Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial

Details

Name

Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial

Synonyms

• 3-methylcrotonyl-CoA carboxylase 1
• 3-methylcrotonyl-CoA carboxylase biotin-containing subunit
• 3-methylcrotonyl-CoA:carbon dioxide ligase subunit alpha
• 6.4.1.4
• MCCA
• MCCase subunit alpha

Gene Name

MCCC1

Organism

Humans

Amino acid sequence

>lcl|BSEQ0000887|Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial
MAAASAVSVLLVAAERNRWHRLPSLLLPPRTWVWRQRTMKYTTATGRNITKVLIANRGEI
ACRVMRTAKKLGVQTVAVYSEADRNSMHVDMADEAYSIGPAPSQQSYLSMEKIIQVAKTS
AAQAIHPGCGFLSENMEFAELCKQEGIIFIGPPPSAIRDMGIKSTSKSIMAAAGVPVVEG
YHGEDQSDQCLKEHARRIGYPVMIKAVRGGGGKGMRIVRSEQEFQEQLESARREAKKSFN
DDAMLIEKFVDTPRHVEVQVFGDHHGNAVYLFERDCSVQRRHQKIIEEAPAPGIKSEVRK
KLGEAAVRAAKAVNYVGAGTVEFIMDSKHNFCFMEMNTRLQVEHPVTEMITGTDLVEWQL
RIAAGEKIPLSQEEITLQGHAFEARIYAEDPSNNFMPVAGPLVHLSTPRADPSTRIETGV
RQGDEVSVHYDPMIAKLVVWAADRQAALTKLRYSLRQYNIVGLHTNIDFLLNLSGHPEFE
AGNVHTDFIPQHHKQLLLSRKAAAKESLCQAALGLILKEKAMTDTFTLQAHDQFSPFSSS
SGRRLNISYTRNMTLKDGKNNVAIAVTYNHDGSYSMQIEDKTFQVLGNLYSEGDCTYLKC
SVNGVASKAKLIILENTIYLFSKEGSIEIDIPVPKYLSSVSSQETQGGPLAPMTGTIEKV
FVKAGDKVKAGDSLMVMIAMKMEHTIKSPKDGTVKKVFYREGAQANRHTPLVEFEEEESD
KRESE

Number of residues

725

Molecular Weight

80472.45

Theoretical pI

7.86

GO Classification

Functions

ATP binding / biotin binding / biotin carboxylase activity / metal ion binding / methylcrotonoyl-CoA carboxylase activity

Processes

biotin metabolic process / branched-chain amino acid catabolic process / cellular nitrogen compound metabolic process / leucine catabolic process / small molecule metabolic process / vitamin metabolic process / water-soluble vitamin metabolic process

Components

cytosol / mitochondrial inner membrane / mitochondrial matrix / mitochondrion

General Function

Methylcrotonoyl-coa carboxylase activity

Specific Function

Biotin-attachment subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism.

Pfam Domain Function

• Biotin_lipoyl (PF00364)
• Biotin_carb_C (PF02785)
• Biotin_carb_N (PF00289)
• CPSase_L_D2 (PF02786)

Transmembrane Regions

Not Available

Cellular Location

Mitochondrion matrix

Gene sequence

>lcl|BSEQ0010310|Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial (MCCC1)
ATGGGTGTGGAGGCAAAGAACCATGAAGTACACAACAGCCACAGGCAGATGAAGCATATT
CCATCGGCCCCGCTCCCTCCCAGCAGAGCTACCTATCTATGGAGAAAATCATTCAAGTGG
CCAAGACCTCTGCTGCACAGCACATCCAAATCCATAATGGCTGCTGCTGGAGTACCTGTT
GTGGAGGGTTATCATGGTGAGGACCAATCAGACCAGTGCCTGAAGGAACACGCCAGGAGA
ATTGGCTATCCTGTCATGATTAAAGCCGTCCGGGGTGGAGGAGGAAAAGGAATGAGGATT
GTTAGATCAGAACAAGAATTTCAAGAACAGTTAGAGTCAGCACGGAGAGAAGCTAAGAAG
TCTTTCAATGATGATGCTATGCTGATCGAGAAGTTTGTAGACACACCGAGGCATGTAGAA
GTCCAGGTGTTTGGTGATCACCATGGCAATGCTGTGTACTTGTTTGAAAGAGACTGTAGT
GTGCAGAGGCGACATCAGAAGATCATTGAGGAGGCCCCAGCGCCTGGTATTAAATCTGAA
GTAAGAAAAAAGCTGGGAGAAGCTGCAGTCAGAGCTGCTAAAGCTGTAAATTATGTTGGA
GCAGGGACTGTGGAGTTTATTATGGACTCAAAACATAATTTCTGTTTCATGGAGATGAAT
ACAAGGCTGCAAGTGGAACATCCTGTTACTGAGATGATCACAGGAACTGACTTGGTGGAG
TGGCAGCTTAGAATTGCAGCAGGAGAGAAGATTCCTTTGAGCCAGGAAGAAATAACTCTG
CAGGGCCATGCCTTCGAAGCTAGAATATATGCAGAAGATCCTAGCAATAACTTCATGCCT
GTGGCAGGCCCATTAGTGCACCTCTCTACTCCTCGAGCAGACCCTTCCACCAGGATTGAA
ACTGGAGTACGGCAAGGAGACGAAGTTTCCGTGCATTATGACCCCATGATTGCGAAGCTG
GTCGTGTGGGCAGCAGATCGCCAGGCGGCATTGACAAAACTGAGGTACAGCCTTCGTCAG
TACAATATTGTTGGACTGCACACCAACATTGACTTCTTACTCAACCTGTCTGGCCACCCA
GAGTTTGAAGCTGGGAACGTGCACACTGATTTCATCCCTCAACACCACAAACAGTTGTTG
CTCAGTCGGAAGGCTGCAGCCAAAGAGTCTTTATGCCAGGCAGCCCTGGGTCTCATCCTC
AAGGAGAAAGCCATGACCGACACTTTCACTCTTCAGGCACATGATCAATTCTCTCCATTT
TCGTCTAGCAGTGGAAGAAGACTGAATATCTCGTATACCAGAAACATGACTCTTAAAGAT
GGTAAAAACAATGTAGCCATAGCTGTAACGTATAACCATGATGGGTCTTATAGCATGCAG
ATTGAAGATAAAACTTTCCAAGTCCTTGGTAATCTTTACAGCGAGGGAGACTGCACTTAC
CTGAAATGTTCTGTTAATGGAGTTGCTAGTAAAGCGAAGCTGATTATCCTGGAAAACACT
ATTTACCTATTTTCCAAGGAAGGAAGTATTGAGATTGACATTCCAGTCCCCAAATACTTA
TCTTCTGTGAGCTCACAAGAAACTCAGGGCGGCCCCTTAGCTCCTATGACTGGAACCATT
GAAAAGGTGTTTGTCAAAGCTGGAGACAAAGTGAAAGCGGGAGATTCCCTCATGGTTATG
ATCGCCATGAAGATGGAGCATACCATAAAGTCTCCAAAGGATGGCACAGTAAAGAAAGTG
TTCTACAGAGAAGGTGCTCAGGCCAACAGACACACTCCTTTAGTCGAGTTTGAGGAGGAA
GAATCAGACAAAAGGGAATCGGAATAA

Chromosome Location

3

Locus

3q27

External Identifiers

Resource	Link
UniProtKB ID	Q96RQ3
UniProtKB Entry Name	MCCA_HUMAN
GenBank Protein ID	12382296
GenBank Gene ID	AF310972
GenAtlas ID	MCCC1
HGNC ID	HGNC:6936

General References

1. Gallardo ME, Desviat LR, Rodriguez JM, Esparza-Gordillo J, Perez-Cerda C, Perez B, Rodriguez-Pombo P, Criado O, Sanz R, Morton DH, Gibson KM, Le TP, Ribes A, de Cordoba SR, Ugarte M, Penalva MA: The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism. Am J Hum Genet. 2001 Feb;68(2):334-46. Epub 2001 Jan 17. [Article]
2. Obata K, Fukuda T, Morishita R, Abe S, Asakawa S, Yamaguchi S, Yoshino M, Ihara K, Murayama K, Shigemoto K, Shimizu N, Kondo I: Human biotin-containing subunit of 3-methylcrotonyl-CoA carboxylase gene (MCCA): cDNA sequence, genomic organization, localization to chromosomal band 3q27, and expression. Genomics. 2001 Mar 1;72(2):145-52. [Article]
3. Holzinger A, Roschinger W, Lagler F, Mayerhofer PU, Lichtner P, Kattenfeld T, Thuy LP, Nyhan WL, Koch HG, Muntau AC, Roscher AA: Cloning of the human MCCA and MCCB genes and mutations therein reveal the molecular cause of 3-methylcrotonyl-CoA: carboxylase deficiency. Hum Mol Genet. 2001 Jun 1;10(12):1299-306. [Article]
4. Baumgartner MR, Almashanu S, Suormala T, Obie C, Cole RN, Packman S, Baumgartner ER, Valle D: The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency. J Clin Invest. 2001 Feb;107(4):495-504. [Article]
5. 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
7. Stadler SC, Polanetz R, Meier S, Mayerhofer PU, Herrmann JM, Anslinger K, Roscher AA, Roschinger W, Holzinger A: Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA carboxylase. Biochem Biophys Res Commun. 2005 Sep 2;334(3):939-46. [Article]
8. Chu CH, Cheng D: Expression, purification, characterization of human 3-methylcrotonyl-CoA carboxylase (MCCC). Protein Expr Purif. 2007 Jun;53(2):421-7. Epub 2007 Feb 2. [Article]
9. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
10. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
11. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
12. Dantas MF, Suormala T, Randolph A, Coelho D, Fowler B, Valle D, Baumgartner MR: 3-Methylcrotonyl-CoA carboxylase deficiency: mutation analysis in 28 probands, 9 symptomatic and 19 detected by newborn screening. Hum Mutat. 2005 Aug;26(2):164. [Article]
13. Uematsu M, Sakamoto O, Sugawara N, Kumagai N, Morimoto T, Yamaguchi S, Hasegawa Y, Kobayashi H, Ihara K, Yoshino M, Watanabe Y, Inokuchi T, Yokoyama T, Kiwaki K, Nakamura K, Endo F, Tsuchiya S, Ohura T: Novel mutations in five Japanese patients with 3-methylcrotonyl-CoA carboxylase deficiency. J Hum Genet. 2007;52(12):1040-3. Epub 2007 Oct 30. [Article]
14. Nguyen KV, Naviaux RK, Patra S, Barshop BA, Nyhan WL: Novel mutations in the human MCCA and MCCB gene causing methylcrotonylglycinuria. Mol Genet Metab. 2011 Feb;102(2):218-21. doi: 10.1016/j.ymgme.2010.10.008. Epub 2010 Oct 20. [Article]
15. Cho SY, Park HD, Lee YW, Ki CS, Lee SY, Sohn YB, Park SW, Kim SH, Ji S, Kim SJ, Choi EW, Kim CH, Ko AR, Paik KH, Lee DH, Jin DK: Mutational spectrum in eight Korean patients with 3-methylcrotonyl-CoA carboxylase deficiency. Clin Genet. 2012 Jan;81(1):96-8. doi: 10.1111/j.1399-0004.2011.01704.x. [Article]
16. Morscher RJ, Grunert SC, Burer C, Burda P, Suormala T, Fowler B, Baumgartner MR: A single mutation in MCCC1 or MCCC2 as a potential cause of positive screening for 3-methylcrotonyl-CoA carboxylase deficiency. Mol Genet Metab. 2012 Apr;105(4):602-6. doi: 10.1016/j.ymgme.2011.12.018. Epub 2011 Dec 31. [Article]
17. Grunert SC, Stucki M, Morscher RJ, Suormala T, Burer C, Burda P, Christensen E, Ficicioglu C, Herwig J, Kolker S, Moslinger D, Pasquini E, Santer R, Schwab KO, Wilcken B, Fowler B, Yue WW, Baumgartner MR: 3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical, enzymatic and molecular studies in 88 individuals. Orphanet J Rare Dis. 2012 May 29;7:31. doi: 10.1186/1750-1172-7-31. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB00121	Biotin	approved, investigational, nutraceutical	unknown	cofactor	Details