P11310 (ACADM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Medium-chain specific acyl-CoA dehydrogenase, mitochondrial
Short name=MCAD
EC=1.3.8.7

Gene names

Name:

ACADM

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	421 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	This enzyme is specific for acyl chain lengths of 4 to 16.
Catalytic activity	A medium-chain acyl-CoA + electron-transfer flavoprotein = a medium-chain trans-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein.
Cofactor	FAD.
Pathway	Lipid metabolism; mitochondrial fatty acid beta-oxidation.
Subunit structure	Homotetramer. Interacts with the heterodimeric electron transfer flavoprotein ETF. Ref.12 Ref.13 Ref.14
Subcellular location	Mitochondrion matrix.
Involvement in disease	Acyl-CoA dehydrogenase medium-chain deficiency (ACADMD) [MIM:201450]: An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29
Miscellaneous	A number of straight-chain acyl-CoA dehydrogenases of different substrate specificities are present in mammalian tissues. Utilizes the electron transfer flavoprotein (ETF) as electron acceptor that transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase).
Sequence similarities	Belongs to the acyl-CoA dehydrogenase family.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle cell differentiation Inferred from electronic annotation. Source: Compara carnitine biosynthetic process Inferred from mutant phenotype PubMed 16972171. Source: BHF-UCL carnitine metabolic process, CoA-linked Inferred from mutant phenotype PubMed 16972171. Source: BHF-UCL fatty acid beta-oxidation using acyl-CoA dehydrogenase Inferred from direct assay Ref.19PubMed 19224950. Source: BHF-UCL glycogen biosynthetic process Inferred from electronic annotation. Source: Compara liver development Inferred from electronic annotation. Source: Compara medium-chain fatty acid catabolic process Inferred from direct assay PubMed 1970566. Source: BHF-UCL post-embryonic development Inferred from electronic annotation. Source: Compara regulation of gluconeogenesis Inferred from electronic annotation. Source: Compara response to cold Inferred from electronic annotation. Source: Compara response to starvation Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from direct assay PubMed 21237683. Source: UniProtKB mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro identical protein binding Inferred from direct assay PubMed 19224950. Source: BHF-UCL medium-chain-acyl-CoA dehydrogenase activity Inferred from direct assay Ref.19PubMed 19224950PubMed 1970566. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P11310-1)

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: P11310-2)

The sequence of this isoform differs from the canonical sequence as follows:
     10-10: R → RCSLQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 25

25

Mitochondrion

Chain

26 – 421

396

Medium-chain specific acyl-CoA dehydrogenase, mitochondrial

PRO_0000000502

Regions

Nucleotide binding

158 – 167

10

FAD

Nucleotide binding

191 – 193

3

FAD

Nucleotide binding

306 – 308

3

FAD

Nucleotide binding

316 – 317

2

FAD

Nucleotide binding

374 – 378

5

FAD

Nucleotide binding

403 – 405

3

FAD

Region

278 – 281

4

Substrate binding

Sites

Active site

401

1

Proton acceptor

Binding site

167

1

Substrate; via carbonyl oxygen

Binding site

216

1

Substrate

Binding site

402

1

Substrate; via amide nitrogen

Binding site

413

1

Substrate

Amino acid modifications

Modified residue

279

1

N6-acetyllysine Ref.10

Modified residue

301

1

N6-acetyllysine Ref.10

Natural variations

Alternative sequence

10

1

R → RCSLQ in isoform 2.

VSP_038420

Natural variant

53

1

R → C in ACADMD.

VAR_000317

Natural variant

67

1

Y → H in ACADMD; mild. Ref.27

VAR_013698

Natural variant

78

1

I → T in ACADMD. Ref.27

VAR_015954

Natural variant

115 – 116

2

Missing in ACADMD.

VAR_000318

Natural variant

116

1

C → Y in ACADMD. Ref.24

VAR_015955

Natural variant

121

1

T → I in ACADMD. Ref.27

VAR_015956

Natural variant

132

1

P → R in a breast cancer sample; somatic mutation. Ref.30

VAR_035716

Natural variant

149

1

M → I in ACADMD. Ref.18

VAR_000319

Natural variant

193

1

T → A in ACADMD; the thermostability is markedly decreased. Ref.24 Ref.25

VAR_000320

Natural variant

195

1

G → R in ACADMD. Ref.23

VAR_000321

Natural variant

206

1

R → L in ACADMD. Ref.26

VAR_015957

Natural variant

244

1

C → R in ACADMD. Ref.18

VAR_000322

Natural variant

245

1

S → L in ACADMD. Ref.28

VAR_013699

Natural variant

267

1

G → R in ACADMD. Ref.18

VAR_000323

Natural variant

281

1

R → T in ACADMD; mild or benign clinical phenotype. Ref.29

VAR_013700

Natural variant

310

1

G → R in ACADMD. Ref.27

VAR_015958

Natural variant

326

1

M → T in ACADMD. Ref.21

VAR_000324

Natural variant

329

1

K → E in ACADMD; most common variant. Ref.9 Ref.16 Ref.17 Ref.19 Ref.20 Ref.26 Ref.29

VAR_000325

Natural variant

336

1

S → R in ACADMD. Ref.21

VAR_000326

Natural variant

352

1

Y → C in ACADMD. Ref.24

VAR_015959

Natural variant

375

1

I → T in ACADMD. Ref.18

VAR_000327

Experimental info

Mutagenesis

86

1

L → M: Strongly reduced rate of electron transfer to ETF. Ref.13

Mutagenesis

98

1

L → W: Strongly reduced rate of electron transfer to ETF. Ref.13

Mutagenesis

100

1

L → Y: Strongly reduced rate of electron transfer to ETF. Ref.13

Mutagenesis

108

1

I → M: Strongly reduced rate of electron transfer to ETF. Ref.13

Mutagenesis

191

1

W → A: Loss of electron transfer to ETF. Ref.14

Mutagenesis

191

1

W → F: Reduces rate of electron transfer to ETF about six-fold. Ref.14

Mutagenesis

237

1

E → A: Strongly reduced rate of electron transfer to ETF. Ref.13 Ref.14

Mutagenesis

384

1

E → A: Reduces rate of electron transfer to ETF three-fold. Ref.13 Ref.14

Mutagenesis

384

1

E → Q: Reduces rate of electron transfer to ETF two-fold. Ref.13 Ref.14

Sequence conflict

356

1

I → T in AAF63626. Ref.3

Secondary structure

1

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421

Helix Strand Turn

Details...

Beta strand

36 – 38

3

Helix

43 – 59

17

Helix

61 – 70

10

Helix

75 – 84

10

Helix

93 – 95

3

Helix

102 – 115

14

Helix

117 – 129

13

Helix

131 – 136

6

Helix

139 – 151

13

Beta strand

156 – 159

4

Beta strand

165 – 168

4

Helix

169 – 171

3

Beta strand

175 – 178

4

Beta strand

180 – 193

14

Turn

194 – 197

4

Beta strand

199 – 206

8

Helix

215 – 217

3

Beta strand

219 – 225

7

Beta strand

231 – 233

3

Beta strand

239 – 241

3

Beta strand

247 – 258

12

Helix

259 – 261

3

Beta strand

262 – 265

4

Turn

266 – 268

3

Helix

269 – 303

35

Beta strand

309 – 312

4

Helix

313 – 315

3

Helix

317 – 345

29

Helix

351 – 376

26

Helix

377 – 379

3

Helix

387 – 394

8

Helix

395 – 398

4

Turn

399 – 401

3

Helix

404 – 417

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 7CD0B5832410581B	FASTA	421	46,588
	10 20 30 40 50 60 MAAGFGRCCR VLRSISRFHW RSQHTKANRQ REPGLGFSFE FTEQQKEFQA TARKFAREEI 70 80 90 100 110 120 IPVAAEYDKT GEYPVPLIRR AWELGLMNTH IPENCGGLGL GTFDACLISE ELAYGCTGVQ 130 140 150 160 170 180 TAIEGNSLGQ MPIIIAGNDQ QKKKYLGRMT EEPLMCAYCV TEPGAGSDVA GIKTKAEKKG 190 200 210 220 230 240 DEYIINGQKM WITNGGKANW YFLLARSDPD PKAPANKAFT GFIVEADTPG IQIGRKELNM 250 260 270 280 290 300 GQRCSDTRGI VFEDVKVPKE NVLIGDGAGF KVAMGAFDKT RPVVAAGAVG LAQRALDEAT 310 320 330 340 350 360 KYALERKTFG KLLVEHQAIS FMLAEMAMKV ELARMSYQRA AWEVDSGRRN TYYASIAKAF 370 380 390 400 410 420 AGDIANQLAT DAVQILGGNG FNTEYPVEKL MRDAKIYQIY EGTSQIQRLI VAREHIDKYK N
	Isoform 2 [UniParc]. Checksum: C6A133404E1B6E70	FASTA	425	47,020
	10 20 30 40 50 60 MAAGFGRCCR CSLQVLRSIS RFHWRSQHTK ANRQREPGLG FSFEFTEQQK EFQATARKFA 70 80 90 100 110 120 REEIIPVAAE YDKTGEYPVP LIRRAWELGL MNTHIPENCG GLGLGTFDAC LISEELAYGC 130 140 150 160 170 180 TGVQTAIEGN SLGQMPIIIA GNDQQKKKYL GRMTEEPLMC AYCVTEPGAG SDVAGIKTKA 190 200 210 220 230 240 EKKGDEYIIN GQKMWITNGG KANWYFLLAR SDPDPKAPAN KAFTGFIVEA DTPGIQIGRK 250 260 270 280 290 300 ELNMGQRCSD TRGIVFEDVK VPKENVLIGD GAGFKVAMGA FDKTRPVVAA GAVGLAQRAL 310 320 330 340 350 360 DEATKYALER KTFGKLLVEH QAISFMLAEM AMKVELARMS YQRAAWEVDS GRRNTYYASI 370 380 390 400 410 420 AKAFAGDIAN QLATDAVQIL GGNGFNTEYP VEKLMRDAKI YQIYEGTSQI QRLIVAREHI DKYKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its expression in enzyme-deficient human tissue." Kelly D.P., Kim J.-J.P., Billadello J.J., Hainline B.E., Chu T.W., Strauss A.W. Proc. Natl. Acad. Sci. U.S.A. 84:4068-4072(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Structural organization and regulatory regions of the human medium-chain acyl-CoA dehydrogenase gene." Zhang Z.F., Kelly D.P., Kim J.-J.P., Zhou Y.Q., Ogden M.L., Whelan A.J., Strauss A.W. Biochemistry 31:81-89(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]	"Medium-chain acyl-CoA dehydrogenase." Sun F., Wang Y., Block G.D. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Colon.
[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. , 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] (ISOFORM 1). Tissue: Heart.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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] (ISOFORM 1). Tissue: Liver.
[8]	Lubec G., Vishwanath V. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 218-235, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[9]	"Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency." Matsubara Y., Narisawa K., Miyabayashi S., Tada K., Coates P.M., Bachmann C., Elsas L.J. II, Pollitt R.J., Rhead W.J., Roe C.R. Biochem. Biophys. Res. Commun. 171:498-505(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 314-342, VARIANT ACADMD GLU-329.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-279 AND LYS-301, MASS SPECTROMETRY.
[11]	"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].
[12]	"Crystal structures of the wild type and the Glu376Gly/Thr255Glu mutant of human medium-chain acyl-CoA dehydrogenase: influence of the location of the catalytic base on substrate specificity." Lee H.J., Wang M., Paschke R., Nandy A., Ghisla S., Kim J.-J.P. Biochemistry 35:12412-12420(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH FAD AND OCTANOYL-COENZYME A, SUBUNIT.
[13]	"Extensive domain motion and electron transfer in the human electron transferring flavoprotein-medium chain acyl-CoA dehydrogenase complex." Toogood H.S., van Thiel A., Basran J., Sutcliffe M.J., Scrutton N.S., Leys D. J. Biol. Chem. 279:32904-32912(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 26-421 IN COMPLEXES WITH FAD AND THE ETFA-ETFB HETERODIMER, MUTAGENESIS OF LEU-86; LEU-98; LEU-100; ILE-108; GLU-237 AND GLU-384, SUBUNIT.
[14]	"Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein." Toogood H.S., van Thiel A., Scrutton N.S., Leys D. J. Biol. Chem. 280:30361-30366(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEXES WITH FAD AND THE ETFA-ETFB HETERODIMER, MUTAGENESIS OF TRP-191; GLU-237 AND GLU-384, SUBUNIT.
[15]	"Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene." Tanaka K., Yokota I., Coates P.M., Strauss A.W., Kelly D.P., Zhang Z.F., Gregersen N., Andresen B.S., Matsubara Y., Curtis D., Chen Y.-T. Hum. Mutat. 1:271-279(1992) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS ACADMD.
[16]	"Molecular basis of medium chain acyl-coenzyme A dehydrogenase deficiency. An A to G transition at position 985 that causes a lysine-304 to glutamate substitution in the mature protein is the single prevalent mutation." Yokota I., Indo Y., Coates P.M., Tanaka K. J. Clin. Invest. 86:1000-1003(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ACADMD GLU-329.
[17]	"Molecular characterization of inherited medium-chain acyl-CoA dehydrogenase deficiency." Kelly D.P., Whelan A.J., Ogden M.L., Alpers R., Zhang Z.F., Bellus G., Gregersen N., Dorland L., Strauss A.W. Proc. Natl. Acad. Sci. U.S.A. 87:9236-9240(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ACADMD GLU-329.
[18]	"Molecular survey of a prevalent mutation, 985A-to-G transition, and identification of five infrequent mutations in the medium-chain Acyl-CoA dehydrogenase (MCAD) gene in 55 patients with MCAD deficiency." Yokota I., Coates P.M., Hale D.E., Rinaldo P., Tanaka K. Am. J. Hum. Genet. 49:1280-1291(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ACADMD ILE-149; ARG-244; ARG-267 AND THR-375.
[19]	"Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: identification of a lys329 to glu mutation in the MCAD gene, and expression of inactive mutant enzyme protein in E. coli." Gregersen N., Andresen B.S., Bross P., Winter V., Ruediger N., Engst S., Christensen E., Kelly D., Strauss A.W., Koelvraa S., Bolund L., Ghisla S. Hum. Genet. 86:545-551(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ACADMD GLU-329.
[20]	"Frequency of the G985 MCAD mutation in the general population." Blakemore A.I., Singleton H., Pollitt R.J., Engel P.C., Kolvraa S., Gregersen N., Curtis D. Lancet 337:298-299(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ACADMD GLU-329 FREQUENCY.
[21]	"Disease-causing mutations in exon 11 of the medium-chain acyl-CoA dehydrogenase gene." Andresen B.S., Jensen T.G., Bross P., Knudsen I., Winter V., Koelvraa S., Bolund L., Ding J.-H., Chen Y.-T., van Hove J.L.K., Curtis D., Yokota I., Tanaka K., Kim J.-J.P., Gregersen N. Am. J. Hum. Genet. 54:975-988(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ACADMD THR-326 AND ARG-336.
[22]	"Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal screening shows high incidence and unexpected mutation frequencies." Ziadeh R., Hoffman E.P., Finegold D.N., Hoop R.C., Brackett J.C., Strauss A.W., Naylor E.W. Pediatr. Res. 37:675-678(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ACADMD 115-GLY-CYS-116 DEL.
[23]	"A novel mutation in medium chain acyl-CoA dehydrogenase causes sudden neonatal death." Brackett J.C., Sims H.F., Steiner R.D., Nunge M., Zimmerman E.M., Demartinville B., Rinaldo P., Slaugh R., Strauss A.W. J. Clin. Invest. 94:1477-1483(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ACADMD ARG-195.
[24]	"The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in compound heterozygous patients: is there correlation between genotype and phenotype?" Andresen B.S., Bross P., Udvari S., Kirk J., Gray G., Kmoch S., Chamoles N., Knudsen I., Winter V., Wilcken B., Yokota I., Hart K., Packman S., Harpey J.P., Saudubray J.-M., Hale D.E., Bolund L., Koelvraa S., Gregersen N. Hum. Mol. Genet. 6:695-707(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ACADMD TYR-116; ALA-193 AND CYS-352.
[25]	"Biochemical characterization of a variant human medium-chain acyl-CoA dehydrogenase with a disease-associated mutation localized in the active site." Kuchler B., Abdel-Ghany A.G., Bross P., Nandy A., Rasched I., Ghisla S. Biochem. J. 337:225-230(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT ACADMD ALA-193.
[26]	"Identification of a novel mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency." Yang B.-Z., Ding J.-H., Zhou C., Dimachkie M.M., Sweetman L., Dasouki M.J., Wilkinson J., Roe C.R. Mol. Genet. Metab. 69:259-262(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ACADMD LEU-206 AND GLU-329.
[27]	"Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency." Andresen B.S., Dobrowolski S.F., O'Reilly L., Muenzer J., McCandless S.E., Frazier D.M., Udvari S., Bross P., Knudsen I., Banas R., Chace D.H., Engel P.C., Naylor E.W., Gregersen N. Am. J. Hum. Genet. 68:1408-1418(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ACADMD HIS-67; THR-78; ILE-121 AND ARG-310.
[28]	"Molecular and functional characterization of mild MCAD deficiency." Zschocke J., Schulze A., Lindner M., Fiesel S., Olgemoller K., Hoffmann G.F., Penzien J., Ruiter J.P.N., Wanders R.J.A., Mayatepek E. Hum. Genet. 108:404-408(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ACADMD LEU-245.
[29]	"Compound heterozygosity in four asymptomatic siblings with medium-chain acyl-CoA dehydrogenase deficiency." Albers S., Levy H.L., Irons M., Strauss A.W., Marsden D. J. Inherit. Metab. Dis. 24:417-418(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ACADMD THR-281 AND GLU-329.
[30]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-132.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M16827 mRNA. Translation: AAA51566.1.
M91432 , M91421, M91422, M91423, M91425, M91426, M91427, M91428, M91429, M91430, M91431 Genomic DNA. Translation: AAA59567.1.
AF251043 mRNA. Translation: AAF63626.1.
AK312629 mRNA. Translation: BAG35514.1.
AL357314 Genomic DNA. Translation: CAI22390.1.
CH471059 Genomic DNA. Translation: EAX06401.1.
BC005377 mRNA. Translation: AAH05377.1.
M60505 Genomic DNA. Translation: AAB59625.1.

IPI

IPI00005040.
IPI00895801.

PIR

DEHUCM. A29031.

RefSeq

NP_000007.1. NM_000016.4.
NP_001120800.1. NM_001127328.1.

UniGene

Hs.445040.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EGC	X-ray	2.60	A/B/C/D	26-421	[»]
1EGD	X-ray	2.40	A/B/C/D	26-421	[»]
1EGE	X-ray	2.75	A/B/C/D	26-421	[»]
1T9G	X-ray	2.90	A/B/C/D	26-421	[»]
2A1T	X-ray	2.80	A/B/C/D	1-421	[»]

ProteinModelPortal

P11310.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34281N.

IntAct

P11310. 5 interactions.

STRING

9606.ENSP00000409612.

PTM databases

PhosphoSite

P11310.

Polymorphism databases

DMDM

113017.

2D gel databases

REPRODUCTION-2DPAGE

IPI00005040.

UCD-2DPAGE

P11310.

Proteomic databases

PaxDb

P11310.

PRIDE

P11310.

Protocols and materials databases

DNASU

34.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000370841; ENSP00000359878; ENSG00000117054.
ENST00000420607; ENSP00000409612; ENSG00000117054.

GeneID

34.

KEGG

hsa:34.

UCSC

uc001dgw.4. human.
uc009wbp.3. human.

Organism-specific databases

CTD

34.

GeneCards

GC01P076190.

HGNC

HGNC:89. ACADM.

HPA

HPA006198.
HPA026542.

MIM

201450. phenotype.
607008. gene.

neXtProt

NX_P11310.

Orphanet

42. Medium chain acyl-CoA dehydrogenase deficiency.

PharmGKB

PA24425.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1960.

HOGENOM

HOG000131659.

HOVERGEN

HBG000224.

KO

K00249.

OrthoDB

EOG4G7BZB.

PhylomeDB

P11310.

Enzyme and pathway databases

BioCyc

MetaCyc:HS04089-MONOMER.

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P11310.

UniPathway

UPA00660.

Gene expression databases

ArrayExpress

P11310.

Bgee

P11310.

CleanEx

HS_ACADM.

Genevestigator

P11310.

GermOnline

ENSG00000117054. Homo sapiens.

Family and domain databases

Gene3D

1.10.540.10. 1 hit.
2.40.110.10. 1 hit.

InterPro

IPR006089. Acyl-CoA_DH_CS.
IPR006092. Acyl-CoA_DH_N.
IPR006090. Acyl-CoA_Oxase/DH_1.
IPR006091. Acyl-CoA_Oxase/DH_cen-dom.
IPR009075. AcylCo_DH/oxidase_C.
IPR013786. AcylCoA_DH/ox_N.
IPR009100. AcylCoA_DH/oxidase.
[Graphical view]

Pfam

PF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]

SUPFAM

SSF56645. AcylCoA_dehyd_NM. 1 hit.
SSF47203. AcylCoADH_C_like. 1 hit.

PROSITE

PS00072. ACYL_COA_DH_1. 1 hit.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P11310.

GenomeRNAi

34.

NextBio

131.

SOURCE

Search...

Entry information

Entry name

ACADM_HUMAN

Accession

Primary (citable) accession number: P11310
Secondary accession number(s): Q5T4U4, Q9NYF1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 161 of the entry and version 1 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.