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Q9NUB1 (ACS2L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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-coenzyme A synthetase 2-like, mitochondrial

EC=6.2.1.1
Alternative name(s):
Acetate--CoA ligase 2
Acetyl-CoA synthetase 2
Short name=AceCS2
Acyl-CoA synthetase short-chain family member 1
Gene names
Name:ACSS1
Synonyms:ACAS2L, KIAA1846
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length689 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Important for maintaining normal body temperature during fasting and for energy homeostasis. Essential for energy expenditure under ketogenic conditions By similarity. Converts acetate to acetyl-CoA so that it can be used for oxidation through the tricarboxylic cycle to produce ATP and CO2. Ref.7

Catalytic activity

ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA.

Enzyme regulation

Inhibited by acetylation at Lys-642 and activated by deacetylation. Ref.7

Subunit structure

Interacts with SIRT3.

Subcellular location

Mitochondrion matrix Ref.7.

Post-translational modification

Reversibly acetylated on Lys-642. The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation. Ref.7

Sequence similarities

Belongs to the ATP-dependent AMP-binding enzyme family.

Sequence caution

The sequence BAB55390.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAC03853.1 differs from that shown. Reason: Frameshift at position 250.

The sequence BAC03853.1 differs from that shown. Reason: Sequencing errors.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NUB1-1)

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: Q9NUB1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     446-447: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9NUB1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MAARTLGRGVGRLLGSLRGLSG → MRRRKERQPWDRFHFLHFAPHG
     23-143: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q9NUB1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     556-575: SGHRLGTAEIEDAIADHPAV → LQIVGFFREAIRNSGDLLEH
     576-689: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3737Mitochondrion Ref.7
Chain38 – 689652Acetyl-coenzyme A synthetase 2-like, mitochondrial
PRO_0000000596

Regions

Compositional bias45 – 539Poly-Ala

Amino acid modifications

Modified residue3961N6-acetyllysine Ref.8
Modified residue6421N6-acetyllysine Ref.7

Natural variations

Alternative sequence1 – 2222MAART…RGLSG → MRRRKERQPWDRFHFLHFAP HG in isoform 3.
VSP_044693
Alternative sequence23 – 143121Missing in isoform 3.
VSP_044694
Alternative sequence446 – 4472Missing in isoform 2.
VSP_007249
Alternative sequence556 – 57520SGHRL…DHPAV → LQIVGFFREAIRNSGDLLEH in isoform 4.
VSP_045546
Alternative sequence576 – 689114Missing in isoform 4.
VSP_045547
Natural variant4881V → M. Ref.1 Ref.4
Corresponds to variant rs6050249 [ dbSNP | Ensembl ].
VAR_048184

Experimental info

Mutagenesis6421K → Q: Loss of activity. Ref.7
Sequence conflict2331K → I in BAG54524. Ref.1
Sequence conflict2771V → M in AAH39261. Ref.4

Secondary structure

... 689
Helix Strand Turn

Details...

Sequences

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

Last modified April 23, 2003. Version 2.
Checksum: 66E84E39302AD08B

FASTA68974,857
        10         20         30         40         50         60 
MAARTLGRGV GRLLGSLRGL SGQPARPPCG VSAPRRAASG PSGSAPAVAA AAAQPGSYPA 

        70         80         90        100        110        120 
LSAQAAREPA AFWGPLARDT LVWDTPYHTV WDCDFSTGKI GWFLGGQLNV SVNCLDQHVR 

       130        140        150        160        170        180 
KSPESVALIW ERDEPGTEVR ITYRELLETT CRLANTLKRH GVHRGDRVAI YMPVSPLAVA 

       190        200        210        220        230        240 
AMLACARIGA VHTVIFAGFS AESLAGRIND AKCKVVITFN QGLRGGRVVE LKKIVDEAVK 

       250        260        270        280        290        300 
HCPTVQHVLV AHRTDNKVHM GDLDVPLEQE MAKEDPVCAP ESMGSEDMLF MLYTSGSTGM 

       310        320        330        340        350        360 
PKGIVHTQAG YLLYAALTHK LVFDHQPGDI FGCVADIGWI TGHSYVVYGP LCNGATSVLF 

       370        380        390        400        410        420 
ESTPVYPNAG RYWETVERLK INQFYGAPTA VRLLLKYGDA WVKKYDRSSL RTLGSVGEPI 

       430        440        450        460        470        480 
NCEAWEWLHR VVGDSRCTLV DTWWQTETGG ICIAPRPSEE GAEILPAMAM RPFFGIVPVL 

       490        500        510        520        530        540 
MDEKGSVVEG SNVSGALCIS QAWPGMARTI YGDHQRFVDA YFKAYPGYYF TGDGAYRTEG 

       550        560        570        580        590        600 
GYYQITGRMD DVINISGHRL GTAEIEDAIA DHPAVPESAV IGYPHDIKGE AAFAFIVVKD 

       610        620        630        640        650        660 
SAGDSDVVVQ ELKSMVATKI AKYAVPDEIL VVKRLPKTRS GKVMRRLLRK IITSEAQELG 

       670        680 
DTTTLEDPSI IAEILSVYQK CKDKQAAAK 

« Hide

Isoform 2 [UniParc].

Checksum: 99888770D7E10BA4
Show »

FASTA68774,627
Isoform 3 [UniParc].

Checksum: 061B9CF91C387B3F
Show »

FASTA56862,722
Isoform 4 [UniParc].

Checksum: 4D419E89EB8DF015
Show »

FASTA57562,688

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 169-689 (ISOFORM 1), VARIANT MET-488.
Tissue: Placenta, Thalamus and Tongue.
[2]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT MET-488.
Tissue: Brain and Testis.
[5]"Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.
DNA Res. 8:85-95(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 336-689 (ISOFORM 1).
Tissue: Brain.
[6]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[7]"Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2."
Schwer B., Bunkenborg J., Verdin R.O., Andersen J.S., Verdin E.
Proc. Natl. Acad. Sci. U.S.A. 103:10224-10229(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-642, MUTAGENESIS OF LYS-642, FUNCTION, ENZYME REGULATION, PROTEIN SEQUENCE OF N-TERMINUS, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.
[8]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-396, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Crystal structures of human SIRT3 displaying substrate-induced conformational changes."
Jin L., Wei W., Jiang Y., Peng H., Cai J., Mao C., Dai H., Choy W., Bemis J.E., Jirousek M.R., Milne J.C., Westphal C.H., Perni R.B.
J. Biol. Chem. 284:24394-24405(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 638-649 IN COMPLEX WITH SIRT3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK027817 mRNA. Translation: BAB55390.1. Different initiation.
AK092295 mRNA. Translation: BAC03853.1. Sequence problems.
AK127566 mRNA. Translation: BAG54524.1.
AK296306 mRNA. Translation: BAG59005.1.
AL035661, AL080312 Genomic DNA. Translation: CAI21828.1.
AL080312, AL035661 Genomic DNA. Translation: CAI18917.1.
CH471133 Genomic DNA. Translation: EAX10106.1.
CH471133 Genomic DNA. Translation: EAX10109.1.
BC039261 mRNA. Translation: AAH39261.1.
BC044588 mRNA. Translation: AAH44588.1.
AB058749 mRNA. Translation: BAB47475.1.
CCDSCCDS13167.1. [Q9NUB1-1]
CCDS58764.1. [Q9NUB1-3]
CCDS58765.1. [Q9NUB1-4]
RefSeqNP_001239604.1. NM_001252675.1. [Q9NUB1-2]
NP_001239605.1. NM_001252676.1. [Q9NUB1-3]
NP_001239606.1. NM_001252677.1. [Q9NUB1-4]
NP_115890.2. NM_032501.3. [Q9NUB1-1]
UniGeneHs.529353.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3GLRX-ray1.80B638-649[»]
3GLTX-ray2.10B638-649[»]
3GLUX-ray2.50B638-649[»]
4BVEX-ray2.05B638-647[»]
4BVFX-ray2.70B638-647[»]
4BVGX-ray2.50B638-647[»]
4C78X-ray2.00C638-647[»]
ProteinModelPortalQ9NUB1.
SMRQ9NUB1. Positions 55-679.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000316924.

Chemistry

DrugBankDB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.

PTM databases

PhosphoSiteQ9NUB1.

Polymorphism databases

DMDM30172968.

Proteomic databases

MaxQBQ9NUB1.
PaxDbQ9NUB1.
PRIDEQ9NUB1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000323482; ENSP00000316924; ENSG00000154930. [Q9NUB1-1]
ENST00000432802; ENSP00000388793; ENSG00000154930. [Q9NUB1-4]
ENST00000542618; ENSP00000437657; ENSG00000154930. [Q9NUB1-3]
GeneID84532.
KEGGhsa:84532.
UCSCuc002wub.3. human. [Q9NUB1-1]
uc002wuc.3. human. [Q9NUB1-2]

Organism-specific databases

CTD84532.
GeneCardsGC20M024986.
H-InvDBHIX0015699.
HGNCHGNC:16091. ACSS1.
HPAHPA041014.
HPA043228.
MIM614355. gene.
neXtProtNX_Q9NUB1.
PharmGKBPA24430.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0365.
HOVERGENHBG014401.
InParanoidQ9NUB1.
KOK01895.
OMATEGGYYQ.
OrthoDBEOG77T140.
PhylomeDBQ9NUB1.
TreeFamTF354241.

Enzyme and pathway databases

BRENDA6.2.1.1. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ9NUB1.
BgeeQ9NUB1.
CleanExHS_ACSS1.
GenevestigatorQ9NUB1.

Family and domain databases

InterProIPR011904. Ac_CoA_lig.
IPR025110. AMP-bd_C.
IPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
[Graphical view]
PfamPF00501. AMP-binding. 1 hit.
PF13193. AMP-binding_C. 1 hit.
[Graphical view]
TIGRFAMsTIGR02188. Ac_CoA_lig_AcsA. 1 hit.
PROSITEPS00455. AMP_BINDING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSACSS1. human.
EvolutionaryTraceQ9NUB1.
GenomeRNAi84532.
NextBio74375.
PROQ9NUB1.
SOURCESearch...

Entry information

Entry nameACS2L_HUMAN
AccessionPrimary (citable) accession number: Q9NUB1
Secondary accession number(s): B3KXL2 expand/collapse secondary AC list , B4DJZ3, D3DW48, F5H6F4, F8W7Y1, Q5TF42, Q8IV99, Q8N234, Q96JI1, Q96JX6, Q9NU28
Entry history
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: April 23, 2003
Last modified: July 9, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM