Q4G176 (ACSF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acyl-CoA synthetase family member 3, mitochondrial
EC=6.2.1.-

Gene names

Name:	ACSF3
ORF Names:	PSEC0197

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.8
Subcellular location	Mitochondrion Ref.8.
Involvement in disease	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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8
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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fatty acid biosynthetic process Inferred from direct assay PubMed 21846720. Source: UniProtKB malonate catabolic process Inferred from direct assay PubMed 21642549PubMed 21846720. Source: UniProtKB
Cellular_component	mitochondrion Inferred from direct assay PubMed 21846720. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW malonyl-CoA synthetase activity Inferred from direct assay PubMed 21642549PubMed 21846720. 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
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.8		VAR_066504
	Natural variant	243	1	P → L in CMAMMA. Ref.8 Corresponds to variant rs140986055 [ dbSNP | Ensembl ].		VAR_066505
	Natural variant	358	1	T → I in CMAMMA. Ref.8		VAR_066506
	Natural variant	359	1	E → K in CMAMMA. Ref.8 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.8		VAR_066508
	Natural variant	465 – 470	6	Missing in CMAMMA.		VAR_066509
	Natural variant	471	1	R → Q in CMAMMA. Ref.8		VAR_066510
	Natural variant	471	1	R → W in CMAMMA. Ref.8 Corresponds to variant rs138680796 [ dbSNP | Ensembl ].		VAR_066511
	Natural variant	480	1	G → S in CMAMMA. Ref.8		VAR_066512
	Natural variant	558	1	R → W in CMAMMA. Ref.8 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

	Sequence		Length	Mass (Da)
	Q4G176 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 60F0D5020817EF70	FASTA	576	64,130
	10 20 30 40 50 60 MLPHVVLTFR RLGCALASCR LAPARHRGSG LLHTAPVARS DRSAPVFTRA LAFGDRIALV 70 80 90 100 110 120 DQHGRHTYRE LYSRSLRLSQ EICRLCGCVG GDLREERVSF LCANDASYVV AQWASWMSGG 130 140 150 160 170 180 VAVPLYRKHP AAQLEYVICD SQSSVVLASQ EYLELLSPVV RKLGVPLLPL TPAIYTGAVE 190 200 210 220 230 240 EPAEVPVPEQ GWRNKGAMII YTSGTTGRPK GVLSTHQNIR AVVTGLVHKW AWTKDDVILH 250 260 270 280 290 300 VLPLHHVHGV VNALLCPLWV GATCVMMPEF SPQQVWEKFL SSETPRINVF MAVPTIYTKL 310 320 330 340 350 360 MEYYDRHFTQ PHAQDFLRAV CEEKIRLMVS GSAALPLPVL EKWKNITGHT LLERYGMTEI 370 380 390 400 410 420 GMALSGPLTT AVRLPGSVGT PLPGVQVRIV SENPQREACS YTIHAEGDER GTKVTPGFEE 430 440 450 460 470 480 KEGELLVRGP SVFREYWNKP EETKSAFTLD GWFKTGDTVV FKDGQYWIRG RTSVDIIKTG 490 500 510 520 530 540 GYKVSALEVE WHLLAHPSIT DVAVIGVPDM TWGQRVTAVV TLREGHSLSH RELKEWARNV 550 560 570 LAPYAVPSEL VLVEEIPRNQ MGKIDKKALI RHFHPS

References

	« Hide 'large scale' referencesShow '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. , 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].
[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. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [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. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [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. , 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].
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY.
[7]	"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].
[8]	"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. , Valayannopoulos V., Geschwind M.D., Gavrilov D.K., Nyhan W.L., Biesecker L.G., Venditti C.P. Nat. Genet. 43:883-886(2011) [PubMed] [Europe PMC] [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. Hs.720526.
3D structure databases
ProteinModelPortal	Q4G176.
SMR	Q4G176. Positions 43-564.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000320646.
PTM databases
PhosphoSite	Q4G176.
Polymorphism databases
DMDM	296439438.
Proteomic databases
PaxDb	Q4G176.
PRIDE	Q4G176.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000317447; ENSP00000320646; ENSG00000176715. ENST00000406948; ENSP00000384627; ENSG00000176715.
GeneID	197322.
KEGG	hsa:197322.
UCSC	uc002fmp.3. human.
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.
Orphanet	289504. Combined malonic and methylmalonic acidemia.
PharmGKB	PA162375375.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0318.
HOGENOM	HOG000229983.
HOVERGEN	HBG100430.
InParanoid	Q4G176.
OMA	ALEVEWH.
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
GenomeRNAi	197322.
NextBio	89644.
SOURCE	Search...

Entry information

Entry name

ACSF3_HUMAN

Accession

Primary (citable) accession number: Q4G176
Secondary accession number(s): A8K4J8 , C9JQL6, Q6INA0, Q8N2F7

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 69 of the entry and version 3 of the sequence. [Complete 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.