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Protein

Ubiquitin-conjugating enzyme E2 variant 1

Gene

UBE2V1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes.7 Publications

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: UniProtKB
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: HGNC
  • positive regulation of NF-kappaB transcription factor activity Source: HGNC
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • postreplication repair Source: GO_Central
  • protein K63-linked ubiquitination Source: UniProtKB
  • protein polyubiquitination Source: ProtInc
  • regulation of DNA repair Source: ProtInc
  • regulation of transcription, DNA-templated Source: UniProtKB
  • stimulatory C-type lectin receptor signaling pathway Source: Reactome
  • T cell receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BRENDAi2.3.2.B6. 2681.
ReactomeiR-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-937039. IRAK1 recruits IKK complex.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
R-HSA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ13404.
SIGNORiQ13404.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-conjugating enzyme E2 variant 1
Short name:
UEV-1
Alternative name(s):
CROC-1
TRAF6-regulated IKK activator 1 beta Uev1A
Gene namesi
Name:UBE2V1
Synonyms:CROC1, UBE2V, UEV1
ORF Names:P/OKcl.19
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:12494. UBE2V1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HGNC
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • nucleus Source: UniProtKB
  • protein complex Source: MGI
  • UBC13-UEV1A complex Source: UniProtKB
  • ubiquitin conjugating enzyme complex Source: HGNC
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi387521.
387522.
7335.
OpenTargetsiENSG00000244687.
PharmGKBiPA37142.

Polymorphism and mutation databases

BioMutaiUBE2V1.
DMDMi259016163.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000826002 – 147Ubiquitin-conjugating enzyme E2 variant 1Add BLAST146

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ13404.
MaxQBiQ13404.
PaxDbiQ13404.
PeptideAtlasiQ13404.
PRIDEiQ13404.
TopDownProteomicsiQ13404-4. [Q13404-4]

PTM databases

iPTMnetiQ13404.
PhosphoSitePlusiQ13404.
SwissPalmiQ13404.

Expressioni

Tissue specificityi

Highly expressed in thyroid, pancreas, spinal cord, lymph node, trachea, adrenal gland, bone marrow and pancreas. Detected at low levels in heart, breast, placenta, brain, liver, kidney, stomach and lung.2 Publications

Inductioni

Down-regulated during differentiation of cultured colon adenocarcinoma cells.1 Publication

Gene expression databases

BgeeiENSG00000244687.
ExpressionAtlasiQ13404. baseline and differential.
GenevisibleiQ13404. HS.

Interactioni

Subunit structurei

Heterodimer with UBE2N. Interacts (UBE2V2-UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity. Interacts with TRAF6.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FAM168AQ925673EBI-1050671,EBI-7957930
RNF111Q6ZNA42EBI-1050671,EBI-2129175
TRIM32Q130493EBI-1050671,EBI-742790
UBE2NP6108818EBI-1050671,EBI-1052908
UBQLN1Q9UMX05EBI-1050671,EBI-741480
UBQLN1Q9UMX0-23EBI-1050671,EBI-10173939
XIAPP981703EBI-1050671,EBI-517127
ZNRF1Q8ND252EBI-1050671,EBI-2129250

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113183. 81 interactors.
132321. 14 interactors.
DIPiDIP-41911N.
IntActiQ13404. 120 interactors.
MINTiMINT-5002796.
STRINGi9606.ENSP00000340305.

Structurei

Secondary structure

1147
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi11 – 25Combined sources15
Beta strandi31 – 39Combined sources9
Beta strandi47 – 53Combined sources7
Beta strandi56 – 58Combined sources3
Turni59 – 62Combined sources4
Beta strandi64 – 70Combined sources7
Turni73 – 77Combined sources5
Beta strandi81 – 86Combined sources6
Beta strandi91 – 93Combined sources3
Turni95 – 97Combined sources3
Helixi102 – 104Combined sources3
Helixi106 – 109Combined sources4
Helixi117 – 128Combined sources12
Turni131 – 135Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2A4DX-ray1.69A8-147[»]
2C2VX-ray2.90C/F/I/L8-147[»]
2HLWNMR-A8-147[»]
ProteinModelPortaliQ13404.
SMRiQ13404.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13404.

Family & Domainsi

Sequence similaritiesi

Belongs to the ubiquitin-conjugating enzyme family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0896. Eukaryota.
ENOG4111MDW. LUCA.
GeneTreeiENSGT00740000115534.
HOGENOMiHOG000036561.
HOVERGENiHBG054552.
InParanoidiQ13404.
KOiK10704.
K20656.
OMAiPANKKIP.
OrthoDBiEOG091G0SMT.
TreeFamiTF316971.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR000608. UBQ-conjugat_E2.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF00179. UQ_con. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 3 (identifier: Q13404-4) [UniParc]FASTAAdd to basket
Also known as: Isoform 2

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
MAATTGSGVK VPRNFRLLEE LEEGQKGVGD GTVSWGLEDD EDMTLTRWTG
60 70 80 90 100
MIIGPPRTIY ENRIYSLKIE CGPKYPEAPP FVRFVTKINM NGVNSSNGVV
110 120 130 140
DPRAISVLAK WQNSYSIKVV LQELRRLMMS KENMKLPQPP EGQCYSN
Length:147
Mass (Da):16,495
Last modified:September 22, 2009 - v2
Checksum:iBA53837F21977B3F
GO
Isoform 1 (identifier: Q13404-1) [UniParc]FASTAAdd to basket
Also known as: CROC-1B, UEV-1B, Isoform 4

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: MAATTGS → MAYKFRTHSP...PHETYFCITT

Show »
Length:221
Mass (Da):25,797
Checksum:i6EE5C0FCC8CBBEE6
GO
Isoform 2 (identifier: Q13404-2) [UniParc]FASTAAdd to basket
Also known as: CROC-1A, UEV-1A

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MAATTGSGVKVPRN → MPGEVQASYLKSQSKLSDEGRLEPRKFHCKGSKSPSQ

Show »
Length:170
Mass (Da):19,228
Checksum:i9D3A8AC1EBEB22A6
GO
Isoform 4 (identifier: Q13404-6) [UniParc]FASTAAdd to basket
Also known as: UEV-1As

The sequence of this isoform differs from the canonical sequence as follows:
     1-44: Missing.
     45-57: LTRWTGMIIGPPR → MKEDLNLENFTAK

Show »
Length:103
Mass (Da):11,842
Checksum:i76C152A73DE9AC40
GO
Isoform 5 (identifier: Q13404-7) [UniParc]FASTAAdd to basket
Also known as: Isoform 3

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: MAATTGS → MPGEVQASYLKSQSKLSDEGRLEPRKFHCK

Show »
Length:170
Mass (Da):19,307
Checksum:i5B2E8C6FFDF51510
GO
Isoform 6 (identifier: Q13404-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     58-99: Missing.

Note: No experimental confirmation available.
Show »
Length:105
Mass (Da):11,766
Checksum:iD7C2659FBA3FC719
GO

Sequence cautioni

The sequence AAH08944 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAC16955 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform 1 (identifier: Q13404-1)
Sequence conflicti71 – 81SPHETYFCITT → WPTSSAQCYSP in AAC02755 (PubMed:9418904).CuratedAdd BLAST11

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0380321 – 44Missing in isoform 4. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_0380331 – 14MAATT…KVPRN → MPGEVQASYLKSQSKLSDEG RLEPRKFHCKGSKSPSQ in isoform 2. 2 PublicationsAdd BLAST14
Alternative sequenceiVSP_0380341 – 7MAATTGS → MAYKFRTHSPEALEQLYPWE CFVFCLIIFGTFTNQIHKWS HTYFGLPRWVTLLQDWHVIL PRKHHRIHHVSPHETYFCIT T in isoform 1. 3 Publications7
Alternative sequenceiVSP_0380351 – 7MAATTGS → MPGEVQASYLKSQSKLSDEG RLEPRKFHCK in isoform 5. 1 Publication7
Alternative sequenceiVSP_03803645 – 57LTRWT…IGPPR → MKEDLNLENFTAK in isoform 4. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_04481858 – 99Missing in isoform 6. 1 PublicationAdd BLAST42

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39360 mRNA. Translation: AAB72015.1.
U39361 mRNA. Translation: AAB72016.1.
U49278 mRNA. Translation: AAC02757.1.
U97279 mRNA. Translation: AAC02780.1.
U97280 mRNA. Translation: AAC02755.1.
U97281 mRNA. Translation: AAC02756.1.
AY008273 mRNA. Translation: AAG24229.1.
BT007382 mRNA. Translation: AAP36046.1.
DA580976 mRNA. No translation available.
AL034423 Genomic DNA. Translation: CAB76864.1.
AL034423 Genomic DNA. Translation: CAB76865.1.
AL034423 Genomic DNA. Translation: CAC16954.1.
AL034423 Genomic DNA. Translation: CAC16955.2. Different initiation.
AL034423 Genomic DNA. Translation: CAI19382.1.
AL034423 Genomic DNA. Translation: CAI19383.1.
CH471077 Genomic DNA. Translation: EAW75635.1.
CH471077 Genomic DNA. Translation: EAW75634.1.
CH471077 Genomic DNA. Translation: EAW75636.1.
BC000468 mRNA. Translation: AAH00468.1.
BC008944 mRNA. Translation: AAH08944.2. Different initiation.
CCDSiCCDS13426.1. [Q13404-7]
CCDS13427.1. [Q13404-6]
CCDS33483.1. [Q13404-4]
CCDS58775.1. [Q13404-8]
RefSeqiNP_001027459.1. NM_001032288.2. [Q13404-4]
NP_001244322.1. NM_001257393.1. [Q13404-7]
NP_001244323.1. NM_001257394.1. [Q13404-6]
NP_001244325.1. NM_001257396.1. [Q13404-8]
NP_068823.2. NM_021988.5. [Q13404-7]
NP_071887.1. NM_022442.5. [Q13404-6]
NP_954595.1. NM_199144.2. [Q13404-7]
NP_954673.1. NM_199203.2.
UniGeneiHs.420529.
Hs.744839.

Genome annotation databases

EnsembliENST00000340309; ENSP00000340305; ENSG00000244687. [Q13404-7]
ENST00000371657; ENSP00000360720; ENSG00000244687. [Q13404-8]
ENST00000371674; ENSP00000360739; ENSG00000244687. [Q13404-4]
ENST00000371677; ENSP00000360742; ENSG00000244687. [Q13404-7]
ENST00000415862; ENSP00000407770; ENSG00000244687. [Q13404-6]
GeneIDi387522.
7335.
KEGGihsa:387522.
hsa:7335.
UCSCiuc002xva.5. human. [Q13404-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39360 mRNA. Translation: AAB72015.1.
U39361 mRNA. Translation: AAB72016.1.
U49278 mRNA. Translation: AAC02757.1.
U97279 mRNA. Translation: AAC02780.1.
U97280 mRNA. Translation: AAC02755.1.
U97281 mRNA. Translation: AAC02756.1.
AY008273 mRNA. Translation: AAG24229.1.
BT007382 mRNA. Translation: AAP36046.1.
DA580976 mRNA. No translation available.
AL034423 Genomic DNA. Translation: CAB76864.1.
AL034423 Genomic DNA. Translation: CAB76865.1.
AL034423 Genomic DNA. Translation: CAC16954.1.
AL034423 Genomic DNA. Translation: CAC16955.2. Different initiation.
AL034423 Genomic DNA. Translation: CAI19382.1.
AL034423 Genomic DNA. Translation: CAI19383.1.
CH471077 Genomic DNA. Translation: EAW75635.1.
CH471077 Genomic DNA. Translation: EAW75634.1.
CH471077 Genomic DNA. Translation: EAW75636.1.
BC000468 mRNA. Translation: AAH00468.1.
BC008944 mRNA. Translation: AAH08944.2. Different initiation.
CCDSiCCDS13426.1. [Q13404-7]
CCDS13427.1. [Q13404-6]
CCDS33483.1. [Q13404-4]
CCDS58775.1. [Q13404-8]
RefSeqiNP_001027459.1. NM_001032288.2. [Q13404-4]
NP_001244322.1. NM_001257393.1. [Q13404-7]
NP_001244323.1. NM_001257394.1. [Q13404-6]
NP_001244325.1. NM_001257396.1. [Q13404-8]
NP_068823.2. NM_021988.5. [Q13404-7]
NP_071887.1. NM_022442.5. [Q13404-6]
NP_954595.1. NM_199144.2. [Q13404-7]
NP_954673.1. NM_199203.2.
UniGeneiHs.420529.
Hs.744839.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2A4DX-ray1.69A8-147[»]
2C2VX-ray2.90C/F/I/L8-147[»]
2HLWNMR-A8-147[»]
ProteinModelPortaliQ13404.
SMRiQ13404.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113183. 81 interactors.
132321. 14 interactors.
DIPiDIP-41911N.
IntActiQ13404. 120 interactors.
MINTiMINT-5002796.
STRINGi9606.ENSP00000340305.

PTM databases

iPTMnetiQ13404.
PhosphoSitePlusiQ13404.
SwissPalmiQ13404.

Polymorphism and mutation databases

BioMutaiUBE2V1.
DMDMi259016163.

Proteomic databases

EPDiQ13404.
MaxQBiQ13404.
PaxDbiQ13404.
PeptideAtlasiQ13404.
PRIDEiQ13404.
TopDownProteomicsiQ13404-4. [Q13404-4]

Protocols and materials databases

DNASUi387522.
7335.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340309; ENSP00000340305; ENSG00000244687. [Q13404-7]
ENST00000371657; ENSP00000360720; ENSG00000244687. [Q13404-8]
ENST00000371674; ENSP00000360739; ENSG00000244687. [Q13404-4]
ENST00000371677; ENSP00000360742; ENSG00000244687. [Q13404-7]
ENST00000415862; ENSP00000407770; ENSG00000244687. [Q13404-6]
GeneIDi387522.
7335.
KEGGihsa:387522.
hsa:7335.
UCSCiuc002xva.5. human. [Q13404-4]

Organism-specific databases

CTDi387522.
7335.
DisGeNETi387521.
387522.
7335.
GeneCardsiUBE2V1.
HGNCiHGNC:12494. UBE2V1.
MIMi602995. gene.
neXtProtiNX_Q13404.
OpenTargetsiENSG00000244687.
PharmGKBiPA37142.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0896. Eukaryota.
ENOG4111MDW. LUCA.
GeneTreeiENSGT00740000115534.
HOGENOMiHOG000036561.
HOVERGENiHBG054552.
InParanoidiQ13404.
KOiK10704.
K20656.
OMAiPANKKIP.
OrthoDBiEOG091G0SMT.
TreeFamiTF316971.

Enzyme and pathway databases

BRENDAi2.3.2.B6. 2681.
ReactomeiR-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-937039. IRAK1 recruits IKK complex.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
R-HSA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ13404.
SIGNORiQ13404.

Miscellaneous databases

ChiTaRSiUBE2V1. human.
EvolutionaryTraceiQ13404.
GeneWikiiUBE2V1.
PROiQ13404.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000244687.
ExpressionAtlasiQ13404. baseline and differential.
GenevisibleiQ13404. HS.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR000608. UBQ-conjugat_E2.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF00179. UQ_con. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUB2V1_HUMAN
AccessioniPrimary (citable) accession number: Q13404
Secondary accession number(s): E1P629
, Q13403, Q13532, Q5TGE0, Q5TGE3, Q96H34, Q9GZT0, Q9GZW1, Q9H4J3, Q9H4J4, Q9UKL1, Q9UM48, Q9UM49, Q9UM50
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: September 22, 2009
Last modified: November 30, 2016
This is version 172 of the entry and version 2 of the sequence. [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

Miscellaneous

In human, TMEM189/KUA and UBE2V1/UEV1 are adjacent genes which can produce independent proteins and can also be fused to form a TMEM189-UBE2V1 hybrid protein.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.