ACSM6_HUMAN
ID ACSM6_HUMAN Reviewed; 480 AA.
AC Q6P461; A4FU95; A4IF38; Q5VZX2; Q6ZTX1;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 3.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Acyl-coenzyme A synthetase ACSM6, mitochondrial;
DE EC=6.2.1.2 {ECO:0000250|UniProtKB:Q08AH1};
DE AltName: Full=Acyl-CoA synthetase medium-chain family member 6;
DE Flags: Precursor;
GN Name=ACSM6; Synonyms=C10orf129;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-415 (ISOFORM 3), AND VARIANTS GLY-19 AND SER-40.
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP REVIEW.
RX PubMed=27351777; DOI=10.1080/17425255.2016.1206888;
RA van der Sluis R., Erasmus E.;
RT "Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its
RT role in fatty acid metabolism and the detoxification of benzoic acid and
RT aspirin.";
RL Expert Opin. Drug Metab. Toxicol. 12:1169-1179(2016).
CC -!- FUNCTION: Catalyzes the activation of fatty acids by CoA to produce an
CC acyl-CoA, the first step in fatty acid metabolism.
CC {ECO:0000250|UniProtKB:Q08AH1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a medium chain fatty acid + ATP + CoA = a medium-chain fatty
CC acyl-CoA + AMP + diphosphate; Xref=Rhea:RHEA:48340,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:59558, ChEBI:CHEBI:90546, ChEBI:CHEBI:456215; EC=6.2.1.2;
CC Evidence={ECO:0000250|UniProtKB:Q08AH1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48341;
CC Evidence={ECO:0000250|UniProtKB:Q08AH1};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q08AH1};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q08AH1};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9BEA2}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6P461-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P461-2; Sequence=VSP_033908, VSP_033910, VSP_033911;
CC Name=3;
CC IsoId=Q6P461-3; Sequence=VSP_033909;
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI04211.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI04212.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI12989.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK126134; BAC86458.1; -; mRNA.
DR EMBL; AL157834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC063654; AAH63654.1; -; mRNA.
DR EMBL; BC104210; AAI04211.1; ALT_INIT; mRNA.
DR EMBL; BC104211; AAI04212.1; ALT_INIT; mRNA.
DR EMBL; BC112988; AAI12989.1; ALT_INIT; mRNA.
DR CCDS; CCDS7440.2; -. [Q6P461-1]
DR RefSeq; NP_997204.2; NM_207321.2. [Q6P461-1]
DR AlphaFoldDB; Q6P461; -.
DR SMR; Q6P461; -.
DR STRING; 9606.ENSP00000340296; -.
DR iPTMnet; Q6P461; -.
DR PhosphoSitePlus; Q6P461; -.
DR BioMuta; ACSM6; -.
DR PaxDb; Q6P461; -.
DR PeptideAtlas; Q6P461; -.
DR PRIDE; Q6P461; -.
DR Antibodypedia; 48989; 62 antibodies from 17 providers.
DR DNASU; 142827; -.
DR Ensembl; ENST00000341686.7; ENSP00000340296.3; ENSG00000173124.14. [Q6P461-1]
DR Ensembl; ENST00000394005.3; ENSP00000377573.3; ENSG00000173124.14. [Q6P461-1]
DR GeneID; 142827; -.
DR KEGG; hsa:142827; -.
DR MANE-Select; ENST00000394005.4; ENSP00000377573.3; NM_207321.3; NP_997204.2.
DR UCSC; uc001kke.4; human. [Q6P461-1]
DR CTD; 142827; -.
DR GeneCards; ACSM6; -.
DR HGNC; HGNC:31665; ACSM6.
DR HPA; ENSG00000173124; Group enriched (lymphoid tissue, pancreas, skin, stomach, urinary bladder).
DR neXtProt; NX_Q6P461; -.
DR OpenTargets; ENSG00000173124; -.
DR PharmGKB; PA134905303; -.
DR VEuPathDB; HostDB:ENSG00000173124; -.
DR eggNOG; KOG1175; Eukaryota.
DR GeneTree; ENSGT00940000165168; -.
DR HOGENOM; CLU_000022_59_10_1; -.
DR InParanoid; Q6P461; -.
DR OMA; SNKYYPH; -.
DR OrthoDB; 683933at2759; -.
DR PhylomeDB; Q6P461; -.
DR TreeFam; TF354287; -.
DR PathwayCommons; Q6P461; -.
DR Reactome; R-HSA-77352; Beta oxidation of butanoyl-CoA to acetyl-CoA.
DR BioGRID-ORCS; 142827; 5 hits in 1060 CRISPR screens.
DR ChiTaRS; ACSM6; human.
DR GenomeRNAi; 142827; -.
DR Pharos; Q6P461; Tdark.
DR PRO; PR:Q6P461; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q6P461; protein.
DR Bgee; ENSG00000173124; Expressed in thymus and 53 other tissues.
DR ExpressionAtlas; Q6P461; baseline and differential.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047760; F:butyrate-CoA ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0015645; F:fatty acid ligase activity; IBA:GO_Central.
DR GO; GO:0004321; F:fatty-acyl-CoA synthase activity; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0031956; F:medium-chain fatty acid-CoA ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006637; P:acyl-CoA metabolic process; IBA:GO_Central.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Fatty acid metabolism; GTP-binding;
KW Ligase; Lipid metabolism; Magnesium; Metal-binding; Mitochondrion;
KW Nucleotide-binding; Reference proteome; Transit peptide.
FT TRANSIT 1..21
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 22..480
FT /note="Acyl-coenzyme A synthetase ACSM6, mitochondrial"
FT /id="PRO_0000337112"
FT BINDING 226..234
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 366..371
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 453
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 468
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..155
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033908"
FT VAR_SEQ 65
FT /note="D -> DNGLQLHPCCCKRQDFILFHGVIFHVD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033909"
FT VAR_SEQ 332..341
FT /note="SYRFKSLKQC -> RVYSVPLPKQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033910"
FT VAR_SEQ 342..480
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033911"
FT VARIANT 19
FT /note="E -> G (in dbSNP:rs591157)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_063090"
FT VARIANT 40
FT /note="C -> S (in dbSNP:rs11188225)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_063091"
FT VARIANT 227
FT /note="K -> R (in dbSNP:rs7090248)"
FT /id="VAR_043606"
SQ SEQUENCE 480 AA; 53585 MW; E33F51846DBB8253 CRC64;
MLGRFQPFSL VRSFRLGFEA CCYPNQKCAT QTIRPPDSRC LVQAVSQNFN FAKDVLDQWS
QLEKDGLRGP YPALWKVSAK GEEDKWSFER MTQLSKKAAS ILSDTCALSH GDRLMIILPP
TPEAYWICLA CVRLGITFVP GSPQLTAKKI RYQLRMSKAQ CIVANEAMAP VVNSAVSDCP
TLKTKLLVSD KSYDGWLDFK KLIQVAPPKQ TYMRTKSQDP MAIFFTKGTT GAPKMVEYSQ
YGLGMGFSQA SRRWMDLQPT DVLWSLGDAF GGSLSLSAVL GTWFQGACVF LCHMPTFCPE
TVLNVLSRFP ITTLSANPEM YQELLQHKCF TSYRFKSLKQ CVAAGGPISP GVIEDWKRIT
KLDIYEGYGQ TETGLLCATS KTIKLKPSSL GKPLPPYIVQ IVDENSNLLP PGEEGNIAIR
IKLNQPASLY CPHMVSWEEY ASARGHMLYL TGDRGIMDED GYFWWSGRVD DVANALGQRL
