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Protein

Mitochondrial-processing peptidase subunit alpha

Gene

PMPCA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cleaves presequences (transit peptides) from mitochondrial protein precursors.1 Publication

Catalytic activityi

Release of N-terminal transit peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2.

GO - Molecular functioni

  • metalloendopeptidase activity Source: UniProtKB
  • zinc ion binding Source: GO_Central

GO - Biological processi

  • protein processing involved in protein targeting to mitochondrion Source: GO_Central
  • proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Enzyme and pathway databases

ReactomeiR-HSA-1268020. Mitochondrial protein import.
SignaLinkiQ10713.

Protein family/group databases

MEROPSiM16.971.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial-processing peptidase subunit alpha (EC:3.4.24.64)
Alternative name(s):
Alpha-MPP
P-55
Gene namesi
Name:PMPCA
Synonyms:INPP5E, KIAA0123, MPPA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:18667. PMPCA.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: UniProtKB
  • mitochondrial inner membrane Source: UniProtKB
  • mitochondrial matrix Source: UniProtKB-SubCell
  • mitochondrion Source: LIFEdb
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia, autosomal recessive, 2 (SCAR2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR2 is characterized by onset of impaired motor development and ataxic gait in early childhood. Additional features often include loss of fine motor skills, dysarthria, nystagmus, cerebellar signs, and delayed cognitive development with intellectual disability.
See also OMIM:213200
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti96 – 961S → L in SCAR2. 1 Publication
VAR_076237
Natural varianti256 – 2561V → M in SCAR2. 1 Publication
Corresponds to variant rs746549806 [ dbSNP | Ensembl ].
VAR_076238
Natural varianti377 – 3771A → T in SCAR2; impairs cleavage of FXN; does not impair cleavage of DLD, NFS1 and PRDX3. 1 Publication
VAR_076239
Natural varianti515 – 5151G → R in SCAR2. 1 Publication
VAR_076240

Keywords - Diseasei

Disease mutation, Mental retardation, Neurodegeneration

Organism-specific databases

MIMi213200. phenotype.
PharmGKBiPA38629.

Polymorphism and mutation databases

DMDMi29840846.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3333MitochondrionCombined sourcesAdd
BLAST
Chaini34 – 525492Mitochondrial-processing peptidase subunit alphaPRO_0000026767Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei64 – 641N6-succinyllysineBy similarity
Modified residuei299 – 2991N6-acetyllysineCombined sources

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ10713.
PaxDbiQ10713.
PeptideAtlasiQ10713.
PRIDEiQ10713.

PTM databases

iPTMnetiQ10713.
PhosphoSiteiQ10713.

Expressioni

Tissue specificityi

Ubiquitously expressed with highest expression in fetal tissues and adult brain, cerebellum and cerebellar vermis.1 Publication

Gene expression databases

BgeeiENSG00000165688.
CleanExiHS_INPP5E.
HS_PMPCA.
ExpressionAtlasiQ10713. baseline and differential.
GenevisibleiQ10713. HS.

Organism-specific databases

HPAiHPA021648.
HPA063735.

Interactioni

Subunit structurei

Heterodimer of alpha and beta subunits.By similarity

Protein-protein interaction databases

BioGridi116811. 27 interactions.
IntActiQ10713. 4 interactions.
MINTiMINT-3026454.
STRINGi9606.ENSP00000360782.

Structurei

3D structure databases

ProteinModelPortaliQ10713.
SMRiQ10713. Positions 68-487.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M16 family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2067. Eukaryota.
COG0612. LUCA.
GeneTreeiENSGT00550000074666.
HOGENOMiHOG000206848.
HOVERGENiHBG106890.
InParanoidiQ10713.
KOiK01412.
OMAiMNYLKYH.
OrthoDBiEOG091G07S9.
PhylomeDBiQ10713.
TreeFamiTF105031.

Family and domain databases

Gene3Di3.30.830.10. 2 hits.
InterProiIPR011249. Metalloenz_LuxS/M16.
IPR011237. Pept_M16_dom.
IPR011765. Pept_M16_N.
IPR001431. Pept_M16_Zn_BS.
IPR007863. Peptidase_M16_C.
[Graphical view]
PfamiPF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 1 hit.
[Graphical view]
SUPFAMiSSF63411. SSF63411. 2 hits.
PROSITEiPS00143. INSULINASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q10713-1) [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
MAAVVLAATR LLRGSGSWGC SRLRFGPPAY RRFSSGGAYP NIPLSSPLPG
60 70 80 90 100
VPKPVFATVD GQEKFETKVT TLDNGLRVAS QNKFGQFCTV GILINSGSRY
110 120 130 140 150
EAKYLSGIAH FLEKLAFSST ARFDSKDEIL LTLEKHGGIC DCQTSRDTTM
160 170 180 190 200
YAVSADSKGL DTVVALLADV VLQPRLTDEE VEMTRMAVQF ELEDLNLRPD
210 220 230 240 250
PEPLLTEMIH EAAYRENTVG LHRFCPTENV AKINREVLHS YLRNYYTPDR
260 270 280 290 300
MVLAGVGVEH EHLVDCARKY LLGVQPAWGS AEAVDIDRSV AQYTGGIAKL
310 320 330 340 350
ERDMSNVSLG PTPIPELTHI MVGLESCSFL EEDFIPFAVL NMMMGGGGSF
360 370 380 390 400
SAGGPGKGMF SRLYLNVLNR HHWMYNATSY HHSYEDTGLL CIHASADPRQ
410 420 430 440 450
VREMVEIITK EFILMGGTVD TVELERAKTQ LTSMLMMNLE SRPVIFEDVG
460 470 480 490 500
RQVLATRSRK LPHELCTLIR NVKPEDVKRV ASKMLRGKPA VAALGDLTDL
510 520
PTYEHIQTAL SSKDGRLPRT YRLFR
Length:525
Mass (Da):58,253
Last modified:April 11, 2003 - v2
Checksum:i2751E7FCDC864E3F
GO
Isoform 2 (identifier: Q10713-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MAAVVLAATR...GAYPNIPLSS → MKRNTLVELL...MGVSVTARHQ
     47-177: Missing.

Note: No experimental confirmation available.
Show »
Length:394
Mass (Da):44,866
Checksum:iE384C96ECCDCDD70
GO

Sequence cautioni

The sequence AAH33103 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAA04643 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAA09472 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti495 – 4951G → C in AAH22949 (PubMed:15489334).Curated
Sequence conflicti505 – 5051H → D in BAA04643 (PubMed:7788527).Curated

Mass spectrometryi

Molecular mass is 54624.57 Da from positions 33 - 525. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti96 – 961S → L in SCAR2. 1 Publication
VAR_076237
Natural varianti256 – 2561V → M in SCAR2. 1 Publication
Corresponds to variant rs746549806 [ dbSNP | Ensembl ].
VAR_076238
Natural varianti377 – 3771A → T in SCAR2; impairs cleavage of FXN; does not impair cleavage of DLD, NFS1 and PRDX3. 1 Publication
VAR_076239
Natural varianti515 – 5151G → R in SCAR2. 1 Publication
VAR_076240

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4646MAAVV…IPLSS → MKRNTLVELLTFWKNWHFRL LLDLTAKMKFCLRWKSMGVS VTARHQ in isoform 2. 1 PublicationVSP_054916Add
BLAST
Alternative sequencei47 – 177131Missing in isoform 2. 1 PublicationVSP_054917Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21064 mRNA. Translation: BAA04643.1. Different initiation.
D50913 mRNA. Translation: BAA09472.2. Different initiation.
AK296617 mRNA. Translation: BAG59225.1.
AL592301 Genomic DNA. Translation: CAI13945.1.
CH471090 Genomic DNA. Translation: EAW88232.1.
BC022949 mRNA. Translation: AAH22949.1.
BC033103 mRNA. Translation: AAH33103.2. Different initiation.
BC111399 mRNA. Translation: AAI11400.1.
BC132724 mRNA. Translation: AAI32725.1.
BC136599 mRNA. Translation: AAI36600.1.
CCDSiCCDS35180.1. [Q10713-1]
CCDS65192.1. [Q10713-2]
RefSeqiNP_001269873.1. NM_001282944.1. [Q10713-2]
NP_001269875.1. NM_001282946.1.
NP_055975.1. NM_015160.2. [Q10713-1]
UniGeneiHs.495471.

Genome annotation databases

EnsembliENST00000371717; ENSP00000360782; ENSG00000165688. [Q10713-1]
ENST00000399219; ENSP00000416702; ENSG00000165688. [Q10713-2]
GeneIDi23203.
KEGGihsa:23203.
UCSCiuc004chl.5. human. [Q10713-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21064 mRNA. Translation: BAA04643.1. Different initiation.
D50913 mRNA. Translation: BAA09472.2. Different initiation.
AK296617 mRNA. Translation: BAG59225.1.
AL592301 Genomic DNA. Translation: CAI13945.1.
CH471090 Genomic DNA. Translation: EAW88232.1.
BC022949 mRNA. Translation: AAH22949.1.
BC033103 mRNA. Translation: AAH33103.2. Different initiation.
BC111399 mRNA. Translation: AAI11400.1.
BC132724 mRNA. Translation: AAI32725.1.
BC136599 mRNA. Translation: AAI36600.1.
CCDSiCCDS35180.1. [Q10713-1]
CCDS65192.1. [Q10713-2]
RefSeqiNP_001269873.1. NM_001282944.1. [Q10713-2]
NP_001269875.1. NM_001282946.1.
NP_055975.1. NM_015160.2. [Q10713-1]
UniGeneiHs.495471.

3D structure databases

ProteinModelPortaliQ10713.
SMRiQ10713. Positions 68-487.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116811. 27 interactions.
IntActiQ10713. 4 interactions.
MINTiMINT-3026454.
STRINGi9606.ENSP00000360782.

Protein family/group databases

MEROPSiM16.971.

PTM databases

iPTMnetiQ10713.
PhosphoSiteiQ10713.

Polymorphism and mutation databases

DMDMi29840846.

Proteomic databases

EPDiQ10713.
PaxDbiQ10713.
PeptideAtlasiQ10713.
PRIDEiQ10713.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371717; ENSP00000360782; ENSG00000165688. [Q10713-1]
ENST00000399219; ENSP00000416702; ENSG00000165688. [Q10713-2]
GeneIDi23203.
KEGGihsa:23203.
UCSCiuc004chl.5. human. [Q10713-1]

Organism-specific databases

CTDi23203.
GeneCardsiPMPCA.
H-InvDBHIX0169363.
HGNCiHGNC:18667. PMPCA.
HPAiHPA021648.
HPA063735.
MIMi213200. phenotype.
613036. gene.
neXtProtiNX_Q10713.
PharmGKBiPA38629.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2067. Eukaryota.
COG0612. LUCA.
GeneTreeiENSGT00550000074666.
HOGENOMiHOG000206848.
HOVERGENiHBG106890.
InParanoidiQ10713.
KOiK01412.
OMAiMNYLKYH.
OrthoDBiEOG091G07S9.
PhylomeDBiQ10713.
TreeFamiTF105031.

Enzyme and pathway databases

ReactomeiR-HSA-1268020. Mitochondrial protein import.
SignaLinkiQ10713.

Miscellaneous databases

ChiTaRSiPMPCA. human.
GeneWikiiPMPCA.
GenomeRNAii23203.
PROiQ10713.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165688.
CleanExiHS_INPP5E.
HS_PMPCA.
ExpressionAtlasiQ10713. baseline and differential.
GenevisibleiQ10713. HS.

Family and domain databases

Gene3Di3.30.830.10. 2 hits.
InterProiIPR011249. Metalloenz_LuxS/M16.
IPR011237. Pept_M16_dom.
IPR011765. Pept_M16_N.
IPR001431. Pept_M16_Zn_BS.
IPR007863. Peptidase_M16_C.
[Graphical view]
PfamiPF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 1 hit.
[Graphical view]
SUPFAMiSSF63411. SSF63411. 2 hits.
PROSITEiPS00143. INSULINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMPPA_HUMAN
AccessioniPrimary (citable) accession number: Q10713
Secondary accession number(s): B4DKL3
, E7ET61, Q16639, Q5SXM9, Q8N513
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 11, 2003
Last modified: September 7, 2016
This is version 156 of the entry and version 2 of the sequence. [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

Caution

Does not seem to have a protease activity as it lack the zinc-binding site.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.