Q4G176 (ACSF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 58.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Acyl-CoA synthetase family member 3, mitochondrial EC=6.2.1.- | ||||
| Gene names |
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| 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 | 576 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 | Catalyzes the initial reaction in intramitochondrial fatty acid synthesis, by activating malonate and methylmalonate, but not acetate, into their respective CoA thioester. May have some preference toward very-long-chain substrates. Ref.6 Ref.9 |
| Subcellular location | |
| Involvement in disease | Defects in ACSF3 are the cause of combined malonic and methylmalonic aciduria (CMAMMA) [MIM:614265]. A metabolic disease characterized by malonic and methylmalonic aciduria, with urinary excretion of much larger amounts of methylmalonic acid than malonic acid, in the presence of normal malonyl-CoA decarboxylase activity. Clinical features include coma, ketoacidosis, hypoglycemia, failure to thrive, microcephaly, dystonia, axial hypotonia and/or developmental delay, and neurologic manifestations including seizures, psychiatric disease and/or cognitive decline. Ref.9 |
| Sequence similarities | Belongs to the ATP-dependent AMP-binding enzyme family. |
| Sequence caution | The sequence AAH72391.1 differs from that shown. Reason: Aberrant splicing. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Fatty acid metabolism Lipid metabolism |
| Cellular component | Mitochondrion |
| Coding sequence diversity | Polymorphism |
| Domain | Transit peptide |
| Ligand | ATP-binding Nucleotide-binding |
| Molecular function | Ligase |
| PTM | Acetylation |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological process | fatty acid metabolic process Inferred from direct assay Ref.6. Source: UniProtKB |
| Cellular component | mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW acid-thiol ligase activityInferred from direct assay Ref.6. Source: UniProtKB |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Transit peptide | 1 – 83 | 83 | Mitochondrion Potential | ||||||
| Chain | 84 – 576 | 493 | Acyl-CoA synthetase family member 3, mitochondrial | PRO_0000315800 | |||||
Regions | |||||||||
| Nucleotide binding | 202 – 210 | 9 | ATP By similarity | ||||||
Sites | |||||||||
| Binding site | 457 | 1 | ATP By similarity | ||||||
| Binding site | 471 | 1 | ATP By similarity | ||||||
| Binding site | 563 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 439 | 1 | N6-acetyllysine Ref.7 | ||||||
Natural variations | |||||||||
| Natural variant | 2 | 1 | L → P. Ref.5 Corresponds to variant rs7188200 [ dbSNP | Ensembl ]. | VAR_038306 | |||||
| Natural variant | 17 | 1 | A → P. Ref.5 Corresponds to variant rs11547019 [ dbSNP | Ensembl ]. | VAR_038307 | |||||
| Natural variant | 198 | 1 | M → R in CMAMMA. Ref.9 | VAR_066504 | |||||
| Natural variant | 243 | 1 | P → L in CMAMMA. Ref.9 Corresponds to variant rs140986055 [ dbSNP | Ensembl ]. | VAR_066505 | |||||
| Natural variant | 358 | 1 | T → I in CMAMMA. Ref.9 | VAR_066506 | |||||
| Natural variant | 359 | 1 | E → K in CMAMMA. Ref.9 Corresponds to variant rs150487794 [ dbSNP | Ensembl ]. | VAR_066507 | |||||
| Natural variant | 372 | 1 | V → M. Ref.5 Corresponds to variant rs3743979 [ dbSNP | Ensembl ]. | VAR_038308 | |||||
| Natural variant | 462 | 1 | K → T in CMAMMA. Ref.9 | VAR_066508 | |||||
| Natural variant | 465 – 470 | 6 | Missing in CMAMMA. | VAR_066509 | |||||
| Natural variant | 471 | 1 | R → Q in CMAMMA. Ref.9 | VAR_066510 | |||||
| Natural variant | 471 | 1 | R → W in CMAMMA. Ref.9 Corresponds to variant rs138680796 [ dbSNP | Ensembl ]. | VAR_066511 | |||||
| Natural variant | 480 | 1 | G → S in CMAMMA. Ref.9 | VAR_066512 | |||||
| Natural variant | 558 | 1 | R → W in CMAMMA. Ref.9 Corresponds to variant rs141090143 [ dbSNP | Ensembl ]. | VAR_066513 | |||||
Experimental info | |||||||||
| Sequence conflict | 148 | 1 | A → V in AAH28399. Ref.5 | ||||||
| Sequence conflict | 278 | 1 | K → E in BAC11654. Ref.2 | ||||||
Sequences
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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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [2] | "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. Isogai T.DNA Res. 12:117-126(2005) [PubMed: 16303743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Embryo. |
| [3] | "The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. Pennacchio L.A.Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | 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]. |
| [5] | "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], VARIANTS PRO-2; PRO-17 AND MET-372. Tissue: Brain. |
| [6] | "Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome." Watkins P.A., Maiguel D., Jia Z., Pevsner J. J. Lipid Res. 48:2736-2750(2007) [PubMed: 17762044] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY. |
| [7] | "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-439, MASS SPECTROMETRY. |
| [8] | "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]. |
| [9] | "Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria." Sloan J.L., Johnston J.J., Manoli I., Chandler R.J., Krause C., Carrillo-Carrasco N., Chandrasekaran S.D., Sysol J.R., O'Brien K., Hauser N.S., Sapp J.C., Dorward H.M., Huizing M., Barshop B.A., Berry S.A., James P.M., Champaigne N.L., de Lonlay P. Venditti C.P.Nat. Genet. 43:883-886(2011) [PubMed: 21841779] [Abstract] Cited for: VARIANTS CMAMMA ARG-198; LEU-243; ILE-358; LYS-359; THR-462; 465-GLN--GLY-470 DEL; GLN-471; TRP-471; SER-480 AND TRP-558, FUNCTION, SUBCELLULAR LOCATION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AK075499 mRNA. Translation: BAC11654.1. AK290963 mRNA. Translation: BAF83652.1. AC009113 Genomic DNA. No translation available. AC135782 Genomic DNA. No translation available. CH471184 Genomic DNA. Translation: EAW66744.1. BC028399 mRNA. Translation: AAH28399.1. BC072391 mRNA. Translation: AAH72391.1. Sequence problems. |
| IPI | IPI00166395. IPI00450347. |
| RefSeq | NP_001120686.1. NM_001127214.2. NP_001230208.1. NM_001243279.1. NP_777577.2. NM_174917.3. |
| UniGene | Hs.461727. |
3D structure databases | |
| ProteinModelPortal | Q4G176. |
| SMR | Q4G176. Positions 40-572. |
| ModBase | Search... |
PTM databases | |
| PhosphoSite | Q4G176. |
Polymorphism databases | |
| DMDM | 296439438. |
Proteomic databases | |
| PRIDE | Q4G176. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000317447; ENSP00000320646; ENSG00000176715. ENST00000406948; ENSP00000384627; ENSG00000176715. |
| GeneID | 197322. |
| KEGG | hsa:197322. |
Organism-specific databases | |
| CTD | 197322. |
| GeneCards | GC16P089160. |
| H-InvDB | HIX0013347. |
| HGNC | HGNC:27288. ACSF3. |
| HPA | HPA008322. HPA008323. |
| MIM | 614245. gene. 614265. phenotype. |
| neXtProt | NX_Q4G176. |
| PharmGKB | PA162375375. |
| GenAtlas | Search... |
Phylogenomic databases | |
| GeneTree | ENSGT00530000062988. |
| HOGENOM | HBG547964. |
| HOVERGEN | HBG100430. |
| InParanoid | Q4G176. |
| OMA | EEIPRNQ. |
| OrthoDB | EOG4NCMCN. |
| PhylomeDB | Q4G176. |
Gene expression databases | |
| ArrayExpress | Q4G176. |
| Bgee | Q4G176. |
| CleanEx | HS_ACSF3. |
| Genevestigator | Q4G176. |
Family and domain databases | |
| InterPro | IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. [Graphical view] |
| Pfam | PF00501. AMP-binding. 1 hit. [Graphical view] |
| PROSITE | PS00455. AMP_BINDING. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| SOURCE | Search... |
Entry information
| Entry name | ACSF3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q4G176 Secondary accession number(s): A8K4J8 Q8N2F7 | ||||||||
| Entry history |
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| 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 16 Human chromosome 16: 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 |
| SIMILARITY comments Index of protein domains and families |

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