Q9HCC0 (MCCB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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 carboxylase 2
3-methylcrotonyl-CoA carboxylase non-biotin-containing subunit
3-methylcrotonyl-CoA:carbon dioxide ligase subunit beta

Gene names

Name:	MCCC2
Synonyms:	MCCB

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	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 Ref.2 Ref.8.
Involvement in disease	Methylcrotonoyl-CoA carboxylase 2 deficiency (MCC2D) [MIM:210210]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.3 Ref.4 Ref.11
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 Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome coenzyme A metabolic process Inferred from electronic annotation. Source: Compara leucine catabolic process Traceable author statement Ref.2. Source: UniProtKB
Cellular_component	mitochondrial inner membrane Traceable author statement. Source: Reactome mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW methylcrotonoyl-CoA carboxylase activity Non-traceable author statement Ref.2. 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 – 22	22	Mitochondrion Potential
	Chain	23 – 563	541	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 MCC2D; severe and mild form. Ref.3 Corresponds to variant rs28934883 [ dbSNP | Ensembl ].		VAR_012792
	Natural variant	155	1	R → Q in MCC2D; mild form. Ref.3		VAR_012793
	Natural variant	167	1	C → R in MCC2D. Ref.2 Corresponds to variant rs28934884 [ dbSNP | Ensembl ].		VAR_012794
	Natural variant	173	1	S → L in MCC2D; severe form. Ref.3		VAR_012795
	Natural variant	193	1	R → C in MCC2D; mild form. Ref.3		VAR_012796
	Natural variant	218	1	A → T in MCC2D. Ref.2		VAR_012797
	Natural variant	268	1	R → T in MCC2D; asymptomatic form. Ref.4		VAR_012798
	Natural variant	280	1	D → Y in MCC2D. Ref.11		VAR_067199
	Natural variant	310	1	P → R in MCC2D; mild form. Ref.3		VAR_012799
	Natural variant	339	1	V → M in MCC2D; severe form. Ref.3		VAR_012800
	Natural variant	437	1	I → V in MCC2D; mild form.		VAR_012801
	Natural variant	459	1	P → S in MCC2D. Ref.11		VAR_067200
	Natural variant	478	1	A → G. Corresponds to variant rs35068278 [ dbSNP | Ensembl ].		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 [UniParc]. 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, VARIANTS MCC2D 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MCC2D 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MCC2D 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] [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 (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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Testis and Uterus.
[8]	"Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA carboxylase." Stadler S.C., Polanetz R., Meier S., Mayerhofer P.U., Herrmann J.M., Anslinger K., Roscher A.A., Roschinger W., Holzinger A. Biochem. Biophys. Res. Commun. 334:939-946(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-28, SUBCELLULAR LOCATION. Tissue: Kidney.
[9]	The European IMAGE consortium Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 469-563.
[10]	"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].
[11]	"Mutational spectrum in eight Korean patients with 3-methylcrotonyl-CoA carboxylase deficiency." Cho S.Y., Park H.D., Lee Y.W., Ki C.S., Lee S.Y., Sohn Y.B., Park S.W., Kim S.H., Ji S., Kim S.J., Choi E.W., Kim C.H., Ko A.R., Paik K.H., Lee D.H., Jin D.K. Clin. Genet. 81:96-98(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCC2D TYR-280 AND SER-459.
+	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. NM_022132.4.
UniGene	Hs.604789.
3D structure databases
ProteinModelPortal	Q9HCC0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HCC0. 10 interactions.
MINT	MINT-8051924.
STRING	9606.ENSP00000343657.
PTM databases
PhosphoSite	Q9HCC0.
Polymorphism databases
DMDM	20138731.
2D gel databases
REPRODUCTION-2DPAGE	IPI00784044.
Proteomic databases
PaxDb	Q9HCC0.
PRIDE	Q9HCC0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000323375; ENSP00000327308; ENSG00000131844. ENST00000340941; ENSP00000343657; ENSG00000131844. ENST00000575361; ENSP00000460647; ENSG00000262057.
GeneID	64087.
KEGG	hsa:64087.
UCSC	uc003kbs.4. human.
Organism-specific databases
CTD	64087.
GeneCards	GC05P070918.
HGNC	HGNC:6937. MCCC2.
HPA	HPA038301.
MIM	210210. phenotype. 609014. gene.
neXtProt	NX_Q9HCC0.
Orphanet	6. Isolated 3-methylcrotonyl-CoA carboxylase deficiency.
PharmGKB	PA30681.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4799.
HOGENOM	HOG000218692.
HOVERGEN	HBG052424.
InParanoid	Q9HCC0.
KO	K01969.
OMA	KFGIFRM.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000131844-MONOMER.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00363; UER00861.
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
DrugBank	DB00121. Biotin.
GenomeRNAi	64087.
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:	May 29, 2013
This is version 121 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.