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Reviewed, UniProtKB/Swiss-Prot Q16531 (DDB1_HUMAN)

Last modified November 25, 2008. Version 78. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    DNA damage-binding protein 1
Alternative name(s):
    Damage-specific DNA-binding protein 1
    UV-damaged DNA-binding factor
    DDB p127 subunit
    DNA damage-binding protein a
      Short name=DDBa
    UV-damaged DNA-binding protein 1
      Short name=UV-DDB 1
    Xeroderma pigmentosum group E-complementing protein
      Short name=XPCe
    XPE-binding factor
      Short name=XPE-BF
    HBV X-associated protein 1
      Short name=XAP-1
Gene names
Name: DDB1
Synonyms: XAP1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1140 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Component of the UV-DDB complex which includes DDB1 and DDB2. The UV-DDB complex interacts with monoubiquitinated histone H2A and binds to XPC via the DDB2 subunit. Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1. DDB1 may recruit specific substrate targeting subunits to the DCX complex. These substrate targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Interacts with AMBRA1, ATG16L1, BTRC, C2ORF37, C4ORF30, DCAF15, DDA1, DET1, DTL, ERCC8, FBXW5, FBXW8, GRWD1, IQWD1, KATNB1, NLE1, NUP43, PAFAH1B1, PHIP, PWP1, RBBP4, RBBP5, RBBP7, RFWD2, VPRBP, WDR5, WDR5B, WDR12, WDR21A, WDR22, WDR23, WDR26, WDR32, WDR39, WDR40A, WDR42, WDR42A, WDR53, WDR57, WDR59, WDR61, WDR68, WSB1, WSB2 and WDTC1. DCX complexes may associate with the COP9 signalosome, and this inhibits the E3 ubiquitin-protein ligase activity of the complex. Interacts with NF2, TSC1 and TSC2. Interacts with Simian virus 5 protein V and the HBV X protein. Interaction with SV5 protein V may prevent the recruitment of DCAF proteins to DCX complexes.

Subcellular location

Cytoplasm. Nucleus. Note= Primarily cytoplasmic. Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage.

Post-translational modification

Ubiquitinated by CUL4A. Subsequently degraded by ubiquitin-dependent proteolysis.

Sequence similarities

Belongs to the DDB1 family.

Sequence annotation (Features)

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Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11401140DNA damage-binding protein 1
PRO_0000079840

Regions

Region1 – 768768Interaction with CDT1
Region391 – 709319Interaction with CUL4A
Region771 – 1140370Interaction with CDT1 and CUL4A

Amino acid modifications

Modified residue81Phosphothreonine By similarity
Modified residue7571Phosphoserine By similarity
Modified residue7661Phosphoserine By similarity

Natural variations

Natural variant4271L → F
VAR_023074

Experimental info

Mutagenesis316 – 3194YLDN → ALAA: Impairs interaction with DDA1
Mutagenesis5371E → A: Slightly impairs interaction with CUL4A
Mutagenesis5611W → A: Strongly impairs interaction with CUL4A
Mutagenesis840 – 8423EAE → AAA: Impairs interaction with AMBRA1, DTL, DET1, VPRBP, WDR22, WDR23 and WDR42A
Mutagenesis910 – 9134MALY → AAAA: Impairs interaction with AMBRA1, DTL and WDR22
Mutagenesis9531W → A: Impairs interaction with AMBRA1, ERCC8, WDR22 and WDR23
Sequence conflict4221D → Y in AAA88883. Ref.3
Sequence conflict5331E → G in CAA05770. Ref.4
Sequence conflict8691A → D in CAA05770. Ref.4
Sequence conflict898 – 8992EL → DV in AAA88883. Ref.3
Sequence conflict898 – 8992EL → DV in CAA05770. Ref.4

Secondary structure

............................................................................................................................................................................................................................. 1140
Helix Strand Turn

Details...