Q9NUB1 (ACS2L_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 93.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended 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 |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 689 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence 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 | |
| Post-translational modification | Reversibly acetylated on Lys-642. The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation. |
| 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. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Mitochondrion |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Transit peptide |
| Ligand | ATP-binding Nucleotide-binding |
| Molecular function | Ligase |
| PTM | Acetylation |
| Technical term | 3D-structure Complete proteome Direct protein sequencing Reference proteome |
| Gene Ontology (GO) | |
| Biological process | acetyl-CoA biosynthetic process Inferred from direct assay Ref.7. Source: UniProtKB ethanol oxidationTraceable author statement. Source: Reactome xenobiotic metabolic processTraceable author statement. Source: Reactome |
| Cellular component | mitochondrial matrix Inferred from direct assay Ref.7. Source: UniProtKB |
| Molecular function | AMP binding Inferred from electronic annotation. Source: InterPro ATP bindingInferred from electronic annotation. Source: UniProtKB-KW acetate-CoA ligase activityInferred from direct assay Ref.7. Source: UniProtKB protein bindingInferred from physical interaction Ref.7Ref.10. Source: UniProtKB |
| Complete GO annotation... | |
Alternative products
| This entry describes 2 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. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Transit peptide | 1 – 37 | 37 | Mitochondrion | ||||||||
| Chain | 38 – 689 | 652 | Acetyl-coenzyme A synthetase 2-like, mitochondrial | PRO_0000000596 | |||||||
Regions | |||||||||||
| Compositional bias | 45 – 53 | 9 | Poly-Ala | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 396 | 1 | N6-acetyllysine Ref.8 | ||||||||
| Modified residue | 642 | 1 | N6-acetyllysine Ref.7 | ||||||||
Natural variations | |||||||||||
| Alternative sequence | 446 – 447 | 2 | Missing in isoform 2. | VSP_007249 | |||||||
| Natural variant | 488 | 1 | V → M. Ref.3 Corresponds to variant rs6050249 [ dbSNP | Ensembl ]. | VAR_048184 | |||||||
Experimental info | |||||||||||
| Mutagenesis | 642 | 1 | K → Q: Loss of activity. Ref.7 | ||||||||
| Sequence conflict | 277 | 1 | V → M in AAH39261. Ref.3 | ||||||||
Secondary structure | |||||||||||
Helix Strand Turn | |||||||||||
| Beta strand | 643 – 645 | 3 | |||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "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. Rogers J.Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [2] | 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. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT MET-488. Tissue: Brain and Testis. |
| [4] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 169-689 (ISOFORM 1). Tissue: Placenta and Tongue. |
| [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: 11347906] [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: 12168954] [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: 16788062] [Abstract] Cited for: ACETYLATION AT LYS-642, MUTAGENESIS OF LYS-642, FUNCTION, ENZYME REGULATION, PROTEIN SEQUENCE OF N-TERMINUS, 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., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-396, MASS SPECTROMETRY. |
| [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: 21269460] [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: 19535340] [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 | 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. AK027817 mRNA. Translation: BAB55390.1. Different initiation. AK092295 mRNA. Translation: BAC03853.1. Sequence problems. AB058749 mRNA. Translation: BAB47475.1. | ||||||||||||||||||||||||
| IPI | IPI00216932. IPI00248961. | ||||||||||||||||||||||||
| RefSeq | NP_115890.2. NM_032501.2. | ||||||||||||||||||||||||
| UniGene | Hs.529353. | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||||||||||||||
| ProteinModelPortal | Q9NUB1. | ||||||||||||||||||||||||
| SMR | Q9NUB1. Positions 49-679. | ||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||
| STRING | Q9NUB1. | ||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||
| PhosphoSite | Q9NUB1. | ||||||||||||||||||||||||
Polymorphism databases | |||||||||||||||||||||||||
| DMDM | 30172968. | ||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||
| PRIDE | Q9NUB1. | ||||||||||||||||||||||||
Protocols and materials databases | |||||||||||||||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENST00000323482; ENSP00000316924; ENSG00000154930. | ||||||||||||||||||||||||
| GeneID | 84532. | ||||||||||||||||||||||||
| KEGG | hsa:84532. | ||||||||||||||||||||||||
| NMPDR | fig|9606.3.peg.19997. | ||||||||||||||||||||||||
| UCSC | uc002wub.1. human. uc002wuc.1. human. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| CTD | 84532. | ||||||||||||||||||||||||
| GeneCards | GC20M024986. | ||||||||||||||||||||||||
| H-InvDB | HIX0015699. | ||||||||||||||||||||||||
| HGNC | HGNC:16091. ACSS1. | ||||||||||||||||||||||||
| MIM | 614355. gene. | ||||||||||||||||||||||||
| neXtProt | NX_Q9NUB1. | ||||||||||||||||||||||||
| PharmGKB | PA24430. | ||||||||||||||||||||||||
| HUGE | Search... | ||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| GeneTree | ENSGT00550000074278. | ||||||||||||||||||||||||
| HOVERGEN | HBG014401. | ||||||||||||||||||||||||
| InParanoid | Q9NUB1. | ||||||||||||||||||||||||
| OMA | LDQHVQK. | ||||||||||||||||||||||||
| OrthoDB | EOG4RFKS6. | ||||||||||||||||||||||||
| PhylomeDB | Q9NUB1. | ||||||||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||||||||
| BRENDA | 6.2.1.1. 2681. | ||||||||||||||||||||||||
| Reactome | REACT_111217. Metabolism. | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| ArrayExpress | Q9NUB1. | ||||||||||||||||||||||||
| Bgee | Q9NUB1. | ||||||||||||||||||||||||
| CleanEx | HS_ACSS1. | ||||||||||||||||||||||||
| Genevestigator | Q9NUB1. | ||||||||||||||||||||||||
| GermOnline | ENSG00000154930. Homo sapiens. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR011904. Ac_CoA_lig. IPR024597. Acyl-CoA_synth_DUF3448. IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. [Graphical view] | ||||||||||||||||||||||||
| KO | K01895. | ||||||||||||||||||||||||
| PANTHER | PTHR24095:SF42. PTHR24095:SF42. 1 hit. | ||||||||||||||||||||||||
| Pfam | PF00501. AMP-binding. 1 hit. PF11930. DUF3448. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| TIGRFAMs | TIGR02188. Ac_CoA_lig_AcsA. 1 hit. | ||||||||||||||||||||||||
| PROSITE | PS00455. AMP_BINDING. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other | |||||||||||||||||||||||||
| DrugBank | DB00131. Adenosine monophosphate. DB00171. Adenosine triphosphate. | ||||||||||||||||||||||||
| NextBio | 74375. | ||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||
Entry information
| Entry name | ACS2L_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9NUB1 Secondary accession number(s): D3DW48 Q9NU28 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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
| Human chromosome 20 Human chromosome 20: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with