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UniProtKB - Q9H2U2 (IPYR2_HUMAN)

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Protein

Inorganic pyrophosphatase 2, mitochondrial

Gene

PPA2

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

Functioni

Hydrolyzes inorganic pyrophosphate (PubMed:27523597). This activity is essential for correct regulation of mitochondrial membrane potential, and mitochondrial organization and function (PubMed:27523598).2 Publications

Catalytic activityi

Diphosphate + H2O = 2 phosphate.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi164Magnesium 1By similarity1
Metal bindingi169Magnesium 1By similarity1
Metal bindingi169Magnesium 2By similarity1
Metal bindingi201Magnesium 1By similarity1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

  • diphosphate metabolic process Source: Reactome
  • regulation of mitochondrial membrane potential Source: UniProtKB
  • tRNA aminoacylation for protein translation Source: Reactome
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase
LigandMagnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.6.1.1 2681
ReactomeiR-HSA-379726 Mitochondrial tRNA aminoacylation
R-HSA-71737 Pyrophosphate hydrolysis

Names & Taxonomyi

Protein namesi
Recommended name:
Inorganic pyrophosphatase 2, mitochondrial (EC:3.6.1.1)
Alternative name(s):
Pyrophosphatase SID6-306
Pyrophosphate phospho-hydrolase 2
Short name:
PPase 2
Gene namesi
Name:PPA2
ORF Names:HSPC124
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000138777.19
HGNCiHGNC:28883 PPA2
MIMi609988 gene
neXtProtiNX_Q9H2U2

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

Sudden cardiac failure, alcohol-induced (SCFAI)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disease characterized by sudden death due to unexpected cardiac arrest following ingestion of small amounts of alcohol.
See also OMIM:617223
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077872228P → L in SCFAI; decreased pyroposphatase activity. 1 PublicationCorresponds to variant dbSNP:rs138215926EnsemblClinVar.1
Sudden cardiac failure, infantile (SCFI)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by sudden death within the first 2 years of life due to unexpected cardiac arrest. Some patients manifest hypertrophic cardiomyopathy, lipid accumulation in myocardium, degeneration of mitochondrial cristae, metabolic acidosis, and elevated plasma lactate levels. SCFI transmission pattern is consistent with autosomal recessive inheritance.
See also OMIM:617222
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07786661S → P in SCFI; loss of function in regulation of mitochondrial membrane potential. 1 Publication1
Natural variantiVAR_07786794M → V in SCFI. 1 PublicationCorresponds to variant dbSNP:rs1057517679Ensembl.1
Natural variantiVAR_077868106M → I in SCFI. 1 PublicationCorresponds to variant dbSNP:rs1057517680Ensembl.1
Natural variantiVAR_077869127R → L in SCFI. 1 PublicationCorresponds to variant dbSNP:rs139076647EnsemblClinVar.1
Natural variantiVAR_077870167P → L in SCFI; decreased pyroposphatase activity. 1 PublicationCorresponds to variant dbSNP:rs546693824EnsemblClinVar.1
Natural variantiVAR_077873294Q → P in SCFI. 1 PublicationCorresponds to variant dbSNP:rs1057517678Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi27068
MalaCardsiPPA2
MIMi617222 phenotype
617223 phenotype
OpenTargetsiENSG00000138777
PharmGKBiPA142671159

Polymorphism and mutation databases

BioMutaiPPA2
DMDMi116242592

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 32MitochondrionCombined sources1 PublicationAdd BLAST32
ChainiPRO_000002541133 – 334Inorganic pyrophosphatase 2, mitochondrialAdd BLAST302

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei216N6-succinyllysineBy similarity1
Modified residuei224N6-acetyllysineBy similarity1
Modified residuei259N6-succinyllysineBy similarity1
Modified residuei261N6-acetyllysineCombined sources1
Modified residuei317PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9H2U2
MaxQBiQ9H2U2
PaxDbiQ9H2U2
PeptideAtlasiQ9H2U2
PRIDEiQ9H2U2
ProteomicsDBi80594
80595 [Q9H2U2-2]
80596 [Q9H2U2-3]
80597 [Q9H2U2-4]

2D gel databases

OGPiQ9H2U2

PTM databases

iPTMnetiQ9H2U2
PhosphoSitePlusiQ9H2U2
SwissPalmiQ9H2U2

Expressioni

Tissue specificityi

Detected in brain, gastric carcinoma, lung, ovary, skeletal muscle, umbilical cord blood and a cell line derived from kidney proximal tubule epithelium.1 Publication

Gene expression databases

BgeeiENSG00000138777
CleanExiHS_PPA2
ExpressionAtlasiQ9H2U2 baseline and differential
GenevisibleiQ9H2U2 HS

Organism-specific databases

HPAiHPA030888
HPA031671
HPA031672

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi117979, 40 interactors
IntActiQ9H2U2, 9 interactors
STRINGi9606.ENSP00000343885

Structurei

3D structure databases

ProteinModelPortaliQ9H2U2
SMRiQ9H2U2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the PPase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1626 Eukaryota
COG0221 LUCA
GeneTreeiENSGT00390000017004
HOVERGENiHBG000491
InParanoidiQ9H2U2
KOiK01507
OMAiIVDKWHY
OrthoDBiEOG091G0KFV
PhylomeDBiQ9H2U2
TreeFamiTF300887

Family and domain databases

CDDicd00412 pyrophosphatase, 1 hit
Gene3Di3.90.80.10, 1 hit
InterProiView protein in InterPro
IPR008162 Pyrophosphatase
IPR036649 Pyrophosphatase_sf
PANTHERiPTHR10286 PTHR10286, 1 hit
PfamiView protein in Pfam
PF00719 Pyrophosphatase, 1 hit
SUPFAMiSSF50324 SSF50324, 1 hit
PROSITEiView protein in PROSITE
PS00387 PPASE, 1 hit

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H2U2-1) [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
MSALLRLLRT GAPAAACLRL GTSAGTGSRR AMALYHTEER GQPCSQNYRL 
        60         70         80         90        100
FFKNVTGHYI SPFHDIPLKV NSKEENGIPM KKARNDEYEN LFNMIVEIPR 
       110        120        130        140        150
WTNAKMEIAT KEPMNPIKQY VKDGKLRYVA NIFPYKGYIW NYGTLPQTWE 
       160        170        180        190        200
DPHEKDKSTN CFGDNDPIDV CEIGSKILSC GEVIHVKILG ILALIDEGET 
       210        220        230        240        250
DWKLIAINAN DPEASKFHDI DDVKKFKPGY LEATLNWFRL YKVPDGKPEN 
       260        270        280        290        300
QFAFNGEFKN KAFALEVIKS THQCWKALLM KKCNGGAINC TNVQISDSPF 
       310        320        330 
RCTQEEARSL VESVSSSPNK ESNEEEQVWH FLGK
Length:334
Mass (Da):37,920
Last modified:October 17, 2006 - v2
Checksum:iF8C85F64CDA447F1
GO
Isoform 2 (identifier: Q9H2U2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     74-74: E → EDTEAQGIFIDLSKIW

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:349
Mass (Da):39,638
Checksum:i44938DDEB36C8789
GO
Isoform 3 (identifier: Q9H2U2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     148-176: Missing.

Show »
Length:305
Mass (Da):34,658
Checksum:iACC551F07BE228AE
GO
Isoform 4 (identifier: Q9H2U2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     53-53: K → N
     54-219: Missing.

Note: No experimental confirmation available.
Show »
Length:168
Mass (Da):18,916
Checksum:i9CADD542FA7E7569
GO
Isoform 5 (identifier: Q9H2U2-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     75-176: Missing.

Note: No experimental confirmation available.
Show »
Length:232
Mass (Da):25,992
Checksum:i2D41198AF19951A5
GO

Sequence cautioni

The sequence AAF29088 differs from that shown. Aberrant splicing.Curated
The sequence AAF29088 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA84701 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA91184 differs from that shown. Reason: Erroneous termination at position 59. Translated as Tyr.Curated
The sequence BAG59609 differs from that shown. Intron retention.Curated
The sequence CAB66590 differs from that shown. Reason: Frameshift at position 75.Curated
The sequence CAB66590 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti11G → V in BAA84701 (Ref. 1) Curated1
Sequence conflicti11G → V in AAG36781 (Ref. 2) Curated1
Sequence conflicti19R → G in CAB66590 (PubMed:11230166).Curated1
Sequence conflicti103N → K in CAB66590 (PubMed:11230166).Curated1
Sequence conflicti241Y → C in CAB66590 (PubMed:11230166).Curated1
Sequence conflicti288I → T in CAB66590 (PubMed:11230166).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07786661S → P in SCFI; loss of function in regulation of mitochondrial membrane potential. 1 Publication1
Natural variantiVAR_07786794M → V in SCFI. 1 PublicationCorresponds to variant dbSNP:rs1057517679Ensembl.1
Natural variantiVAR_077868106M → I in SCFI. 1 PublicationCorresponds to variant dbSNP:rs1057517680Ensembl.1
Natural variantiVAR_077869127R → L in SCFI. 1 PublicationCorresponds to variant dbSNP:rs139076647EnsemblClinVar.1
Natural variantiVAR_077870167P → L in SCFI; decreased pyroposphatase activity. 1 PublicationCorresponds to variant dbSNP:rs546693824EnsemblClinVar.1
Natural variantiVAR_077871172E → K in SCFI and SCFAI; loss of function in regulation of mitochondrial membrane potential; decreased pyroposphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs146013446EnsemblClinVar.1
Natural variantiVAR_077872228P → L in SCFAI; decreased pyroposphatase activity. 1 PublicationCorresponds to variant dbSNP:rs138215926EnsemblClinVar.1
Natural variantiVAR_019723282K → N3 PublicationsCorresponds to variant dbSNP:rs13787Ensembl.1
Natural variantiVAR_077873294Q → P in SCFI. 1 PublicationCorresponds to variant dbSNP:rs1057517678Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01164953K → N in isoform 4. 1 Publication1
Alternative sequenceiVSP_01165054 – 219Missing in isoform 4. 1 PublicationAdd BLAST166
Alternative sequenceiVSP_01165174E → EDTEAQGIFIDLSKIW in isoform 2. 2 Publications1
Alternative sequenceiVSP_04625675 – 176Missing in isoform 5. 1 PublicationAdd BLAST102
Alternative sequenceiVSP_011652148 – 176Missing in isoform 3. 2 PublicationsAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB026722 mRNA Translation: BAA84701.1 Different initiation.
AF217187 mRNA Translation: AAG36781.1
AK000466 mRNA Translation: BAA91184.1 Sequence problems.
AK297096 mRNA Translation: BAG59609.1 Sequence problems.
AC004066 Genomic DNA No translation available.
AC106888 Genomic DNA Translation: AAY41040.1
BC022803 mRNA Translation: AAH22803.1
BC039462 mRNA Translation: AAH39462.2
BC057219 mRNA Translation: AAH57219.1
AF161473 mRNA Translation: AAF29088.1 Sequence problems.
AL136655 mRNA Translation: CAB66590.2 Sequence problems.
CCDSiCCDS34043.1 [Q9H2U2-4]
CCDS3667.1 [Q9H2U2-1]
CCDS3668.2 [Q9H2U2-3]
CCDS3669.2 [Q9H2U2-6]
RefSeqiNP_008834.3, NM_006903.4 [Q9H2U2-3]
NP_789842.2, NM_176866.2 [Q9H2U2-6]
NP_789843.2, NM_176867.3 [Q9H2U2-4]
NP_789845.1, NM_176869.2 [Q9H2U2-1]
UniGeneiHs.654957

Genome annotation databases

EnsembliENST00000341695; ENSP00000343885; ENSG00000138777 [Q9H2U2-1]
ENST00000348706; ENSP00000313061; ENSG00000138777 [Q9H2U2-3]
ENST00000354147; ENSP00000340352; ENSG00000138777 [Q9H2U2-4]
ENST00000432483; ENSP00000389957; ENSG00000138777 [Q9H2U2-6]
GeneIDi27068
KEGGihsa:27068
UCSCiuc003hxl.4 human [Q9H2U2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIPYR2_HUMAN
AccessioniPrimary (citable) accession number: Q9H2U2
Secondary accession number(s): B4DLP7
, F8WDN9, I6L9B6, Q4W5E9, Q6PG51, Q8TBW0, Q96E55, Q9H0T0, Q9NX37, Q9P033, Q9ULX0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: October 17, 2006
Last modified: June 20, 2018
This is version 151 of the entry and version 2 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. SIMILARITY comments
    Index of protein domains and families

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