RBX1

Ring-box 1, E3 ubiquitin protein ligase
PDB rendering based on 1ldj.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1LDJ​, 1LDK​, 1U6G​, 2HYE​, 2LGV​, 3DPL​, 3DQV​, 3RTR​, 4F52​, 4P5O​
Identifiers
Symbols	RBX1 ; BA554C12.1; RNF75; ROC1
External IDs	OMIM: 603814 MGI: 1891829 HomoloGene: 6872 GeneCards: RBX1 Gene
Gene ontology Molecular function • ubiquitin-protein transferase activity • protein binding • zinc ion binding • ligase activity • NEDD8 transferase activity • ubiquitin protein ligase binding • protein complex binding • ubiquitin-ubiquitin ligase activity • ubiquitin protein ligase activity • cullin family protein binding Cellular component • nucleoplasm • cytosol • SCF ubiquitin ligase complex • VCB complex • cullin-RING ubiquitin ligase complex • Cul2-RING ubiquitin ligase complex • Cul3-RING ubiquitin ligase complex • Cul4A-RING E3 ubiquitin ligase complex • Cul4B-RING E3 ubiquitin ligase complex • Cul5-RING ubiquitin ligase complex • Cul7-RING ubiquitin ligase complex • nuclear SCF ubiquitin ligase complex Biological process • DNA repair • protein monoubiquitination • Notch signaling pathway • viral process • protein ubiquitination • translesion synthesis • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process • DNA damage response, detection of DNA damage • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • proteasome-mediated ubiquitin-dependent protein catabolic process • protein neddylation • regulation of transcription from RNA polymerase II promoter in response to hypoxia • cellular response to hypoxia • negative regulation of canonical Wnt signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9978	100043674
Ensembl	ENSG00000100387	ENSMUSG00000022400
UniProt	P62877	P62878
RefSeq (mRNA)	NM_014248	n/a
RefSeq (protein)	NP_055063	n/a
Location (UCSC)	Chr 22: 40.95 – 40.97 Mb	Chr 15: 81.47 – 81.48 Mb
PubMed search

RING-box protein 1 is a protein that in humans is encoded by the RBX1 gene.^[1][2]

Function

This gene encodes an evolutionarily conserved protein that interacts with cullins. The protein plays a unique role in the ubiquitination reaction by heterodimerizing with cullin-1 to catalyze ubiquitin polymerization. It also may be involved in the regulation of protein turn-over.^[3]

Interactions

RBX1 has been shown to interact with:

• CAND1,^[4][5]
• CUL1,^{[2][6][4][5][7][8]}
• CUL2,^[2][6]
• CUL4A,^[2][6][9]
• CUL5^[2][10]
• CUL7,^[6]
• DCUN1D1,^[5] and
• P70-S6 Kinase 1.^[11]

References

1. Kamura T, Koepp DM, Conrad MN, Skowyra D, Moreland RJ, Iliopoulos O, Lane WS, Kaelin WG, Elledge SJ, Conaway RC, Harper JW, Conaway JW (Apr 1999). "Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase". Science 284 (5414): 657–61. doi:10.1126/science.284.5414.657. PMID 10213691.
2. Ohta T, Michel JJ, Schottelius AJ, Xiong Y (Apr 1999). "ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity". Molecular Cell 3 (4): 535–41. doi:10.1016/S1097-2765(00)80482-7. PMID 10230407.
3. "Entrez Gene: RBX1 ring-box 1".
4. Min KW, Hwang JW, Lee JS, Park Y, Tamura TA, Yoon JB (May 2003). "TIP120A associates with cullins and modulates ubiquitin ligase activity". The Journal of Biological Chemistry 278 (18): 15905–10. doi:10.1074/jbc.M213070200. PMID 12609982.
5. Kim AY, Bommeljé CC, Lee BE, Yonekawa Y, Choi L, Morris LG, Huang G, Kaufman A, Ryan RJ, Hao B, Ramanathan Y, Singh B (Nov 2008). "SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation". The Journal of Biological Chemistry 283 (48): 33211–20. doi:10.1074/jbc.M804440200. PMC 2586271. PMID 18826954.
6. Dias DC, Dolios G, Wang R, Pan ZQ (Dec 2002). "CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex". Proceedings of the National Academy of Sciences of the United States of America 99 (26): 16601–6. doi:10.1073/pnas.252646399. PMC 139190. PMID 12481031.
7. Kim J, Kim JH, Lee SH, Kim DH, Kang HY, Bae SH, Pan ZQ, Seo YS (Jul 2002). "The novel human DNA helicase hFBH1 is an F-box protein". The Journal of Biological Chemistry 277 (27): 24530–7. doi:10.1074/jbc.M201612200. PMID 11956208.
8. Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP (Apr 2002). "Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex". Nature 416 (6882): 703–9. doi:10.1038/416703a. PMID 11961546.
9. Guerrero-Santoro J, Kapetanaki MG, Hsieh CL, Gorbachinsky I, Levine AS, Rapić-Otrin V (Jul 2008). "The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A". Cancer Research 68 (13): 5014–22. doi:10.1158/0008-5472.CAN-07-6162. PMID 18593899.
10. Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA (Sep 2008). "Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation". Cell 134 (6): 995–1006. doi:10.1016/j.cell.2008.07.022. PMC 2628631. PMID 18805092.
11. Panasyuk G, Nemazanyy I, Filonenko V, Gout I (May 2008). "Ribosomal protein S6 kinase 1 interacts with and is ubiquitinated by ubiquitin ligase ROC1". Biochemical and Biophysical Research Communications 369 (2): 339–43. doi:10.1016/j.bbrc.2008.02.016. PMID 18279656.

Further reading

• Skowyra D, Koepp DM, Kamura T, Conrad MN, Conaway RC, Conaway JW, Elledge SJ, Harper JW (Apr 1999). "Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1". Science 284 (5414): 662–5. doi:10.1126/science.284.5414.662. PMID 10213692.
• Tan P, Fuchs SY, Chen A, Wu K, Gomez C, Ronai Z, Pan ZQ (Apr 1999). "Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha". Molecular Cell 3 (4): 527–33. doi:10.1016/S1097-2765(00)80481-5. PMID 10230406.
• Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (Oct 1999). "A family of mammalian F-box proteins". Current Biology 9 (20): 1180–2. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037.
• Kamura T, Conrad MN, Yan Q, Conaway RC, Conaway JW (Nov 1999). "The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2". Genes & Development 13 (22): 2928–33. doi:10.1101/gad.13.22.2928. PMC 317157. PMID 10579999.
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 1999). "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
• Seddiqi N, Charbonnier F, Goudou D, Belkadi L, Rieger F, Alliel PM (Dec 1999). "Genomic organization and expression of the ubiquitin-proteasome complex-associated protein Rbx1/ROC1/Hrt1". Cellular and Molecular Biology 45 (8): 1131–7. PMID 10643962.
• Read MA, Brownell JE, Gladysheva TB, Hottelet M, Parent LA, Coggins MB, Pierce JW, Podust VN, Luo RS, Chau V, Palombella VJ (Apr 2000). "Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha". Molecular and Cellular Biology 20 (7): 2326–33. doi:10.1128/MCB.20.7.2326-2333.2000. PMC 85397. PMID 10713156.
• Furukawa M, Zhang Y, McCarville J, Ohta T, Xiong Y (Nov 2000). "The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1". Molecular and Cellular Biology 20 (21): 8185–97. doi:10.1128/MCB.20.21.8185-8197.2000. PMC 86428. PMID 11027288.
• Maeda I, Ohta T, Koizumi H, Fukuda M (Apr 2001). "In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3". FEBS Letters 494 (3): 181–5. doi:10.1016/S0014-5793(01)02343-2. PMID 11311237.
• Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ (May 2001). "Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome". Science 292 (5520): 1382–5. doi:10.1126/science.1059780. PMID 11337588.
• Fukuchi M, Imamura T, Chiba T, Ebisawa T, Kawabata M, Tanaka K, Miyazono K (May 2001). "Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins". Molecular Biology of the Cell 12 (5): 1431–43. doi:10.1091/mbc.12.5.1431. PMC 34595. PMID 11359933.
• Kamura T, Burian D, Yan Q, Schmidt SL, Lane WS, Querido E, Branton PE, Shilatifard A, Conaway RC, Conaway JW (Aug 2001). "Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase". The Journal of Biological Chemistry 276 (32): 29748–53. doi:10.1074/jbc.M103093200. PMID 11384984.
• Wu K, Chen A, Tan P, Pan ZQ (Jan 2002). "The Nedd8-conjugated ROC1-CUL1 core ubiquitin ligase utilizes Nedd8 charged surface residues for efficient polyubiquitin chain assembly catalyzed by Cdc34". The Journal of Biological Chemistry 277 (1): 516–27. doi:10.1074/jbc.M108008200. PMID 11675391.
• Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL (Dec 2001). "Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy". Proceedings of the National Academy of Sciences of the United States of America 98 (25): 14440–5. doi:10.1073/pnas.251541198. PMC 64700. PMID 11717410.
• Kim J, Kim JH, Lee SH, Kim DH, Kang HY, Bae SH, Pan ZQ, Seo YS (Jul 2002). "The novel human DNA helicase hFBH1 is an F-box protein". The Journal of Biological Chemistry 277 (27): 24530–7. doi:10.1074/jbc.M201612200. PMID 11956208.
• Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP (Apr 2002). "Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex". Nature 416 (6882): 703–9. doi:10.1038/416703a. PMID 11961546.
• Yoshida Y, Chiba T, Tokunaga F, Kawasaki H, Iwai K, Suzuki T, Ito Y, Matsuoka K, Yoshida M, Tanaka K, Tai T (Jul 2002). "E3 ubiquitin ligase that recognizes sugar chains". Nature 418 (6896): 438–42. doi:10.1038/nature00890. PMID 12140560.
• Brower CS, Sato S, Tomomori-Sato C, Kamura T, Pause A, Stearman R, Klausner RD, Malik S, Lane WS, Sorokina I, Roeder RG, Conaway JW, Conaway RC (Aug 2002). "Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase". Proceedings of the National Academy of Sciences of the United States of America 99 (16): 10353–8. doi:10.1073/pnas.162424199. PMC 124918. PMID 12149480.