P05166 (PCCB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Propionyl-CoA carboxylase beta chain, mitochondrial
Short name=PCCase subunit beta
EC=6.4.1.3

Alternative name(s):
Propanoyl-CoA:carbon dioxide ligase subunit beta

Gene names

Name:

PCCB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	539 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 + propanoyl-CoA + HCO3- = ADP + phosphate + (S)-methylmalonyl-CoA.
Pathway	Metabolic intermediate metabolism; propanoyl-CoA degradation; succinyl-CoA from propanoyl-CoA: step 1/3.
Subunit structure	Probably a dodecamer composed of six biotin-containing alpha subunits and six beta subunits.
Subcellular location	Mitochondrion matrix Ref.6.
Involvement in disease	Defects in PCCB are the cause of propionic acidemia type II (PA-2) [MIM:606054]. PA-2 is a life-threatening disease characterized by episodic vomiting, lethargy and ketosis, neutropenia, periodic thrombocytopenia, hypogammaglobulinemia, developmental retardation, and intolerance to protein. Ref.3 Ref.8 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16
Sequence similarities	Belongs to the AccD/PCCB family. Contains 1 carboxyltransferase domain.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	fatty acid beta-oxidation Traceable author statement. Source: Reactome
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW propionyl-CoA carboxylase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 28	28	Mitochondrion Ref.6
	Chain	29 – 539	511	Propionyl-CoA carboxylase beta chain, mitochondrial		PRO_0000000293
Regions
	Domain	38 – 531	494	Carboxyltransferase
	Region	325 – 358	34	Acyl-CoA binding Potential
Amino acid modifications
	Modified residue	60	1	N6-acetyllysine By similarity
Natural variations
	Natural variant	17	1	L → M in PA-2. Ref.11		VAR_009080
	Natural variant	44	1	R → P in PA-2.		VAR_000271
	Natural variant	67	1	R → S in PA-2. Ref.15		VAR_023847
	Natural variant	106	1	S → R in PA-2.		VAR_000272
	Natural variant	107	1	V → M in PA-2. Ref.15		VAR_023848
	Natural variant	112	1	G → D in PA-2. Ref.15		VAR_023849
	Natural variant	131	1	G → R in PA-2.		VAR_000273
	Natural variant	140	1	K → KICK in PA-2.		VAR_009081
	Natural variant	153	1	A → P in PA-2. Ref.16		VAR_023850
	Natural variant	165	1	R → Q in PA-2; does not affect either heteromeric or homomeric assembly. Ref.13 Ref.15		VAR_023851
	Natural variant	165	1	R → W in PA-2. Ref.16		VAR_000274
	Natural variant	168	1	E → K in PA-2; common mutation. Ref.11 Ref.15		VAR_000275
	Natural variant	188	1	G → R in PA-2. Ref.15		VAR_023852
	Natural variant	198	1	G → D in PA-2.		VAR_000276
	Natural variant	205	1	V → D in PA-2. Ref.11		VAR_009082
	Natural variant	228	1	P → L in PA-2.		VAR_009083
	Natural variant	246	1	G → V in PA-2. Ref.15		VAR_023853
	Natural variant	287	1	P → S. Ref.1 Corresponds to variant rs2228310 [ dbSNP | Ensembl ].		VAR_048163
	Natural variant	341	1	Missing in PA-2.		VAR_023854
	Natural variant	408	1	Missing in PA-2.		VAR_000277
	Natural variant	410	1	R → W in PA-2. Ref.10 Ref.15 Ref.16		VAR_000278
	Natural variant	428	1	T → I in PA-2. Ref.14 Ref.16 Corresponds to variant rs28934887 [ dbSNP | Ensembl ].		VAR_009084
	Natural variant	430	1	I → L in PA-2. Ref.14		VAR_023855
	Natural variant	435	1	Y → C in PA-2. Ref.14		VAR_023856
	Natural variant	439	1	Y → C in PA-2. Ref.14		VAR_023857
	Natural variant	442	1	M → T in PA-2. Ref.11		VAR_009085
	Natural variant	468	1	A → T in PA-2. Ref.14		VAR_023858
	Natural variant	497	1	A → V in PA-2; common mutation; does not affect either heteromeric or homomeric assembly. Ref.13		VAR_000279
	Natural variant	512	1	R → C in PA-2; affects heteromeric and homomeric assembly. Ref.13 Ref.16		VAR_000280
	Natural variant	519	1	L → P in PA-2; affects heteromeric and homomeric assembly. Ref.13		VAR_000281
	Natural variant	536	1	N → D in PA-2; affects heteromeric and homomeric assembly. Ref.13		VAR_009086
Experimental info
	Sequence conflict	58 – 59	2	QH → HD in AAB28900. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P05166 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: A2DAAC00312D3C0F	FASTA	539	58,216
	10 20 30 40 50 60 MAAALRVAAV GARLSVLASG LRAAVRSLCS QATSVNERIE NKRRTALLGG GQRRIDAQHK 70 80 90 100 110 120 RGKLTARERI SLLLDPGSFV ESDMFVEHRC ADFGMAADKN KFPGDSVVTG RGRINGRLVY 130 140 150 160 170 180 VFSQDFTVFG GSLSGAHAQK ICKIMDQAIT VGAPVIGLND SGGARIQEGV ESLAGYADIF 190 200 210 220 230 240 LRNVTASGVI PQISLIMGPC AGGAVYSPAL TDFTFMVKDT SYLFITGPDV VKSVTNEDVT 250 260 270 280 290 300 QEELGGAKTH TTMSGVAHRA FENDVDALCN LRDFFNYLPL SSQDPAPVRE CHDPSDRLVP 310 320 330 340 350 360 ELDTIVPLES TKAYNMVDII HSVVDEREFF EIMPNYAKNI IVGFARMNGR TVGIVGNQPK 370 380 390 400 410 420 VASGCLDINS SVKGARFVRF CDAFNIPLIT FVDVPGFLPG TAQEYGGIIR HGAKLLYAFA 430 440 450 460 470 480 EATVPKVTVI TRKAYGGAYD VMSSKHLCGD TNYAWPTAEI AVMGAKGAVE IIFKGHENVE 490 500 510 520 530 AAQAEYIEKF ANPFPAAVRG FVDDIIQPSS TRARICCDLD VLASKKVQRP WRKHANIPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Correction of the metabolic defect in propionic acidemia fibroblasts by microinjection of a full-length cDNA or RNA transcript encoding the propionyl-CoA carboxylase beta subunit." Lamhonwah A.-M., Leclerc D., Loyer M., Clarizio R., Gravel R.A. Genomics 19:500-505(1994) [PubMed: 8188292] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-287. Tissue: Fibroblast, Kidney and Liver.
[2]	"The molecular defect in propionic acidemia: exon skipping caused by an 8-bp deletion from an intron in the PCCB allele." Ohura T., Ogasawara M., Ikeda H., Narisawa K., Tada K. Hum. Genet. 92:397-402(1993) [PubMed: 8225321] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver and Placenta.
[3]	"Human propionyl-CoA carboxylase beta subunit gene: exon-intron definition and mutation spectrum in Spanish and Latin American propionic acidemia patients." Rodriguez-Pombo P., Hoenicka J., Muro S., Perez B., Perez-Cerda C., Richard E., Desviat L.R., Ugarte M. Am. J. Hum. Genet. 63:360-369(1998) [PubMed: 9683601] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PA-2. Tissue: Blood and Skin fibroblast.
[4]	"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]. Tissue: Pancreas and Skin.
[5]	"Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes." Lamhonwah A.-M., Barankiewicz T.J., Willard H.F., Mahuran D.J., Quan F., Gravel R.A. Proc. Natl. Acad. Sci. U.S.A. 83:4864-4868(1986) [PubMed: 3460076] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 289-443.
[6]	"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: 16023992] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-33, SUBCELLULAR LOCATION. Tissue: Kidney.
[7]	Lamhonwah A.-M. Submitted (DEC-1986) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[8]	"An unusual insertion/deletion in the gene encoding the beta-subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia." Tahara T., Kraus J.P., Rosenberg L.E. Proc. Natl. Acad. Sci. U.S.A. 87:1372-1376(1990) [PubMed: 2154743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 401-433, VARIANT PA-2 ILE-408 DEL. Tissue: Skin fibroblast.
[9]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Three independent mutations in the same exon of the PCCB gene: differences between Caucasian and Japanese propionic acidaemia." Tahara T., Kraus J.P., Ohura T., Rosenberg L.E., Fenton W.A. J. Inherit. Metab. Dis. 16:353-360(1993) [PubMed: 8411997] [Abstract] Cited for: VARIANTS PA-2 TRP-410 AND ILE-408 DEL.
[11]	"Identification of novel mutations in the PCCB gene in European propionic acidemia patients." Muro S., Rodriguez-Pombo P., Perez B., Perez-Cerda C., Desviat L.R., Sperl W., Skladal D., Sass J.O., Ugarte M. Hum. Mutat. 14:89-90(1999) [PubMed: 10447268] [Abstract] Cited for: VARIANTS PA-2 MET-17; LYS-168; ASP-205 AND THR-442.
[12]	"Overview of mutations in the PCCA and PCCB genes causing propionic acidemia." Ugarte M., Perez-Cerda C., Rodriguez-Pombo P., Desviat L.R., Perez B., Richard E., Muro S., Campeau E., Ohura T., Gravel R.A. Hum. Mutat. 14:275-282(1999) [PubMed: 10502773] [Abstract] Cited for: REVIEW ON PA VARIANTS.
[13]	"Effect of PCCB gene mutations on the heteromeric and homomeric assembly of propionyl-CoA carboxylase." Muro S., Perez B., Desviat L.R., Rodriguez-Pombo P., Perez-Cerda C., Clavero S., Ugarte M. Mol. Genet. Metab. 74:476-483(2001) [PubMed: 11749052] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS PA-2 GLN-165; VAL-497; CYS-512; PRO-519 AND ASP-536.
[14]	"Unexpectedly high prevalence of the mild form of propionic acidemia in Japan: presence of a common mutation and possible clinical implications." Yorifuji T., Kawai M., Muroi J., Mamada M., Kurokawa K., Shigematsu Y., Hirano S., Sakura N., Yoshida I., Kuhara T., Endo F., Mitsubuchi H., Nakahata T. Hum. Genet. 111:161-165(2002) [PubMed: 12189489] [Abstract] Cited for: VARIANTS PA-2 ILE-428; LEU-430; CYS-435; CYS-439 AND THR-468.
[15]	"Propionic acidemia: identification of twenty-four novel mutations in Europe and North America." Perez B., Desviat L.R., Rodriguez-Pombo P., Clavero S., Navarrete R., Perez-Cerda C., Ugarte M. Mol. Genet. Metab. 78:59-67(2003) [PubMed: 12559849] [Abstract] Cited for: VARIANTS PA-2 SER-67; MET-107; ASP-112; GLN-165; LYS-168; ARG-188; VAL-246; ILE-341 DEL AND TRP-410.
[16]	"Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia." Yang X., Sakamoto O., Matsubara Y., Kure S., Suzuki Y., Aoki Y., Yamaguchi S., Takahashi Y., Nishikubo T., Kawaguchi C., Yoshioka A., Kimura T., Hayasaka K., Kohno Y., Iinuma K., Ohura T. Mol. Genet. Metab. 81:335-342(2004) [PubMed: 15059621] [Abstract] Cited for: VARIANTS PA-2 PRO-153; TRP-165; TRP-410; ILE-428 AND CYS-512.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X73424 mRNA. Translation: CAA51825.1. S67325 mRNA. Translation: AAB28900.1. AJ006487 , AJ006488, AJ006489, AJ006490, AJ006491, AJ006492, AJ006493, AJ006494, AJ006495, AJ006496, AJ006497, AJ006498, AJ006499 Genomic DNA. Translation: CAA07066.1. BC013768 mRNA. Translation: AAH13768.1. BC053661 mRNA. Translation: AAH53661.1. M13573 mRNA. Translation: AAA60036.1. M31167 Genomic DNA. Translation: AAA60037.1. M31169 Genomic DNA. Translation: AAA60038.1.
IPI	IPI00007247.
PIR	T45009.
RefSeq	NP_000523.2. NM_000532.4.
UniGene	Hs.63788.
3D structure databases
ProteinModelPortal	P05166.
SMR	P05166. Positions 37-539.
ModBase	Search...
Protein-protein interaction databases
IntAct	P05166. 4 interactions.
MINT	MINT-3004663.
STRING	P05166.
PTM databases
PhosphoSite	P05166.
Polymorphism databases
DMDM	124106304.
Proteomic databases
PeptideAtlas	P05166.
PRIDE	P05166.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000251654; ENSP00000251654; ENSG00000114054.
GeneID	5096.
KEGG	hsa:5096.
UCSC	uc003eqy.1. human.
Organism-specific databases
CTD	5096.
GeneCards	GC03P135969.
H-InvDB	HIX0020182.
HGNC	HGNC:8654. PCCB.
HPA	HPA036939. HPA036940.
MIM	232050. gene. 606054. phenotype.
neXtProt	NX_P05166.
Orphanet	35. Propionic acidemia.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13877.
HOVERGEN	HBG003970.
InParanoid	P05166.
OMA	VTGYGMI.
PhylomeDB	P05166.
Enzyme and pathway databases
BRENDA	6.4.1.3. 2681.
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	P05166.
Bgee	P05166.
CleanEx	HS_PCCB.
Genevestigator	P05166.
GermOnline	ENSG00000114054. Homo sapiens.
Family and domain databases
InterPro	IPR000022. Carboxyl_trans. IPR011763. COA_CT_C. IPR011762. COA_CT_N. [Graphical view]
KO	K01966.
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. DB00161. L-Valine.
NextBio	19660.
SOURCE	Search...

Entry information

Entry name

PCCB_HUMAN

Accession

Primary (citable) accession number: P05166
Secondary accession number(s): Q16813, Q96CX0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 120 of the entry and version 3 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.