Reviewed, UniProtKB/Swiss-Prot Q08AH3 (ACS2A_HUMAN)

Names and origin

Protein names

Recommended name:
    Acyl-coenzyme A synthetase ACSM2A, mitochondrial
    EC=6.2.1.2
Alternative name(s):
    Acyl-CoA synthetase medium-chain family member 2A
    Middle-chain acyl-CoA synthetase 2A
    Butyryl coenzyme A synthetase 2A
    Butyrate--CoA ligase 2A

Gene names

Name:	ACSM2A
Synonyms:	ACSM2, MACS2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	577 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	Has medium-chain fatty acid:CoA ligase activity with broad substrate specificity (in vitro). Acts on acids from C4 to C(11) and on the corresponding 3-hydroxy- and 2,3- or 3,4-unsaturated acids (in vitro) By similarity.
Catalytic activity	ATP + an acid + CoA = AMP + diphosphate + an acyl-CoA.
Cofactor	Magnesium or manganese.
Subunit structure	Monomer By similarity.
Subcellular location	Mitochondrion matrix By similarity.
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family.
Sequence caution	The sequence AAC23497.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Ligase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW butyrate-CoA ligase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 46

46

Mitochondrion Potential

Chain

47 – 577

531

Acyl-coenzyme A synthetase ACSM2A, mitochondrial

PRO_0000306093

Regions

Nucleotide binding

221 – 229

9

ATP

Nucleotide binding

359 – 364

6

ATP

Region

469 – 471

3

Coenzyme A binding

Region

540 – 542

3

Coenzyme A binding

Sites

Binding site

139

1

Coenzyme A

Binding site

364

1

Substrate

Binding site

446

1

ATP

Binding site

461

1

ATP

Binding site

472

1

Substrate

Binding site

501

1

Coenzyme A

Binding site

532

1

Coenzyme A

Binding site

557

1

ATP

Natural variations

Natural variant

335

1

V → L: dbSNP rs4643305.

VAR_058692

Natural variant

336

1

T → A: dbSNP rs5002299.

VAR_058693

Natural variant

337

1

V → G: dbSNP rs4586421.

VAR_058694

Natural variant

513

1

S → L: dbSNP rs1133607. Ref.4 Ref.7 Ref.8

VAR_035247

Natural variant

561

1

A → T: dbSNP rs1054977.

VAR_035248

Experimental info

Sequence conflict

463

1

N → D in BAG53201. Ref.1

Sequence conflict

463

1

N → D in AAI25177. Ref.3

Sequence conflict

463

1

N → D in AAC23497. Ref.4

Secondary structure

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577

Helix Strand Turn

Details...

Turn

34 – 36

3

Helix

46 – 49

4

Helix

51 – 59

9

Beta strand

67 – 72

6

Beta strand

74 – 76

3

Beta strand

78 – 82

5

Helix

83 – 98

16

Turn

99 – 101

3

Beta strand

108 – 112

5

Helix

117 – 129

13

Beta strand

132 – 135

4

Helix

142 – 152

11

Beta strand

155 – 160

6

Turn

161 – 163

3

Helix

164 – 170

7

Helix

171 – 173

3

Beta strand

179 – 186

8

Beta strand

191 – 193

3

Helix

194 – 200

7

Beta strand

214 – 221

8

Beta strand

224 – 227

4

Beta strand

229 – 234

6

Helix

235 – 245

11

Turn

246 – 249

4

Beta strand

256 – 259

4

Helix

266 – 271

6

Helix

274 – 279

6

Beta strand

282 – 286

5

Helix

293 – 302

10

Beta strand

307 – 309

3

Helix

312 – 319

8

Turn

323 – 325

3

Beta strand

333 – 336

4

Helix

343 – 353

11

Beta strand

358 – 363

6

Turn

364 – 366

3

Beta strand

367 – 371

5

Beta strand

392 – 395

4

Beta strand

408 – 413

6

Helix

430 – 435

6

Beta strand

441 – 450

10

Beta strand

456 – 464

9

Beta strand

466 – 468

3

Beta strand

471 – 473

3

Helix

475 – 483

9

Beta strand

488 – 498

11

Turn

499 – 501

3

Beta strand

502 – 511

10

Helix

513 – 515

3

Helix

520 – 534

15

Helix

537 – 539

3

Beta strand

542 – 546

5

Helix

560 – 567

8

Sequences

	Sequence		Length	Mass (Da)
	Q08AH3-1 [UniParc]. Last modified September 1, 2009. Version 2. Checksum: 16167FC69562436F	FASTA	577	64,223
	10 20 30 40 50 60 MHWLRKVQGL CTLWGTQMSS RTLYINSRQL VSLQWGHQEV PAKFNFASDV LDHWADMEKA 70 80 90 100 110 120 GKRLPSPALW WVNGKGKELM WNFRELSENS QQAANVLSGA CGLQRGDRVA VVLPRVPEWW 130 140 150 160 170 180 LVILGCIRAG LIFMPGTIQM KSTDILYRLQ MSKAKAIVAG DEVIQEVDTV ASECPSLRIK 190 200 210 220 230 240 LLVSEKSCDG WLNFKKLLNE ASTTHHCVET GSQEASAIYF TSGTSGLPKM AEHSYSSLGL 250 260 270 280 290 300 KAKMDAGWTG LQASDIMWTI SDTGWILNIL CSLMEPWALG ACTFVHLLPK FDPLVILKTL 310 320 330 340 350 360 SSYPIKSMMG APIVYRMLLQ QDLSSYKFPH LQNCVTVGES LLPETLENWR AQTGLDIRES 370 380 390 400 410 420 YGQTETGLTC MVSKTMKIKP GYMGTAASCY DVQIIDDKGN VLPPGTEGDI GIRVKPIRPI 430 440 450 460 470 480 GIFSGYVDNP DKTAANIRGD FWLLGDRGIK DEDGYFQFMG RANDIINSSG YRIGPSEVEN 490 500 510 520 530 540 ALMEHPAVVE TAVISSPDPV RGEVVKAFVV LASQFLSHDP EQLTKELQQH VKSVTAPYKY 550 560 570 PRKIEFVLNL PKTVTGKIQR AKLRDKEWKM SGKARAQ

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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[2]	"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: 15616553] [Abstract] 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].
[4]	"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q." Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D. Genomics 60:295-308(1999) [PubMed: 10493829] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 299-577, VARIANT LEU-513.
[5]	"Crystal structure of L64P mutant of human acyl-CoA synthetase medium-chain family member 2A." Structural genomics consortium (SGC) Submitted (FEB-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH AMP AND MAGNESIUM.
[6]	"Structural snapshots for the conformation-dependent catalysis by human medium-chain acyl-coenzyme A synthetase ACSM2A." Kochan G., Pilka E.S., von Delft F., Oppermann U., Yue W.W. J. Mol. Biol. 388:997-1008(2009) [PubMed: 19345228] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 32-577 IN COMPLEXES WITH ATP; COENZYME A; IBUPROFEN AND MAGNESIUM.
[7]	"An acyl-CoA synthetase gene family in chromosome 16p12 may contribute to multiple risk factors." Iwai N., Mannami T., Tomoike H., Ono K., Iwanaga Y. Hypertension 41:1041-1046(2003) [PubMed: 12654705] [Abstract] Cited for: VARIANT LEU-513.
[8]	"The L513S polymorphism in medium-chain acyl-CoA synthetase 2 (MACS2) is associated with risk factors of the metabolic syndrome in a Caucasian study population." Lindner I., Rubin D., Helwig U., Nitz I., Hampe J., Schreiber S., Schrezenmeir J., Doering F. Mol. Nutr. Food Res. 50:270-274(2006) [PubMed: 16521160] [Abstract] Cited for: VARIANT LEU-513.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AK096039 mRNA. Translation: BAG53201.1.
AC137056 Genomic DNA. No translation available.
BC125176 mRNA. Translation: AAI25177.1.
AC003034 Genomic DNA. Translation: AAC23497.1. Sequence problems.

IPI

IPI00644771.

RefSeq

NP_001010845.1.

UniGene

Hs.298252

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VZE	X-ray	2.45	A/B/C	32-577	[»]
2WD9	X-ray	2.60	A/B/C	32-576	[»]
3B7W	X-ray	2.00	A	32-577	[»]
3C5E	X-ray	1.60	A	32-577	[»]
3DAY	X-ray	1.95	A	32-577	[»]
3EQ6	X-ray	2.40	A/B	32-577	[»]
3GPC	X-ray	1.90	A/B	32-577	[»]

ModBase

Search...

Proteomic databases

PRIDE

Q08AH3.

Genome annotation databases

Ensembl

ENST00000219054; ENSP00000219054; ENSG00000183747; Homo sapiens. [Genome view]
ENST00000396104; ENSP00000379411; ENSG00000183747; Homo sapiens. [Genome view]
ENST00000417235; ENSP00000392169; ENSG00000183747; Homo sapiens. [Genome view]
ENST00000424070; ENSP00000394904; ENSG00000183747; Homo sapiens. [Genome view]

GeneID

123876.

KEGG

hsa:123876.

UCSC

uc002dhf.2. human.

Organism-specific databases

CTD

123876.

GeneCards

GC16P020372.

HGNC

HGNC:32017. ACSM2A.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q08AH3.

Enzyme and pathway databases

BRENDA

6.2.1.2. 247.

Gene expression databases

ArrayExpress

Q08AH3.

Bgee

Q08AH3.

Genevestigator

Q08AH3.

Family and domain databases

InterPro

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 Resources

NextBio

81177.

Entry information

Entry name

ACS2A_HUMAN

Accession

Primary (citable) accession number: Q08AH3
Secondary accession number(s): B3KTT9, O75202

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 2, 2007
Last sequence update:	September 1, 2009
Last modified:	October 13, 2009
This is version 26 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.