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Protein

Acetyl-CoA carboxylase 2

Gene

ACACB

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

Functioni

Catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in inhibition of fatty acid and glucose oxidation and enhancement of fat storage (By similarity). May play a role in regulation of mitochondrial fatty acid oxidation through malonyl-CoA-dependent inhibition of carnitine palmitoyltransferase 1 (By similarity).By similarity1 Publication

Catalytic activityi

ATP + acetyl-CoA + HCO3- = ADP + phosphate + malonyl-CoA.2 Publications
ATP + biotin-[carboxyl-carrier-protein] + HCO3- = ADP + phosphate + carboxy-biotin-[carboxyl-carrier-protein].By similarity

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Activity is increased by oligomerization. Activated by citrate. Citrate and MID1IP1 promote oligomerization. Inhibited by malonyl-CoA.2 Publications

Kineticsi

  1. KM=120 µM for ATP1 Publication
  2. KM=110 µM for ATP (isoform 2)1 Publication
  3. KM=58 µM for acetyl-CoA1 Publication
  4. KM=94 µM for acetyl-CoA (isoform 3)1 Publication
  5. KM=6.5 mM for NaHCO3 (isoform 3)1 Publication
  6. KM=3.0 mM for NaHCO31 Publication

    Pathway:imalonyl-CoA biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes malonyl-CoA from acetyl-CoA.
    Proteins known to be involved in this subpathway in this organism are:
    1. Acetyl-CoA carboxylase 1 (ACACA), Acetyl-CoA carboxylase 2 (ACACB)
    This subpathway is part of the pathway malonyl-CoA biosynthesis, which is itself part of Lipid metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes malonyl-CoA from acetyl-CoA, the pathway malonyl-CoA biosynthesis and in Lipid metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi567 – 5671Manganese 1By similarity
    Metal bindingi580 – 5801Manganese 1By similarity
    Metal bindingi580 – 5801Manganese 2By similarity
    Metal bindingi582 – 5821Manganese 2By similarity
    Active sitei584 – 5841By similarity
    Binding sitei1934 – 19341Coenzyme ABy similarity
    Binding sitei2238 – 22381Coenzyme ABy similarity
    Binding sitei2240 – 22401Coenzyme ABy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi458 – 4636ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism

    Keywords - Ligandi

    ATP-binding, Biotin, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS01211-MONOMER.
    BRENDAi6.3.4.14. 2681.
    6.4.1.2. 2681.
    ReactomeiREACT_11082. Import of palmitoyl-CoA into the mitochondrial matrix.
    REACT_11153. Biotin transport and metabolism.
    REACT_147904. Activation of gene expression by SREBF (SREBP).
    REACT_169312. Defective HLCS causes multiple carboxylase deficiency.
    REACT_2122. ChREBP activates metabolic gene expression.
    SABIO-RKO00763.
    UniPathwayiUPA00655; UER00711.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Acetyl-CoA carboxylase 2 (EC:6.4.1.22 Publications)
    Alternative name(s):
    ACC-beta
    Including the following 1 domains:
    Biotin carboxylase (EC:6.3.4.14)
    Gene namesi
    Name:ACACB
    Synonyms:ACC2, ACCB
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:85. ACACB.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: Reactome
    • endomembrane system Source: UniProtKB-SubCell
    • mitochondrial outer membrane Source: Reactome
    • mitochondrion Source: UniProtKB
    • nucleus Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Membrane, Mitochondrion, Nucleus

    Pathology & Biotechi

    Biotechnological usei

    Inhibition of ACACB may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme a potential pharmaceutical target for treatment of obesity and type 2 diabetes.Curated

    Organism-specific databases

    PharmGKBiPA24422.

    Chemistry

    DrugBankiDB00173. Adenine.
    DB00121. Biotin.

    Polymorphism and mutation databases

    BioMutaiACACB.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini? – 2458Acetyl-CoA carboxylase 2CuratedPRO_0000146767
    Transit peptidei1 – ?MitochondrionBy similarity

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei35 – 351Phosphoserine1 Publication
    Modified residuei70 – 701Phosphothreonine1 Publication
    Modified residuei91 – 911Phosphoserine1 Publication
    Modified residuei95 – 951Phosphoserine1 Publication
    Modified residuei200 – 2001Phosphoserine1 Publication
    Modified residuei222 – 2221Phosphoserine; by AMPK1 Publication
    Modified residuei469 – 4691Phosphoserine1 Publication
    Modified residuei929 – 9291N6-biotinyllysinePROSITE-ProRule annotationBy similarity
    Modified residuei1342 – 13421Phosphothreonine1 Publication

    Post-translational modificationi

    Phosphorylated by AMPK, leading to inactivation of the enzyme. Required for the maintenance of skeletal muscle lipid and glucose homeostasis (By similarity).By similarity1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO00763.
    PaxDbiO00763.
    PRIDEiO00763.

    PTM databases

    PhosphoSiteiO00763.

    Expressioni

    Tissue specificityi

    Widely expressed with highest levels in heart, skeletal muscle, liver, adipose tissue, mammary gland, adrenal gland and colon (PubMed:9099716). Isoform 3 is expressed in skeletal muscle, adipose tissue and liver (at protein level) (PubMed:19190759). Isoform 3 is detected at high levels in adipose tissue with lower levels in heart, liver, skeletal muscle and testis (PubMed:19190759).2 Publications

    Gene expression databases

    BgeeiO00763.
    CleanExiHS_ACACB.
    ExpressionAtlasiO00763. baseline and differential.
    GenevisibleiO00763. HS.

    Organism-specific databases

    HPAiHPA006554.

    Interactioni

    Subunit structurei

    Monomer, homodimer, and homotetramer. Can form filamentous polymers. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HLCSP507474EBI-2211739,EBI-3915568

    Protein-protein interaction databases

    BioGridi106550. 4 interactions.
    DIPiDIP-51617N.
    IntActiO00763. 6 interactions.
    MINTiMINT-6800190.
    STRINGi9606.ENSP00000341044.

    Structurei

    Secondary structure

    1
    2458
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi247 – 2537Combined sources
    Beta strandi262 – 2654Combined sources
    Helixi269 – 28719Combined sources
    Beta strandi292 – 2998Combined sources
    Helixi301 – 3055Combined sources
    Helixi309 – 3135Combined sources
    Beta strandi314 – 3196Combined sources
    Helixi325 – 3273Combined sources
    Turni328 – 3303Combined sources
    Helixi332 – 34110Combined sources
    Beta strandi345 – 3484Combined sources
    Helixi353 – 3564Combined sources
    Helixi359 – 3668Combined sources
    Beta strandi370 – 3734Combined sources
    Helixi376 – 3794Combined sources
    Helixi385 – 39410Combined sources
    Turni403 – 4064Combined sources
    Helixi426 – 4316Combined sources
    Helixi437 – 44711Combined sources
    Beta strandi449 – 4557Combined sources
    Beta strandi464 – 4674Combined sources
    Turni470 – 4723Combined sources
    Helixi473 – 48311Combined sources
    Beta strandi489 – 4935Combined sources
    Beta strandi496 – 50712Combined sources
    Beta strandi509 – 5113Combined sources
    Beta strandi513 – 52311Combined sources
    Beta strandi524 – 5274Combined sources
    Beta strandi530 – 5356Combined sources
    Helixi541 – 55818Combined sources
    Beta strandi562 – 57110Combined sources
    Beta strandi572 – 5743Combined sources
    Beta strandi576 – 5827Combined sources
    Helixi589 – 5968Combined sources
    Helixi600 – 6089Combined sources
    Helixi613 – 6153Combined sources
    Helixi617 – 6226Combined sources
    Beta strandi635 – 6373Combined sources
    Beta strandi646 – 6538Combined sources
    Beta strandi669 – 6713Combined sources
    Beta strandi679 – 6857Combined sources
    Beta strandi700 – 70910Combined sources
    Helixi710 – 72415Combined sources
    Helixi728 – 7303Combined sources
    Helixi732 – 74211Combined sources
    Helixi744 – 7485Combined sources
    Helixi754 – 7563Combined sources
    Beta strandi896 – 8983Combined sources
    Beta strandi900 – 9023Combined sources
    Beta strandi903 – 9108Combined sources
    Beta strandi914 – 9163Combined sources
    Beta strandi921 – 9277Combined sources
    Beta strandi930 – 9356Combined sources
    Beta strandi937 – 9448Combined sources
    Beta strandi957 – 9615Combined sources
    Turni1698 – 17003Combined sources
    Helixi1703 – 17119Combined sources
    Helixi1717 – 17193Combined sources
    Helixi1720 – 173213Combined sources
    Beta strandi1742 – 17509Combined sources
    Beta strandi1756 – 17594Combined sources
    Beta strandi1767 – 177711Combined sources
    Beta strandi1786 – 17938Combined sources
    Helixi1798 – 18003Combined sources
    Helixi1804 – 182017Combined sources
    Beta strandi1824 – 18285Combined sources
    Helixi1839 – 18424Combined sources
    Beta strandi1846 – 18505Combined sources
    Helixi1855 – 18573Combined sources
    Beta strandi1859 – 18646Combined sources
    Helixi1866 – 18727Combined sources
    Turni1873 – 18764Combined sources
    Beta strandi1878 – 18858Combined sources
    Beta strandi1888 – 18969Combined sources
    Beta strandi1899 – 19013Combined sources
    Helixi1905 – 192420Combined sources
    Beta strandi1927 – 19315Combined sources
    Beta strandi1933 – 19364Combined sources
    Helixi1938 – 19469Combined sources
    Beta strandi1948 – 19525Combined sources
    Beta strandi1956 – 19605Combined sources
    Helixi1962 – 19698Combined sources
    Helixi1977 – 19815Combined sources
    Helixi1983 – 19864Combined sources
    Turni1987 – 19904Combined sources
    Beta strandi1993 – 19986Combined sources
    Helixi1999 – 201012Combined sources
    Helixi2045 – 20506Combined sources
    Beta strandi2055 – 20573Combined sources
    Beta strandi2072 – 20754Combined sources
    Beta strandi2082 – 20898Combined sources
    Beta strandi2092 – 20998Combined sources
    Beta strandi2104 – 21085Combined sources
    Beta strandi2120 – 21245Combined sources
    Helixi2131 – 214717Combined sources
    Beta strandi2151 – 21544Combined sources
    Helixi2164 – 21685Combined sources
    Helixi2171 – 218313Combined sources
    Beta strandi2189 – 21935Combined sources
    Beta strandi2198 – 22003Combined sources
    Helixi2201 – 22055Combined sources
    Helixi2209 – 22113Combined sources
    Turni2213 – 22153Combined sources
    Beta strandi2216 – 22216Combined sources
    Beta strandi2225 – 22295Combined sources
    Helixi2231 – 22388Combined sources
    Helixi2241 – 225111Combined sources
    Helixi2253 – 22619Combined sources
    Helixi2269 – 229931Combined sources
    Helixi2300 – 23023Combined sources
    Helixi2304 – 23096Combined sources
    Beta strandi2312 – 23176Combined sources
    Helixi2319 – 23213Combined sources
    Helixi2322 – 234423Combined sources
    Helixi2345 – 23484Combined sources
    Helixi2352 – 236514Combined sources
    Helixi2369 – 23768Combined sources
    Helixi2378 – 238811Combined sources
    Helixi2404 – 242017Combined sources
    Turni2423 – 24253Combined sources
    Helixi2426 – 243510Combined sources
    Helixi2439 – 244810Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2DN8NMR-A885-971[»]
    2HJWX-ray2.50A217-775[»]
    2KCCNMR-A891-965[»]
    3FF6X-ray3.19A/B/C/D1693-2450[»]
    3GIDX-ray2.30A/B238-760[»]
    3GLKX-ray2.10A238-760[»]
    3JRWX-ray2.60A217-775[»]
    3JRXX-ray2.50A217-775[»]
    3TDCX-ray2.41A1690-2445[»]
    4HQ6X-ray2.70A217-776[»]
    ProteinModelPortaliO00763.
    SMRiO00763. Positions 237-758, 891-960, 1695-2449.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO00763.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini259 – 761503Biotin carboxylationAdd
    BLAST
    Domaini414 – 609196ATP-graspPROSITE-ProRule annotationAdd
    BLAST
    Domaini888 – 96275Biotinyl-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini1809 – 2305497CarboxyltransferaseAdd
    BLAST

    Sequence similaritiesi

    Contains 1 ATP-grasp domain.PROSITE-ProRule annotation
    Contains 1 biotin carboxylation domain.Curated
    Contains 1 biotinyl-binding domain.PROSITE-ProRule annotationCurated
    Contains 1 carboxyltransferase domain.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0511.
    GeneTreeiENSGT00550000074703.
    HOVERGENiHBG005371.
    InParanoidiO00763.
    KOiK11262.
    OMAiWYEENKK.
    OrthoDBiEOG7HXCPW.
    PhylomeDBiO00763.
    TreeFamiTF300061.

    Family and domain databases

    Gene3Di3.30.1490.20. 1 hit.
    3.30.470.20. 1 hit.
    3.40.50.20. 1 hit.
    3.90.226.10. 3 hits.
    InterProiIPR013537. AcCoA_COase_cen.
    IPR011761. ATP-grasp.
    IPR013815. ATP_grasp_subdomain_1.
    IPR013816. ATP_grasp_subdomain_2.
    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.
    IPR029045. ClpP/crotonase-like_dom.
    IPR011763. COA_CT_C.
    IPR011762. COA_CT_N.
    IPR016185. PreATP-grasp_dom.
    IPR011054. Rudment_hybrid_motif.
    IPR011053. Single_hybrid_motif.
    [Graphical view]
    PfamiPF08326. 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]
    SMARTiSM00878. Biotin_carb_C. 1 hit.
    [Graphical view]
    SUPFAMiSSF51230. SSF51230. 1 hit.
    SSF51246. SSF51246. 1 hit.
    SSF52096. SSF52096. 2 hits.
    SSF52440. SSF52440. 1 hit.
    PROSITEiPS50975. ATP_GRASP. 1 hit.
    PS50979. BC. 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]

    Sequences (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: O00763-1) [UniParc]FASTAAdd to basket

    Also known as: Long

    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
    MVLLLCLSCL IFSCLTFSWL KIWGKMTDSK PITKSKSEAN LIPSQEPFPA
    60 70 80 90 100
    SDNSGETPQR NGEGHTLPKT PSQAEPASHK GPKDAGRRRN SLPPSHQKPP
    110 120 130 140 150
    RNPLSSSDAA PSPELQANGT GTQGLEATDT NGLSSSARPQ GQQAGSPSKE
    160 170 180 190 200
    DKKQANIKRQ LMTNFILGSF DDYSSDEDSV AGSSRESTRK GSRASLGALS
    210 220 230 240 250
    LEAYLTTGEA ETRVPTMRPS MSGLHLVKRG REHKKLDLHR DFTVASPAEF
    260 270 280 290 300
    VTRFGGDRVI EKVLIANNGI AAVKCMRSIR RWAYEMFRNE RAIRFVVMVT
    310 320 330 340 350
    PEDLKANAEY IKMADHYVPV PGGPNNNNYA NVELIVDIAK RIPVQAVWAG
    360 370 380 390 400
    WGHASENPKL PELLCKNGVA FLGPPSEAMW ALGDKIASTV VAQTLQVPTL
    410 420 430 440 450
    PWSGSGLTVE WTEDDLQQGK RISVPEDVYD KGCVKDVDEG LEAAERIGFP
    460 470 480 490 500
    LMIKASEGGG GKGIRKAESA EDFPILFRQV QSEIPGSPIF LMKLAQHARH
    510 520 530 540 550
    LEVQILADQY GNAVSLFGRD CSIQRRHQKI VEEAPATIAP LAIFEFMEQC
    560 570 580 590 600
    AIRLAKTVGY VSAGTVEYLY SQDGSFHFLE LNPRLQVEHP CTEMIADVNL
    610 620 630 640 650
    PAAQLQIAMG VPLHRLKDIR LLYGESPWGV TPISFETPSN PPLARGHVIA
    660 670 680 690 700
    ARITSENPDE GFKPSSGTVQ ELNFRSSKNV WGYFSVAATG GLHEFADSQF
    710 720 730 740 750
    GHCFSWGENR EEAISNMVVA LKELSIRGDF RTTVEYLINL LETESFQNND
    760 770 780 790 800
    IDTGWLDYLI AEKVQAEKPD IMLGVVCGAL NVADAMFRTC MTDFLHSLER
    810 820 830 840 850
    GQVLPADSLL NLVDVELIYG GVKYILKVAR QSLTMFVLIM NGCHIEIDAH
    860 870 880 890 900
    RLNDGGLLLS YNGNSYTTYM KEEVDSYRIT IGNKTCVFEK ENDPTVLRSP
    910 920 930 940 950
    SAGKLTQYTV EDGGHVEAGS SYAEMEVMKM IMTLNVQERG RVKYIKRPGA
    960 970 980 990 1000
    VLEAGCVVAR LELDDPSKVH PAEPFTGELP AQQTLPILGE KLHQVFHSVL
    1010 1020 1030 1040 1050
    ENLTNVMSGF CLPEPVFSIK LKEWVQKLMM TLRHPSLPLL ELQEIMTSVA
    1060 1070 1080 1090 1100
    GRIPAPVEKS VRRVMAQYAS NITSVLCQFP SQQIATILDC HAATLQRKAD
    1110 1120 1130 1140 1150
    REVFFINTQS IVQLVQRYRS GIRGYMKTVV LDLLRRYLRV EHHFQQAHYD
    1160 1170 1180 1190 1200
    KCVINLREQF KPDMSQVLDC IFSHAQVAKK NQLVIMLIDE LCGPDPSLSD
    1210 1220 1230 1240 1250
    ELISILNELT QLSKSEHCKV ALRARQILIA SHLPSYELRH NQVESIFLSA
    1260 1270 1280 1290 1300
    IDMYGHQFCP ENLKKLILSE TTIFDVLPTF FYHANKVVCM ASLEVYVRRG
    1310 1320 1330 1340 1350
    YIAYELNSLQ HRQLPDGTCV VEFQFMLPSS HPNRMTVPIS ITNPDLLRHS
    1360 1370 1380 1390 1400
    TELFMDSGFS PLCQRMGAMV AFRRFEDFTR NFDEVISCFA NVPKDTPLFS
    1410 1420 1430 1440 1450
    EARTSLYSED DCKSLREEPI HILNVSIQCA DHLEDEALVP ILRTFVQSKK
    1460 1470 1480 1490 1500
    NILVDYGLRR ITFLIAQEKE FPKFFTFRAR DEFAEDRIYR HLEPALAFQL
    1510 1520 1530 1540 1550
    ELNRMRNFDL TAVPCANHKM HLYLGAAKVK EGVEVTDHRF FIRAIIRHSD
    1560 1570 1580 1590 1600
    LITKEASFEY LQNEGERLLL EAMDELEVAF NNTSVRTDCN HIFLNFVPTV
    1610 1620 1630 1640 1650
    IMDPFKIEES VRYMVMRYGS RLWKLRVLQA EVKINIRQTT TGSAVPIRLF
    1660 1670 1680 1690 1700
    ITNESGYYLD ISLYKEVTDS RSGNIMFHSF GNKQGPQHGM LINTPYVTKD
    1710 1720 1730 1740 1750
    LLQAKRFQAQ TLGTTYIYDF PEMFRQALFK LWGSPDKYPK DILTYTELVL
    1760 1770 1780 1790 1800
    DSQGQLVEMN RLPGGNEVGM VAFKMRFKTQ EYPEGRDVIV IGNDITFRIG
    1810 1820 1830 1840 1850
    SFGPGEDLLY LRASEMARAE GIPKIYVAAN SGARIGMAEE IKHMFHVAWV
    1860 1870 1880 1890 1900
    DPEDPHKGFK YLYLTPQDYT RISSLNSVHC KHIEEGGESR YMITDIIGKD
    1910 1920 1930 1940 1950
    DGLGVENLRG SGMIAGESSL AYEEIVTISL VTCRAIGIGA YLVRLGQRVI
    1960 1970 1980 1990 2000
    QVENSHIILT GASALNKVLG REVYTSNNQL GGVQIMHYNG VSHITVPDDF
    2010 2020 2030 2040 2050
    EGVYTILEWL SYMPKDNHSP VPIITPTDPI DREIEFLPSR APYDPRWMLA
    2060 2070 2080 2090 2100
    GRPHPTLKGT WQSGFFDHGS FKEIMAPWAQ TVVTGRARLG GIPVGVIAVE
    2110 2120 2130 2140 2150
    TRTVEVAVPA DPANLDSEAK IIQQAGQVWF PDSAYKTAQA VKDFNREKLP
    2160 2170 2180 2190 2200
    LMIFANWRGF SGGMKDMYDQ VLKFGAYIVD GLRQYKQPIL IYIPPYAELR
    2210 2220 2230 2240 2250
    GGSWVVIDAT INPLCIEMYA DKESRGGVLE PEGTVEIKFR KKDLIKSMRR
    2260 2270 2280 2290 2300
    IDPAYKKLME QLGEPDLSDK DRKDLEGRLK AREDLLLPIY HQVAVQFADF
    2310 2320 2330 2340 2350
    HDTPGRMLEK GVISDILEWK TARTFLYWRL RRLLLEDQVK QEILQASGEL
    2360 2370 2380 2390 2400
    SHVHIQSMLR RWFVETEGAV KAYLWDNNQV VVQWLEQHWQ AGDGPRSTIR
    2410 2420 2430 2440 2450
    ENITYLKHDS VLKTIRGLVE ENPEVAVDCV IYLSQHISPA ERAQVVHLLS

    TMDSPAST
    Length:2,458
    Mass (Da):276,541
    Last modified:October 5, 2010 - v3
    Checksum:iED12674A1A8A0706
    GO
    Isoform 2 (identifier: O00763-2) [UniParc]FASTAAdd to basket

    Also known as: Short

    The sequence of this isoform differs from the canonical sequence as follows:
         1118-1187: Missing.

    Show »
    Length:2,388
    Mass (Da):268,166
    Checksum:i10A218FFD1408B68
    GO
    Isoform 3Curated (identifier: O00763-3) [UniParc]FASTAAdd to basket

    Also known as: ACC2.v21 Publication

    The sequence of this isoform differs from the canonical sequence as follows:
         1-202: Missing.
         203-218: AYLTTGEAETRVPTMR → MSPAKCKICFPDREVK

    Show »
    Length:2,256
    Mass (Da):255,093
    Checksum:iA0736151D792EC18
    GO

    Sequence cautioni

    The sequence AAB58382.1 differs from that shown.Many Frameshifts and conflicts.Curated
    The sequence CAE01470.2 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti9 – 91C → R in ABF48723 (PubMed:16854592).Curated
    Sequence conflicti120 – 1201T → I in AAR37018 (Ref. 4) Curated
    Sequence conflicti422 – 4221I → T in AAR37018 (Ref. 4) Curated
    Sequence conflicti1340 – 13401S → N in AAC50571 (PubMed:8670171).Curated
    Sequence conflicti1383 – 13831D → G in AAC50571 (PubMed:8670171).Curated
    Sequence conflicti1425 – 14251V → M in AAC50571 (PubMed:8670171).Curated
    Sequence conflicti1819 – 18213AEG → PEA in AAC50571 (PubMed:8670171).Curated
    Sequence conflicti1892 – 18932MI → IM in AAC50571 (PubMed:8670171).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti193 – 1931R → L in a pancreatic ductal adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_062667
    Natural varianti552 – 5521I → V.
    Corresponds to variant rs16940029 [ dbSNP | Ensembl ].
    VAR_031255
    Natural varianti651 – 6511A → T.
    Corresponds to variant rs2300455 [ dbSNP | Ensembl ].
    VAR_031256
    Natural varianti2141 – 21411V → I.2 Publications
    Corresponds to variant rs2075260 [ dbSNP | Ensembl ].
    VAR_031257

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 202202Missing in isoform 3. 1 PublicationVSP_057081Add
    BLAST
    Alternative sequencei203 – 21816AYLTT…VPTMR → MSPAKCKICFPDREVK in isoform 3. 1 PublicationVSP_057082Add
    BLAST
    Alternative sequencei1118 – 118770Missing in isoform 2. 1 PublicationVSP_000547Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U89344 mRNA. Translation: AAB58382.1. Sequence problems.
    DQ493870 mRNA. Translation: ABF48723.1.
    AJ575431 mRNA. Translation: CAE01470.2. Sequence problems.
    AJ575592 mRNA. Translation: CAE01471.3.
    AY382667 mRNA. Translation: AAR37018.1.
    AC007637 Genomic DNA. No translation available.
    U34591 mRNA. Translation: AAC50571.1.
    CCDSiCCDS31898.1. [O00763-1]
    PIRiS71091.
    RefSeqiNP_001084.3. NM_001093.3. [O00763-1]
    XP_005253933.1. XM_005253876.3. [O00763-1]
    XP_006719428.1. XM_006719365.2. [O00763-1]
    XP_006719430.1. XM_006719367.2. [O00763-3]
    XP_011536561.1. XM_011538259.1. [O00763-1]
    XP_011536562.1. XM_011538260.1. [O00763-1]
    XP_011536563.1. XM_011538261.1. [O00763-1]
    XP_011536564.1. XM_011538262.1. [O00763-1]
    UniGeneiHs.234898.
    Hs.676621.

    Genome annotation databases

    EnsembliENST00000338432; ENSP00000341044; ENSG00000076555.
    ENST00000377848; ENSP00000367079; ENSG00000076555.
    GeneIDi32.
    KEGGihsa:32.
    UCSCiuc001tob.3. human. [O00763-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U89344 mRNA. Translation: AAB58382.1. Sequence problems.
    DQ493870 mRNA. Translation: ABF48723.1.
    AJ575431 mRNA. Translation: CAE01470.2. Sequence problems.
    AJ575592 mRNA. Translation: CAE01471.3.
    AY382667 mRNA. Translation: AAR37018.1.
    AC007637 Genomic DNA. No translation available.
    U34591 mRNA. Translation: AAC50571.1.
    CCDSiCCDS31898.1. [O00763-1]
    PIRiS71091.
    RefSeqiNP_001084.3. NM_001093.3. [O00763-1]
    XP_005253933.1. XM_005253876.3. [O00763-1]
    XP_006719428.1. XM_006719365.2. [O00763-1]
    XP_006719430.1. XM_006719367.2. [O00763-3]
    XP_011536561.1. XM_011538259.1. [O00763-1]
    XP_011536562.1. XM_011538260.1. [O00763-1]
    XP_011536563.1. XM_011538261.1. [O00763-1]
    XP_011536564.1. XM_011538262.1. [O00763-1]
    UniGeneiHs.234898.
    Hs.676621.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2DN8NMR-A885-971[»]
    2HJWX-ray2.50A217-775[»]
    2KCCNMR-A891-965[»]
    3FF6X-ray3.19A/B/C/D1693-2450[»]
    3GIDX-ray2.30A/B238-760[»]
    3GLKX-ray2.10A238-760[»]
    3JRWX-ray2.60A217-775[»]
    3JRXX-ray2.50A217-775[»]
    3TDCX-ray2.41A1690-2445[»]
    4HQ6X-ray2.70A217-776[»]
    ProteinModelPortaliO00763.
    SMRiO00763. Positions 237-758, 891-960, 1695-2449.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi106550. 4 interactions.
    DIPiDIP-51617N.
    IntActiO00763. 6 interactions.
    MINTiMINT-6800190.
    STRINGi9606.ENSP00000341044.

    Chemistry

    BindingDBiO00763.
    ChEMBLiCHEMBL4829.
    DrugBankiDB00173. Adenine.
    DB00121. Biotin.
    GuidetoPHARMACOLOGYi1264.

    PTM databases

    PhosphoSiteiO00763.

    Polymorphism and mutation databases

    BioMutaiACACB.

    Proteomic databases

    MaxQBiO00763.
    PaxDbiO00763.
    PRIDEiO00763.

    Protocols and materials databases

    DNASUi32.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000338432; ENSP00000341044; ENSG00000076555.
    ENST00000377848; ENSP00000367079; ENSG00000076555.
    GeneIDi32.
    KEGGihsa:32.
    UCSCiuc001tob.3. human. [O00763-1]

    Organism-specific databases

    CTDi32.
    GeneCardsiGC12P109577.
    H-InvDBHIX0036741.
    HGNCiHGNC:85. ACACB.
    HPAiHPA006554.
    MIMi601557. gene.
    neXtProtiNX_O00763.
    PharmGKBiPA24422.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0511.
    GeneTreeiENSGT00550000074703.
    HOVERGENiHBG005371.
    InParanoidiO00763.
    KOiK11262.
    OMAiWYEENKK.
    OrthoDBiEOG7HXCPW.
    PhylomeDBiO00763.
    TreeFamiTF300061.

    Enzyme and pathway databases

    UniPathwayiUPA00655; UER00711.
    BioCyciMetaCyc:HS01211-MONOMER.
    BRENDAi6.3.4.14. 2681.
    6.4.1.2. 2681.
    ReactomeiREACT_11082. Import of palmitoyl-CoA into the mitochondrial matrix.
    REACT_11153. Biotin transport and metabolism.
    REACT_147904. Activation of gene expression by SREBF (SREBP).
    REACT_169312. Defective HLCS causes multiple carboxylase deficiency.
    REACT_2122. ChREBP activates metabolic gene expression.
    SABIO-RKO00763.

    Miscellaneous databases

    ChiTaRSiACACB. human.
    EvolutionaryTraceiO00763.
    GeneWikiiACACB.
    GenomeRNAii32.
    NextBioi123.
    PROiO00763.
    SOURCEiSearch...

    Gene expression databases

    BgeeiO00763.
    CleanExiHS_ACACB.
    ExpressionAtlasiO00763. baseline and differential.
    GenevisibleiO00763. HS.

    Family and domain databases

    Gene3Di3.30.1490.20. 1 hit.
    3.30.470.20. 1 hit.
    3.40.50.20. 1 hit.
    3.90.226.10. 3 hits.
    InterProiIPR013537. AcCoA_COase_cen.
    IPR011761. ATP-grasp.
    IPR013815. ATP_grasp_subdomain_1.
    IPR013816. ATP_grasp_subdomain_2.
    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.
    IPR029045. ClpP/crotonase-like_dom.
    IPR011763. COA_CT_C.
    IPR011762. COA_CT_N.
    IPR016185. PreATP-grasp_dom.
    IPR011054. Rudment_hybrid_motif.
    IPR011053. Single_hybrid_motif.
    [Graphical view]
    PfamiPF08326. 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]
    SMARTiSM00878. Biotin_carb_C. 1 hit.
    [Graphical view]
    SUPFAMiSSF51230. SSF51230. 1 hit.
    SSF51246. SSF51246. 1 hit.
    SSF52096. SSF52096. 2 hits.
    SSF52440. SSF52440. 1 hit.
    PROSITEiPS50975. ATP_GRASP. 1 hit.
    PS50979. BC. 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]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Human acetyl-CoA carboxylase 2. Molecular cloning, characterization, chromosomal mapping, and evidence for two isoforms."
      Abu-Elheiga L., Almarza-Ortega D.B., Baldini A., Wakil S.J.
      J. Biol. Chem. 272:10669-10677(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
      Tissue: Liver.
    2. "Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes."
      Cheng D., Chu C.-H., Chen L., Feder J.N., Mintier G.A., Wu Y., Cook J.W., Harpel M.R., Locke G.A., An Y., Tamura J.K.
      Protein Expr. Purif. 51:11-21(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, ENZYME REGULATION, VARIANT ILE-2141.
    3. "Corrected sequence for human acetyl-CoA carboxylase 2 obtained by alignment to human genomic DNA and PCR cloning from human skeletal muscle and heart cDNA."
      Peng X.R., Lindgren K., Corneliussen B.
      Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ILE-2141.
      Tissue: Heart.
    4. "Alternative splicing in the human acetyl-CoA carboxylase 2 (ACC2) gene."
      Mao J., Wakil S.J.
      Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Heart.
    5. "The finished DNA sequence of human chromosome 12."
      Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
      , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
      Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "Identification of a second human acetyl-CoA carboxylase gene."
      Widmer J., Fassihi K.S., Schlichter S.C., Wheeler K.S., Crute B.E., King N., Nutile-Mcmenemy N., Noll W.W., Daniel S., Ha J., Kim K.-H., Witters L.A.
      Biochem. J. 316:915-922(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1324-2109.
      Tissue: Adipose tissue.
    7. Cited for: SUBCELLULAR LOCATION.
    8. "Regulation of 5'AMP-activated protein kinase activity and substrate utilization in exercising human skeletal muscle."
      Wojtaszewski J.F., MacDonald C., Nielsen J.N., Hellsten Y., Hardie D.G., Kemp B.E., Kiens B., Richter E.A.
      Am. J. Physiol. 284:E813-E822(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-222 BY AMPK.
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    10. "ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus."
      Castle J.C., Hara Y., Raymond C.K., Garrett-Engele P., Ohwaki K., Kan Z., Kusunoki J., Johnson J.M.
      PLoS ONE 4:E4369-E4369(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ALTERNATIVE SPLICING (ISOFORM 3), TISSUE SPECIFICITY.
    11. Cited for: CATALYTIC ACTIVITY, SUBUNIT, ENZYME REGULATION, INTERACTION WITH MID1IP1.
    12. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35; THR-70; SER-91; SER-95; SER-200; SER-469 AND THR-1342, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    13. "Crystal structure of the biotin carboxylase domain of human acetyl-CoA carboxylase 2."
      Cho Y.S., Lee J.I., Shin D., Kim H.T., Cheon Y.H., Seo C.I., Kim Y.E., Hyun Y.L., Lee Y.S., Sugiyama K., Park S.Y., Ro S., Cho J.M., Lee T.G., Heo Y.S.
      Proteins 70:268-272(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 217-775.
    14. "Solution structure of RSGI RUH-053, an apo-biotin carboxy carrier protein from human transcarboxylase."
      RIKEN structural genomics initiative (RSGI)
      Submitted (OCT-2006) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 885-971.
    15. Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-193.

    Entry informationi

    Entry nameiACACB_HUMAN
    AccessioniPrimary (citable) accession number: O00763
    Secondary accession number(s): A6NK36
    , Q16852, Q1HEC1, Q6KE87, Q6KE89, Q6TY48
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: October 5, 2010
    Last modified: July 22, 2015
    This is version 155 of the entry and version 3 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, Allosteric enzyme, Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    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.