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Protein

mRNA-capping enzyme

Gene

RNGTT

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

Functioni

Bifunctional mRNA-capping enzyme exhibiting RNA 5'-triphosphatase activity in the N-terminal part and mRNA guanylyltransferase activity in the C-terminal part. Catalyzes the first two steps of cap formation: by removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end, and by transferring the gmp moiety of GTP to the 5'-diphosphate terminus.3 Publications

Catalytic activityi

A 5'-phosphopolynucleotide + H2O = a polynucleotide + phosphate.
GTP + (5')pp-Pur-mRNA = diphosphate + G(5')ppp-Pur-mRNA.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei126For RNA 5'-triphosphatase activityBy similarity1
Active sitei294N6-GMP-lysine intermediate1 Publication1
Binding sitei299GTPBy similarity1
Binding sitei315GTPSequence analysis1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi343 – 345GTPSequence analysis3
Nucleotide bindingi458 – 460GTPSequence analysis3
Nucleotide bindingi528 – 533GTPSequence analysis6

GO - Molecular functioni

GO - Biological processi

  • 7-methylguanosine mRNA capping Source: UniProtKB
  • RNA processing Source: UniProtKB
  • transcription from RNA polymerase II promoter Source: Reactome
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Nucleotidyltransferase, Transferase

Keywords - Biological processi

Host-virus interaction, mRNA capping, mRNA processing

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS03479-MONOMER.
ZFISH:HS03479-MONOMER.
BRENDAi2.7.7.50. 2681.
ReactomeiR-HSA-167160. RNA Pol II CTD phosphorylation and interaction with CE.
R-HSA-72086. mRNA Capping.
R-HSA-77075. RNA Pol II CTD phosphorylation and interaction with CE.

Names & Taxonomyi

Protein namesi
Recommended name:
mRNA-capping enzyme
Alternative name(s):
HCAP1
HCE
Including the following 2 domains:
Polynucleotide 5'-triphosphatase (EC:3.1.3.33)
Alternative name(s):
mRNA 5'-triphosphatase
Short name:
TPase
mRNA guanylyltransferase (EC:2.7.7.50)
Alternative name(s):
GTP--RNA guanylyltransferase
Short name:
GTase
Gene namesi
Name:RNGTT
Synonyms:CAP1A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:10073. RNGTT.

Subcellular locationi

GO - Cellular componenti

  • nucleoplasm Source: Reactome
  • nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi234E → A: No effect on GTase activity. 1 Publication1
Mutagenesisi294K → A: Loss of GTase activity. 1 Publication1
Mutagenesisi299R → A: Loss of GTase activity. 1 Publication1
Mutagenesisi345E → A: Loss of GTase activity. 1 Publication1
Mutagenesisi458K → A: Loss of GTase activity. 2 Publications1
Mutagenesisi460K → A: Loss of GTase activity. 2 Publications1
Mutagenesisi528R → A: Strongly reduced GTase activity. 1 Publication1
Mutagenesisi530R → A: Loss of GTase activity. 1 Publication1
Mutagenesisi532D → A: Loss of GTase activity. 1 Publication1
Mutagenesisi533K → A: Loss of GTase activity. 1 Publication1

Organism-specific databases

DisGeNETi8732.
OpenTargetsiENSG00000111880.
PharmGKBiPA34446.

Chemistry databases

DrugBankiDB02325. Isopropyl Alcohol.

Polymorphism and mutation databases

BioMutaiRNGTT.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002101081 – 597mRNA-capping enzymeAdd BLAST597

Proteomic databases

EPDiO60942.
MaxQBiO60942.
PaxDbiO60942.
PeptideAtlasiO60942.
PRIDEiO60942.

PTM databases

DEPODiO60942.
iPTMnetiO60942.
PhosphoSitePlusiO60942.

Expressioni

Tissue specificityi

Isoform 1 and isoform 4 (at a lesser extent) are expressed in cerebrum, cerebellum, thyroid, lung, heart, liver, kidney, spleen, large intestine, testis, skin and muscle.

Gene expression databases

BgeeiENSG00000111880.
CleanExiHS_RNGTT.
GenevisibleiO60942. HS.

Organism-specific databases

HPAiHPA003750.

Interactioni

Subunit structurei

Interacts with POLR2A (via C-terminus); this enhances guanylyltransferase activity. Binds (via GTase domain) to the elongating phosphorylated form of RNA polymerase II; can form direct interactions with the phosphorylated POLR2A C-terminal domain and indirect interactions via bound RNA (By similarity). Interacts with SUPT5H and RNMT. Interacts with HIV-1 Tat.By similarity3 Publications

Protein-protein interaction databases

BioGridi114270. 11 interactors.
DIPiDIP-61014N.
IntActiO60942. 4 interactors.
STRINGi9606.ENSP00000358497.

Structurei

Secondary structure

1597
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni21 – 23Combined sources3
Beta strandi24 – 27Combined sources4
Helixi33 – 38Combined sources6
Helixi41 – 43Combined sources3
Helixi47 – 57Combined sources11
Beta strandi60 – 66Combined sources7
Helixi77 – 80Combined sources4
Turni81 – 83Combined sources3
Beta strandi85 – 88Combined sources4
Helixi100 – 110Combined sources11
Beta strandi120 – 125Combined sources6
Beta strandi127 – 130Combined sources4
Helixi131 – 143Combined sources13
Helixi149 – 159Combined sources11
Helixi167 – 177Combined sources11
Helixi180 – 182Combined sources3
Beta strandi232 – 235Combined sources4
Beta strandi241 – 243Combined sources3
Helixi247 – 261Combined sources15
Beta strandi265 – 267Combined sources3
Beta strandi270 – 275Combined sources6
Turni278 – 280Combined sources3
Helixi281 – 285Combined sources5
Beta strandi289 – 295Combined sources7
Beta strandi298 – 304Combined sources7
Beta strandi306 – 308Combined sources3
Beta strandi310 – 314Combined sources5
Beta strandi319 – 324Combined sources6
Beta strandi339 – 351Combined sources13
Beta strandi354 – 367Combined sources14
Helixi372 – 374Combined sources3
Helixi377 – 387Combined sources11
Helixi389 – 394Combined sources6
Turni395 – 397Combined sources3
Beta strandi398 – 401Combined sources4
Turni403 – 405Combined sources3
Beta strandi406 – 412Combined sources7
Helixi418 – 424Combined sources7
Beta strandi437 – 446Combined sources10
Beta strandi451 – 459Combined sources9
Helixi462 – 464Combined sources3
Beta strandi466 – 476Combined sources11
Beta strandi484 – 490Combined sources7
Beta strandi498 – 501Combined sources4
Helixi507 – 509Combined sources3
Beta strandi512 – 520Combined sources9
Beta strandi523 – 529Combined sources7
Helixi539 – 550Combined sources12
Helixi555 – 563Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C46X-ray1.60A/B/C/D1-219[»]
3S24X-ray3.01A/B/C/D/E/F/G229-567[»]
ProteinModelPortaliO60942.
SMRiO60942.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60942.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 212TPaseAdd BLAST212
Regioni229 – 597GTaseAdd BLAST369
Regioni330 – 386Interaction with POLR2ABy similarityAdd BLAST57

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi195 – 205Asp/Glu-richAdd BLAST11

Sequence similaritiesi

In the N-terminal section; belongs to the non-receptor class of the protein-tyrosine phosphatase family.Curated
In the C-terminal section; belongs to the eukaryotic GTase family.Curated

Phylogenomic databases

eggNOGiKOG2386. Eukaryota.
COG5226. LUCA.
GeneTreeiENSGT00530000063473.
HOVERGENiHBG006332.
InParanoidiO60942.
KOiK13917.
OMAiRFNERSP.
OrthoDBiEOG091G063D.
PhylomeDBiO60942.
TreeFamiTF314914.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR000340. Dual-sp_phosphatase_cat-dom.
IPR017074. mRNA_cap_enz_bifunc.
IPR001339. mRNA_cap_enzyme.
IPR013846. mRNA_cap_enzyme_C.
IPR012340. NA-bd_OB-fold.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR016130. Tyr_Pase_AS.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00782. DSPc. 1 hit.
PF03919. mRNA_cap_C. 1 hit.
PF01331. mRNA_cap_enzyme. 1 hit.
[Graphical view]
PIRSFiPIRSF036958. mRNA_capping_HCE. 1 hit.
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 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: O60942-1) [UniParc]FASTAAdd to basket
Also known as: HCE1, HCAP1A

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
MAHNKIPPRW LNCPRRGQPV AGRFLPLKTM LGPRYDSQVA EENRFHPSML
60 70 80 90 100
SNYLKSLKVK MGLLVDLTNT SRFYDRNDIE KEGIKYIKLQ CKGHGECPTT
110 120 130 140 150
ENTETFIRLC ERFNERNPPE LIGVHCTHGF NRTGFLICAF LVEKMDWSIE
160 170 180 190 200
AAVATFAQAR PPGIYKGDYL KELFRRYGDI EEAPPPPLLP DWCFEDDEDE
210 220 230 240 250
DEDEDGKKES EPGSSASFGK RRKERLKLGA IFLEGVTVKG VTQVTTQPKL
260 270 280 290 300
GEVQQKCHQF CGWEGSGFPG AQPVSMDKQN IKLLDLKPYK VSWKADGTRY
310 320 330 340 350
MMLIDGTNEV FMIDRDNSVF HVSNLEFPFR KDLRMHLSNT LLDGEMIIDR
360 370 380 390 400
VNGQAVPRYL IYDIIKFNSQ PVGDCDFNVR LQCIEREIIS PRHEKMKTGL
410 420 430 440 450
IDKTQEPFSV RNKPFFDICT SRKLLEGNFA KEVSHEMDGL IFQPTGKYKP
460 470 480 490 500
GRCDDILKWK PPSLNSVDFR LKITRMGGEG LLPQNVGLLY VGGYERPFAQ
510 520 530 540 550
IKVTKELKQY DNKIIECKFE NNSWVFMRQR TDKSFPNAYN TAMAVCNSIS
560 570 580 590
NPVTKEMLFE FIDRCTAASQ GQKRKHHLDP DTELMPPPPP KRPRPLT
Length:597
Mass (Da):68,557
Last modified:August 1, 1998 - v1
Checksum:i51CEEC1B190603DE
GO
Isoform 2 (identifier: O60942-2) [UniParc]FASTAAdd to basket
Also known as: HCE1A

The sequence of this isoform differs from the canonical sequence as follows:
     424-446: Missing.

Show »
Length:574
Mass (Da):66,042
Checksum:iCFE64E51F6F88232
GO
Isoform 3 (identifier: O60942-3) [UniParc]FASTAAdd to basket
Also known as: HCE1B

The sequence of this isoform differs from the canonical sequence as follows:
     424-446: Missing.
     481-597: Missing.

Show »
Length:457
Mass (Da):52,533
Checksum:i4F3B52CA4F6CC56B
GO
Isoform 4 (identifier: O60942-4) [UniParc]FASTAAdd to basket
Also known as: HCAP1B

The sequence of this isoform differs from the canonical sequence as follows:
     504-597: TKELKQYDNK...PPPKRPRPLT → CLFIFSVLFL...KISCSSTLGG

Show »
Length:541
Mass (Da):61,705
Checksum:iDF795898785EC2D4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti30M → I in AAB91559 (PubMed:9371772).Curated1
Sequence conflicti212P → T in AAH19954 (PubMed:15489334).Curated1
Sequence conflicti484Q → P in AAB91559 (PubMed:9371772).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046481594R → H.1 PublicationCorresponds to variant rs17856595dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003202424 – 446Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_003203481 – 597Missing in isoform 3. 1 PublicationAdd BLAST117
Alternative sequenceiVSP_003204504 – 597TKELK…PRPLT → CLFIFSVLFLDVLLSGIHQN LANNNQHIKISCSSTLGG in isoform 4. 1 PublicationAdd BLAST94

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF025654 mRNA. Translation: AAB91559.1.
AB009022 mRNA. Translation: BAA25894.1.
AB009023 mRNA. Translation: BAA25895.1.
AB009024 mRNA. Translation: BAA25896.1.
AB012142 mRNA. Translation: BAA25198.1.
AB012143 mRNA. Translation: BAA25199.1.
AL079342
, AL096868, AL133408, AL445530 Genomic DNA. Translation: CAI22537.1.
AL096868
, AL079342, AL133408, AL445530 Genomic DNA. Translation: CAI21547.1.
AL133408
, AL079342, AL096868, AL445530 Genomic DNA. Translation: CAI21542.1.
AL445530
, AL079342, AL096868, AL133408 Genomic DNA. Translation: CAI22048.1.
CH471051 Genomic DNA. Translation: EAW48566.1.
CH471051 Genomic DNA. Translation: EAW48567.1.
CH471051 Genomic DNA. Translation: EAW48569.1.
CH471051 Genomic DNA. Translation: EAW48570.1.
BC019954 mRNA. Translation: AAH19954.1.
CCDSiCCDS5017.1. [O60942-1]
CCDS69153.1. [O60942-2]
PIRiJC5936.
JC5937.
RefSeqiNP_001273355.1. NM_001286426.1. [O60942-2]
NP_001273357.1. NM_001286428.1.
NP_003791.3. NM_003800.4. [O60942-1]
UniGeneiHs.567378.
Hs.627135.

Genome annotation databases

EnsembliENST00000369475; ENSP00000358487; ENSG00000111880. [O60942-2]
ENST00000369485; ENSP00000358497; ENSG00000111880. [O60942-1]
ENST00000538899; ENSP00000442609; ENSG00000111880. [O60942-3]
GeneIDi8732.
KEGGihsa:8732.
UCSCiuc003pmr.4. human. [O60942-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF025654 mRNA. Translation: AAB91559.1.
AB009022 mRNA. Translation: BAA25894.1.
AB009023 mRNA. Translation: BAA25895.1.
AB009024 mRNA. Translation: BAA25896.1.
AB012142 mRNA. Translation: BAA25198.1.
AB012143 mRNA. Translation: BAA25199.1.
AL079342
, AL096868, AL133408, AL445530 Genomic DNA. Translation: CAI22537.1.
AL096868
, AL079342, AL133408, AL445530 Genomic DNA. Translation: CAI21547.1.
AL133408
, AL079342, AL096868, AL445530 Genomic DNA. Translation: CAI21542.1.
AL445530
, AL079342, AL096868, AL133408 Genomic DNA. Translation: CAI22048.1.
CH471051 Genomic DNA. Translation: EAW48566.1.
CH471051 Genomic DNA. Translation: EAW48567.1.
CH471051 Genomic DNA. Translation: EAW48569.1.
CH471051 Genomic DNA. Translation: EAW48570.1.
BC019954 mRNA. Translation: AAH19954.1.
CCDSiCCDS5017.1. [O60942-1]
CCDS69153.1. [O60942-2]
PIRiJC5936.
JC5937.
RefSeqiNP_001273355.1. NM_001286426.1. [O60942-2]
NP_001273357.1. NM_001286428.1.
NP_003791.3. NM_003800.4. [O60942-1]
UniGeneiHs.567378.
Hs.627135.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C46X-ray1.60A/B/C/D1-219[»]
3S24X-ray3.01A/B/C/D/E/F/G229-567[»]
ProteinModelPortaliO60942.
SMRiO60942.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114270. 11 interactors.
DIPiDIP-61014N.
IntActiO60942. 4 interactors.
STRINGi9606.ENSP00000358497.

Chemistry databases

DrugBankiDB02325. Isopropyl Alcohol.

PTM databases

DEPODiO60942.
iPTMnetiO60942.
PhosphoSitePlusiO60942.

Polymorphism and mutation databases

BioMutaiRNGTT.

Proteomic databases

EPDiO60942.
MaxQBiO60942.
PaxDbiO60942.
PeptideAtlasiO60942.
PRIDEiO60942.

Protocols and materials databases

DNASUi8732.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000369475; ENSP00000358487; ENSG00000111880. [O60942-2]
ENST00000369485; ENSP00000358497; ENSG00000111880. [O60942-1]
ENST00000538899; ENSP00000442609; ENSG00000111880. [O60942-3]
GeneIDi8732.
KEGGihsa:8732.
UCSCiuc003pmr.4. human. [O60942-1]

Organism-specific databases

CTDi8732.
DisGeNETi8732.
GeneCardsiRNGTT.
HGNCiHGNC:10073. RNGTT.
HPAiHPA003750.
MIMi603512. gene.
neXtProtiNX_O60942.
OpenTargetsiENSG00000111880.
PharmGKBiPA34446.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2386. Eukaryota.
COG5226. LUCA.
GeneTreeiENSGT00530000063473.
HOVERGENiHBG006332.
InParanoidiO60942.
KOiK13917.
OMAiRFNERSP.
OrthoDBiEOG091G063D.
PhylomeDBiO60942.
TreeFamiTF314914.

Enzyme and pathway databases

BioCyciMetaCyc:HS03479-MONOMER.
ZFISH:HS03479-MONOMER.
BRENDAi2.7.7.50. 2681.
ReactomeiR-HSA-167160. RNA Pol II CTD phosphorylation and interaction with CE.
R-HSA-72086. mRNA Capping.
R-HSA-77075. RNA Pol II CTD phosphorylation and interaction with CE.

Miscellaneous databases

ChiTaRSiRNGTT. human.
EvolutionaryTraceiO60942.
GeneWikiiRNGTT.
GenomeRNAii8732.
PROiO60942.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111880.
CleanExiHS_RNGTT.
GenevisibleiO60942. HS.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR000340. Dual-sp_phosphatase_cat-dom.
IPR017074. mRNA_cap_enz_bifunc.
IPR001339. mRNA_cap_enzyme.
IPR013846. mRNA_cap_enzyme_C.
IPR012340. NA-bd_OB-fold.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR016130. Tyr_Pase_AS.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00782. DSPc. 1 hit.
PF03919. mRNA_cap_C. 1 hit.
PF01331. mRNA_cap_enzyme. 1 hit.
[Graphical view]
PIRSFiPIRSF036958. mRNA_capping_HCE. 1 hit.
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMCE1_HUMAN
AccessioniPrimary (citable) accession number: O60942
Secondary accession number(s): E1P513
, E1P514, O43483, O60257, O60351, Q5TCW8, Q8WUM8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 1, 1998
Last modified: November 30, 2016
This is version 165 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

Miscellaneous

Isoform 2 to isoform 4 lack mRNA 5'-guanylyltransferase activity due to disruptions of the GTase domain.

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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.