ACACA

Protein identityUniProt · HPA

UniProt accession

Q13085

Gene

ACACA

Ensembl

ENSG00000278540

Chromosome

17

Canonical length

2346 aa

Protein class

Disease related genes, Enzymes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoli fibrillar center,Actin filaments,Cytosol

Quaternary structure

Homotetramer

OverviewNCBI Gene

Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5' sequence and encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

2346 residues, UniProt reviewed canonical sequence.

>Q13085|ACACA
     1  MDEPSPLAQP LELNQHSRFI IGSVSEDNSE DEISNLVKLD LLEEKEGSLS PASVGSDTLS
    61  DLGISSLQDG LALHIRSSMS GLHLVKQGRD RKKIDSQRDF TVASPAEFVT RFGGNKVIEK
   121  VLIANNGIAA VKCMRSIRRW SYEMFRNERA IRFVVMVTPE DLKANAEYIK MADHYVPVPG
   181  GPNNNNYANV ELILDIAKRI PVQAVWAGWG HASENPKLPE LLLKNGIAFM GPPSQAMWAL
   241  GDKIASSIVA QTAGIPTLPW SGSGLRVDWQ ENDFSKRILN VPQELYEKGY VKDVDDGLQA
   301  AEEVGYPVMI KASEGGGGKG IRKVNNADDF PNLFRQVQAE VPGSPIFVMR LAKQSRHLEV
   361  QILADQYGNA ISLFGRDCSV QRRHQKIIEE APATIATPAV FEHMEQCAVK LAKMVGYVSA
   421  GTVEYLYSQD GSFYFLELNP RLQVEHPCTE MVADVNLPAA QLQIAMGIPL YRIKDIRMMY
   481  GVSPWGDSPI DFEDSAHVPC PRGHVIAARI TSENPDEGFK PSSGTVQELN FRSNKNVWGY
   541  FSVAAAGGLH EFADSQFGHC FSWGENREEA ISNMVVALKE LSIRGDFRTT VEYLIKLLET
   601  ESFQMNRIDT GWLDRLIAEK VQAERPDTML GVVCGALHVA DVSLRNSVSN FLHSLERGQV
   661  LPAHTLLNTV DVELIYEGVK YVLKVTRQSP NSYVVIMNGS CVEVDVHRLS DGGLLLSYDG
   721  SSYTTYMKEE VDRYRITIGN KTCVFEKEND PSVMRSPSAG KLIQYIVEDG GHVFAGQCYA
   781  EIEVMKMVMT LTAVESGCIH YVKRPGAALD PGCVLAKMQL DNPSKVQQAE LHTGSLPRIQ
   841  STALRGEKLH RVFHYVLDNL VNVMNGYCLP DPFFSSKVKD WVERLMKTLR DPSLPLLELQ
   901  DIMTSVSGRI PPNVEKSIKK EMAQYASNIT SVLCQFPSQQ IANILDSHAA TLNRKSEREV
   961  FFMNTQSIVQ LVQRYRSGIR GHMKAVVMDL LRQYLRVETQ FQNGHYDKCV FALREENKSD
  1021  MNTVLNYIFS HAQVTKKNLL VTMLIDQLCG RDPTLTDELL NILTELTQLS KTTNAKVALR
  1081  ARQVLIASHL PSYELRHNQV ESIFLSAIDM YGHQFCIENL QKLILSETSI FDVLPNFFYH
  1141  SNQVVRMAAL EVYVRRAYIA YELNSVQHRQ LKDNTCVVEF QFMLPTSHPN RGNIPTLNRM
  1201  SFSSNLNHYG MTHVASVSDV LLDNSFTPPC QRMGGMVSFR TFEDFVRIFD EVMGCFSDSP
  1261  PQSPTFPEAG HTSLYDEDKV PRDEPIHILN VAIKTDCDIE DDRLAAMFRE FTQQNKATLV
  1321  DHGIRRLTFL VAQKDFRKQV NYEVDRRFHR EFPKFFTFRA RDKFEEDRIY RHLEPALAFQ
  1381  LELNRMRNFD LTAIPCANHK MHLYLGAAKV EVGTEVTDYR FFVRAIIRHS DLVTKEASFE
  1441  YLQNEGERLL LEAMDELEVA FNNTNVRTDC NHIFLNFVPT VIMDPSKIEE SVRSMVMRYG
  1501  SRLWKLRVLQ AELKINIRLT PTGKAIPIRL FLTNESGYYL DISLYKEVTD SRTAQIMFQA
  1561  YGDKQGPLHG MLINTPYVTK DLLQSKRFQA QSLGTTYIYD IPEMFRQSLI KLWESMSTQA
  1621  FLPSPPLPSD MLTYTELVLD DQGQLVHMNR LPGGNEIGMV AWKMTFKSPE YPEGRDIIVI
  1681  GNDITYRIGS FGPQEDLLFL RASELARAEG IPRIYVSANS GARIGLAEEI RHMFHVAWVD
  1741  PEDPYKGYRY LYLTPQDYKR VSALNSVHCE HVEDEGESRY KITDIIGKEE GIGPENLRGS
  1801  GMIAGESSLA YNEIITISLV TCRAIGIGAY LVRLGQRTIQ VENSHLILTG AGALNKVLGR
  1861  EVYTSNNQLG GIQIMHNNGV THCTVCDDFE GVFTVLHWLS YMPKSVHSSV PLLNSKDPID
  1921  RIIEFVPTKT PYDPRWMLAG RPHPTQKGQW LSGFFDYGSF SEIMQPWAQT VVVGRARLGG
  1981  IPVGVVAVET RTVELSIPAD PANLDSEAKI IQQAGQVWFP DSAFKTYQAI KDFNREGLPL
  2041  MVFANWRGFS GGMKDMYDQV LKFGAYIVDG LRECCQPVLV YIPPQAELRG GSWVVIDSSI
  2101  NPRHMEMYAD RESRGSVLEP EGTVEIKFRR KDLVKTMRRV DPVYIHLAER LGTPELSTAE
  2161  RKELENKLKE REEFLIPIYH QVAVQFADLH DTPGRMQEKG VISDILDWKT SRTFFYWRLR
  2221  RLLLEDLVKK KIHNANPELT DGQIQAMLRR WFVEVEGTVK AYVWDNNKDL AEWLEKQLTE
  2281  EDGVHSVIEE NIKCISRDYV LKQIRSLVQA NPEVAMDSII HMTQHISPTQ RAEVIRILST
  2341  MDSPST

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACACA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

28 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACACA.

Disease | AllUniProt

Conditions ACACA is implicated in, by any mechanism.

• Acetyl-CoA carboxylase-alpha deficiency (ACACAD) MIM:613933

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 462 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Acetyl-CoA: carboxylase deficiency

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.22

gnomAD pLI

1

gnomAD missense Z

7.24

DepMap mean gene effect

-0.38

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• acetyl-CoA metabolic process
• cellular response to prostaglandin E stimulus
• fatty acid biosynthetic process
• fatty-acyl-CoA biosynthetic process
• lipid homeostasis
• malonyl-CoA biosynthetic process
• protein homotetramerization
• tissue homeostasis

Molecular functions

• acetyl-CoA carboxylase activity
• ATP binding
• identical protein binding
• metal ion binding

Cellular components

• actin cytoskeleton
• cytosol
• fibrillar center
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Biotin/lipoyl attachment
• Biotin-binding site
• Carbamoyl phosphate synthase, ATP-binding domain
• Biotin carboxylase-like, N-terminal domain
• Biotin carboxylase, C-terminal
• Single hybrid motif
• Rudiment single hybrid motif
• ATP-grasp fold
• Acetyl-coenzyme A carboxyltransferase, N-terminal
• Acetyl-coenzyme A carboxyltransferase, C-terminal
• Biotin carboxylation domain
• Acetyl-CoA carboxylase, central domain
• ATP-grasp fold, subdomain 1
• Pre-ATP-grasp domain superfamily
• ClpP/crotonase-like domain superfamily
• Acetyl-coenzyme A carboxylase carboxyl transferase subunit beta
• Acetyl-CoA carboxylase, BT domain
• Acetyl-CoA carboxylase
• Biotin carboxylase, N-terminal domain
• Biotin-requiring enzyme
• Carboxyl transferase domain
• Biotin carboxylase C-terminal domain
• Carbamoyl-phosphate synthase L chain, ATP binding domain
• Acetyl-CoA carboxylase, central region
• Acetyl-CoA carboxylase, BT domain

KeywordsUniProt

• Acetylation
• Allosteric enzyme
• Alternative promoter usage
• ATP-binding
• Biotin
• Cytoplasm
• Fatty acid biosynthesis
• Fatty acid metabolism
• Ligase
• Lipid biosynthesis
• Lipid metabolism
• Magnesium
• Manganese
• Metal-binding
• Multifunctional enzyme
• Nucleotide-binding
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of ACACA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MID1IP1
• AKR1B10
• BRCA1
• MYC
• SIRT1