Reviewed, UniProtKB/Swiss-Prot Q9CQJ4 (RING2_MOUSE)

Names and origin

Protein names

Recommended name:
    E3 ubiquitin-protein ligase RING2
    EC=6.3.2.-
Alternative name(s):
    RING finger protein 2
    RING finger protein 1B
      Short name=RING1b

Gene names

Name:	Rnf2
Synonyms:	DinG, Ring1b

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	336 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	E3 ubiquitin-protein ligase that mediates monoubiquitination of 'Lys-119' of histone H2A, thereby playing a central role in histone code and gene regulation. H2A 'Lys-119' ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. May be involved in the initiation of both imprinted and random X inactivation. Essential component of the Polycomb group (PcG) multiprotein PRC1 complex, a complex required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex act via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. Acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 and BMI1/PCGF4 may rather act as a modulator of RNF2/RING2 activity. Ref.6 Ref.7
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Component of some chromatin-associated Polycomb complex (PcG). Component of repressive BCOR complex containing Polycomb group subcomplex at least composed of RYBP, PCGF1, BCOR and RING1 By similarity. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2/RING2, MBLR, L3MBTL2 and YAF2. Component of chromatin-associated class II PcG repressive complex 1 (PRC1/hPRC-H) at least composed of PCGF2/RNF110, BMI1/PCGF4, CBX2/M33, CBX4/PC2, CBX8/PC3, PHC1, PHC2, PHC3, SCMH1, RING1 and RNF2/RING2. Interacts with RYBP, HIP2 and TFCP2. Association to the chromosomal DNA is cell-cycle dependent. Ref.6 Ref.1 Ref.5 Ref.9
Subcellular location	Nucleus. Note: Enriched on inactive X chromosome (Xi) in female trophoblast stem (TS) cells as well as differentiating embryonic stem (ES) cells. The enrichment on Xi is transient during TS and ES cell differentiation. The association with Xi is mitotically stable in non-differentiated TS cells. Ref.6 Ref.8
Sequence similarities	Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Chromosomal protein Nucleus
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase Repressor
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	anterior/posterior axis specification Ref.6 Inferred from mutant phenotype. Source: MGI gastrulation with mouth forming second Inferred from mutant phenotype. Source: MGI histone ubiquitination Ref.7 Inferred from direct assay. Source: MGI mitotic cell cycle Inferred from mutant phenotype. Source: MGI modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: MGI transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	PcG protein complex Inferred from direct assay. Source: MGI nuclear body Ref.6 Inferred from direct assay. Source: MGI sex chromatin Ref.7 Inferred from direct assay. Source: MGI ubiquitin ligase complex Inferred from direct assay. Source: MGI
Molecular function	chromatin binding Ref.6 Inferred from direct assay. Source: MGI protein binding Ref.5 Ref.6 Inferred from physical interaction. Source: UniProtKB transcription repressor activity Inferred from mutant phenotype. Source: MGI ubiquitin-protein ligase activity Inferred from direct assay. Source: MGI zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Aof2	Q6ZQ88	1	EBI-927321,EBI-1216284
Csnk2a1	Q61177	1	EBI-927321,EBI-1216438
Fbxl10	Q6P1G2	1	EBI-927321,EBI-1216214
Pcgf2	P23798	4	EBI-927321,EBI-926857
Phc1	Q64028	1	EBI-927321,EBI-927346
Ring1	O35730	1	EBI-927321,EBI-929310
Rybp	Q8CCI5	1	EBI-927321,EBI-929290
Skp1	Q9WTX5	1	EBI-927321,EBI-1202363

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 336

336

E3 ubiquitin-protein ligase RING2

PRO_0000056039

Regions

Zinc finger

51 – 91

41

RING-type

Region

1 – 179

179

Interaction with HIP2 By similarity

Amino acid modifications

Modified residue

168

1

Phosphoserine By similarity

Experimental info

Sequence conflict

253

1

N → H in BAC41075. Ref.2

Sequence conflict

299

1

S → T in BAC41075. Ref.2

Sequence conflict

304

1

V → L in BAC41075. Ref.2

Sequence conflict

332 – 336

5

TKEHK → FTASGNVR in CAA73380. Ref.1

Secondary structure

1

.

.

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336

Helix Strand Turn

Details...

Helix

21 – 25

5

Helix

46 – 49

4

Turn

52 – 54

3

Beta strand

55 – 57

3

Beta strand

59 – 64

6

Turn

65 – 67

3

Beta strand

70 – 72

3

Helix

73 – 81

9

Turn

88 – 90

3

Helix

97 – 99

3

Beta strand

100 – 102

3

Helix

104 – 113

10

Sequences

	Sequence		Length	Mass (Da)
	Q9CQJ4-1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 84BA5B3E044DB7EC	FASTA	336	37,623
	10 20 30 40 50 60 MSQAVQTNGT QPLSKTWELS LYELQRTPQE AITDGLEIVV SPRSLHSELM CPICLDMLKN 70 80 90 100 110 120 TMTTKECLHR FCADCIITAL RSGNKECPTC RKKLVSKRSL RPDPNFDALI SKIYPSRDEY 130 140 150 160 170 180 EAHQERVLAR INKHNNQQAL SHSIEEGLKI QAMNRLQRGK KQQIENGSGA EDNGDSSHCS 190 200 210 220 230 240 NASTHSNQEA GPSNKRTKTS DDSGLELDNN NAAVAIDPVM DGASEIELVF RPHPTLMEKD 250 260 270 280 290 300 DSAQTRYIKT SGNATVDHLS KYLAVRLALE ELRSKGESNQ MNLDTASEKQ YTIYIATASG 310 320 330 QFTVLNGSFS LELVSEKYWK VNKPMELYYA PTKEHK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Ring1A is a transcriptional repressor that interacts with the Polycomb-M33 protein and is expressed at rhombomere boundaries in the mouse hindbrain." Schoorlemmer J., Marcos-Gutierrez C., Were F., Martinez R., Garcia E., Satijn D.P.E., Otte A.P., Vidal M. EMBO J. 16:5930-5942(1997) [PubMed: 9312051] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CBX2. Strain: NIH Swiss.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: B-cell and Ovary.
[3]	"Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)." Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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]. Strain: Czech II. Tissue: Mammary tumor.
[5]	"RYBP, a new repressor protein that interacts with components of the mammalian Polycomb complex, and with the transcription factor YY1." Garcia E., Marcos-Gutierrez C., del Mar Lorente M., Moreno J.C., Vidal M. EMBO J. 18:3404-3418(1999) [PubMed: 10369680] [Abstract] Cited for: INTERACTION WITH RYBP AND RING1.
[6]	"Involvement of the Polycomb-group gene Ring1B in the specification of the anterior-posterior axis in mice." Suzuki M., Mizutani-Koseki Y., Fujimura Y., Miyagishima H., Kaneko T., Takada Y., Akasaka T., Tanzawa H., Takihara Y., Nakano M., Masumoto H., Vidal M., Isono K., Koseki H. Development 129:4171-4183(2002) [PubMed: 12183370] [Abstract] Cited for: INTERACTION WITH CBX2; RNF110; PHC1; PHC2; RNF1 AND BMI1, FUNCTION, SUBCELLULAR LOCATION.
[7]	"Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation." de Napoles M., Mermoud J.E., Wakao R., Tang Y.A., Endoh M., Appanah R., Nesterova T.B., Silva J., Otte A.P., Vidal M., Koseki H., Brockdorff N. Dev. Cell 7:663-676(2004) [PubMed: 15525528] [Abstract] Cited for: ENZYME ACTIVITY, FUNCTION.
[8]	"Ring1b-mediated H2A ubiquitination associates with inactive X chromosomes and is involved in initiation of X inactivation." Fang J., Chen T., Chadwick B., Li E., Zhang Y. J. Biol. Chem. 279:52812-52815(2004) [PubMed: 15509584] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Mammalian polyhomeotic homologues Phc2 and Phc1 act in synergy to mediate polycomb repression of Hox genes." Isono K., Fujimura Y., Shinga J., Yamaki M., O-Wang J., Takihara Y., Murahashi Y., Takada Y., Mizutani-Koseki Y., Koseki H. Mol. Cell. Biol. 25:6694-6706(2005) [PubMed: 16024804] [Abstract] Cited for: INTERACTION WITH PHC2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

Y12880 mRNA. Translation: CAA73380.1.
Y12783 mRNA. Translation: CAA73321.1.
AK145767 mRNA. Translation: BAE26638.1.
AK012358 mRNA. Translation: BAB28186.1.
AK013124 mRNA. Translation: BAB28663.1.
AK030319 mRNA. Translation: BAC26898.1.
AK090066 mRNA. Translation: BAC41075.1.
CT010297 mRNA. Translation: CAJ18505.1.
BC020122 mRNA. Translation: AAH20122.1.

IPI

IPI00133880.

RefSeq

NP_035407.1.

UniGene

Mm.441344

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CKL	X-ray	2.00	B	1-159	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9CQJ4. 52 interactions.

Genome annotation databases

Ensembl

ENSMUSG00000026484. Mus musculus. [Contig view]

GeneID

19821.

KEGG

mmu:19821.

Organism-specific databases

MGI

MGI:1101759. Rnf2.

Phylogenomic databases

HOGENOM

Q9CQJ4.

HOVERGEN

Q9CQJ4.

OMA

Q9CQJ4. MELYFAP.

Gene expression databases

ArrayExpress

Q9CQJ4.

Bgee

Q9CQJ4.

CleanEx

MM_RNF2.

GermOnline

ENSMUSG00000026484. Mus musculus.

Family and domain databases

InterPro

IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR017907. Znf_RING_CS.
[Graphical view]

Pfam

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

SMART

SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

297285.

SOURCE

Search...

Entry information

Entry name

RING2_MOUSE

Accession

Primary (citable) accession number: Q9CQJ4
Secondary accession number(s): O35699 , O35729, Q4FJV5, Q8C1X8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	June 1, 2001
Last modified:	June 16, 2009
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)