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Protein

E3 ubiquitin-protein ligase BRE1B

Gene

RNF40

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1). H2BK120ub1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation (H3K4me and H3K79me, respectively). It thereby plays a central role in histone code and gene regulation. The RNF20/40 complex forms a H2B ubiquitin ligase complex in cooperation with the E2 enzyme UBE2A or UBE2B; reports about the cooperation with UBE2E1/UBCH are contradictory. Required for transcriptional activation of Hox genes.2 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.2 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri948 – 987RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • mRNA 3'-UTR binding Source: UniProtKB
  • protein-containing complex binding Source: Ensembl
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin conjugating enzyme binding Source: Ensembl
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: Ensembl

GO - Biological processi

  • histone H2B ubiquitination Source: UniProtKB
  • histone monoubiquitination Source: UniProtKB
  • negative regulation of mRNA polyadenylation Source: UniProtKB
  • positive regulation of histone H2B ubiquitination Source: UniProtKB
  • positive regulation of proteasomal protein catabolic process Source: Ensembl
  • positive regulation of protein polyubiquitination Source: Ensembl
  • protein ubiquitination Source: Reactome
  • response to peptide hormone Source: Ensembl
  • ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Molecular functionChromatin regulator, Transferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
SIGNORiO75150
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase BRE1B (EC:2.3.2.272 Publications)
Short name:
BRE1-B
Alternative name(s):
95 kDa retinoblastoma-associated protein
Short name:
RBP95
RING finger protein 40
RING-type E3 ubiquitin transferase BRE1BCurated
Gene namesi
Name:RNF40
Synonyms:BRE1B, KIAA0661
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000103549.21
HGNCiHGNC:16867 RNF40
MIMi607700 gene
neXtProtiNX_O75150

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi109L → S: Abolishes interaction with RB1. 1 Publication1
Mutagenesisi111C → M: Abolishes interaction with RB1. 1 Publication1
Mutagenesisi113E → Q: Abolishes interaction with RB1. 1 Publication1

Organism-specific databases

DisGeNETi9810
PharmGKBiPA34440

Polymorphism and mutation databases

BioMutaiRNF40

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000558391 – 1001E3 ubiquitin-protein ligase BRE1BAdd BLAST1001

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei20N6-acetyllysineBy similarity1
Modified residuei42PhosphoserineBy similarity1
Modified residuei355N6-acetyllysineBy similarity1
Modified residuei517N6-acetyllysineBy similarity1
Modified residuei528PhosphoserineBy similarity1
Cross-linki578Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki579Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei585PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO75150
MaxQBiO75150
PaxDbiO75150
PeptideAtlasiO75150
PRIDEiO75150

PTM databases

iPTMnetiO75150
PhosphoSitePlusiO75150

Expressioni

Tissue specificityi

Ubiquitously expressed. Expressed at higher level in testis, heart and pancreas, while it is only weakly expressed in lung, skeletal muscle and small intestine.1 Publication

Gene expression databases

BgeeiENSG00000103549
CleanExiHS_RNF40
ExpressionAtlasiO75150 baseline and differential
GenevisibleiO75150 HS

Organism-specific databases

HPAiHPA041330
HPA054227

Interactioni

Subunit structurei

Component of the RNF20/40 complex (also known as BRE1 complex) probably composed of 2 copies of RNF20/BRE1A and 2 copies of RNF40/BRE1B. Interacts with UBE2E1/UBCH6. Interacts with RB1 and WAC.4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • ubiquitin conjugating enzyme binding Source: Ensembl
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115149, 91 interactors
CORUMiO75150
IntActiO75150, 35 interactors
MINTiO75150
STRINGi9606.ENSP00000325677

Structurei

3D structure databases

ProteinModelPortaliO75150
SMRiO75150
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili44 – 91Sequence analysisAdd BLAST48
Coiled coili189 – 377Sequence analysisAdd BLAST189
Coiled coili437 – 525Sequence analysisAdd BLAST89
Coiled coili627 – 946Sequence analysisAdd BLAST320

Sequence similaritiesi

Belongs to the BRE1 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri948 – 987RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG0978 Eukaryota
ENOG410Y5C6 LUCA
HOVERGENiHBG080312
InParanoidiO75150
KOiK10696
OrthoDBiEOG091G01SA
PhylomeDBiO75150
TreeFamiTF323183

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR013956 E3_ubiquit_lig_Bre1
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR23163 PTHR23163, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75150-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSGPGNKRAA GDGGSGPPEK KLSREEKTTT TLIEPIRLGG ISSTEEMDLK
60 70 80 90 100
VLQFKNKKLA ERLEQRQACE DELRERIEKL EKRQATDDAT LLIVNRYWAQ
110 120 130 140 150
LDETVEALLR CHESQGELSS APEAPGTQEG PTCDGTPLPE PGTSELRDPL
160 170 180 190 200
LMQLRPPLSE PALAFVVALG ASSSEEVELE LQGRMEFSKA AVSRVVEASD
210 220 230 240 250
RLQRRVEELC QRVYSRGDSE PLSEAAQAHT RELGRENRRL QDLATQLQEK
260 270 280 290 300
HHRISLEYSE LQDKVTSAET KVLEMETTVE DLQWDIEKLR KREQKLNKHL
310 320 330 340 350
AEALEQLNSG YYVSGSSSGF QGGQITLSMQ KFEMLNAELE ENQELANSRM
360 370 380 390 400
AELEKLQAEL QGAVRTNERL KVALRSLPEE VVRETGEYRM LQAQFSLLYN
410 420 430 440 450
ESLQVKTQLD EARGLLLATK NSHLRHIEHM ESDELGLQKK LRTEVIQLED
460 470 480 490 500
TLAQVRKEYE MLRIEFEQNL AANEQAGPIN REMRHLISSL QNHNHQLKGD
510 520 530 540 550
AQRYKRKLRE VQAEIGKLRA QASGSAHSTP NLGHPEDSGV SAPAPGKEEG
560 570 580 590 600
GPGPVSTPDN RKEMAPVPGT TTTTTSVKKE ELVPSEEDFQ GITPGAQGPS
610 620 630 640 650
SRGREPEARP KRELQEREGP SLGPPPVASA LSRADREKAK VEETKRKESE
660 670 680 690 700
LLKGLRAELK KAQESQKEMK LLLDMYKSAP KEQRDKVQLM AAERKAKAEV
710 720 730 740 750
DELRSRIREL EERDRRESKK IADEDALRRI RQAEEQIEHL QRKLGATKQE
760 770 780 790 800
EEALLSEMDV TGQAFEDMQE QNGRLLQQLR EKDDANFKLM SERIKANQIH
810 820 830 840 850
KLLREEKDEL GEQVLGLKSQ VDAQLLTVQK LEEKERALQG SLGGVEKELT
860 870 880 890 900
LRSQALELNK RKAVEAAQLA EDLKVQLEHV QTRLREIQPC LAESRAAREK
910 920 930 940 950
ESFNLKRAQE DISRLRRKLE KQRKVEVYAD ADEILQEEIK EYKARLTCPC
960 970 980 990 1000
CNTRKKDAVL TKCFHVFCFE CVRGRYEARQ RKCPKCNAAF GAHDFHRIYI

S
Length:1,001
Mass (Da):113,650
Last modified:November 30, 2010 - v4
Checksum:i82D7CD183EDD5EFC
GO
Isoform 3 (identifier: O75150-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     822-838: DAQLLTVQKLEEKERAL → WPPPACRLELERWGSWP
     839-1001: Missing.

Note: No experimental confirmation available.
Show »
Length:838
Mass (Da):94,796
Checksum:i87B68E08B358A730
GO
Isoform 4 (identifier: O75150-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     332-431: Missing.

Note: No experimental confirmation available.
Show »
Length:901
Mass (Da):102,046
Checksum:i445DD31CF7511205
GO

Sequence cautioni

The sequence BAA31636 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAE45869 differs from that shown. Aberrant splicing.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti56N → D in BAB55092 (PubMed:14702039).Curated1
Sequence conflicti96R → L in AAG13723 (PubMed:10944455).Curated1
Sequence conflicti108L → P in BAB55092 (PubMed:14702039).Curated1
Sequence conflicti172S → G in BAB55092 (PubMed:14702039).Curated1
Sequence conflicti387E → K in CAH10518 (PubMed:17974005).Curated1
Sequence conflicti562K → E in CAE45869 (PubMed:17974005).Curated1
Sequence conflicti600S → F in CAE45869 (PubMed:17974005).Curated1
Sequence conflicti714D → N in BAB55092 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055021463R → H. Corresponds to variant dbSNP:rs11556801Ensembl.1
Natural variantiVAR_055022615Q → R5 PublicationsCorresponds to variant dbSNP:rs7195142Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016681332 – 431Missing in isoform 4. 1 PublicationAdd BLAST100
Alternative sequenceiVSP_016682822 – 838DAQLL…KERAL → WPPPACRLELERWGSWP in isoform 3. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_016683839 – 1001Missing in isoform 3. 1 PublicationAdd BLAST163

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF122819 mRNA Translation: AAG13723.1
AB014561 mRNA Translation: BAA31636.2 Different initiation.
AK027406 mRNA Translation: BAB55092.1
BX640763 mRNA Translation: CAE45869.1 Sequence problems.
CR627431 mRNA Translation: CAH10518.1
AC106886 Genomic DNA No translation available.
BC004527 mRNA Translation: AAH04527.2
BC006133 mRNA Translation: AAH06133.1
BC011769 mRNA Translation: AAH11769.1
BC018647 mRNA Translation: AAH18647.1
BC030802 mRNA Translation: AAH30802.2
CCDSiCCDS10691.1 [O75150-1]
CCDS55994.1 [O75150-4]
PIRiJC7363
RefSeqiNP_001193962.1, NM_001207033.1
NP_001193963.1, NM_001207034.1
NP_001273501.1, NM_001286572.2
NP_055586.1, NM_014771.3
UniGeneiHs.65238

Genome annotation databases

EnsembliENST00000324685; ENSP00000325677; ENSG00000103549
ENST00000357890; ENSP00000350563; ENSG00000103549
GeneIDi9810
KEGGihsa:9810
UCSCiuc002dzq.4 human [O75150-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiBRE1B_HUMAN
AccessioniPrimary (citable) accession number: O75150
Secondary accession number(s): Q6AHZ6
, Q6N005, Q7L3T6, Q8N615, Q96T18, Q9BSV9, Q9HC82
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: November 30, 2010
Last modified: May 23, 2018
This is version 158 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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