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Protein

Citrate synthase, mitochondrial

Gene

CS

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

Functioni

Miscellaneous

Citrate synthase is found in nearly all cells capable of oxidative metabolism.

Catalytic activityi

Acetyl-CoA + H2O + oxaloacetate = citrate + CoA.PROSITE-ProRule annotation

Pathwayi: tricarboxylic acid cycle

This protein is involved in step 1 of the subpathway that synthesizes isocitrate from oxaloacetate.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Citrate synthase, mitochondrial (CS)
  2. Aconitate hydratase, mitochondrial (ACO2)
This subpathway is part of the pathway tricarboxylic acid cycle, which is itself part of Carbohydrate metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes isocitrate from oxaloacetate, the pathway tricarboxylic acid cycle and in Carbohydrate metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei301PROSITE-ProRule annotation1
Active sitei347PROSITE-ProRule annotation1
Active sitei402PROSITE-ProRule annotation1

GO - Molecular functioni

  • citrate (Si)-synthase activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

  • carbohydrate metabolic process Source: UniProtKB
  • tricarboxylic acid cycle Source: Reactome

Keywordsi

Molecular functionTransferase
Biological processTricarboxylic acid cycle

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000062485-MONOMER
BRENDAi2.3.3.1 2681
ReactomeiR-HSA-1268020 Mitochondrial protein import
R-HSA-71403 Citric acid cycle (TCA cycle)
UniPathwayiUPA00223; UER00717

Names & Taxonomyi

Protein namesi
Recommended name:
Citrate synthase, mitochondrial (EC:2.3.3.1)
Alternative name(s):
Citrate (Si)-synthase
Gene namesi
Name:CS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000062485.18
HGNCiHGNC:2422 CS
MIMi118950 gene
neXtProtiNX_O75390

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi393K → R: Does not inhibit methylation. 1 Publication1
Mutagenesisi395K → R: Inhibits methylation. 1 Publication1

Organism-specific databases

DisGeNETi1431
OpenTargetsiENSG00000062485
PharmGKBiPA26928

Chemistry databases

DrugBankiDB03182 Alpha-Fluoro-Carboxymethyldethia Coenzyme a Complex
DB04272 Citric Acid
DB01992 Coenzyme A
DB03499 Malate Ion
DB04230 Nitromethyldethia Coenzyme A
DB02637 Oxaloacetate Ion
DB01969 Trifluoroacetonyl Coenzyme A

Polymorphism and mutation databases

BioMutaiCS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 27MitochondrionAdd BLAST27
ChainiPRO_000000547128 – 466Citrate synthase, mitochondrialAdd BLAST439

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57N6-succinyllysineBy similarity1
Modified residuei76N6-acetyllysine; alternateBy similarity1
Modified residuei76N6-succinyllysine; alternateBy similarity1
Modified residuei103N6-succinyllysineBy similarity1
Modified residuei193N6-succinyllysineBy similarity1
Modified residuei321N6-acetyllysine; alternateBy similarity1
Modified residuei321N6-succinyllysine; alternateBy similarity1
Modified residuei327N6-acetyllysine; alternateCombined sources1
Modified residuei327N6-succinyllysine; alternateBy similarity1
Modified residuei375N6-acetyllysine; alternateCombined sources1
Modified residuei375N6-succinyllysine; alternateBy similarity1
Modified residuei382N6-acetyllysineCombined sources1
Modified residuei393N6-acetyllysine; alternateCombined sources1
Modified residuei393N6-succinyllysine; alternateBy similarity1
Modified residuei395N6,N6,N6-trimethyllysine2 Publications1
Modified residuei450N6-succinyllysineBy similarity1
Modified residuei459N6-acetyllysine; alternateBy similarity1
Modified residuei459N6-succinyllysine; alternateBy similarity1

Post-translational modificationi

Methylated (PubMed:28391595, PubMed:28887308). Trimethylation at Lys-395 by CSKMT decreases citrate synthase activity (PubMed:28887308).2 Publications

Keywords - PTMi

Acetylation, Methylation

Proteomic databases

EPDiO75390
MaxQBiO75390
PaxDbiO75390
PeptideAtlasiO75390
PRIDEiO75390
ProteomicsDBi49963
TopDownProteomicsiO75390

PTM databases

CarbonylDBiO75390
iPTMnetiO75390
PhosphoSitePlusiO75390
SwissPalmiO75390

Expressioni

Gene expression databases

BgeeiENSG00000062485
CleanExiHS_CS
ExpressionAtlasiO75390 baseline and differential
GenevisibleiO75390 HS

Organism-specific databases

HPAiCAB075750
CAB075751
CAB075752
CAB075753
CAB075754
HPA038460
HPA038461

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi107818, 38 interactors
CORUMiO75390
IntActiO75390, 24 interactors
STRINGi9606.ENSP00000342056

Structurei

Secondary structure

1466
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi33 – 55Combined sources23
Beta strandi59 – 64Combined sources6
Helixi65 – 69Combined sources5
Turni70 – 74Combined sources5
Beta strandi76 – 79Combined sources4
Beta strandi82 – 86Combined sources5
Turni87 – 89Combined sources3
Beta strandi90 – 93Combined sources4
Helixi98 – 104Combined sources7
Helixi116 – 125Combined sources10
Helixi131 – 143Combined sources13
Helixi149 – 157Combined sources9
Helixi164 – 174Combined sources11
Helixi175 – 178Combined sources4
Helixi180 – 186Combined sources7
Helixi191 – 193Combined sources3
Helixi194 – 221Combined sources28
Helixi236 – 244Combined sources9
Helixi249 – 261Combined sources13
Helixi270 – 280Combined sources11
Helixi285 – 296Combined sources12
Helixi299 – 302Combined sources4
Helixi304 – 319Combined sources16
Helixi325 – 337Combined sources13
Helixi355 – 367Combined sources13
Helixi372 – 391Combined sources20
Beta strandi394 – 399Combined sources6
Helixi401 – 403Combined sources3
Helixi405 – 411Combined sources7
Helixi417 – 419Combined sources3
Helixi420 – 441Combined sources22
Beta strandi450 – 452Combined sources3
Helixi454 – 462Combined sources9

3D structure databases

ProteinModelPortaliO75390
SMRiO75390
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the citrate synthase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2617 Eukaryota
COG0372 LUCA
GeneTreeiENSGT00390000006813
HOGENOMiHOG000130831
HOVERGENiHBG005336
InParanoidiO75390
KOiK01647
OMAiTVGWCAQ
OrthoDBiEOG091G068F
PhylomeDBiO75390
TreeFamiTF300398

Family and domain databases

Gene3Di1.10.230.10, 1 hit
1.10.580.10, 2 hits
InterProiView protein in InterPro
IPR016142 Citrate_synth-like_lrg_a-sub
IPR016143 Citrate_synth-like_sm_a-sub
IPR002020 Citrate_synthase
IPR019810 Citrate_synthase_AS
IPR010109 Citrate_synthase_euk
IPR036969 Citrate_synthase_sf
PANTHERiPTHR11739 PTHR11739, 1 hit
PfamiView protein in Pfam
PF00285 Citrate_synt, 1 hit
PRINTSiPR00143 CITRTSNTHASE
SUPFAMiSSF48256 SSF48256, 1 hit
TIGRFAMsiTIGR01793 cit_synth_euk, 1 hit
PROSITEiView protein in PROSITE
PS00480 CITRATE_SYNTHASE, 1 hit

Sequencei

Sequence statusi: Complete.

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

O75390-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALLTAAARL LGTKNASCLV LAARHASASS TNLKDILADL IPKEQARIKT
60 70 80 90 100
FRQQHGKTVV GQITVDMMYG GMRGMKGLVY ETSVLDPDEG IRFRGFSIPE
110 120 130 140 150
CQKLLPKAKG GEEPLPEGLF WLLVTGHIPT EEQVSWLSKE WAKRAALPSH
160 170 180 190 200
VVTMLDNFPT NLHPMSQLSA AVTALNSESN FARAYAQGIS RTKYWELIYE
210 220 230 240 250
DSMDLIAKLP CVAAKIYRNL YREGSGIGAI DSNLDWSHNF TNMLGYTDHQ
260 270 280 290 300
FTELTRLYLT IHSDHEGGNV SAHTSHLVGS ALSDPYLSFA AAMNGLAGPL
310 320 330 340 350
HGLANQEVLV WLTQLQKEVG KDVSDEKLRD YIWNTLNSGR VVPGYGHAVL
360 370 380 390 400
RKTDPRYTCQ REFALKHLPN DPMFKLVAQL YKIVPNVLLE QGKAKNPWPN
410 420 430 440 450
VDAHSGVLLQ YYGMTEMNYY TVLFGVSRAL GVLAQLIWSR ALGFPLERPK
460
SMSTEGLMKF VDSKSG
Length:466
Mass (Da):51,712
Last modified:January 4, 2005 - v2
Checksum:i459CB29C0BA06997
GO

Sequence cautioni

The sequence CAE45911 differs from that shown. Intron retention.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55H → R in CAE45911 (PubMed:17974005).Curated1
Sequence conflicti127H → C in AAC25560 (PubMed:9809442).Curated1
Sequence conflicti183R → Q in AAC25560 (PubMed:9809442).Curated1
Sequence conflicti187Q → R in AAC25560 (PubMed:9809442).Curated1
Sequence conflicti203M → V in AAC25560 (PubMed:9809442).Curated1
Sequence conflicti222R → W in AAC25560 (PubMed:9809442).Curated1
Sequence conflicti255T → M in AAC25560 (PubMed:9809442).Curated1
Sequence conflicti282L → F in AAQ13428 (PubMed:12549038).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF047042 mRNA Translation: AAC25560.1
AF053631 mRNA Translation: AAQ13428.1
AK074956 mRNA Translation: BAC11314.1
BX640838 mRNA Translation: CAE45911.1 Sequence problems.
BC000105 mRNA Translation: AAH00105.3
BC010106 mRNA Translation: AAH10106.1
BC072016 mRNA Translation: AAH72016.1
BT007414 mRNA Translation: AAP36082.1
CCDSiCCDS8913.1
RefSeqiNP_004068.2, NM_004077.2
UniGeneiHs.743252

Genome annotation databases

EnsembliENST00000351328; ENSP00000342056; ENSG00000062485
GeneIDi1431
KEGGihsa:1431
UCSCiuc001skr.2 human

Similar proteinsi

Entry informationi

Entry nameiCISY_HUMAN
AccessioniPrimary (citable) accession number: O75390
Secondary accession number(s): Q71UT9
, Q7KZH0, Q96FZ8, Q9BWN8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 4, 2005
Last modified: July 18, 2018
This is version 171 of the entry and version 2 of the sequence. See 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 12
    Human chromosome 12: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

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