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Protein

Zinc finger E-box-binding homeobox 2

Gene

ZEB2

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

Functioni

Transcriptional inhibitor that binds to DNA sequence 5'-CACCT-3' in different promoters. Represses transcription of E-cadherin.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri211 – 234C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri241 – 263C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri282 – 304C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri310 – 334C2H2-type 4; atypicalPROSITE-ProRule annotationAdd BLAST25
Zinc fingeri581 – 605C2H2-type 5; atypicalPROSITE-ProRule annotationAdd BLAST25
DNA bindingi644 – 703Homeobox; atypicalAdd BLAST60
Zinc fingeri999 – 1021C2H2-type 6PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri1027 – 1049C2H2-type 7PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri1055 – 1076C2H2-type 8; atypicalPROSITE-ProRule annotationAdd BLAST22

GO - Molecular functioni

GO - Biological processi

  • developmental pigmentation Source: BHF-UCL
  • melanocyte migration Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • nervous system development Source: UniProtKB
  • positive regulation of melanin biosynthetic process Source: BHF-UCL
  • positive regulation of melanocyte differentiation Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of melanosome organization Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

SignaLinkiO60315.
SIGNORiO60315.

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger E-box-binding homeobox 2
Alternative name(s):
Smad-interacting protein 1
Short name:
SMADIP1
Zinc finger homeobox protein 1b
Gene namesi
Name:ZEB2
Synonyms:KIAA0569, SIP1, ZFHX1B, ZFX1B
ORF Names:HRIHFB2411
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:14881. ZEB2.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Mowat-Wilson syndrome (MOWS)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA complex developmental disorder characterized by mental retardation, delayed motor development, epilepsy, microcephaly and a wide spectrum of clinically heterogeneous features suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels. Affected patients show an easily recognizable facial appearance with deep set eyes and hypertelorism, medially divergent, broad eyebrows, prominent columella, pointed chin and uplifted, notched ear lobes. Some patients manifest Hirschsprung disease.
See also OMIM:235730
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02701699Missing in MOWS. 1 Publication1
Natural variantiVAR_027017953R → G in MOWS. 1 Publication1
Natural variantiVAR_0270181119Q → R in MOWS. 1 PublicationCorresponds to variant rs137852983dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Epilepsy, Hirschsprung disease, Mental retardation

Organism-specific databases

DisGeNETi9839.
MalaCardsiZEB2.
MIMi235730. phenotype.
OpenTargetsiENSG00000169554.
Orphaneti261552. Mowat-Wilson syndrome due to a ZEB2 point mutation.
261537. Mowat-Wilson syndrome due to monosomy 2q22.
PharmGKBiPA162409612.

Polymorphism and mutation databases

BioMutaiZEB2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000472361 – 1214Zinc finger E-box-binding homeobox 2Add BLAST1214

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei142PhosphoserineCombined sources1
Modified residuei356PhosphoserineBy similarity1
Modified residuei360PhosphoserineCombined sources1
Modified residuei364PhosphoserineBy similarity1
Modified residuei377N6-acetyllysineCombined sources1
Cross-linki391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei647PhosphoserineCombined sources1
Modified residuei731PhosphoserineBy similarity1
Modified residuei780PhosphoserineBy similarity1
Modified residuei782PhosphothreonineCombined sources1
Modified residuei784PhosphoserineCombined sources1
Cross-linki866Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki866Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei1122PhosphoserineCombined sources1
Modified residuei1124PhosphoserineBy similarity1
Modified residuei1203PhosphoserineBy similarity1

Post-translational modificationi

Sumoylation on Lys-391 and Lys-866 is promoted by the E3 SUMO-protein ligase CBX4, and impairs interaction with CTBP1 and transcription repression activity.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO60315.
MaxQBiO60315.
PaxDbiO60315.
PeptideAtlasiO60315.
PRIDEiO60315.

PTM databases

iPTMnetiO60315.
PhosphoSitePlusiO60315.

Expressioni

Gene expression databases

BgeeiENSG00000169554.
CleanExiHS_SIP1.
HS_ZEB2.
ExpressionAtlasiO60315. baseline and differential.
GenevisibleiO60315. HS.

Organism-specific databases

HPAiHPA003456.

Interactioni

Subunit structurei

Binds activated SMAD1, activated SMAD2 and activated SMAD3; binding with SMAD4 is not detected (By similarity). Interacts with CBX4 and CTBP1.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
EHMT2Q96KQ76EBI-717614,EBI-744366
MTA1Q1333012EBI-717614,EBI-714236
MTA2O947764EBI-717614,EBI-1783035

Protein-protein interaction databases

BioGridi115175. 21 interactors.
IntActiO60315. 23 interactors.
MINTiMINT-1181379.
STRINGi9606.ENSP00000302501.

Structurei

Secondary structure

11214
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi654 – 665Combined sources12
Helixi671 – 681Combined sources11
Helixi685 – 700Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DA7NMR-A647-704[»]
ProteinModelPortaliO60315.
SMRiO60315.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60315.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni437 – 487SMAD-MH2 binding domainBy similarityAdd BLAST51

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1084 – 1214Glu-rich (acidic)Add BLAST131

Sequence similaritiesi

Contains 8 C2H2-type zinc fingers.PROSITE-ProRule annotation
Contains 1 homeobox DNA-binding domain.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri211 – 234C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri241 – 263C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri282 – 304C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri310 – 334C2H2-type 4; atypicalPROSITE-ProRule annotationAdd BLAST25
Zinc fingeri581 – 605C2H2-type 5; atypicalPROSITE-ProRule annotationAdd BLAST25
Zinc fingeri999 – 1021C2H2-type 6PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri1027 – 1049C2H2-type 7PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri1055 – 1076C2H2-type 8; atypicalPROSITE-ProRule annotationAdd BLAST22

Keywords - Domaini

Homeobox, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IMF7. Eukaryota.
ENOG410ZQ40. LUCA.
GeneTreeiENSGT00630000089829.
HOGENOMiHOG000264256.
HOVERGENiHBG004697.
InParanoidiO60315.
KOiK09299.
OMAiLDHSRSN.
OrthoDBiEOG091G0F7Y.
PhylomeDBiO60315.
TreeFamiTF331759.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
3.30.160.60. 6 hits.
InterProiIPR008598. Di19_Zn_binding_dom.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF05605. zf-Di19. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
SM00355. ZnF_C2H2. 8 hits.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 5 hits.
PS50157. ZINC_FINGER_C2H2_2. 6 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60315-1) [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
MKQPIMADGP RCKRRKQANP RRKNVVNYDN VVDTGSETDE EDKLHIAEDD
60 70 80 90 100
GIANPLDQET SPASVPNHES SPHVSQALLP REEEEDEIRE GGVEHPWHNN
110 120 130 140 150
EILQASVDGP EEMKEDYDTM GPEATIQTAI NNGTVKNANC TSDFEEYFAK
160 170 180 190 200
RKLEERDGHA VSIEEYLQRS DTAIIYPEAP EELSRLGTPE ANGQEENDLP
210 220 230 240 250
PGTPDAFAQL LTCPYCDRGY KRLTSLKEHI KYRHEKNEEN FSCPLCSYTF
260 270 280 290 300
AYRTQLERHM VTHKPGTDQH QMLTQGAGNR KFKCTECGKA FKYKHHLKEH
310 320 330 340 350
LRIHSGEKPY ECPNCKKRFS HSGSYSSHIS SKKCIGLISV NGRMRNNIKT
360 370 380 390 400
GSSPNSVSSS PTNSAITQLR NKLENGKPLS MSEQTGLLKI KTEPLDFNDY
410 420 430 440 450
KVLMATHGFS GTSPFMNGGL GATSPLGVHP SAQSPMQHLG VGMEAPLLGF
460 470 480 490 500
PTMNSNLSEV QKVLQIVDNT VSRQKMDCKA EEISKLKGYH MKDPCSQPEE
510 520 530 540 550
QGVTSPNIPP VGLPVVSHNG ATKSIIDYTL EKVNEAKACL QSLTTDSRRQ
560 570 580 590 600
ISNIKKEKLR TLIDLVTDDK MIENHNISTP FSCQFCKESF PGPIPLHQHE
610 620 630 640 650
RYLCKMNEEI KAVLQPHENI VPNKAGVFVD NKALLLSSVL SEKGMTSPIN
660 670 680 690 700
PYKDHMSVLK AYYAMNMEPN SDELLKISIA VGLPQEFVKE WFEQRKVYQY
710 720 730 740 750
SNSRSPSLER SSKPLAPNSN PPTKDSLLPR SPVKPMDSIT SPSIAELHNS
760 770 780 790 800
VTNCDPPLRL TKPSHFTNIK PVEKLDHSRS NTPSPLNLSS TSSKNSHSSS
810 820 830 840 850
YTPNSFSSEE LQAEPLDLSL PKQMKEPKSI IATKNKTKAS SISLDHNSVS
860 870 880 890 900
SSSENSDEPL NLTFIKKEFS NSNNLDNKST NPVFSMNPFS AKPLYTALPP
910 920 930 940 950
QSAFPPATFM PPVQTSIPGL RPYPGLDQMS FLPHMAYTYP TGAATFADMQ
960 970 980 990 1000
QRRKYQRKQG FQGELLDGAQ DYMSGLDDMT DSDSCLSRKK IKKTESGMYA
1010 1020 1030 1040 1050
CDLCDKTFQK SSSLLRHKYE HTGKRPHQCQ ICKKAFKHKH HLIEHSRLHS
1060 1070 1080 1090 1100
GEKPYQCDKC GKRFSHSGSY SQHMNHRYSY CKREAEEREA AEREAREKGH
1110 1120 1130 1140 1150
LEPTELLMNR AYLQSITPQG YSDSEERESM PRDGESEKEH EKEGEDGYGK
1160 1170 1180 1190 1200
LGRQDGDEEF EEEEEESENK SMDTDPETIR DEEETGDHSM DDSSEDGKME
1210
TKSDHEEDNM EDGM
Length:1,214
Mass (Da):136,447
Last modified:August 1, 1998 - v1
Checksum:iB578FD91339C3FDD
GO
Isoform 2 (identifier: O60315-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     111-134: Missing.

Note: No experimental confirmation available.
Show »
Length:1,190
Mass (Da):133,806
Checksum:iB9E3278A9EEF8AAC
GO

Sequence cautioni

The sequence BAA25495 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1155D → G in BAH11928 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02701699Missing in MOWS. 1 Publication1
Natural variantiVAR_027017953R → G in MOWS. 1 Publication1
Natural variantiVAR_035563983D → N in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_0270181119Q → R in MOWS. 1 PublicationCorresponds to variant rs137852983dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044797111 – 134Missing in isoform 2. 1 PublicationAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY029472 Genomic DNA. Translation: AAK52081.1.
AB056507 mRNA. Translation: BAB40819.1.
AB011141 mRNA. Translation: BAA25495.2. Different initiation.
AK294928 mRNA. Translation: BAH11928.1.
AC009951 Genomic DNA. No translation available.
AC010130 Genomic DNA. No translation available.
BC127102 mRNA. Translation: AAI27103.1.
AB015341 mRNA. Translation: BAA34798.1.
CCDSiCCDS2186.1. [O60315-1]
CCDS54403.1. [O60315-2]
RefSeqiNP_001165124.1. NM_001171653.1. [O60315-2]
NP_055610.1. NM_014795.3. [O60315-1]
XP_006712944.1. XM_006712881.3. [O60315-1]
XP_006712945.1. XM_006712882.3. [O60315-1]
UniGeneiHs.34871.

Genome annotation databases

EnsembliENST00000409487; ENSP00000386854; ENSG00000169554. [O60315-1]
ENST00000539609; ENSP00000443792; ENSG00000169554. [O60315-2]
ENST00000558170; ENSP00000454157; ENSG00000169554. [O60315-1]
ENST00000627532; ENSP00000487174; ENSG00000169554. [O60315-1]
ENST00000637267; ENSP00000490293; ENSG00000169554. [O60315-1]
GeneIDi9839.
KEGGihsa:9839.
UCSCiuc002tvu.4. human. [O60315-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY029472 Genomic DNA. Translation: AAK52081.1.
AB056507 mRNA. Translation: BAB40819.1.
AB011141 mRNA. Translation: BAA25495.2. Different initiation.
AK294928 mRNA. Translation: BAH11928.1.
AC009951 Genomic DNA. No translation available.
AC010130 Genomic DNA. No translation available.
BC127102 mRNA. Translation: AAI27103.1.
AB015341 mRNA. Translation: BAA34798.1.
CCDSiCCDS2186.1. [O60315-1]
CCDS54403.1. [O60315-2]
RefSeqiNP_001165124.1. NM_001171653.1. [O60315-2]
NP_055610.1. NM_014795.3. [O60315-1]
XP_006712944.1. XM_006712881.3. [O60315-1]
XP_006712945.1. XM_006712882.3. [O60315-1]
UniGeneiHs.34871.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DA7NMR-A647-704[»]
ProteinModelPortaliO60315.
SMRiO60315.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115175. 21 interactors.
IntActiO60315. 23 interactors.
MINTiMINT-1181379.
STRINGi9606.ENSP00000302501.

PTM databases

iPTMnetiO60315.
PhosphoSitePlusiO60315.

Polymorphism and mutation databases

BioMutaiZEB2.

Proteomic databases

EPDiO60315.
MaxQBiO60315.
PaxDbiO60315.
PeptideAtlasiO60315.
PRIDEiO60315.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000409487; ENSP00000386854; ENSG00000169554. [O60315-1]
ENST00000539609; ENSP00000443792; ENSG00000169554. [O60315-2]
ENST00000558170; ENSP00000454157; ENSG00000169554. [O60315-1]
ENST00000627532; ENSP00000487174; ENSG00000169554. [O60315-1]
ENST00000637267; ENSP00000490293; ENSG00000169554. [O60315-1]
GeneIDi9839.
KEGGihsa:9839.
UCSCiuc002tvu.4. human. [O60315-1]

Organism-specific databases

CTDi9839.
DisGeNETi9839.
GeneCardsiZEB2.
GeneReviewsiZEB2.
HGNCiHGNC:14881. ZEB2.
HPAiHPA003456.
MalaCardsiZEB2.
MIMi235730. phenotype.
605802. gene.
neXtProtiNX_O60315.
OpenTargetsiENSG00000169554.
Orphaneti261552. Mowat-Wilson syndrome due to a ZEB2 point mutation.
261537. Mowat-Wilson syndrome due to monosomy 2q22.
PharmGKBiPA162409612.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IMF7. Eukaryota.
ENOG410ZQ40. LUCA.
GeneTreeiENSGT00630000089829.
HOGENOMiHOG000264256.
HOVERGENiHBG004697.
InParanoidiO60315.
KOiK09299.
OMAiLDHSRSN.
OrthoDBiEOG091G0F7Y.
PhylomeDBiO60315.
TreeFamiTF331759.

Enzyme and pathway databases

SignaLinkiO60315.
SIGNORiO60315.

Miscellaneous databases

ChiTaRSiZEB2. human.
EvolutionaryTraceiO60315.
GeneWikiiZEB2.
GenomeRNAii9839.
PROiO60315.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169554.
CleanExiHS_SIP1.
HS_ZEB2.
ExpressionAtlasiO60315. baseline and differential.
GenevisibleiO60315. HS.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
3.30.160.60. 6 hits.
InterProiIPR008598. Di19_Zn_binding_dom.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF05605. zf-Di19. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
SM00355. ZnF_C2H2. 8 hits.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 5 hits.
PS50157. ZINC_FINGER_C2H2_2. 6 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiZEB2_HUMAN
AccessioniPrimary (citable) accession number: O60315
Secondary accession number(s): A0JP09
, B7Z2P2, F5H814, Q9UED1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: August 1, 1998
Last modified: November 30, 2016
This is version 179 of the entry and version 1 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.