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Protein

Propionyl-CoA carboxylase alpha chain, mitochondrial

Gene

PCCA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalytic activityi

ATP + propanoyl-CoA + HCO3- = ADP + phosphate + (S)-methylmalonyl-CoA.

Cofactori

Pathwayi: propanoyl-CoA degradation

This protein is involved in step 1 of the subpathway that synthesizes succinyl-CoA from propanoyl-CoA.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Propionyl-CoA carboxylase alpha chain, mitochondrial (PCCA), Propionyl-CoA carboxylase beta chain, mitochondrial (PCCB)
  2. no protein annotated in this organism
  3. no protein annotated in this organism
This subpathway is part of the pathway propanoyl-CoA degradation, which is itself part of Metabolic intermediate metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes succinyl-CoA from propanoyl-CoA, the pathway propanoyl-CoA degradation and in Metabolic intermediate metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei177ATPBy similarity1
Binding sitei261ATPBy similarity1
Binding sitei296ATPBy similarity1
Active sitei353By similarity1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • biotin binding Source: ProtInc
  • enzyme binding Source: UniProtKB
  • metal ion binding Source: InterPro
  • propionyl-CoA carboxylase activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionLigase
LigandATP-binding, Biotin, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000175198-MONOMER
ReactomeiR-HSA-196780 Biotin transport and metabolism
R-HSA-3371599 Defective HLCS causes multiple carboxylase deficiency
R-HSA-71032 Propionyl-CoA catabolism
SABIO-RKiP05165
UniPathwayiUPA00945; UER00908

Names & Taxonomyi

Protein namesi
Recommended name:
Propionyl-CoA carboxylase alpha chain, mitochondrial (EC:6.4.1.3)
Short name:
PCCase subunit alpha
Alternative name(s):
Propanoyl-CoA:carbon dioxide ligase subunit alpha
Gene namesi
Name:PCCA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000175198.14
HGNCiHGNC:8653 PCCA
MIMi232000 gene
neXtProtiNX_P05165

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Propionic acidemia type I (PA-1)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionLife-threatening disease characterized by episodic vomiting, lethargy and ketosis, neutropenia, periodic thrombocytopenia, hypogammaglobulinemia, developmental retardation, and intolerance to protein.
See also OMIM:606054
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00908775A → P in PA-1. 1 PublicationCorresponds to variant dbSNP:rs794727479EnsemblClinVar.1
Natural variantiVAR_00908877R → W in PA-1. 2 PublicationsCorresponds to variant dbSNP:rs141371306Ensembl.1
Natural variantiVAR_009089138A → T in PA-1. 1 PublicationCorresponds to variant dbSNP:rs202247814EnsemblClinVar.1
Natural variantiVAR_009090164I → T in PA-1. 1 PublicationCorresponds to variant dbSNP:rs202247815EnsemblClinVar.1
Natural variantiVAR_023843197G → E in PA-1. 1 Publication1
Natural variantiVAR_009091229M → K in PA-1. 1 PublicationCorresponds to variant dbSNP:rs375628794EnsemblClinVar.1
Natural variantiVAR_009092297Q → R in PA-1. 1 Publication1
Natural variantiVAR_009093368D → G in PA-1. 1 Publication1
Natural variantiVAR_009094373M → K in PA-1; unstable protein. 1 PublicationCorresponds to variant dbSNP:rs121964958EnsemblClinVar.1
Natural variantiVAR_009095379G → V in PA-1. 1 PublicationCorresponds to variant dbSNP:rs794727087EnsemblClinVar.1
Natural variantiVAR_023844398C → R in PA-1. 1 Publication1
Natural variantiVAR_009096399R → Q in PA-1. 1 Publication1
Natural variantiVAR_009097423P → L in PA-1. 1 Publication1
Natural variantiVAR_023845532Missing in PA-1. 1 Publication1
Natural variantiVAR_009099559W → L in PA-1. 1 PublicationCorresponds to variant dbSNP:rs118169528EnsemblClinVar.1
Natural variantiVAR_009100631G → R in PA-1. 1 PublicationCorresponds to variant dbSNP:rs796052018Ensembl.1
Natural variantiVAR_009101668G → R in PA-1. 1 PublicationCorresponds to variant dbSNP:rs771438170EnsemblClinVar.1
Natural variantiVAR_009102712Missing in PA-1. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5095
GeneReviewsiPCCA
MalaCardsiPCCA
MIMi606054 phenotype
OpenTargetsiENSG00000175198
Orphaneti35 Propionic acidemia
PharmGKBiPA32992

Chemistry databases

DrugBankiDB00121 Biotin

Polymorphism and mutation databases

BioMutaiPCCA
DMDMi308153661

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 52Mitochondrion1 PublicationAdd BLAST52
ChainiPRO_000000283753 – 728Propionyl-CoA carboxylase alpha chain, mitochondrialAdd BLAST676

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei65N6-acetyllysine; alternateBy similarity1
Modified residuei65N6-succinyllysine; alternateBy similarity1
Modified residuei119N6-succinyllysineBy similarity1
Modified residuei150N6-acetyllysine; alternateBy similarity1
Modified residuei150N6-succinyllysine; alternateBy similarity1
Modified residuei200N6-acetyllysine; alternateBy similarity1
Modified residuei200N6-succinyllysine; alternateBy similarity1
Modified residuei252PhosphoserineBy similarity1
Modified residuei262N6-succinyllysineBy similarity1
Modified residuei328N6-acetyllysine; alternateBy similarity1
Modified residuei328N6-succinyllysine; alternateBy similarity1
Modified residuei385N6-succinyllysineBy similarity1
Modified residuei407N6-succinyllysineBy similarity1
Modified residuei496N6-acetyllysineBy similarity1
Modified residuei502N6-succinyllysineBy similarity1
Modified residuei513N6-succinyllysineBy similarity1
Modified residuei648N6-succinyllysineBy similarity1
Modified residuei694N6-biotinyllysinePROSITE-ProRule annotationBy similarity1

Post-translational modificationi

Acetylated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP05165
MaxQBiP05165
PaxDbiP05165
PeptideAtlasiP05165
PRIDEiP05165
ProteomicsDBi51814
51815 [P05165-2]

PTM databases

iPTMnetiP05165
PhosphoSitePlusiP05165
SwissPalmiP05165

Expressioni

Gene expression databases

BgeeiENSG00000175198
CleanExiHS_PCCA
ExpressionAtlasiP05165 baseline and differential
GenevisibleiP05165 HS

Organism-specific databases

HPAiHPA041716
HPA047792

Interactioni

Subunit structurei

Probably a dodecamer composed of six biotin-containing alpha subunits and six beta subunits (Probable). Interacts (via the biotin carboxylation domain) with SIRT4 (PubMed:23438705). Interacts with SIRT3 and SIRT5 (PubMed:23438705).Curated1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
PCCBP051663EBI-2211679,EBI-1371908

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111128, 26 interactors
DIPiDIP-57493N
IntActiP05165, 16 interactors
MINTiP05165
STRINGi9606.ENSP00000365462

Structurei

Secondary structure

1728
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi199 – 201Combined sources3
Helixi202 – 212Combined sources11
Beta strandi214 – 220Combined sources7
Turni226 – 228Combined sources3
Beta strandi230 – 234Combined sources5
Helixi235 – 252Combined sources18
Beta strandi258 – 262Combined sources5
Beta strandi265 – 268Combined sources4
Beta strandi665 – 667Combined sources3
Beta strandi669 – 673Combined sources5
Beta strandi688 – 691Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CQYNMR-A176-270[»]
2JKUX-ray1.50A658-728[»]
ProteinModelPortaliP05165
SMRiP05165
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05165

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini62 – 509Biotin carboxylationAdd BLAST448
Domaini181 – 378ATP-graspPROSITE-ProRule annotationAdd BLAST198
Domaini653 – 728Biotinyl-bindingPROSITE-ProRule annotationAdd BLAST76

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0238 Eukaryota
COG4770 LUCA
GeneTreeiENSGT00550000074675
HOGENOMiHOG000008989
HOVERGENiHBG000555
InParanoidiP05165
KOiK01965
OMAiGGNMSIQ
OrthoDBiEOG091G06RG
PhylomeDBiP05165
TreeFamiTF354220

Family and domain databases

InterProiView protein in InterPro
IPR011761 ATP-grasp
IPR005481 BC-like_N
IPR001882 Biotin_BS
IPR011764 Biotin_carboxylation_dom
IPR005482 Biotin_COase_C
IPR000089 Biotin_lipoyl
IPR005479 CbamoylP_synth_lsu-like_ATP-bd
IPR016185 PreATP-grasp_dom_sf
IPR011054 Rudment_hybrid_motif
IPR011053 Single_hybrid_motif
PfamiView protein in Pfam
PF02785 Biotin_carb_C, 1 hit
PF00289 Biotin_carb_N, 1 hit
PF00364 Biotin_lipoyl, 1 hit
PF02786 CPSase_L_D2, 1 hit
SMARTiView protein in SMART
SM00878 Biotin_carb_C, 1 hit
SUPFAMiSSF51230 SSF51230, 1 hit
SSF51246 SSF51246, 1 hit
SSF52440 SSF52440, 1 hit
PROSITEiView protein in PROSITE
PS50975 ATP_GRASP, 1 hit
PS50979 BC, 1 hit
PS00188 BIOTIN, 1 hit
PS50968 BIOTINYL_LIPOYL, 1 hit
PS00866 CPSASE_1, 1 hit
PS00867 CPSASE_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P05165-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAGFWVGTAP LVAAGRRGRW PPQQLMLSAA LRTLKHVLYY SRQCLMVSRN
60 70 80 90 100
LGSVGYDPNE KTFDKILVAN RGEIACRVIR TCKKMGIKTV AIHSDVDASS
110 120 130 140 150
VHVKMADEAV CVGPAPTSKS YLNMDAIMEA IKKTRAQAVH PGYGFLSENK
160 170 180 190 200
EFARCLAAED VVFIGPDTHA IQAMGDKIES KLLAKKAEVN TIPGFDGVVK
210 220 230 240 250
DAEEAVRIAR EIGYPVMIKA SAGGGGKGMR IAWDDEETRD GFRLSSQEAA
260 270 280 290 300
SSFGDDRLLI EKFIDNPRHI EIQVLGDKHG NALWLNEREC SIQRRNQKVV
310 320 330 340 350
EEAPSIFLDA ETRRAMGEQA VALARAVKYS SAGTVEFLVD SKKNFYFLEM
360 370 380 390 400
NTRLQVEHPV TECITGLDLV QEMIRVAKGY PLRHKQADIR INGWAVECRV
410 420 430 440 450
YAEDPYKSFG LPSIGRLSQY QEPLHLPGVR VDSGIQPGSD ISIYYDPMIS
460 470 480 490 500
KLITYGSDRT EALKRMADAL DNYVIRGVTH NIALLREVII NSRFVKGDIS
510 520 530 540 550
TKFLSDVYPD GFKGHMLTKS EKNQLLAIAS SLFVAFQLRA QHFQENSRMP
560 570 580 590 600
VIKPDIANWE LSVKLHDKVH TVVASNNGSV FSVEVDGSKL NVTSTWNLAS
610 620 630 640 650
PLLSVSVDGT QRTVQCLSRE AGGNMSIQFL GTVYKVNILT RLAAELNKFM
660 670 680 690 700
LEKVTEDTSS VLRSPMPGVV VAVSVKPGDA VAEGQEICVI EAMKMQNSMT
710 720
AGKTGTVKSV HCQAGDTVGE GDLLVELE
Length:728
Mass (Da):80,059
Last modified:October 5, 2010 - v4
Checksum:i065F64186A0B8CCC
GO
Isoform 2 (identifier: P05165-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     36-61: Missing.

Show »
Length:702
Mass (Da):77,048
Checksum:iB75C63581796ED53
GO
Isoform 3 (identifier: P05165-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     634-680: Missing.

Show »
Length:681
Mass (Da):75,002
Checksum:iCF5795BE08D8BD5B
GO

Sequence cautioni

The sequence AAA60035 differs from that shown. Reason: Frameshift at positions 374, 378, 380 and 395.Curated
The sequence AAH00140 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAK61392 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA32763 differs from that shown. Reason: Frameshift at position 23.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti61K → E in BAG60571 (PubMed:14702039).Curated1
Sequence conflicti93H → Y in BAG59350 (Ref. 4) Curated1
Sequence conflicti373M → R in AAA60035 (PubMed:3460076).Curated1
Sequence conflicti378 – 379KG → RS in AAA60035 (PubMed:3460076).Curated2
Sequence conflicti558N → H in AAA60035 (PubMed:3460076).Curated1
Sequence conflicti610T → A in BAG59350 (Ref. 4) Curated1
Sequence conflicti679D → A in AAA36424 (PubMed:3555348).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00908775A → P in PA-1. 1 PublicationCorresponds to variant dbSNP:rs794727479EnsemblClinVar.1
Natural variantiVAR_00908877R → W in PA-1. 2 PublicationsCorresponds to variant dbSNP:rs141371306Ensembl.1
Natural variantiVAR_009089138A → T in PA-1. 1 PublicationCorresponds to variant dbSNP:rs202247814EnsemblClinVar.1
Natural variantiVAR_009090164I → T in PA-1. 1 PublicationCorresponds to variant dbSNP:rs202247815EnsemblClinVar.1
Natural variantiVAR_023843197G → E in PA-1. 1 Publication1
Natural variantiVAR_009091229M → K in PA-1. 1 PublicationCorresponds to variant dbSNP:rs375628794EnsemblClinVar.1
Natural variantiVAR_009092297Q → R in PA-1. 1 Publication1
Natural variantiVAR_009093368D → G in PA-1. 1 Publication1
Natural variantiVAR_009094373M → K in PA-1; unstable protein. 1 PublicationCorresponds to variant dbSNP:rs121964958EnsemblClinVar.1
Natural variantiVAR_009095379G → V in PA-1. 1 PublicationCorresponds to variant dbSNP:rs794727087EnsemblClinVar.1
Natural variantiVAR_023844398C → R in PA-1. 1 Publication1
Natural variantiVAR_009096399R → Q in PA-1. 1 Publication1
Natural variantiVAR_009097423P → L in PA-1. 1 Publication1
Natural variantiVAR_009098475I → V. Corresponds to variant dbSNP:rs35719359EnsemblClinVar.1
Natural variantiVAR_023845532Missing in PA-1. 1 Publication1
Natural variantiVAR_023846551V → F1 PublicationCorresponds to variant dbSNP:rs61749895EnsemblClinVar.1
Natural variantiVAR_009099559W → L in PA-1. 1 PublicationCorresponds to variant dbSNP:rs118169528EnsemblClinVar.1
Natural variantiVAR_009100631G → R in PA-1. 1 PublicationCorresponds to variant dbSNP:rs796052018Ensembl.1
Natural variantiVAR_009101668G → R in PA-1. 1 PublicationCorresponds to variant dbSNP:rs771438170EnsemblClinVar.1
Natural variantiVAR_009102712Missing in PA-1. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03985736 – 61Missing in isoform 2. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_044458634 – 680Missing in isoform 3. 1 PublicationAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF385926 mRNA Translation: AAL66189.1
AY035808
, AY035786, AY035787, AY035788, AY035789, AY035790, AY035791, AY035792, AY035793, AY035794, AY035795, AY035796, AY035797, AY035798, AY035799, AY035800, AY035801, AY035802, AY035803, AY035804, AY035805, AY035806, AY035807 Genomic DNA Translation: AAK61392.1 Different initiation.
AK296771 mRNA Translation: BAG59350.1
AK298318 mRNA Translation: BAG60571.1
AL355338 Genomic DNA No translation available.
AL356575 Genomic DNA No translation available.
AL136526 Genomic DNA No translation available.
AL353697 Genomic DNA No translation available.
CH471085 Genomic DNA Translation: EAX09034.1
BC000140 mRNA Translation: AAH00140.1 Different initiation.
X14608 mRNA Translation: CAA32763.1 Frameshift.
S55656 mRNA Translation: AAB25345.1
M13572 mRNA Translation: AAA60035.1 Frameshift.
M26121 mRNA Translation: AAA36424.1
CCDSiCCDS45065.1 [P05165-2]
CCDS53878.1 [P05165-3]
CCDS9496.2 [P05165-1]
PIRiS04613 A27883
RefSeqiNP_000273.2, NM_000282.3 [P05165-1]
NP_001121164.1, NM_001127692.2 [P05165-2]
NP_001171475.1, NM_001178004.1 [P05165-3]
UniGeneiHs.733632
Hs.80741

Genome annotation databases

EnsembliENST00000376279; ENSP00000365456; ENSG00000175198 [P05165-3]
ENST00000376285; ENSP00000365462; ENSG00000175198 [P05165-1]
ENST00000376286; ENSP00000365463; ENSG00000175198 [P05165-2]
GeneIDi5095
KEGGihsa:5095
UCSCiuc001voo.4 human [P05165-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPCCA_HUMAN
AccessioniPrimary (citable) accession number: P05165
Secondary accession number(s): B4DKY8
, B4DPF9, C9JPQ8, Q15979, Q8WXQ7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: October 5, 2010
Last modified: June 20, 2018
This is version 212 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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