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P11497 (ACACA_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Acetyl-CoA carboxylase 1

Short name=ACC1
EC=6.4.1.2
Alternative name(s):
ACC-alpha

Including the following 1 domains:

  1. Biotin carboxylase
    EC=6.3.4.14
Gene names
Name:Acaca
Synonyms:Acac
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length2345 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the rate-limiting reaction in the biogenesis of long-chain fatty acids. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.

Catalytic activity

ATP + acetyl-CoA + HCO3- = ADP + phosphate + malonyl-CoA.

ATP + biotin-[carboxyl-carrier-protein] + CO2 = ADP + phosphate + carboxy-biotin-[carboxyl-carrier-protein].

Cofactor

Biotin.

Binds 2 manganese ions per subunit By similarity.

Enzyme regulation

Activity is increased by oligomerization. Citrate and MID1IP1 promote oligomerization By similarity. Activity is increased by phosphorylation.

Pathway

Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA: step 1/1.

Subunit structure

Monomer, homodimer, and homotetramer. Can form filamentous polymers. Interacts in its inactive phosphorylated form with the BRCT domains of BRCA1 which prevents ACACA dephosphorylation and inhibits lipid synthesis. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity By similarity.

Subcellular location

Cytoplasm.

Post-translational modification

The N-terminus is blocked.

Phosphorylation on Ser-1262 is required for interaction with BRCA1 By similarity.

Phosphorylation at Ser-79 by AMPK inactivates enzyme activity. Phosphorylated in vitro at Ser-1200 and Ser-1215 by AMPK; the relevance of phosphorylation of these sites in vivo is however unclear. Ref.5 Ref.6 Ref.9 Ref.10

Sequence similarities

Contains 1 ATP-grasp domain.

Contains 1 biotin carboxylation domain.

Contains 1 biotinyl-binding domain.

Contains 1 carboxyltransferase domain.

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Biotin
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionLigase
   PTMAcetylation
Phosphoprotein
   Technical termAllosteric enzyme
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processacetyl-CoA metabolic process

Inferred from direct assay PubMed 12949377. Source: RGD

fatty acid biosynthetic process

Inferred from direct assay PubMed 11735100. Source: RGD

malonyl-CoA biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

protein homotetramerization

Inferred from sequence or structural similarity. Source: UniProtKB

response to drug

Inferred from expression pattern PubMed 16979414. Source: RGD

response to organic cyclic compound

Inferred from mutant phenotype PubMed 12842871. Source: RGD

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay PubMed 12949377. Source: RGD

acetyl-CoA carboxylase activity

Inferred from direct assay PubMed 11735100PubMed 12949377. Source: RGD

biotin binding

Inferred from mutant phenotype PubMed 12949377. Source: RGD

biotin carboxylase activity

Inferred from electronic annotation. Source: UniProtKB-EC

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P11497-1)

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.
Isoform 2 (identifier: P11497-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1189-1196: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 23452345Acetyl-CoA carboxylase 1
PRO_0000146765

Regions

Domain116 – 617502Biotin carboxylation
Domain274 – 465192ATP-grasp
Domain751 – 81767Biotinyl-binding
Domain1697 – 2193497Carboxyltransferase
Nucleotide binding314 – 3196ATP Potential

Sites

Active site4401 By similarity
Metal binding4231Manganese 1 By similarity
Metal binding4361Manganese 1 By similarity
Metal binding4361Manganese 2 By similarity
Metal binding4381Manganese 2 By similarity
Binding site18221Coenzyme A By similarity
Binding site21261Coenzyme A By similarity
Binding site21281Coenzyme A By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue51Phosphoserine By similarity
Modified residue231Phosphoserine By similarity
Modified residue251Phosphoserine By similarity
Modified residue291Phosphoserine By similarity
Modified residue521Phosphoserine By similarity
Modified residue771Phosphoserine
Modified residue791Phosphoserine; by AMPK Ref.9
Modified residue7851N6-biotinyllysine
Modified residue12001Phosphoserine; by AMPK; in vitro Ref.6 Ref.9
Modified residue12151Phosphoserine; by AMPK; in vitro Ref.9
Modified residue12621Phosphoserine By similarity
Modified residue13331N6-acetyllysine By similarity

Natural variations

Alternative sequence1189 – 11968Missing in isoform 2.
VSP_011753

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1989. Version 1.
Checksum: 78E9CF9ADE1E8771

FASTA2,345265,194
        10         20         30         40         50         60 
MDEPSPLAKT LELNQHSRFI IGSVSEDNSE DEISNLVKLD LEEKEGSLSP ASVSSDTLSD 

        70         80         90        100        110        120 
LGISALQDGL AFHMRSSMSG LHLVKQGRDR KKIDSQRDFT VASPAEFVTR FGGNKVIEKV 

       130        140        150        160        170        180 
LIANNGIAAV KCMRSIRRWS YEMFRNERAI RFVVMVTPED LKANAEYIKM ADHYVPVPGG 

       190        200        210        220        230        240 
ANNNNYANVE LILDIAKRIP VQAVWAGWGH ASENPKLPEL LLKNGIAFMG PPSQAMWALG 

       250        260        270        280        290        300 
DKIASSIVAQ TAGIPTLPWS GSGLRVDWQE NDFSKRILNV PQDLYEKGYV KDVDDGLKAA 

       310        320        330        340        350        360 
EEVGYPVMIK ASEGGGGKGI RKVNNADDFP NLFRQVQAEV PGSPIFVMRL AKQSRHLEVQ 

       370        380        390        400        410        420 
ILADQYGNAI SLFGRDCSVQ RRHQKIIEEA PAAIATPAVF EHMEQCAVKL AKMVGYVSAG 

       430        440        450        460        470        480 
TVEYLYSQDG SFYFLELNPR LQVEHPCTEM VADVNLPAAQ LQIAMGIPLF RIKDIRMMYG 

       490        500        510        520        530        540 
VSPWGDAPID FENSAHVPCP RGHVIAARIT SENPDEGFKP SSGTVQELNF RSNKNVWGYF 

       550        560        570        580        590        600 
SVAAAGGLHE FADSQFGHCF SWGENREEAI SNMVVALKEL SIRGDFRTTV EYLIKLLETE 

       610        620        630        640        650        660 
SFQLNRIDTG WLDRLIAEKV QAERPDTMLG VVCGALHVAD VNLRNSISNF LHSLERGQVL 

       670        680        690        700        710        720 
PAHTLLNTVD VELIYEGIKY VLKVTRQSPN SYVVIMNGSC VEVDVHRLSD GGLLLSYDGS 

       730        740        750        760        770        780 
SYTTYMKEEV DRYRITIGNK TCVFEKENDP SVMRSPSAGK LIQYIVEDGG HVFAGQCYAE 

       790        800        810        820        830        840 
IEVMKMVMTL TAVESGCIHY VKRPGAALDP GCVIAKMQLD NPSKVQQAEL HTGSLPQIQS 

       850        860        870        880        890        900 
TALRGEKLHR VFHYVLDNLV NVMNGYCLPD PFFSSKVKDW VERLMKTLRD PSLPLLELQD 

       910        920        930        940        950        960 
IMTSVSGRIP LNVEKSIKKE MAQYASNITS VLCQFPSQQI ANILDSHAAT LNRKSEREVF 

       970        980        990       1000       1010       1020 
FMNTQSIVQL VQRYRSGIRG HMKAVVMDLL RQYLRVETQF QNGHYDKCVF ALREENKSDM 

      1030       1040       1050       1060       1070       1080 
NTVLNYIFSH AQVTKKNLLV TMLIDQLCGR DPTLTDELLN ILTELTQLSK TTNAKVALRA 

      1090       1100       1110       1120       1130       1140 
RQVLIASHLP SYDVRHNQVE SIFLSAIDMY GHQFCIENLQ KLILSETSIF DVLPNFFYHS 

      1150       1160       1170       1180       1190       1200 
NQVVRMAALE VYVRRAYIAY ELNSVQHRQL KDNTCVVEFQ FMLPTSHPNR GNIPTLNRMS 

      1210       1220       1230       1240       1250       1260 
FASNLNHYGM THVASVSDVL LDNAFTPPCQ RMGGMVSFRT FEDFVRIFDE VMGCFCDSPP 

      1270       1280       1290       1300       1310       1320 
QSPTFPESGH TSLYDEDKVP RDEPIHILNV AIKTDGDIED DRLAAMFREF TQQNKATLVE 

      1330       1340       1350       1360       1370       1380 
HGIRRLTFLV AQKDFRKQVN CEVDQRFHRE FPKFFTFRAR DKFEEDRIYR HLEPALAFQL 

      1390       1400       1410       1420       1430       1440 
ELNRMRNFDL TAIPCANHKM HLYLGAAKVE VGTEVTDYRF FVRAIIRHSD LVTKEASFEY 

      1450       1460       1470       1480       1490       1500 
LQNEGERLLL EAMDELEVAF NNTNVRTDCN HIFLNFVPTV IMDPSKIEES VRSMVMRYGS 

      1510       1520       1530       1540       1550       1560 
RLWKLRVLQA ELKINIRLTT TGKAIPIRLF LTNESGYYLD ISLYKEVTDS RTAQIMFQAY 

      1570       1580       1590       1600       1610       1620 
GDKQGPLHGM LINTPYVTKD LLQSKRFQAQ SLGTTYIYDI PEMFRQSLIK LWESMSTQAF 

      1630       1640       1650       1660       1670       1680 
LPSPPLPSDI LTYTELVLDD QGQLVHMNRL PGGNEIGMVA WKMSLKSPEY PDGRDVIVIG 

      1690       1700       1710       1720       1730       1740 
NDITYRIGSF GPQEDLLFLR ASELARAEGI PRIYVAANSG ARIGLAEEIR HMFHVAWVDS 

      1750       1760       1770       1780       1790       1800 
EDPYKGYKYL YLTPQDYKRV SALNSVHCEH VEDEGESRYK ITDIIGKEEG LGAENLRGSG 

      1810       1820       1830       1840       1850       1860 
MIAGESSLAY DEIITISLVT CRAIGIGAYL VRLGQRTIQV ENSHLILTGA GALNKVLGRE 

      1870       1880       1890       1900       1910       1920 
VYTSNNQLGG IQIMHNNGVT HCTVCDDFEG VFTVLHWLSY MPKNVHSSVP LLNSKDPIDR 

      1930       1940       1950       1960       1970       1980 
IIEFVPTKAP YDPRWMLAGR PHPTQKGQWL SGFFDYGSFS EIMQPWAQTV VVGRARLGGI 

      1990       2000       2010       2020       2030       2040 
PVGVVAVETR TVELSVPADP ANLDSEAKII QQAGQVWFPD SAFKTYQAIK DFNREGLPLM 

      2050       2060       2070       2080       2090       2100 
VFANWRGFSG GMKDMYDQVL KFGAYIVDGL RECSQPVMVY IPPQAELRGG SWVVIDPTIN 

      2110       2120       2130       2140       2150       2160 
PRHMEMYADR ESRGSVLEPE GTVEIKFRKK DLVKTMRRVD PVYIRLAERL GTPELSPTER 

      2170       2180       2190       2200       2210       2220 
KELESKLKER EEFLIPIYHQ VAVQFADLHD TPGRMQEKGV INDILDWKTS RTFFYWRLRR 

      2230       2240       2250       2260       2270       2280 
LLLEDLVKKK IHSANPELTD GQIQAMLRRW FVEVEGTVKA YVWDNNKDLV EWLEKQLTEE 

      2290       2300       2310       2320       2330       2340 
DGVRSVIEEN IKYISRDYVL KQIRSLVQAN PEVAMDSIVH MTQHISPTQR AEVVRILSTM 


DSPST 

« Hide

Isoform 2 [UniParc].

Checksum: 9590EEFFE39D73CD
Show »

FASTA2,337264,328

References

« Hide 'large scale' references
[1]"Structure of the coding sequence and primary amino acid sequence of acetyl-coenzyme A carboxylase."
Lopez-Casillas F., Bai D.-H., Luo X., Kong I.-S., Hermodson M.A., Kim K.-H.
Proc. Natl. Acad. Sci. U.S.A. 85:5784-5788(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Structural features of the acetyl-CoA carboxylase gene: mechanisms for the generation of mRNAs with 5' end heterogeneity."
Luo X.N., Park K., Lopez-Casillas F., Kim K.-H.
Proc. Natl. Acad. Sci. U.S.A. 86:4042-4046(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Fine-mapping and comprehensive transcript analysis reveals nonsynonymous variants within a novel 1.17 Mb blood pressure QTL region on rat chromosome 10."
Saad Y., Garrett M.R., Manickavasagam E., Yerga-Woolwine S., Farms P., Radecki T., Joe B.
Genomics 89:343-353(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: Dahl salt-sensitive and Lewis.
[4]"Heterogeneity at the 5' end of rat acetyl-coenzyme A carboxylase mRNA. Lipogenic conditions enhance synthesis of a unique mRNA in liver."
Lopez-Casillas F., Kim K.-H.
J. Biol. Chem. 264:7176-7184(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-33.
[5]"Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase."
Munday M.R., Campbell D.G., Carling D., Hardie D.G.
Eur. J. Biochem. 175:331-338(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 76-85 AND 1198-1201, PHOSPHORYLATION AT SER-77; SER-79 AND SER-1200.
[6]"Acetyl-CoA carboxylase mRNA species with or without inhibitory coding sequence for Ser-1200 phosphorylation."
Kong I.-S., Lopez-Casillas F., Kim K.-H.
J. Biol. Chem. 265:13695-13701(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1167-1200 (ISOFORMS 1 AND 2), PHOSPHORYLATION AT SER-1200.
[7]"Unique structural features and differential phosphorylation of the 280-kDa component (isozyme) of rat liver acetyl-CoA carboxylase."
Winz R., Hess D., Aebersold R., Brownsey R.W.
J. Biol. Chem. 269:14438-14445(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY.
Strain: Wistar.
Tissue: Liver.
[8]"Analysis of the biotin-binding site on acetyl-CoA carboxylase from rat."
Bai D.-H., Moon T.-W., Lopez-Casillas F., Andrews P.C., Kim K.-H.
Eur. J. Biochem. 182:239-245(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOTIN-BINDING SITE.
[9]"Diurnal rhythm of phosphorylation of rat liver acetyl-CoA carboxylase by the AMP-activated protein kinase, demonstrated using freeze-clamping. Effects of high fat diets."
Davies S.P., Carling D., Munday M.R., Hardie D.G.
Eur. J. Biochem. 203:615-623(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-79; SER-1200 AND SER-1215.
[10]"Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A."
Winder W.W., Wilson H.A., Hardie D.G., Rasmussen B.B., Hutber C.A., Call G.B., Clayton R.D., Conley L.M., Yoon S., Zhou B.
J. Appl. Physiol. 82:219-225(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY AMPK.
[11]"Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS."
Moser K., White F.M.
J. Proteome Res. 5:98-104(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J03808 mRNA. Translation: AAA40653.1.
M26731 Genomic DNA. Translation: AAA40652.1.
EF121986 mRNA. Translation: ABL63425.1.
EF121987 mRNA. Translation: ABL63426.1.
M26195 mRNA. Translation: AAA40654.1.
M26196 mRNA. Translation: AAA40655.1.
M26197 mRNA. Translation: AAA40656.1.
M55315 mRNA. No translation available.
PIRA35578.
RefSeqNP_071529.1. NM_022193.1.
UniGeneRn.163753.
Rn.217177.
Rn.44372.

3D structure databases

ProteinModelPortalP11497.
SMRP11497. Positions 96-615, 741-833, 1791-2118.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248868. 1 interaction.
STRING10116.ENSRNOP00000050703.

Chemistry

BindingDBP11497.
ChEMBLCHEMBL2397.

PTM databases

PhosphoSiteP11497.

Proteomic databases

PaxDbP11497.
PRIDEP11497.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID60581.
KEGGrno:60581.

Organism-specific databases

CTD31.
RGD621248. Acaca.

Phylogenomic databases

eggNOGCOG0511.
HOGENOMHOG000214115.
HOVERGENHBG005371.
InParanoidP11497.
KOK11262.

Enzyme and pathway databases

BRENDA6.4.1.2. 5301.
UniPathwayUPA00655; UER00711.

Gene expression databases

GenevestigatorP11497.

Family and domain databases

Gene3D3.30.1490.20. 1 hit.
3.30.470.20. 1 hit.
3.40.50.20. 1 hit.
InterProIPR013537. AcCoA_COase_cen.
IPR011761. ATP-grasp.
IPR013815. ATP_grasp_subdomain_1.
IPR013816. ATP_grasp_subdomain_2.
IPR001882. Biotin_BS.
IPR011764. Biotin_carboxylation_dom.
IPR005482. Biotin_COase_C.
IPR000089. Biotin_lipoyl.
IPR005481. CarbamoylP_synth_lsu_N.
IPR000022. Carboxyl_trans.
IPR005479. CbamoylP_synth_lsu-like_ATP-bd.
IPR011763. COA_CT_C.
IPR011762. COA_CT_N.
IPR016185. PreATP-grasp_dom.
IPR011054. Rudment_hybrid_motif.
IPR011053. Single_hybrid_motif.
[Graphical view]
PfamPF08326. ACC_central. 1 hit.
PF02785. Biotin_carb_C. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF01039. Carboxyl_trans. 1 hit.
PF00289. CPSase_L_chain. 1 hit.
PF02786. CPSase_L_D2. 1 hit.
[Graphical view]
SMARTSM00878. Biotin_carb_C. 1 hit.
[Graphical view]
SUPFAMSSF51230. SSF51230. 1 hit.
SSF51246. SSF51246. 1 hit.
SSF52440. SSF52440. 1 hit.
PROSITEPS50975. ATP_GRASP. 1 hit.
PS50979. BC. 1 hit.
PS00188. BIOTIN. 1 hit.
PS50968. BIOTINYL_LIPOYL. 1 hit.
PS50989. COA_CT_CTER. 1 hit.
PS50980. COA_CT_NTER. 1 hit.
PS00866. CPSASE_1. 1 hit.
PS00867. CPSASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio612298.
PROP11497.

Entry information

Entry nameACACA_RAT
AccessionPrimary (citable) accession number: P11497
Secondary accession number(s): A1EC79, P97902
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: March 19, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways