Human Gene PCCA (uc001voo.3)
  Description: Homo sapiens propionyl CoA carboxylase, alpha polypeptide (PCCA), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA.
RefSeq Summary (NM_000282): The protein encoded by this gene is the alpha subunit of the heterodimeric mitochondrial enzyme Propionyl-CoA carboxylase. PCCA encodes the biotin-binding region of this enzyme. Mutations in either PCCA or PCCB (encoding the beta subunit) lead to an enzyme deficiency resulting in propionic acidemia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010].
Transcript (Including UTRs)
   Position: hg19 chr13:100,741,269-101,182,691 Size: 441,423 Total Exon Count: 24 Strand: +
Coding Region
   Position: hg19 chr13:100,741,375-101,182,420 Size: 441,046 Coding Exon Count: 24 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr13:100,741,269-101,182,691)mRNA (may differ from genome)Protein (728 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PCCA_HUMAN
DESCRIPTION: RecName: Full=Propionyl-CoA carboxylase alpha chain, mitochondrial; Short=PCCase subunit alpha; EC=6.4.1.3; AltName: Full=Propanoyl-CoA:carbon dioxide ligase subunit alpha; Flags: Precursor;
CATALYTIC ACTIVITY: ATP + propanoyl-CoA + HCO(3)(-) = ADP + phosphate + (S)-methylmalonyl-CoA.
COFACTOR: Biotin.
PATHWAY: Metabolic intermediate metabolism; propanoyl-CoA degradation; succinyl-CoA from propanoyl-CoA: step 1/3.
SUBUNIT: Probably a dodecamer composed of six biotin-containing alpha subunits and six beta subunits.
SUBCELLULAR LOCATION: Mitochondrion matrix.
DISEASE: Defects in PCCA are the cause of propionic acidemia type I (PA-1) [MIM:606054]. PA-1 is a life-threatening disease characterized by episodic vomiting, lethargy and ketosis, neutropenia, periodic thrombocytopenia, hypogammaglobulinemia, developmental retardation, and intolerance to protein.
SIMILARITY: Contains 1 ATP-grasp domain.
SIMILARITY: Contains 1 biotin carboxylation domain.
SIMILARITY: Contains 1 biotinyl-binding domain.
SEQUENCE CAUTION: Sequence=AAA60035.1; Type=Frameshift; Positions=374, 378, 380, 395; Sequence=AAH00140.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAK61392.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAA32763.1; Type=Frameshift; Positions=23;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PCCA";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PCCA
CDC HuGE Published Literature: PCCA
Positive Disease Associations: Coronary Artery Disease , Erythrocyte Count , Hemoglobins , Stroke
Related Studies:
  1. Coronary Artery Disease
    , , . [PubMed 0]
  2. Erythrocyte Count
    , , . [PubMed 0]
  3. Hemoglobins
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PCCA
Diseases sorted by gene-association score: propionicacidemia* (1600), pcca-related propionic acidemia* (100), bile duct adenocarcinoma (9), methylmalonic acidemia (7), multiple carboxylase deficiency (7), organic acidemia (7), amino acid metabolic disorder (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.96 RPKM in Adrenal Gland
Total median expression: 321.95 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -43.90106-0.414 Picture PostScript Text
3' UTR -44.41271-0.164 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011761 - ATP-grasp
IPR013816 - ATP_grasp_subdomain_2
IPR001882 - Biotin_BS
IPR011764 - Biotin_carboxylation_dom
IPR005482 - Biotin_COase_C
IPR000089 - Biotin_lipoyl
IPR005481 - CarbamoylP_synth_lsu_N
IPR005479 - CbamoylP_synth_lsu-like_ATP-bd
IPR016185 - PreATP-grasp_fold
IPR011054 - Rudment_hybrid_motif
IPR011053 - Single_hybrid_motif

Pfam Domains:
PF00289 - Biotin carboxylase, N-terminal domain
PF00364 - Biotin-requiring enzyme
PF02222 - ATP-grasp domain
PF02785 - Biotin carboxylase C-terminal domain
PF02786 - Carbamoyl-phosphate synthase L chain, ATP binding domain
PF07478 - D-ala D-ala ligase C-terminus
PF08443 - RimK-like ATP-grasp domain

SCOP Domains:
51230 - Single hybrid motif
51246 - Rudiment single hybrid motif
52440 - PreATP-grasp domain
56059 - Glutathione synthetase ATP-binding domain-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2CQY - NMR MuPIT 2JKU - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P05165
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologGenome BrowserNo ortholog
Gene Details   Gene Details 
Gene Sorter   Gene Sorter 
  Ensembl WormBase 
  Protein Sequence Protein Sequence 
  Alignment Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004658 propionyl-CoA carboxylase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0009374 biotin binding
GO:0016874 ligase activity
GO:0019899 enzyme binding
GO:0046872 metal ion binding

Biological Process:
GO:0006768 biotin metabolic process

Cellular Component:
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  AF385926 - Homo sapiens propionyl-CoA carboxylase alpha subunit (PCCA) mRNA, complete cds; nuclear gene for mitochondrial product.
AK298318 - Homo sapiens cDNA FLJ56469 complete cds, highly similar to Propionyl-CoA carboxylase alpha chain, mitochondrial precursor (EC 6.4.1.3).
AK225288 - Homo sapiens mRNA for propionyl-Coenzyme A carboxylase, alpha polypeptide precursor variant, clone: HEP01581.
AK315503 - Homo sapiens cDNA, FLJ96567, highly similar to Homo sapiens propionyl Coenzyme A carboxylase, alpha polypeptide(PCCA), mRNA.
AK225299 - Homo sapiens mRNA for propionyl-Coenzyme A carboxylase, alpha polypeptide precursor variant, clone: HEP01941.
AK296771 - Homo sapiens cDNA FLJ59564 complete cds, highly similar to Propionyl-CoA carboxylase alpha chain, mitochondrial precursor (EC 6.4.1.3).
BC000140 - Homo sapiens propionyl Coenzyme A carboxylase, alpha polypeptide, mRNA (cDNA clone MGC:5056 IMAGE:3048998), complete cds.
X14608 - Human mRNA for propionyl-CoA carboxylase alpha-chain (EC 6.4.1.3).
KJ901624 - Synthetic construct Homo sapiens clone ccsbBroadEn_11018 PCCA gene, encodes complete protein.
KR709426 - Synthetic construct Homo sapiens clone CCSBHm_00002077 PCCA (PCCA) mRNA, encodes complete protein.
KR709427 - Synthetic construct Homo sapiens clone CCSBHm_00002087 PCCA (PCCA) mRNA, encodes complete protein.
KR709428 - Synthetic construct Homo sapiens clone CCSBHm_00002094 PCCA (PCCA) mRNA, encodes complete protein.
KR709429 - Synthetic construct Homo sapiens clone CCSBHm_00002102 PCCA (PCCA) mRNA, encodes complete protein.
S79219 - metastasis-associated gene [human, highly metastatic lung cell subline Anip[937], mRNA Partial, 978 nt].
DQ583220 - Homo sapiens piRNA piR-50332, complete sequence.
AK055982 - Homo sapiens cDNA FLJ31420 fis, clone NT2NE2000369, moderately similar to PROPIONYL-COA CARBOXYLASE ALPHA CHAIN PRECURSOR (EC 6.4.1.3).
Z36837 - H.sapiens (xs79) mRNA, 413bp.
S55656 - pccA=propionyl CoA carboxylase alpha subunit [human, liver, mRNA Partial, 89 nt].
M13572 - Human propionyl-CoA carboxylase alpha chain mRNA.
AL122056 - Homo sapiens mRNA; cDNA DKFZp434P088 (from clone DKFZp434P088).
M26121 - Human propionyl-CoA carboxylase (PCC) mRNA, 3' end.
JD207996 - Sequence 189020 from Patent EP1572962.
JD143111 - Sequence 124135 from Patent EP1572962.
JD553493 - Sequence 534517 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00280 - Valine, leucine and isoleucine degradation
hsa00640 - Propanoate metabolism
hsa01100 - Metabolic pathways

BioCyc Knowledge Library
PROPIONMET-PWY - methylmalonyl pathway
PWY-5328 - superpathway of methionine degradation
PWY3DJ-0 - isoleucine degradation
PWY3DJ-86 - valine degradation

Reactome (by CSHL, EBI, and GO)

Protein P05165 (Reactome details) participates in the following event(s):

R-HSA-2993447 HLCS biotinylates 6x(PCCA:PCCB)
R-HSA-71031 propionyl-CoA + CO2 + ATP <=> D-methylmalonyl-CoA + ADP + orthophosphate
R-HSA-196780 Biotin transport and metabolism
R-HSA-3371599 Defective HLCS causes multiple carboxylase deficiency
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors
R-HSA-3323169 Defects in biotin (Btn) metabolism
R-HSA-71032 Propionyl-CoA catabolism
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-3296482 Defects in vitamin and cofactor metabolism
R-HSA-77289 Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-1430728 Metabolism
R-HSA-5668914 Diseases of metabolism
R-HSA-8978868 Fatty acid metabolism
R-HSA-1643685 Disease
R-HSA-556833 Metabolism of lipids

-  Other Names for This Gene
  Alternate Gene Symbols: B4DKY8, B4DPF9, C9JPQ8, NM_000282, NP_000273, P05165, PCCA_HUMAN, Q15979, Q8WXQ7
UCSC ID: uc001voo.3
RefSeq Accession: NM_000282
Protein: P05165 (aka PCCA_HUMAN)
CCDS: CCDS9496.2, CCDS45065.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene PCCA:
propionic-a (Propionic Acidemia)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000282.3
exon count: 24CDS single in 3' UTR: no RNA size: 2577
ORF size: 2187CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4574.00frame shift in genome: no % Coverage: 99.50
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.