:26620705}.

Disease: Cockayne syndrome A (CSA) [MIM:216400]: A rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer. {ECO:0000269|PubMed:14661080, ECO:0000269|PubMed:15744458, ECO:0000269|PubMed:19894250}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: UV-sensitive syndrome 2 (UVSS2) [MIM:614621]: An autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors. {ECO:0000269|PubMed:19329487}. Note=The disease is caused by variants affecting the gene represented in this entry.

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:		Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair. The CSA complex (DCX(ERCC8) complex) promotes the ubiquitination and subsequent proteasomal degradation of ERCC6 in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair. It is required for the recruitment of XAB2, HMGN1 and TCEA1/TFIIS to a transcription-coupled repair complex which removes RNA polymerase II-blocking lesions from the transcribed strand of active genes. Plays a role in DNA single-strand and double- strand breaks (DSSBs) repair; involved in repair of DSSBs by non- homologous end joining (NHEJ) (PubMed:29545921). {ECO:0000269\|PubMed:16751180, ECO:0000269\|PubMed:16916636, ECO:0000269\|PubMed:16964240, ECO:0000269\|PubMed:29545921}.


Pathway:		Protein modification; protein ubiquitination.
Subunit:		Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Interacts with ERCC6 and KIAA1530/UVSSA. Interacts with a subunit of RNA polymerase II TFIIH. Interacts directly with DDB1 (PubMed:22118460). {ECO:0000269\|PubMed:12732143, ECO:0000269\|PubMed:16751180, ECO:0000269\|PubMed:22118460, ECO:0000269\|PubMed:22466612}.
Subcellular location:		Nucleus {ECO:0000305}. Nucleus matrix {ECO:0000269\|PubMed:26620705}. Note=UV-induced translocation to the nuclear matrix is dependent on ERCC6. {ECO:0000269\|PubMed:26620705}.
Disease:		Cockayne syndrome A (CSA) [MIM:216400]: A rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer. {ECO:0000269\|PubMed:14661080, ECO:0000269\|PubMed:15744458, ECO:0000269\|PubMed:19894250}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		UV-sensitive syndrome 2 (UVSS2) [MIM:614621]: An autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors. {ECO:0000269\|PubMed:19329487}. Note=The disease is caused by variants affecting the gene represented in this entry.