Reviewed, UniProtKB/Swiss-Prot Q9HCC0 (MCCB_HUMAN)

Names and origin

Protein names

Recommended name:
    Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial
      Short name=MCCase subunit beta
    EC=6.4.1.4
Alternative name(s):
    3-methylcrotonyl-CoA:carbon dioxide ligase subunit beta
    3-methylcrotonyl-CoA carboxylase non-biotin-containing subunit
    3-methylcrotonyl-CoA carboxylase 2

Gene names

Name:	MCCC2
Synonyms:	MCCB

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	563 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)

Catalytic activity	ATP + 3-methylcrotonoyl-CoA + HCO3- = ADP + phosphate + 3-methylglutaconyl-CoA.
Pathway	Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 2/3.
Subunit structure	Probably a dodecamer composed of six biotin-containing alpha subunits and six beta subunits.
Subcellular location	Mitochondrion matrix.
Involvement in disease	Defects in MCCC2 are the cause of methylcrotonoyl-CoA carboxylase deficiency type 2 (MCC2 deficiency) [MIM:210210]. MCC2 deficiency is an autosomal recessive disorder of leucine catabolism. The phenotype is variable, ranging from neonatal onset with severe neurological involvement to asymptomatic adults. There is a characteristic organic aciduria with massive excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, usually in combination with a severe secondary carnitine deficiency.
Sequence similarities	Belongs to the accD/PCCB family. Contains 1 carboxyltransferase domain.
Sequence caution	The sequence AAH14897.1 differs from that shown. Reason: Frameshift at position 359.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	leucine catabolic process Ref.2 Traceable author statement. Source: UniProtKB
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW methylcrotonoyl-CoA carboxylase activity Ref.2 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9HCC0-1)

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: Q9HCC0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     209-246: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 563		Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial		PRO_0000000291
Regions
	Domain	55 – 557	503	Carboxyltransferase
	Region	343 – 372	30	Acyl-CoA binding Potential
Natural variations
	Alternative sequence	209 – 246	38	Missing in isoform 2.		VSP_000069
	Natural variant	99	1	E → Q in MCC2 deficiency; severe and mild form. dbSNP rs28934883. Ref.3		VAR_012792
	Natural variant	155	1	R → Q in MCC2 deficiency; mild form. Ref.3		VAR_012793
	Natural variant	167	1	C → R in MCC2 deficiency. dbSNP rs28934884. Ref.2		VAR_012794
	Natural variant	173	1	S → L in MCC2 deficiency; severe form. Ref.3		VAR_012795
	Natural variant	193	1	R → C in MCC2 deficiency; mild form. Ref.3		VAR_012796
	Natural variant	218	1	A → T in MCC2 deficiency. Ref.2		VAR_012797
	Natural variant	268	1	R → T in MCC2 deficiency; asymptomatic form. Ref.4		VAR_012798
	Natural variant	310	1	P → R in MCC2 deficiency; mild form. Ref.3		VAR_012799
	Natural variant	339	1	V → M in MCC2 deficiency; severe form. Ref.3		VAR_012800
	Natural variant	437	1	I → V in MCC2 deficiency; mild form.		VAR_012801
	Natural variant	478	1	A → G: dbSNP rs35068278.		VAR_038630

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 8E3D401AF52DC7D2	FASTA	563	61,333
	10 20 30 40 50 60 MWAVLRLALR PCARASPAGP RAYHGDSVAS LGTQPDLGSA LYQENYKQMK ALVNQLHERV 70 80 90 100 110 120 EHIKLGGGEK ARALHISRGK LLPRERIDNL IDPGSPFLEL SQFAGYQLYD NEEVPGGGII 130 140 150 160 170 180 TGIGRVSGVE CMIIANDATV KGGAYYPVTV KKQLRAQEIA MQNRLPCIYL VDSGGAYLPR 190 200 210 220 230 240 QADVFPDRDH FGRTFYNQAI MSSKNIAQIA VVMGSCTAGG AYVPAMADEN IIVRKQGTIF 250 260 270 280 290 300 LAGPPLVKAA TGEEVSAEDL GGADLHCRKS GVSDHWALDD HHALHLTRKV VRNLNYQKKL 310 320 330 340 350 360 DVTIEPSEEP LFPADELYGI VGANLKRSFD VREVIARIVD GSRFTEFKAF YGDTLVTGFA 370 380 390 400 410 420 RIFGYPVGIV GNNGVLFSES AKKGTHFVQL CCQRNIPLLF LQNITGFMVG REYEAEGIAK 430 440 450 460 470 480 DGAKMVAAVA CAQVPKITLI IGGSYGAGNY GMCGRAYSPR FLYIWPNARI SVMGGEQAAN 490 500 510 520 530 540 VLATITKDQR AREGKQFSSA DEAALKEPII KKFEEEGNPY YSSARVWDDG IIDPADTRLV 550 560 LGLSFSAALN APIEKTDFGI FRM
	Isoform 2. Checksum: 344050ABB7A9DE8A	FASTA	525	57,519
	10 20 30 40 50 60 MWAVLRLALR PCARASPAGP RAYHGDSVAS LGTQPDLGSA LYQENYKQMK ALVNQLHERV 70 80 90 100 110 120 EHIKLGGGEK ARALHISRGK LLPRERIDNL IDPGSPFLEL SQFAGYQLYD NEEVPGGGII 130 140 150 160 170 180 TGIGRVSGVE CMIIANDATV KGGAYYPVTV KKQLRAQEIA MQNRLPCIYL VDSGGAYLPR 190 200 210 220 230 240 QADVFPDRDH FGRTFYNQAI MSSKNIAQVK AATGEEVSAE DLGGADLHCR KSGVSDHWAL 250 260 270 280 290 300 DDHHALHLTR KVVRNLNYQK KLDVTIEPSE EPLFPADELY GIVGANLKRS FDVREVIARI 310 320 330 340 350 360 VDGSRFTEFK AFYGDTLVTG FARIFGYPVG IVGNNGVLFS ESAKKGTHFV QLCCQRNIPL 370 380 390 400 410 420 LFLQNITGFM VGREYEAEGI AKDGAKMVAA VACAQVPKIT LIIGGSYGAG NYGMCGRAYS 430 440 450 460 470 480 PRFLYIWPNA RISVMGGEQA ANVLATITKD QRAREGKQFS SADEAALKEP IIKKFEEEGN 490 500 510 520 PYYSSARVWD DGIIDPADTR LVLGLSFSAA LNAPIEKTDF GIFRM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human non-biotin containing subunit gene of 3-methylcrotonyl-CoA carboxylase (MCCB)." Fukuda T., Otsuka H., Morishita R., Takemoto Y., Sone M., Nakao M., Abe S., Kondo I. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[2]	"The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism." Gallardo M.E., Desviat L.R., Rodriguez J.M., Esparza-Gordillo J., Perez-Cerda C., Perez B., Rodriguez-Pombo P., Criado O., Sanz R., Morton D.H., Gibson K.M., Le T.P., Ribes A., Rodriguez de Cordoba S., Ugarte M., Penalva M.A. Am. J. Hum. Genet. 68:334-346(2001) [PubMed: 11170888] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MCC2 DEFICIENCY ARG-167 AND THR-218.
[3]	"The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency." Baumgartner M.R., Almashanu S., Suormala T., Obie C., Cole R.N., Packman S., Baumgartner E.R., Valle D. J. Clin. Invest. 107:495-504(2001) [PubMed: 11181649] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MCC2 DEFICIENCY GLN-99; GLN-155; LEU-173; CYS-193; ARG-310 AND MET-339.
[4]	"Cloning of the human MCCA and MCCB genes and mutations therein reveal the molecular cause of 3-methylcrotonyl-CoA: carboxylase deficiency." Holzinger A., Roeschinger W., Lagler F., Mayerhofer P.U., Lichtner P., Kattenfeld T., Thuy L.P., Nyhan W.L., Koch H.G., Muntau A.C., Roscher A.A. Hum. Mol. Genet. 10:1299-1306(2001) [PubMed: 11406611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MCC2 DEFICIENCY THR-268.
[5]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [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 (JUL-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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Testis and Uterus.
[8]	The European IMAGE consortium Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 469-563.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB050049 mRNA. Translation: BAB16880.1. AB050050 Genomic DNA. Translation: BAB41121.1. AF310971 mRNA. Translation: AAG53094.1. AF301000 mRNA. Translation: AAK16404.1. AF261884 mRNA. Translation: AAK49409.1. AC138832 Genomic DNA. No translation available. CH471084 Genomic DNA. Translation: EAW95693.1. BC014897 mRNA. Translation: AAH14897.1. Frameshift. BC065027 mRNA. Translation: AAH65027.1. AL079298 mRNA. Translation: CAB45194.1.
IPI	IPI00784044. IPI00789428.
RefSeq	NP_071415.1.
UniGene	Hs.604789
3D structure databases
SMR	Q9HCC0. Positions 47-552.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9HCC0.
2-D gel databases
REPRODUCTION-2DPAGE	IPI00784044.
Proteomic databases
PRIDE	Q9HCC0.
Genome annotation databases
Ensembl	ENST00000340941; ENSP00000343657; ENSG00000131844; Homo sapiens. [Genome view]
GeneID	64087.
KEGG	hsa:64087.
UCSC	uc003kbs.2. human.
Organism-specific databases
CTD	64087.
GeneCards	GC05P070918.
H-InvDB	HIX0004928. HIX0057666.
HGNC	HGNC:6937. MCCC2.
MIM	210210. phenotype. 609014. gene.
Orphanet	6. 3-methylcrotonylglycinuria.
PharmGKB	PA30681.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09096.
HOGENOM	HBG461319.
HOVERGEN	Q9HCC0.
InParanoid	Q9HCC0.
OMA	AYHGDSV.
OrthoDB	EOG9WHC56.
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-10082.
BRENDA	6.4.1.4. 247.
Reactome	REACT_13. Metabolism of amino acids.
Gene expression databases
ArrayExpress	Q9HCC0.
Bgee	Q9HCC0.
CleanEx	HS_MCCC2.
Genevestigator	Q9HCC0.
GermOnline	ENSG00000131844. Homo sapiens.
Family and domain databases
InterPro	IPR000022. Carboxyl_trans. IPR011763. COA_CT_C. IPR011762. COA_CT_N. [Graphical view]
Pfam	PF01039. Carboxyl_trans. 1 hit. [Graphical view]
PROSITE	PS50989. COA_CT_CTER. 1 hit. PS50980. COA_CT_NTER. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00121. Biotin.
NextBio	65884.
SOURCE	Search...

Entry information

Entry name

MCCB_HUMAN

Accession

Primary (citable) accession number: Q9HCC0
Secondary accession number(s): A6NIY9, Q96C27, Q9Y4L7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 5, 2002
Last sequence update:	March 1, 2001
Last modified:	January 19, 2010
This is version 90 of the entry and version 1 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.