Q9UBF6 (RBX2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RING-box protein 2
Short name=Rbx2

Alternative name(s):
CKII beta-binding protein 1
Short name=CKBBP1
RING finger protein 7
Regulator of cullins 2
Sensitive to apoptosis gene protein

Gene names

Name:	RNF7
Synonyms:	RBX2, ROC2, SAG

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	113 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex which mediates 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 to the complex and brings it into close proximity to the substrate. Promotes the neddylation of CUL5 via its interaction with UBE2F. May play a role in protecting cells from apoptosis induced by redox agents. Ref.10
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Probable part of SCF complexes, which consist of SKP1, CUL1, RNF7/RBX2 and a F-box protein. Interacts (preferentially) with CUL5. Also interacts (with lower preference) with CUL1, CUL2, CUL3, CUL4A and CUL4B. Interacts with UBE2F. Interacts with CSNK2B, the interaction is not affected by phosphorylation by CK2. Ref.2 Ref.10 Ref.12
Subcellular location	Cytoplasm. Nucleus Ref.3.
Tissue specificity	Expressed in heart, liver, skeletal muscle and pancreas. At very low levels expressed in brain, placenta and lung. Ref.1
Induction	By 1,10-phenanthroline. Ref.3
Domain	The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion.
Post-translational modification	Phosphorylation by CK2 is required for efficient degradation of NFKBIA and CDKN1B.
Sequence similarities	Belongs to the RING-box family. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intrinsic apoptotic signaling pathway in response to oxidative stress Traceable author statement Ref.3. Source: ProtInc negative regulation of apoptotic process Traceable author statement Ref.3. Source: ProtInc protein neddylation Inferred from direct assay Ref.12. Source: UniProtKB protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway response to redox state Traceable author statement Ref.3. Source: ProtInc
Cellular_component	Cul5-RING ubiquitin ligase complex Inferred from direct assay PubMed 22405651. Source: MGI cytoplasm Non-traceable author statement Ref.3. Source: UniProtKB nucleus Non-traceable author statement Ref.3. Source: UniProtKB
Molecular_function	NEDD8 ligase activity Inferred from direct assay Ref.12. Source: UniProtKB copper ion binding Traceable author statement Ref.3. Source: ProtInc zinc ion binding Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IKBKG	Q9Y6K9	3	EBI-398632,EBI-81279
vif	P12504	4	EBI-398632,EBI-779991	From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UBF6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9UBF6-2)

Also known as: SAG-v;

The sequence of this isoform differs from the canonical sequence as follows:
     60-113: ACLRCQAENK...QDWVVQRIGK → EGIGVRNWSE...SHQPCLDDHR

Note: Inactive.

Isoform 3 (identifier: Q9UBF6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     57-113: VMDACLRCQA...QDWVVQRIGK → MPVLDVKLKTNKRTVLWSGENVIIPSTTAACPCG

Isoform 4 (identifier: Q9UBF6-4)

The sequence of this isoform differs from the canonical sequence as follows:
     59-74: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 113

113

RING-box protein 2

PRO_0000056023

Regions

Zinc finger

61 – 103

43

RING-type

Sites

Metal binding

50

1

Zinc 1 By similarity

Metal binding

53

1

Zinc 1 By similarity

Metal binding

61

1

Zinc 3 By similarity

Metal binding

64

1

Zinc 3 By similarity

Metal binding

73

1

Zinc 3 By similarity

Metal binding

80

1

Zinc 2 By similarity

Metal binding

82

1

Zinc 2 By similarity

Metal binding

85

1

Zinc 1 By similarity

Metal binding

87

1

Zinc 3 By similarity

Metal binding

88

1

Zinc 1 By similarity

Metal binding

99

1

Zinc 2 By similarity

Metal binding

102

1

Zinc 2 By similarity

Amino acid modifications

Modified residue

10

1

Phosphothreonine; by CK2 Ref.11

Natural variations

Alternative sequence

57 – 113

57

VMDAC…QRIGK → MPVLDVKLKTNKRTVLWSGE NVIIPSTTAACPCG in isoform 3.

VSP_041444

Alternative sequence

59 – 74

16

Missing in isoform 4.

VSP_044525

Alternative sequence

60 – 113

54

ACLRC…QRIGK → EGIGVRNWSEALNLINASEM GFDCRSGSTALAVPSVSLAS HQPCLDDHR in isoform 2.

VSP_008449

Experimental info

Sequence conflict

23

1

K → T in AAD30147. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

113

Helix Strand Turn

Details...

Turn

51 – 54

4

Helix

64 – 67

4

Turn

70 – 72

3

Beta strand

75 – 78

4

Beta strand

83 – 85

3

Helix

86 – 92

7

Turn

93 – 95

3

Turn

100 – 102

3

Beta strand

108 – 112

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: CE1E6CAC940C8257	FASTA	113	12,683
	10 20 30 40 50 60 MADVEDGEET CALASHSGSS GSKSGGDKMF SLKKWNAVAM WSWDVECDTC AICRVQVMDA 70 80 90 100 110 CLRCQAENKQ EDCVVVWGEC NHSFHNCCMS LWVKQNNRCP LCQQDWVVQR IGK
	Isoform 2 (SAG-v) [UniParc]. Checksum: 77A887E012AEE520	FASTA	108	11,557
	10 20 30 40 50 60 MADVEDGEET CALASHSGSS GSKSGGDKMF SLKKWNAVAM WSWDVECDTC AICRVQVMDE 70 80 90 100 GIGVRNWSEA LNLINASEMG FDCRSGSTAL AVPSVSLASH QPCLDDHR
	Isoform 3 [UniParc]. Checksum: E26F96D19B016540	FASTA	90	9,642
	10 20 30 40 50 60 MADVEDGEET CALASHSGSS GSKSGGDKMF SLKKWNAVAM WSWDVECDTC AICRVQMPVL 70 80 90 DVKLKTNKRT VLWSGENVII PSTTAACPCG
	Isoform 4 [UniParc]. Checksum: 5277FEE26DCEB81F	FASTA	97	10,876
	10 20 30 40 50 60 MADVEDGEET CALASHSGSS GSKSGGDKMF SLKKWNAVAM WSWDVECDTC AICRVQVMVV 70 80 90 WGECNHSFHN CCMSLWVKQN NRCPLCQQDW VVQRIGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Protein kinase CKII interacts with and phosphorylates the SAG protein containing ring-H2 finger motif." Son M.-Y., Park J.-W., Kim Y.-S., Kang S.-W., Marshak D.R., Park W., Bae Y.-S. Biochem. Biophys. Res. Commun. 263:743-748(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CULLINS.
[3]	"SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents." Duan H., Wang Y., Aviram M., Swaroop M., Loo J.A., Bian J., Tian Y., Mueller T., Bisgaier C.L., Sun Y. Mol. Cell. Biol. 19:3145-3155(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, SUBCELLULAR LOCATION.
[4]	"SAG/ROC2/Rbx2/Hrt2, a component of SCF E3 ubiquitin ligase: genomic structure, a splicing variant, and two family pseudogenes." Swaroop M., Gosink M., Sun Y. DNA Cell Biol. 20:425-434(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Corpus callosum and Uterus.
[7]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Kidney.
[10]	"Yeast homolog of human SAG/ROC2/Rbx2/Hrt2 is essential for cell growth, but not for germination: chip profiling implicates its role in cell cycle regulation." Swaroop M., Wang Y., Miller P., Duan H., Jatkoe T., Madore S.J., Sun Y. Oncogene 19:2855-2866(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CUL1, FUNCTION.
[11]	"Phosphorylation of threonine 10 on CKBBP1/SAG/ROC2/Rbx2 by protein kinase CKII promotes the degradation of IkappaBalpha and p27Kip1." Kim Y.-S., Lee J.-Y., Son M.-Y., Park W., Bae Y.-S. J. Biol. Chem. 278:28462-28469(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-10 BY CK2.
[12]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBE2F.
[13]	"Solution structure of the RING domain of the human RING-box protein 2." RIKEN structural genomics initiative (RSGI) Submitted (AUG-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 40-113.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF164679 mRNA. Translation: AAD55984.1.
AF142060 mRNA. Translation: AAD30147.1.
AF092878 mRNA. Translation: AAD25962.1.
AF312226 mRNA. Translation: AAK37450.1.
BT007348 mRNA. Translation: AAP36012.1.
AK289894 mRNA. Translation: BAF82583.1.
DB272382 mRNA. No translation available.
AC112771 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78991.1.
CH471052 Genomic DNA. Translation: EAW78992.1.
CH471052 Genomic DNA. Translation: EAW78994.1.
CH471052 Genomic DNA. Translation: EAW78995.1.
CH471052 Genomic DNA. Translation: EAW78996.1.
BC005966 mRNA. Translation: AAH05966.1.
BC008627 mRNA. Translation: AAH08627.1.

IPI

IPI00030891.
IPI00033132.
IPI00377253.
IPI00945636.

RefSeq

NP_001188299.1. NM_001201370.1.
NP_055060.1. NM_014245.4.
NP_899060.1. NM_183237.2.

UniGene

Hs.134623.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ECL	NMR	-	A	40-113	[»]

ProteinModelPortal

Q9UBF6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UBF6. 22 interactions.

MINT

MINT-1470812.

STRING

9606.ENSP00000273480.

PTM databases

PhosphoSite

Q9UBF6.

Polymorphism databases

DMDM

37538003.

Proteomic databases

PaxDb

Q9UBF6.

PRIDE

Q9UBF6.

Protocols and materials databases

DNASU

9616.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000273480; ENSP00000273480; ENSG00000114125.
ENST00000393000; ENSP00000376725; ENSG00000114125.
ENST00000477012; ENSP00000419339; ENSG00000114125.
ENST00000480908; ENSP00000419084; ENSG00000114125.

GeneID

9616.

KEGG

hsa:9616.

UCSC

uc003euc.3. human.
uc003eud.3. human.
uc021xeu.1. human.

Organism-specific databases

CTD

9616.

GeneCards

GC03P141457.

HGNC

HGNC:10070. RNF7.

HPA

HPA036995.

MIM

603863. gene.

neXtProt

NX_Q9UBF6.

PharmGKB

PA34444.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5194.

HOVERGEN

HBG001507.

InParanoid

Q9UBF6.

KO

K10611.

OMA

DICAICR.

OrthoDB

EOG42BX9Z.

PhylomeDB

Q9UBF6.

Enzyme and pathway databases

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q9UBF6.

Bgee

Q9UBF6.

CleanEx

HS_RNF7.
HS_SAG.

Genevestigator

Q9UBF6.

GermOnline

ENSG00000114125. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR024766. Znf_RING_H2.
[Graphical view]

Pfam

PF12678. zf-rbx1. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UBF6.

GenomeRNAi

9616.

NextBio

36073.

SOURCE

Search...

Entry information

Entry name

RBX2_HUMAN

Accession

Primary (citable) accession number: Q9UBF6
Secondary accession number(s): A8K1H9 , A8MTB5, C9JYL3, D3DNF7, D3DNF8, Q9BXN8, Q9Y5M7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2003
Last sequence update:	May 1, 2000
Last modified:	May 29, 2013
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.