| General information | | DisProt: | DP00156 | | Name: | UV excision repair protein RAD23 homolog A | | Synonym(s): | RD23A_HUMAN
DNA-repair protein hHR23A
hHR23A
| | First appeared in release: | Release 1.1 (12/01/2003) | | UniProt: | P54725 | | UniGene: | Hs.643267 | | SwissProt: | RD23A_HUMAN | | TrEMBL: | | | NCBI (GI): | 1709983 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 363 | | Percent disordered: | 40% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MAVTITLKTL QQQTFKIRME PDETVKVLKE KIEAEKGRDA FPVAGQKLIY AGKILSDDVP - 60
IRDYRIDEKN FVVVMVTKTK AGQGTSAPPE ASPTAAPESS TSFPPAPTSG MSHPPPAARE - 120
DKSPSEESAP TTSPESVSGS VPSSGSSGRE EDAASTLVTG SEYETMLTEI MSMGYERERV - 180
VAALRASYNN PHRAVEYLLT GIPGSPEPEH GSVQESQVSE QPATEAAGEN PLEFLRDQPQ - 240
FQNMRQVIQQ NPALLPALLQ QLGQENPQLL QQISRHQEQF IQMLNEPPGE LADISDVEGE - 300
VGAIGEEAPQ MNYIQVTPQE KEAIERLKAL GFPESLVIQA YFACEKNENL AANFLLSQNF - 360
DDE
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| Functional narrative |
HHR23A functions in nucleotide excision repair and proteasome-mediated protein degradation. HHR23a or HHR23b (the two human Rad23 orthologs) form a complex with xeroderma pigmentosum complementation C protein that binds specificity to bulky DNA lesions, such as those formed from UV damage. The binding triggers the recruitment of downstream repair proteins to the damage site. HHR23a/b contain four structural domains, including UBL, UBA1, XPC, and UBA2, which are connected by disordered unstructured flexible linker regions. Addition of the S5a proteasomal subunit or ubiquitin causes a conformational change in the structure of the protein, from a closed to an opened state by blocking UBL/UBA domain interactions. Experimental evidence suggests that linker regions remain flexible in the opened state, which no longer engages in intramolecular domain interactions.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered - Extended | | Name: | | | Location: | 79 - 160 | | Length: | 82 | | Region sequence: |
TKAGQGTSAPPEASPTAAPESSTSFPPAPTSGMSHPPPAAREDKSPSEESAPTTSPESVS
GSVPSSGSSGREEDAASTLVTG | | Modification type: | | | PDB: | | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Molecular assembly
Entropic chain
| | Functional subclasses: | Flexible linkers/spacers
| Detection methods:
- Nuclear magnetic resonance (NMR)
| References:
- Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. "DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a." Proc Natl Acad Sci U S A. 2003; 100(22): 12694-12699. PubMed: 14557549
| Comments:
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| Region 2 | | Type: | Disordered - Extended | | Name: | | | Location: | 201 - 231 | | Length: | 31 | | Region sequence: |
GIPGSPEPEHGSVQESQVSEQPATEAAGENP | | Modification type: | | | PDB: | | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Entropic chain
Molecular assembly
| | Functional subclasses: | Flexible linkers/spacers
| Detection methods:
- Nuclear magnetic resonance (NMR)
| References:
- Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. "DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a." Proc Natl Acad Sci U S A. 2003; 100(22): 12694-12699. PubMed: 14557549
| Comments:
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| Region 3 | | Type: | Disordered - Extended | | Name: | | | Location: | 283 - 316 | | Length: | 34 | | Region sequence: |
MLNEPPGELADISDVEGEVGAIGEEAPQMNYIQV | | Modification type: | | | PDB: | | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Molecular assembly
Entropic chain
| | Functional subclasses: | Flexible linkers/spacers
| Detection methods:
- Nuclear magnetic resonance (NMR)
| References:
- Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. "DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a." Proc Natl Acad Sci U S A. 2003; 100(22): 12694-12699. PubMed: 14557549
| Comments:
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| Region 4 | | Type: | Ordered | | Name: | UBL | | Location: | 3 - 78 | | Length: | 76 | | Region sequence: |
VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIR
DYRIDEKNFVVVMVTK | | Modification type: | Engineered
| | PDB: | | | Structural/functional type: | Function arises from the ordered state
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR)
| References:
- Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. "DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a." Proc Natl Acad Sci U S A. 2003; 100(22): 12694-12699. PubMed: 14557549
| Comments:The UBL region interacts with UBA domains of the same protein. It is unable to bind to both simultaneously, but does so in equilibrium with each.
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| Region 5 | | Type: | Ordered | | Name: | UBA1 | | Location: | 161 - 200 | | Length: | 40 | | Region sequence: |
SEYETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLT | | Modification type: | Engineered
| | PDB: | | | Structural/functional type: | Function arises from the ordered state
Relationship to function unknown
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR)
| References:
- Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. "DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a." Proc Natl Acad Sci U S A. 2003; 100(22): 12694-12699. PubMed: 14557549
| Comments:The UBA1 domain binds with the UBL domain of the same protein. It does so at equilibrium with UBA2.
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| Region 6 | | Type: | Ordered | | Name: | XBC-binding | | Location: | 232 - 282 | | Length: | 51 | | Region sequence: |
LEFLRDQPQFQNMRQVIQQNPALLPALLQQLGQENPQLLQQISRHQEQFIQ | | Modification type: | Engineered
| | PDB: | | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Unknown
| | Functional subclasses: | Unknown
| Detection methods:
- Nuclear magnetic resonance (NMR)
| References:
- Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. "DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a." Proc Natl Acad Sci U S A. 2003; 100(22): 12694-12699. PubMed: 14557549
| Comments:
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| Region 7 | | Type: | Ordered | | Name: | UBA2 | | Location: | 317 - 359 | | Length: | 43 | | Region sequence: |
TPQEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLLSQN | | Modification type: | Engineered
| | PDB: | | | Structural/functional type: | Function arises from the ordered state
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR)
| References:
- Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. "DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a." Proc Natl Acad Sci U S A. 2003; 100(22): 12694-12699. PubMed: 14557549
| Comments:The UBA2 domain binds with the UBL domain of the same protein. It does so at equilibrium with UBA1.
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