Reviewed, UniProtKB/Swiss-Prot P62877 (RBX1_HUMAN)

Names and origin

Protein names

Recommended name:
    RING-box protein 1
      Short name=Rbx1
Alternative name(s):
    Regulator of cullins 1
    RING finger protein 75
    Protein ZYP

Gene names

Name:	RBX1
Synonyms:	RNF75, ROC1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	108 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of the SCF (SKP1-CUL1-F-box protein) and the CBC(VHL) (CUL2-elonging BC-VHL) E3 ubiquitin ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme, like CDC34, to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M. Ref.9 Ref.10 Ref.16
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2. Part of a SCF-like complex consisting of CUL7, RBX1, SKP1 and FBXW8. Part of CBC(VHL) complexes with elongin BC complex (TCEB1 and TCEB2), CUL2 or CUL5 and VHL. Part of multisubunit E3 ubiquitin ligase complexes with elongin BC complex (TCEB1 and TCEB2), CUL2 and MED8; elongin BC complex (TCEB1 and TCEB2), CUL5 and MUF1. Part of multisubunit complexes with elongin BC complex (TCEB1 and TCEB2), elongin A/TCEB3 or SOCS1 or WSB1 and CUL5. Interacts directly with CUL1 and probably also with CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7. Probably interacts with CDC34. Interacts with COPS6. Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1. Part of an E3 ligase complex composed of RBX1, DDB1, DDB2 and CUL4A or CUL4B. Interacts with UBE2M. Ref.1 Ref.8 Ref.12 Ref.14
Subcellular location	Cytoplasm. Nucleus. Ref.10
Tissue specificity	Widely expressed.
Domain	The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion.
Sequence similarities	Belongs to the RING-box family. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Domain	Zinc-finger
Ligand	Metal-binding Zinc
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW protein neddylation Ref.18 Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	NEDD8 ligase activity Ref.18 Inferred from direct assay. Source: UniProtKB protein binding Ref.18 Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CUL1	Q13616	4	EBI-398523,EBI-359390
CUL5	Q93034	1	EBI-398523,EBI-1057139
VHL	P40337	1	EBI-398523,EBI-301246

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 108

107

RING-box protein 1

PRO_0000056013

Regions

Zinc finger

53 – 98

46

RING-type

Sites

Metal binding

42

1

Zinc 1

Metal binding

45

1

Zinc 1

Metal binding

53

1

Zinc 3

Metal binding

56

1

Zinc 3

Metal binding

68

1

Zinc 3

Metal binding

75

1

Zinc 2

Metal binding

77

1

Zinc 2

Metal binding

80

1

Zinc 1

Metal binding

82

1

Zinc 3

Metal binding

83

1

Zinc 1

Metal binding

94

1

Zinc 2

Metal binding

97

1

Zinc 2

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6

Experimental info

Mutagenesis

53

1

C → A: Strong reduction in ligase activity; when associated with A-56. Ref.1

Mutagenesis

56

1

C → A: Strong reduction in ligase activity; when associated with A-53. Ref.1

Mutagenesis

75

1

C → A: Strong reduction in ligase activity; when associated with A-77. Ref.1

Mutagenesis

77

1

H → A: Strong reduction in ligase activity; when associated with A-75. Ref.1

Sequence conflict

18

1

G → S in AAM21718. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

108

Helix Strand Turn

Details...

Beta strand

22 – 24

3

Beta strand

26 – 33

8

Beta strand

39 – 41

3

Beta strand

43 – 45

3

Turn

49 – 54

6

Helix

55 – 58

4

Turn

63 – 67

5

Beta strand

74 – 76

3

Beta strand

79 – 81

3

Helix

82 – 88

7

Beta strand

97 – 100

4

Sequences

	Sequence		Length	Mass (Da)
	P62877-1 [UniParc]. Last modified August 16, 2004. Version 1. Checksum: 30FC5ADF66096C0E	FASTA	108	12,274
	10 20 30 40 50 60 MAAAMDVDTP SGTNSGAGKK RFEVKKWNAV ALWAWDIVVD NCAICRNHIM DLCIECQANQ 70 80 90 100 ASATSEECTV AWGVCNHAFH FHCISRWLKT RQVCPLDNRE WEFQKYGH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity." Ohta T., Michel J.J., Schottelius A.J., Xiong Y. Mol. Cell 3:535-541(1999) [PubMed: 10230407] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CULLINS, MUTAGENESIS OF CYS-53; CYS-56; CYS-75 AND HIS-77. Tissue: Cervix carcinoma.
[2]	"Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase." Kamura T., Koepp D.M., Conrad M.N., Skowyra D., Moreland R.J., Iliopoulos O., Lane W.S., Kaelin W.G. Jr., Elledge S.J., Conaway R.C., Harper J.W., Conaway J.W. Science 284:657-661(1999) [PubMed: 10213691] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION IN CBC(VHL) COMPLEX.
[3]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:RESEARCH84.1-RESEARCH84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Placenta.
[6]	Bienvenut W.V., Vousden K.H., Lukashchuk N. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-20, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[7]	"Genomic organization and expression of the ubiquitin-proteasome complex-associated protein Rbx1/ROC1/Hrt1." Perin J.-P., Seddiqi N., Charbonnier F., Goudou D., Belkadi L., Rieger F., Alliel P.M. Cell. Mol. Biol. 45:1131-1137(1999) [PubMed: 10643962] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-108. Tissue: Brain.
[8]	"Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha." Tan P., Fuchs S.Y., Chen A., Wu K., Gomez C., Ronai Z., Pan Z.-Q. Mol. Cell 3:527-533(1999) [PubMed: 10230406] [Abstract] Cited for: PROTEIN SEQUENCE OF 92-105, INTERACTION WITH CUL1, IDENTIFICATION IN A COMPLEX WITH CUL1; SKP1 AND SKP2. Tissue: Cervix carcinoma.
[9]	"The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2." Kamura T., Conrad M.N., Yan Q., Conaway R.C., Conaway J.W. Genes Dev. 13:2928-2933(1999) [PubMed: 10579999] [Abstract] Cited for: FUNCTION.
[10]	"The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1." Furukawa M., Zhang Y., McCarville J., Ohta T., Xiong Y. Mol. Cell. Biol. 20:8185-8197(2000) [PubMed: 11027288] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"Muf1, a novel elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase." Kamura T., Burian D., Yan Q., Schmidt S.L., Lane W.S., Querido E., Branton P.E., Shilatifard A., Conaway R.C., Conaway J.W. J. Biol. Chem. 276:29748-29753(2001) [PubMed: 11384984] [Abstract] Cited for: IDENTIFICATION IN E3 UBIQUITIN LIGASE COMPLEX WITH MUF1, IDENTIFICATION IN COMPLEXES WITH CUL5.
[12]	"Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome." Lyapina S., Cope G., Shevchenko A., Serino G., Tsuge T., Zhou C., Wolf D.A., Wei N., Shevchenko A., Deshaies R.J. Science 292:1382-1385(2001) [PubMed: 11337588] [Abstract] Cited for: INTERACTION WITH COPS6.
[13]	"Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase." Brower C.S., Sato S., Tomomori-Sato C., Kamura T., Pause A., Stearman R., Klausner R.D., Malik S., Lane W.S., Sorokina I., Roeder R.G., Conaway J.W., Conaway R.C. Proc. Natl. Acad. Sci. U.S.A. 99:10353-10358(2002) [PubMed: 12149480] [Abstract] Cited for: IDENTIFICATION IN E3 UBIQUITIN LIGASE COMPLEX WITH MED8.
[14]	"CUL7: a DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex." Dias D.C., Dolios G., Wang R., Pan Z.Q. Proc. Natl. Acad. Sci. U.S.A. 99:16601-16606(2002) [PubMed: 12481031] [Abstract] Cited for: IDENTIFICATION IN SCF-LIKE COMPLEX, INTERACTION WITH CUL7.
[15]	"Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase." Wertz I.E., O'Rourke K.M., Zhang Z., Dornan D., Arnott D., Deshaies R.J., Dixit V.M. Science 303:1371-1374(2004) [PubMed: 14739464] [Abstract] Cited for: IDENTIFICATION IN THE DCX DET1-COP1 COMPLEX WITH DDB1; CUL4A; COP1 AND DET1.
[16]	"Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage." Wang H., Zhai L., Xu J., Joo H.-Y., Jackson S., Erdjument-Bromage H., Tempst P., Xiong Y., Zhang Y. Mol. Cell 22:383-394(2006) [PubMed: 16678110] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH DDB1; DDB2; CUL4A AND CUL4B, MASS SPECTROMETRY, FUNCTION.
[17]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[18]	"E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification." Huang D.T., Ayrault O., Hunt H.W., Taherbhoy A.M., Duda D.M., Scott D.C., Borg L.A., Neale G., Murray P.J., Roussel M.F., Schulman B.A. Mol. Cell 33:483-495(2009) [PubMed: 19250909] [Abstract] Cited for: INTERACTION WITH UBE2M.
[19]	"Structure of the Cul1-Rbx1-Skp1-F box Skp2 SCF ubiquitin ligase complex." Zheng N., Schulman B.A., Song L., Miller J.J., Jeffrey P.D., Wang P., Chu C., Koepp D.M., Elledge S.J., Pagano M., Conaway R.C., Conaway J.W., Harper J.W., Pavletich N.P. Nature 416:703-709(2002) [PubMed: 11961546] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 19-108 IN COMPLEX WITH 17-776 OF CUL1, X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN SCF COMPLEX WITH CUL1; SKP1 AND SKP2.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF142059 mRNA. Translation: AAD30146.1.
AF140598 mRNA. Translation: AAD29715.1.
CR456560 mRNA. Translation: CAG30446.1.
AL080242 Genomic DNA. Translation: CAB62925.1.
BC001466 mRNA. Translation: AAH01466.1.
BC017370 mRNA. Translation: AAH17370.2. Different initiation.
AY099360 mRNA. Translation: AAM21718.1.

IPI

IPI00003386.

PIR

T51146.

RefSeq

NP_055063.1.

UniGene

Hs.474949

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LDJ	X-ray	3.00	B	19-108	[»]
1LDK	X-ray	3.10	C	19-108	[»]
1U6G	X-ray	3.10	B	1-108	[»]
2HYE	X-ray	3.10	D	1-108	[»]
3DPL	X-ray	2.60	R	5-108	[»]
3DQV	X-ray	3.00	R/Y	5-108	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P62877. 14 interactions.

Proteomic databases

PRIDE

P62877.

Genome annotation databases

Ensembl

ENSG00000100387. Homo sapiens. [Contig view]

GeneID

9978.

KEGG

hsa:9978.

Organism-specific databases

GeneCards

GC22P039671.

H-InvDB

HIX0021436.
HIX0080252.

HGNC

HGNC:9928. RBX1.

HPA

HPA003038.

MIM

603814. gene.

PharmGKB

PA34299.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P62877.

HOVERGEN

P62877.

OMA

P62877. KWTAVAF.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.

Reactome

REACT_6185. HIV Infection.

Gene expression databases

ArrayExpress

P62877.

Bgee

P62877.

CleanEx

HS_RBX1.

GermOnline

ENSG00000100387. Homo sapiens.

Family and domain databases

InterPro

IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
[Graphical view]

Pfam

PF00097. zf-C3HC4. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

37682.

SOURCE

Search...

Entry information

Entry name

RBX1_HUMAN

Accession

Primary (citable) accession number: P62877
Secondary accession number(s): Q8N6Z8 , Q9D1S2, Q9WUK9, Q9Y254

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	August 16, 2004
Last modified:	June 16, 2009
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)