cd01805

ubiquitin-like (Ubl) domain found in the Rad23 protein family

CDD entry
Member databaseCDD
CDD typedomain
Short nameUbl_Rad23
SetUbl1_cv_Nsp3_N-like

Description

The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.
[9, 3, 18, 52, 22, 48, 7, 15, 16, 45, 12, 24, 8, 17, 50, 40, 28, 21, 10, 43, 20, 30, 4, 25, 47, 2, 41, 11, 37, 44, 33, 14, 51, 36, 23, 46, 38, 1, 13, 31, 27, 42, 29, 5, 32, 26, 35, 6, 49, 34, 39, 19]

References

1.The carboxy-terminal domain of the XPC protein plays a crucial role in nucleotide excision repair through interactions with transcription factor IIH. Uchida A, Sugasawa K, Masutani C, Dohmae N, Araki M, Yokoi M, Ohkuma Y, Hanaoka F. DNA Repair (Amst) 1, 449-61, (2002). PMID: 12509233

2.Biochemical and structural analysis of the interaction between the UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr. Withers-Ward ES, Mueller TD, Chen IS, Feigon J. Biochemistry 39, 14103-12, (2000). View articlePMID: 11087358

3.The yeast E4 ubiquitin ligase Ufd2 interacts with the ubiquitin-like domains of Rad23 and Dsk2 via a novel and distinct ubiquitin-like binding domain. Hanzelmann P, Stingele J, Hofmann K, Schindelin H, Raasi S. J Biol Chem 285, 20390-8, (2010). PMID: 20427284

4.Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular protein implicated in nucleotide excision DNA repair. Withers-Ward ES, Jowett JB, Stewart SA, Xie YM, Garfinkel A, Shibagaki Y, Chow SA, Shah N, Hanaoka F, Sawitz DG, Armstrong RW, Souza LM, Chen IS. J Virol 71, 9732-42, (1997). PMID: 9371639

5.Ubiquitin binding proteins protect ubiquitin conjugates from disassembly. Hartmann-Petersen R, Hendil KB, Gordon C. FEBS Lett 535, 77-81, (2003). PMID: 12560082

6.Involvement of rhp23, a Schizosaccharomyces pombe homolog of the human HHR23A and Saccharomyces cerevisiae RAD23 nucleotide excision repair genes, in cell cycle control and protein ubiquitination. Elder RT, Song XQ, Chen M, Hopkins KM, Lieberman HB, Zhao Y. Nucleic Acids Res 30, 581-91, (2002). PMID: 11788722

7.Crystallization and preliminary X-ray diffraction studies of the ubiquitin-like (UbL) domain of the human homologue A of Rad23 (hHR23A) protein. Chen YW, Tajima T, Rees M, Garcia-Maya M. Acta Crystallogr Sect F Struct Biol Cryst Commun 65, 930-2, (2009). PMID: 19724136

8.HIV-1 replication through hHR23A-mediated interaction of Vpr with 26S proteasome. Li G, Elder RT, Dubrovsky L, Liang D, Pushkarsky T, Chiu K, Fan T, Sire J, Bukrinsky M, Zhao RY. PLoS One 5, e11371, (2010). PMID: 20614012

9.Rad23 interaction with the proteasome is regulated by phosphorylation of its ubiquitin-like (UbL) domain. Liang RY, Chen L, Ko BT, Shen YH, Li YT, Chen BR, Lin KT, Madura K, Chuang SM. J Mol Biol 426, 4049-4060, (2014). PMID: 25311859

10.Ubiquitin recognition by the DNA repair protein hHR23a. Wang Q, Goh AM, Howley PM, Walters KJ. Biochemistry 42, 13529-35, (2003). PMID: 14621999

11.HR23B is a biomarker for tumor sensitivity to HDAC inhibitor-based therapy. Khan O, Fotheringham S, Wood V, Stimson L, Zhang C, Pezzella F, Duvic M, Kerr DJ, La Thangue NB. Proc Natl Acad Sci U S A 107, 6532-7, (2010). PMID: 20308564

12.Structural determinants for the binding of ubiquitin-like domains to the proteasome. Mueller TD, Feigon J. EMBO J. 22, 4634-45, (2003). View articlePMID: 12970176

13.A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. Sugasawa K, Shimizu Y, Iwai S, Hanaoka F. DNA Repair (Amst) 1, 95-107, (2002). PMID: 12509299

14.Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions. Shimizu Y, Uchimura Y, Dohmae N, Saitoh H, Hanaoka F, Sugasawa K. J Nucleic Acids 2010, 805698, (2010). PMID: 20798892

15.Structural determinants for selective recognition of a Lys48-linked polyubiquitin chain by a UBA domain. Varadan R, Assfalg M, Raasi S, Pickart C, Fushman D. Mol Cell 18, 687-98, (2005). PMID: 15949443

16.Structure of the XPC binding domain of hHR23A reveals hydrophobic patches for protein interaction. Kamionka M, Feigon J. Protein Sci. 13, 2370-7, (2004). View articlePMID: 15322280

17.Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins. Goh AM, Walters KJ, Elsasser S, Verma R, Deshaies RJ, Finley D, Howley PM. BMC Biochem 9, 4, (2008). PMID: 18234089

18.Structures of the Sgt2/SGTA Dimerization Domain with the Get5/UBL4A UBL Domain Reveal an Interaction that Forms a Conserved Dynamic Interface. Chartron JW, Vandervelde DG, Clemons WM Jr. Cell Rep 2, 1620-32, (2012). PMID: 23142665

19.The crystal structure of the ubiquitin-like (UbL) domain of human homologue A of Rad23 (hHR23A) protein. Chen YW, Tajima T, Agrawal S. Protein Eng Des Sel 24, 131-8, (2011). PMID: 21047872

20.Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome. Hiyama H, Yokoi M, Masutani C, Sugasawa K, Maekawa T, Tanaka K, Hoeijmakers JH, Hanaoka F. J. Biol. Chem. 274, 28019-25, (1999). View articlePMID: 10488153

21.Rad23 ubiquitin-associated domains (UBA) inhibit 26 S proteasome-catalyzed proteolysis by sequestering lysine 48-linked polyubiquitin chains. Raasi S, Pickart CM. J. Biol. Chem. 278, 8951-9, (2003). View articlePMID: 12643283

22.Structure of the Sgt2 dimerization domain complexed with the Get5 UBL domain involved in the targeting of tail-anchored membrane proteins to the endoplasmic reticulum. Tung JY, Li YC, Lin TW, Hsiao CD. Acta Crystallogr D Biol Crystallogr 69, 2081-90, (2013). PMID: 24100326

23.Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein. Nishi R, Okuda Y, Watanabe E, Mori T, Iwai S, Masutani C, Sugasawa K, Hanaoka F. Mol Cell Biol 25, 5664-74, (2005). PMID: 15964821

24.Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr. Dieckmann T, Withers-Ward ES, Jarosinski MA, Liu CF, Chen IS, Feigon J. Nat. Struct. Biol. 5, 1042-7, (1998). View articlePMID: 9846873

25.Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23. Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ, Bootsma D. EMBO J 13, 1831-43, (1994). PMID: 8168482

26.The ubiquitin-associated (UBA) 1 domain of Schizosaccharomyces pombe Rhp23 is essential for the recognition of ubiquitin-proteasome system substrates both in vitro and in vivo. Medina B, Paraskevopoulos K, Boehringer J, Sznajder A, Robertson M, Endicott J, Gordon C. J Biol Chem 287, 42344-51, (2012). PMID: 23038266

27.Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. Batty D, Rapic'-Otrin V, Levine AS, Wood RD. J Mol Biol 300, 275-90, (2000). PMID: 10873465

28.Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains of HHR23A. Raasi S, Orlov I, Fleming KG, Pickart CM. J. Mol. Biol. 341, 1367-79, (2004). View articlePMID: 15321727

29.Rad23 escapes degradation because it lacks a proteasome initiation region. Fishbain S, Prakash S, Herrig A, Elsasser S, Matouschek A. Nat Commun 2, 192, (2011). PMID: 21304521

30.Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Mol Cell Biol 17, 6924-31, (1997). PMID: 9372924

31.Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F. J. Biol. Chem. 276, 18665-72, (2001). View articlePMID: 11279143

32.Protein degradation: recognition of ubiquitinylated substrates. Hartmann-Petersen R, Gordon C. Curr Biol 14, R754-6, (2004). PMID: 15380085

33.Binding surface mapping of intra- and interdomain interactions among hHR23B, ubiquitin, and polyubiquitin binding site 2 of S5a. Ryu KS, Lee KJ, Bae SH, Kim BK, Kim KA, Choi BS. J. Biol. Chem. 278, 36621-7, (2003). View articlePMID: 12832454

34.The RAD23 family provides an essential connection between the 26S proteasome and ubiquitylated proteins in Arabidopsis. Farmer LM, Book AJ, Lee KH, Lin YL, Fu H, Vierstra RD. Plant Cell 22, 124-42, (2010). PMID: 20086187

35.Identification and characterization of the rhp23(+) DNA repair gene in Schizosaccharomyces pombe. Lombaerts M, Goeloe JI, den Dulk H, Brandsma JA, Brouwer J. Biochem Biophys Res Commun 268, 210-5, (2000). PMID: 10652237

36.Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning. Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F. Mol Cell 36, 642-53, (2009). PMID: 19941824

37.Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B. Kim B, Ryu KS, Kim HJ, Cho SJ, Choi BS. FEBS J. 272, 2467-76, (2005). View articlePMID: 15885096

38.DNA bending by the human damage recognition complex XPC-HR23B. Janicijevic A, Sugasawa K, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA Repair (Amst) 2, 325-36, (2003). PMID: 12547395

39.The ubiquitin receptor Rad23: at the crossroads of nucleotide excision repair and proteasomal degradation. Dantuma NP, Heinen C, Hoogstraten D. DNA Repair (Amst) 8, 449-60, (2009). PMID: 19223247

40.Evidence for distinct functions for human DNA repair factors hHR23A and hHR23B. Chen L, Madura K. FEBS Lett 580, 3401-8, (2006). PMID: 16712842

41.The DNA repair-ubiquitin-associated HR23 proteins are constituents of neuronal inclusions in specific neurodegenerative disorders without hampering DNA repair. Bergink S, Severijnen LA, Wijgers N, Sugasawa K, Yousaf H, Kros JM, van Swieten J, Oostra BA, Hoeijmakers JH, Vermeulen W, Willemsen R. Neurobiol Dis 23, 708-16, (2006). PMID: 16860562

42.Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH. Mol Cell 2, 223-32, (1998). PMID: 9734359

43.Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B. Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N. Hum Mol Genet 9, 1795-803, (2000). PMID: 10915768

44.Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B. Fujiwara K, Tenno T, Sugasawa K, Jee JG, Ohki I, Kojima C, Tochio H, Hiroaki H, Hanaoka F, Shirakawa M. J. Biol. Chem. 279, 4760-7, (2004). View articlePMID: 14585839

45.DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a. Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. Proc. Natl. Acad. Sci. U.S.A. 100, 12694-9, (2003). View articlePMID: 14557549

46.A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. Genes Dev 17, 1630-45, (2003). PMID: 12815074

47.Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions. Mueller TD, Feigon J. J. Mol. Biol. 319, 1243-55, (2002). View articlePMID: 12079361

48.Structures of Rpn1 T1:Rad23 and hRpn13:hPLIC2 Reveal Distinct Binding Mechanisms between Substrate Receptors and Shuttle Factors of the Proteasome. Chen X, Randles L, Shi K, Tarasov SG, Aihara H, Walters KJ. Structure 24, 1257-1270, (2016). PMID: 27396824

49.Characterization and expression of a rice RAD23 gene. Schultz TF, Quatrano RS. Plant Mol Biol 34, 557-62, (1997). PMID: 9225866

50.Ubiquitin receptor proteins hHR23a and hPLIC2 interact. Kang Y, Zhang N, Koepp DM, Walters KJ. J. Mol. Biol. 365, 1093-101, (2007). View articlePMID: 17098253

51.Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals contacts with both strands of the DNA duplex and spans the DNA adduct. Neher TM, Rechkunova NI, Lavrik OI, Turchi JJ. Biochemistry 49, 669-78, (2010). PMID: 20028083

52.Structure of the Sgt2/Get5 complex provides insights into GET-mediated targeting of tail-anchored membrane proteins. Simon AC, Simpson PJ, Goldstone RM, Krysztofinska EM, Murray JW, High S, Isaacson RL. Proc. Natl. Acad. Sci. U.S.A. 110, 1327-32, (2013). View articlePMID: 23297211

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