PCCA

Protein identityUniProt · HPA

UniProt accession

P05165

Gene

PCCA

Ensembl

ENSG00000175198

Chromosome

13

Canonical length

728 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

728 residues, UniProt reviewed canonical sequence.

>P05165|PCCA
     1  MAGFWVGTAP LVAAGRRGRW PPQQLMLSAA LRTLKHVLYY SRQCLMVSRN LGSVGYDPNE
    61  KTFDKILVAN RGEIACRVIR TCKKMGIKTV AIHSDVDASS VHVKMADEAV CVGPAPTSKS
   121  YLNMDAIMEA IKKTRAQAVH PGYGFLSENK EFARCLAAED VVFIGPDTHA IQAMGDKIES
   181  KLLAKKAEVN TIPGFDGVVK DAEEAVRIAR EIGYPVMIKA SAGGGGKGMR IAWDDEETRD
   241  GFRLSSQEAA SSFGDDRLLI EKFIDNPRHI EIQVLGDKHG NALWLNEREC SIQRRNQKVV
   301  EEAPSIFLDA ETRRAMGEQA VALARAVKYS SAGTVEFLVD SKKNFYFLEM NTRLQVEHPV
   361  TECITGLDLV QEMIRVAKGY PLRHKQADIR INGWAVECRV YAEDPYKSFG LPSIGRLSQY
   421  QEPLHLPGVR VDSGIQPGSD ISIYYDPMIS KLITYGSDRT EALKRMADAL DNYVIRGVTH
   481  NIALLREVII NSRFVKGDIS TKFLSDVYPD GFKGHMLTKS EKNQLLAIAS SLFVAFQLRA
   541  QHFQENSRMP VIKPDIANWE LSVKLHDKVH TVVASNNGSV FSVEVDGSKL NVTSTWNLAS
   601  PLLSVSVDGT QRTVQCLSRE AGGNMSIQFL GTVYKVNILT RLAAELNKFM LEKVTEDTSS
   661  VLRSPMPGVV VAVSVKPGDA VAEGQEICVI EAMKMQNSMT AGKTGTVKSV HCQAGDTVGE
   721  GDLLVELE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PCCA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

206 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PCCA.

Disease | AllUniProt

Conditions PCCA is implicated in, by any mechanism.

• Propionic acidemia type I (PA-1) MIM:606054

Disease | GeneticClinVar

305 pathogenic / likely-pathogenic of 1,579 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Propionic acidemia
• PCCA-related disorder
• Inborn genetic diseases
• Nonpapillary renal cell carcinoma
• Pontocerebellar hypoplasia type 2D

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.91

gnomAD pLI

0

gnomAD missense Z

0.19

DepMap mean gene effect

0.13

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• branched-chain amino acid metabolic process
• fatty acid metabolic process
• short-chain fatty acid catabolic process

Molecular functions

• ATP binding
• biotin binding
• enzyme binding
• metal ion binding
• propionyl-CoA carboxylase activity

Cellular components

• catalytic complex
• cytosol
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Biotin/lipoyl attachment
• Biotin-binding site
• Carbamoyl phosphate synthase, ATP-binding domain
• Biotin carboxylase-like, N-terminal domain
• Biotin carboxylase, C-terminal
• Single hybrid motif
• Rudiment single hybrid motif
• ATP-grasp fold
• Biotin carboxylation domain
• ATP-grasp fold, subdomain 1
• Pre-ATP-grasp domain superfamily
• Biotin-dependent Carboxylase Complex
• Biotin carboxylase, N-terminal domain
• Biotin-requiring enzyme
• Biotin carboxylase C-terminal domain
• Carbamoyl-phosphate synthase L chain, ATP binding domain
• Propionyl-coenzyme A carboxylase, BT domain
• Propionyl-coenzyme A carboxylase BT domain

KeywordsUniProt

• Acetylation
• ATP-binding
• Biotin
• Ligase
• Lipid degradation
• Lipid metabolism
• Magnesium
• Manganese
• Metal-binding
• Mitochondrion
• Nucleotide-binding
• Phosphoprotein
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of PCCA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SIRT3
• SIRT5
• SIRT4
• PCCB