Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Carboxypeptidase A1

Gene

CPA1

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

Functioni

Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.1 Publication

Catalytic activityi

Release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.1 Publication

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi179 – 1791Zinc; catalytic
Metal bindingi182 – 1821Zinc; catalytic
Binding sitei237 – 2371SubstrateBy similarity
Metal bindingi306 – 3061Zinc; catalytic
Active sitei380 – 3801Nucleophile

GO - Molecular functioni

  • metallocarboxypeptidase activity Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

  • proteolysis Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiM14.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Carboxypeptidase A1 (EC:3.4.17.1)
Gene namesi
Name:CPA1
Synonyms:CPA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:2296. CPA1.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

Orphaneti676. Hereditary chronic pancreatitis.
PharmGKBiPA26816.

Polymorphism and mutation databases

BioMutaiCPA1.
DMDMi399196.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 16162 PublicationsAdd
BLAST
Propeptidei17 – 11094Activation peptidePRO_0000004345Add
BLAST
Chaini111 – 419309Carboxypeptidase A1PRO_0000004346Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi248 ↔ 2712 Publications

Keywords - PTMi

Disulfide bond, Zymogen

Proteomic databases

MaxQBiP15085.
PaxDbiP15085.
PeptideAtlasiP15085.
PRIDEiP15085.

PTM databases

PhosphoSiteiP15085.

Expressioni

Gene expression databases

BgeeiP15085.
CleanExiHS_CPA1.
ExpressionAtlasiP15085. baseline.
GenevisibleiP15085. HS.

Organism-specific databases

HPAiCAB025197.
HPA021836.
HPA052215.

Interactioni

Subunit structurei

Monomer. May form a complex with proelastase 2.2 Publications

Protein-protein interaction databases

BioGridi107749. 1 interaction.
DIPiDIP-48699N.
IntActiP15085. 1 interaction.
STRINGi9606.ENSP00000011292.

Structurei

Secondary structure

1
419
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni114 – 1163Combined sources
Helixi125 – 13814Combined sources
Turni140 – 1423Combined sources
Beta strandi143 – 1508Combined sources
Beta strandi156 – 1627Combined sources
Beta strandi171 – 1766Combined sources
Helixi183 – 19917Combined sources
Turni200 – 2023Combined sources
Helixi204 – 2129Combined sources
Beta strandi214 – 2196Combined sources
Helixi223 – 2319Combined sources
Helixi253 – 2553Combined sources
Beta strandi257 – 2604Combined sources
Beta strandi263 – 2686Combined sources
Helixi284 – 29613Combined sources
Beta strandi299 – 3068Combined sources
Beta strandi311 – 3155Combined sources
Helixi326 – 34116Combined sources
Turni342 – 3443Combined sources
Beta strandi349 – 3524Combined sources
Helixi353 – 3564Combined sources
Helixi364 – 3707Combined sources
Beta strandi374 – 3807Combined sources
Beta strandi384 – 3874Combined sources
Helixi393 – 3953Combined sources
Helixi396 – 41621Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2V77X-ray1.60A/B111-419[»]
3FJUX-ray1.60A112-418[»]
ProteinModelPortaliP15085.
SMRiP15085. Positions 17-419.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15085.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni179 – 1824Substrate binding
Regioni254 – 2552Substrate binding
Regioni307 – 3082Substrate binding

Sequence similaritiesi

Belongs to the peptidase M14 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG2866.
GeneTreeiENSGT00760000119103.
HOGENOMiHOG000252967.
HOVERGENiHBG050815.
InParanoidiP15085.
KOiK08779.
OMAiYGQDAAF.
PhylomeDBiP15085.
TreeFamiTF317197.

Family and domain databases

Gene3Di3.30.70.340. 1 hit.
InterProiIPR000834. Peptidase_M14.
IPR003146. Prot_inh_M14A.
IPR009020. Prot_inh_propept.
[Graphical view]
PfamiPF00246. Peptidase_M14. 1 hit.
PF02244. Propep_M14. 1 hit.
[Graphical view]
PRINTSiPR00765. CRBOXYPTASEA.
SMARTiSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMiSSF54897. SSF54897. 1 hit.
PROSITEiPS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P15085-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRGLLVLSVL LGAVFGKEDF VGHQVLRISV ADEAQVQKVK ELEDLEHLQL
60 70 80 90 100
DFWRGPAHPG SPIDVRVPFP SIQAVKIFLE SHGISYETMI EDVQSLLDEE
110 120 130 140 150
QEQMFAFRSR ARSTDTFNYA TYHTLEEIYD FLDLLVAENP HLVSKIQIGN
160 170 180 190 200
TYEGRPIYVL KFSTGGSKRP AIWIDTGIHS REWVTQASGV WFAKKITQDY
210 220 230 240 250
GQDAAFTAIL DTLDIFLEIV TNPDGFAFTH STNRMWRKTR SHTAGSLCIG
260 270 280 290 300
VDPNRNWDAG FGLSGASSNP CSETYHGKFA NSEVEVKSIV DFVKDHGNIK
310 320 330 340 350
AFISIHSYSQ LLMYPYGYKT EPVPDQDELD QLSKAAVTAL ASLYGTKFNY
360 370 380 390 400
GSIIKAIYQA SGSTIDWTYS QGIKYSFTFE LRDTGRYGFL LPASQIIPTA
410
KETWLALLTI MEHTLNHPY
Length:419
Mass (Da):47,140
Last modified:July 1, 1993 - v2
Checksum:i439FAFFFAEE958B1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti139 – 1413NPH → HPG AA sequence (PubMed:8318831).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti208 – 2081A → T.
Corresponds to variant rs34474469 [ dbSNP | Ensembl ].
VAR_048593
Natural varianti276 – 2761H → R.2 Publications
Corresponds to variant rs17849959 [ dbSNP | Ensembl ].
VAR_054311

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67318 mRNA. Translation: CAA47732.1.
AK291493 mRNA. Translation: BAF84182.1.
BT007313 mRNA. Translation: AAP35977.1.
CH236950 Genomic DNA. Translation: EAL24089.1.
CH471070 Genomic DNA. Translation: EAW83763.1.
BC005279 mRNA. Translation: AAH05279.1.
CCDSiCCDS5820.1.
PIRiS29127.
RefSeqiNP_001859.1. NM_001868.3.
UniGeneiHs.2879.

Genome annotation databases

EnsembliENST00000011292; ENSP00000011292; ENSG00000091704.
GeneIDi1357.
KEGGihsa:1357.
UCSCiuc003vpx.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67318 mRNA. Translation: CAA47732.1.
AK291493 mRNA. Translation: BAF84182.1.
BT007313 mRNA. Translation: AAP35977.1.
CH236950 Genomic DNA. Translation: EAL24089.1.
CH471070 Genomic DNA. Translation: EAW83763.1.
BC005279 mRNA. Translation: AAH05279.1.
CCDSiCCDS5820.1.
PIRiS29127.
RefSeqiNP_001859.1. NM_001868.3.
UniGeneiHs.2879.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2V77X-ray1.60A/B111-419[»]
3FJUX-ray1.60A112-418[»]
ProteinModelPortaliP15085.
SMRiP15085. Positions 17-419.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107749. 1 interaction.
DIPiDIP-48699N.
IntActiP15085. 1 interaction.
STRINGi9606.ENSP00000011292.

Chemistry

BindingDBiP15085.
ChEMBLiCHEMBL2088.

Protein family/group databases

MEROPSiM14.001.

PTM databases

PhosphoSiteiP15085.

Polymorphism and mutation databases

BioMutaiCPA1.
DMDMi399196.

Proteomic databases

MaxQBiP15085.
PaxDbiP15085.
PeptideAtlasiP15085.
PRIDEiP15085.

Protocols and materials databases

DNASUi1357.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000011292; ENSP00000011292; ENSG00000091704.
GeneIDi1357.
KEGGihsa:1357.
UCSCiuc003vpx.3. human.

Organism-specific databases

CTDi1357.
GeneCardsiGC07P130020.
HGNCiHGNC:2296. CPA1.
HPAiCAB025197.
HPA021836.
HPA052215.
MIMi114850. gene.
neXtProtiNX_P15085.
Orphaneti676. Hereditary chronic pancreatitis.
PharmGKBiPA26816.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2866.
GeneTreeiENSGT00760000119103.
HOGENOMiHOG000252967.
HOVERGENiHBG050815.
InParanoidiP15085.
KOiK08779.
OMAiYGQDAAF.
PhylomeDBiP15085.
TreeFamiTF317197.

Miscellaneous databases

ChiTaRSiCPA1. human.
EvolutionaryTraceiP15085.
GeneWikiiCarboxypeptidase_A1.
GenomeRNAii1357.
NextBioi5497.
PROiP15085.
SOURCEiSearch...

Gene expression databases

BgeeiP15085.
CleanExiHS_CPA1.
ExpressionAtlasiP15085. baseline.
GenevisibleiP15085. HS.

Family and domain databases

Gene3Di3.30.70.340. 1 hit.
InterProiIPR000834. Peptidase_M14.
IPR003146. Prot_inh_M14A.
IPR009020. Prot_inh_propept.
[Graphical view]
PfamiPF00246. Peptidase_M14. 1 hit.
PF02244. Propep_M14. 1 hit.
[Graphical view]
PRINTSiPR00765. CRBOXYPTASEA.
SMARTiSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMiSSF54897. SSF54897. 1 hit.
PROSITEiPS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "cDNA cloning and sequence analysis of human pancreatic procarboxypeptidase A1."
    Catasus L., Villegas V., Pascual R., Aviles F.X., Wicker-Planquart C., Puigserver A.
    Biochem. J. 287:299-303(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Pancreas.
  2. "Expression and characterization of human pancreatic preprocarboxypeptidase A1 and preprocarboxypeptidase A2."
    Laethem R.M., Blumenkopf T.A., Cory M., Elwell L., Moxham C.P., Ray P.H., Walton L.M., Smith G.K.
    Arch. Biochem. Biophys. 332:8-18(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Pancreas.
  4. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-276.
  5. "Human chromosome 7: DNA sequence and biology."
    Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
    Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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], VARIANT ARG-276.
    Tissue: Pancreas.
  8. "Further studies on the human pancreatic binary complexes involving procarboxypeptidase A."
    Moulard M., Michon T., Kerfelec B., Chapus C.
    FEBS Lett. 261:179-183(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 17-43 AND 114-135, INTERACTION WITH PROELASTASE 2.
  9. "Purification and properties of five different forms of human procarboxypeptidases."
    Pascual R., Burgos F.J., Salva M., Soriano F., Mendez E., Aviles F.X.
    Eur. J. Biochem. 179:609-616(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 17-42.
  10. "Separation of human pancreatic carboxypeptidase A isoenzymes by high performance liquid chromatography."
    Linder D., Linder M., Schade H., Sziegoleit A.
    Biomed. Chromatogr. 7:143-145(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 113-143.
    Tissue: Pancreas.
  11. "Human carboxypeptidase A identifies a BglII RFLP and maps to 7q31-qter."
    Stewart E.A., Craik C.S., Hake L., Bowcock A.M.
    Am. J. Hum. Genet. 46:795-800(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 330-396.
  12. "Direct interaction between a human digestive protease and the mucoadhesive poly(acrylic acid)."
    Pallares I., Fernandez D., Comellas-Bigler M., Fernandez-Recio J., Ventura S., Aviles F.X., Bode W., Vendrell J.
    Acta Crystallogr. D 64:784-791(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 111-419 IN COMPLEX WITH POLYACRYLIC ACID AND ZINC IONS, SUBUNIT, DISULFIDE BOND.
  13. "Mammalian metallopeptidase inhibition at the defense barrier of Ascaris parasite."
    Sanglas L., Aviles F.X., Huber R., Gomis-Rueth F.X., Arolas J.L.
    Proc. Natl. Acad. Sci. U.S.A. 106:1743-1747(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 112-418 IN COMPLEX WITH ASCARIS CARBOXYPEPTIDASE INHIBITOR AND ZINC IONS, SUBUNIT, DISULFIDE BOND.

Entry informationi

Entry nameiCBPA1_HUMAN
AccessioniPrimary (citable) accession number: P15085
Secondary accession number(s): A4D1M1
, Q53XU0, Q9BS67, Q9UCF2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: July 1, 1993
Last modified: July 22, 2015
This is version 152 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

Keywords - Technical termi

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

Documents

  1. Human chromosome 7
    Human chromosome 7: 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. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.