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Protein

TSC22 domain family protein 3

Gene

Tsc22d3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protects T-cells from IL2 deprivation-induced apoptosis through the inhibition of FOXO3A transcriptional activity that leads to the down-regulation of the pro-apoptotic factor BCL2L11. In macrophages, plays a role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL10. In T-cells, inhibits anti-CD3-induced NFKB1 nuclear translocation. In vitro, suppresses AP1 and NFKB1 DNA-binding activities (By similarity). Isoform 1 and isoform 4 inhibit myogenic differentiation and mediate anti-myogenic effects of glucocorticoids by binding and regulating MYOD1 and HDAC1 transcriptional activity resulting in reduced expression of MYOG.By similarity1 Publication

GO - Molecular functioni

  • MRF binding Source: MGI
  • sequence-specific DNA binding transcription factor activity Source: InterPro

GO - Biological processi

  • body fluid secretion Source: Ensembl
  • negative regulation of activation-induced cell death of T cells Source: MGI
  • negative regulation of skeletal muscle tissue development Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • response to osmotic stress Source: MGI
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_346473. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
TSC22 domain family protein 3
Alternative name(s):
Glucocorticoid-induced leucine zipper protein
TSC22-related-inducible leucine zipper 3
Short name:
Tilz3
Gene namesi
Name:Tsc22d3
Synonyms:Dsip1, Dsipi, Gilz
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1196284. Tsc22d3.

Subcellular locationi

Isoform 1 :
  • Cytoplasm
  • Nucleus

  • Note: Localization depends on differentiation status of myoblasts. In undifferentiated myoblasts, isoform 1 localizes to the cytoplasm, but in differentiating myoblasts, isoform 1 is localized to the nucleus.
Isoform 4 :
  • Cytoplasm
  • Nucleus

  • Note: Localization depends on differentiation status of myoblasts. In undifferentiated myoblasts, isoform 4 localizes to the cytoplasm, but in differentiating myoblasts, isoform 4 is localized to the nucleus.

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 137137TSC22 domain family protein 3PRO_0000219371Add
BLAST

Post-translational modificationi

Isoform 3 is phosphorylated on Ser-30 and Ser-40.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Z2S7.
PaxDbiQ9Z2S7.
PRIDEiQ9Z2S7.

2D gel databases

REPRODUCTION-2DPAGEIPI00265379.

PTM databases

PhosphoSiteiQ9Z2S7.

Expressioni

Tissue specificityi

Constitutively expressed in lung, intestine, kidney and liver, most probably by resident cells from the macrophage lineage. Expression inversely correlates with T-cell activation, being higher in resting cells and lower in cells activated by TCR/CD3 triggering. Isoform 1 and isoform 4 are expressed in spleen and skeletal muscle (at protein level). Isoform 1 is expressed in thymus, lymph nodes, bone marrow, spleen, lung and skeletal muscle.3 Publications

Developmental stagei

Isoform 1 and isoform 4 are expressed in differentiating myoblasts at a time of myotube formation.1 Publication

Inductioni

By glucocorticoids in lymphoid cells and upon IL4, IL10, IL13 or glucocorticoid treatment in monocyte/macrophage cells. Transiently induced by IL2 deprivation in T-cells. Isoform 1 and isoform 4 expression is up-regulated by the synthetic glucocorticoid dexamethasone in differentiating myoblasts.4 Publications

Gene expression databases

BgeeiQ9Z2S7.
CleanExiMM_TSC22D3.
ExpressionAtlasiQ9Z2S7. baseline and differential.
GenevisibleiQ9Z2S7. MM.

Interactioni

Subunit structurei

Can form homodimers, however it is likely to function as a monomer. Interacts with AP1 and NFKB1 (By similarity). Isoform 1 and isoform 4 interact with MYOD1. Isoform 1 interacts with HDAC1; this interaction affects HDAC1 activity on MYOG promoter and thus inhibits MYOD1 transcriptional activity.By similarity2 Publications

Protein-protein interaction databases

BioGridi199919. 7 interactions.
DIPiDIP-48844N.
STRINGi10090.ENSMUSP00000108620.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2S7.
SMRiQ9Z2S7. Positions 58-114.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6060AP1-bindingAdd
BLAST
Regioni76 – 9722Leucine-zipperAdd
BLAST

Domaini

The leucine-zipper is involved in homodimerization.

Sequence similaritiesi

Belongs to the TSC-22/Dip/Bun family.Curated

Phylogenomic databases

eggNOGiNOG329226.
GeneTreeiENSGT00530000063062.
HOGENOMiHOG000015349.
HOVERGENiHBG075918.
InParanoidiQ9Z2S7.
OMAiSTEMFAK.
OrthoDBiEOG7RZ5PT.
PhylomeDBiQ9Z2S7.
TreeFamiTF329224.

Family and domain databases

InterProiIPR000580. TSC-22_Dip_Bun.
[Graphical view]
PANTHERiPTHR12348. PTHR12348. 1 hit.
PfamiPF01166. TSC22. 1 hit.
[Graphical view]
ProDomiPD007152. TSC-22_Dip_Bun. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEiPS01289. TSC22. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Z2S7-1) [UniParc]FASTAAdd to basket

Also known as: Tilz3b

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
MNTEMYQTPM EVAVYQLHNF SISFFSSLLG GDVVSVKLDN SASGASVVAL
60 70 80 90 100
DNKIEQAMDL VKNHLMYAVR EEVEVLKEQI RELLEKNSQL ERENTLLKTL
110 120 130
ASPEQLEKFQ SRLSPEEPAP EAPETPETPE APGGSAV
Length:137
Mass (Da):15,177
Last modified:February 1, 2005 - v2
Checksum:iA11D7B69037F111E
GO
Isoform 2 (identifier: Q9Z2S7-2) [UniParc]FASTAAdd to basket

Also known as: Tilz3a

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: Missing.

Show »
Length:80
Mass (Da):9,040
Checksum:i2174BA0EC92DDCFC
GO
Isoform 3 (identifier: Q9Z2S7-3) [UniParc]FASTAAdd to basket

Also known as: Tilz3c

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: MNTEMYQTPM...GDVVSVKLDN → MAQPKTECRS...TMLSILLFFH

Show »
Length:201
Mass (Da):22,565
Checksum:iB12F0480154A20DE
GO
Isoform 4 (identifier: Q9Z2S7-4) [UniParc]FASTAAdd to basket

Also known as: Long Gilz, L-Gilz

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: MNTEMYQTPM...GDVVSVKLDN → MESQKASSAG...TMLSILLFFH

Show »
Length:234
Mass (Da):25,778
Checksum:iC7CEDB07D24D4185
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti22 – 221I → T in AAD01789 (PubMed:9430225).Curated
Sequence conflicti33 – 331V → L in AAG41221 (Ref. 3) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5757Missing in isoform 2. 2 PublicationsVSP_012690Add
BLAST
Alternative sequencei1 – 4040MNTEM…VKLDN → MAQPKTECRSPVGLDCCNCC LDLANRCELQKEKSGESPGS PFVSNFRQLQEKLVFENLNT DKLNNIMRQDSMEPVVRDPC YLINEGICNRNIDQTMLSIL LFFH in isoform 3. 1 PublicationVSP_012691Add
BLAST
Alternative sequencei1 – 4040MNTEM…VKLDN → MESQKASSAGAHLPAAPDLP EQAAAAAASKPEKMAQPKTE CRSPVGLDCCNCCLDLANRC ELQKEKSGESPGSPFVSNFR QLQEKLVFENLNTDKLNNIM RQDSMEPVVRDPCYLINEGI CNRNIDQTMLSILLFFH in isoform 4. 1 PublicationVSP_055016Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024519 mRNA. Translation: AAD01789.1.
EU818782 mRNA. Translation: ACJ09091.1.
AF201287 mRNA. Translation: AAG41220.1.
AF201288 mRNA. Translation: AAG41221.1.
AF201289 mRNA. Translation: AAG41222.1.
AK083389 mRNA. Translation: BAC38897.1.
AK144196 mRNA. Translation: BAE25761.1.
AL683809 Genomic DNA. Translation: CAM24436.1.
BC028813 mRNA. Translation: AAH28813.1.
CCDSiCCDS30440.1. [Q9Z2S7-1]
CCDS41150.1. [Q9Z2S7-3]
RefSeqiNP_001070832.1. NM_001077364.1. [Q9Z2S7-3]
NP_034416.3. NM_010286.4. [Q9Z2S7-1]
XP_006528562.1. XM_006528499.2. [Q9Z2S7-3]
XP_006528563.1. XM_006528500.2. [Q9Z2S7-3]
XP_006528564.1. XM_006528501.2. [Q9Z2S7-1]
XP_006528566.1. XM_006528503.2. [Q9Z2S7-2]
XP_006528567.1. XM_006528504.2. [Q9Z2S7-3]
XP_006528568.1. XM_006528505.2. [Q9Z2S7-3]
UniGeneiMm.22216.

Genome annotation databases

EnsembliENSMUST00000055738; ENSMUSP00000062589; ENSMUSG00000031431. [Q9Z2S7-1]
ENSMUST00000112996; ENSMUSP00000108620; ENSMUSG00000031431. [Q9Z2S7-3]
GeneIDi14605.
KEGGimmu:14605.
UCSCiuc009ukz.1. mouse. [Q9Z2S7-1]
uc009ulb.1. mouse. [Q9Z2S7-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024519 mRNA. Translation: AAD01789.1.
EU818782 mRNA. Translation: ACJ09091.1.
AF201287 mRNA. Translation: AAG41220.1.
AF201288 mRNA. Translation: AAG41221.1.
AF201289 mRNA. Translation: AAG41222.1.
AK083389 mRNA. Translation: BAC38897.1.
AK144196 mRNA. Translation: BAE25761.1.
AL683809 Genomic DNA. Translation: CAM24436.1.
BC028813 mRNA. Translation: AAH28813.1.
CCDSiCCDS30440.1. [Q9Z2S7-1]
CCDS41150.1. [Q9Z2S7-3]
RefSeqiNP_001070832.1. NM_001077364.1. [Q9Z2S7-3]
NP_034416.3. NM_010286.4. [Q9Z2S7-1]
XP_006528562.1. XM_006528499.2. [Q9Z2S7-3]
XP_006528563.1. XM_006528500.2. [Q9Z2S7-3]
XP_006528564.1. XM_006528501.2. [Q9Z2S7-1]
XP_006528566.1. XM_006528503.2. [Q9Z2S7-2]
XP_006528567.1. XM_006528504.2. [Q9Z2S7-3]
XP_006528568.1. XM_006528505.2. [Q9Z2S7-3]
UniGeneiMm.22216.

3D structure databases

ProteinModelPortaliQ9Z2S7.
SMRiQ9Z2S7. Positions 58-114.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199919. 7 interactions.
DIPiDIP-48844N.
STRINGi10090.ENSMUSP00000108620.

PTM databases

PhosphoSiteiQ9Z2S7.

2D gel databases

REPRODUCTION-2DPAGEIPI00265379.

Proteomic databases

MaxQBiQ9Z2S7.
PaxDbiQ9Z2S7.
PRIDEiQ9Z2S7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000055738; ENSMUSP00000062589; ENSMUSG00000031431. [Q9Z2S7-1]
ENSMUST00000112996; ENSMUSP00000108620; ENSMUSG00000031431. [Q9Z2S7-3]
GeneIDi14605.
KEGGimmu:14605.
UCSCiuc009ukz.1. mouse. [Q9Z2S7-1]
uc009ulb.1. mouse. [Q9Z2S7-3]

Organism-specific databases

CTDi1831.
MGIiMGI:1196284. Tsc22d3.

Phylogenomic databases

eggNOGiNOG329226.
GeneTreeiENSGT00530000063062.
HOGENOMiHOG000015349.
HOVERGENiHBG075918.
InParanoidiQ9Z2S7.
OMAiSTEMFAK.
OrthoDBiEOG7RZ5PT.
PhylomeDBiQ9Z2S7.
TreeFamiTF329224.

Enzyme and pathway databases

ReactomeiREACT_346473. Stimuli-sensing channels.

Miscellaneous databases

NextBioi286388.
PROiQ9Z2S7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Z2S7.
CleanExiMM_TSC22D3.
ExpressionAtlasiQ9Z2S7. baseline and differential.
GenevisibleiQ9Z2S7. MM.

Family and domain databases

InterProiIPR000580. TSC-22_Dip_Bun.
[Graphical view]
PANTHERiPTHR12348. PTHR12348. 1 hit.
PfamiPF01166. TSC22. 1 hit.
[Graphical view]
ProDomiPD007152. TSC-22_Dip_Bun. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEiPS01289. TSC22. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR/CD3-activated cell death."
    D'Adamio F., Zollo O., Moraca R., Ayroldi E., Bruscoli S., Bartoli A., Cannarile L., Migliorati G., Riccardi C.
    Immunity 7:803-812(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INDUCTION.
    Strain: C3H/HeN.
    Tissue: Thymus.
  2. "Glucocorticoid-induced leucine zipper (GILZ) and long GILZ inhibit myogenic differentiation and mediate anti-myogenic effects of glucocorticoids."
    Bruscoli S., Donato V., Velardi E., Di Sante M., Migliorati G., Donato R., Riccardi C.
    J. Biol. Chem. 285:10385-10396(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, INTERACTION WITH MYOD1 AND HDAC1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
    Strain: DBA/2.
    Tissue: Myoblast.
  3. "Identification and characterization of a family of leucine zipper genes related to TSC22."
    Ershler M.A., Belyavsky A.V., Visser J.W.M.
    Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
  4. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: BALB/c and C57BL/6J.
    Tissue: Thymus.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  6. "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).
    Strain: FVB/N.
    Tissue: Liver.
  7. "Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappa B."
    Ayroldi E., Migliorati G., Bruscoli S., Marchetti C., Zollo O., Cannarile L., D'Adamio F., Riccardi C.
    Blood 98:743-753(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. "Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ."
    Mittelstadt P.R., Ashwell J.D.
    J. Biol. Chem. 276:29603-29610(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: HOMODIMERIZATION, INTERACTION WITH JUN AND FOS.
  9. "Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10."
    Berrebi D., Bruscoli S., Cohen N., Foussat A., Migliorati G., Bouchet-Delbos L., Maillot M.-C., Portier A., Couderc J., Galanaud P., Peuchmaur M., Riccardi C., Emilie D.
    Blood 101:729-738(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION.
  10. "GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis."
    Asselin-Labat M.-L., David M., Biola-Vidamment A., Lecoeuche D., Zennaro M.-C., Bertoglio J., Pallardy M.
    Blood 104:215-223(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.

Entry informationi

Entry nameiT22D3_MOUSE
AccessioniPrimary (citable) accession number: Q9Z2S7
Secondary accession number(s): B1AVF3
, C6EX03, Q3UNI6, Q8K160, Q9EQN0, Q9EQN1, Q9EQN2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: February 1, 2005
Last modified: June 24, 2015
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.