Q15181 (IPYR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inorganic pyrophosphatase
EC=3.6.1.1

Alternative name(s):
Pyrophosphate phospho-hydrolase
Short name=PPase

Gene names

Name:	PPA1
Synonyms:	IOPPP, PP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	Diphosphate + H2O = 2 phosphate.
Cofactor	Binds 4 magnesium ions per subunit. Other metal ions can support activity, but at a lower rate. Two magnesium ions are required for the activation of the enzyme and are present before substrate binds, two additional magnesium ions form complexes with substrate and product By similarity.
Subunit structure	Homodimer By similarity.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Expressed ubiquitously. Ref.1
Sequence similarities	Belongs to the PPase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	diphosphate metabolic process Traceable author statement. Source: Reactome phosphate-containing compound metabolic process Traceable author statement Ref.1. Source: ProtInc tRNA aminoacylation for protein translation Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	inorganic diphosphatase activity Inferred from experiment. Source: Reactome magnesium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 289	289	Inorganic pyrophosphatase		PRO_0000137567
Sites
	Metal binding	116	1	Magnesium 1 By similarity
	Metal binding	121	1	Magnesium 1 By similarity
	Metal binding	121	1	Magnesium 2 By similarity
	Metal binding	153	1	Magnesium 1 By similarity
Amino acid modifications
	Modified residue	57	1	N6-acetyllysine Ref.11
	Modified residue	228	1	N6-acetyllysine Ref.11
	Modified residue	250	1	Phosphoserine Ref.12
Natural variations
	Natural variant	57	1	K → N in a breast cancer sample; somatic mutation. Ref.14		VAR_036358
Experimental info
	Sequence conflict	12	1	P → A in AAD24964. Ref.8
	Sequence conflict	84	1	L → I in CAA88494. Ref.10
	Sequence conflict	96 – 97	2	AI → TL in CAA88494. Ref.10
	Sequence conflict	105 – 114	10	GHNDKHTGCC → HEKDKSTNCF in CAA88494. Ref.10
	Sequence conflict	129 – 140	12	VCARG…IGVKV → ILSCGEVIHVKI in CAA88494. Ref.10
	Sequence conflict	146	1	M → L in CAA88494. Ref.10
	Sequence conflict	156	1	V → L in CAA88494. Ref.10
	Sequence conflict	161 – 162	2	VD → AN in CAA88494. Ref.10
	Sequence conflict	165 – 173	9	DAANYNDIN → EASKFHDID in CAA88494. Ref.10
	Sequence conflict	177 – 178	2	RL → KF in CAA88494. Ref.10
	Sequence conflict	187 – 188	2	VD → LN in CAA88494. Ref.10
	Sequence conflict	192	1	R → L in CAA88494. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Q15181 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: E3973C9E6F8CA5CD	FASTA	289	32,660
	10 20 30 40 50 60 MSGFSTEERA APFSLEYRVF LKNEKGQYIS PFHDIPIYAD KDVFHMVVEV PRWSNAKMEI 70 80 90 100 110 120 ATKDPLNPIK QDVKKGKLRY VANLFPYKGY IWNYGAIPQT WEDPGHNDKH TGCCGDNDPI 130 140 150 160 170 180 DVCEIGSKVC ARGEIIGVKV LGILAMIDEG ETDWKVIAIN VDDPDAANYN DINDVKRLKP 190 200 210 220 230 240 GYLEATVDWF RRYKVPDGKP ENEFAFNAEF KDKDFAIDII KSTHDHWKAL VTKKTNGKGI 250 260 270 280 SCMNTTLSES PFKCDPDAAR AIVDALPPPC ESACTVPTDV DKWFHHQKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression profile of human inorganic pyrophosphatase." Fairchild T.A., Patejunas G. Biochim. Biophys. Acta 1447:133-136(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Heart.
[2]	"Putative inorganic pyrophosphatase." Saito T., Hattori A., Miyajima N. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Cloning of a human inorganic pyrophosphatase cDNA." Kanni L., Johansson M., Karlsson A. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning and characterization of a novel human cDNA homology to bovine inorganic pyrophosphatase mRNA." Dai F.Y., Yu L., Hu P.R., Xin Y.R., Xu Y.F., Zhao S.Y. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Adrenal gland.
[6]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Lymph and Uterus.
[8]	"Cloning, expression, affinity purification and characterization of polyhistidine-tagged cytosolic Saccharomyces cerevisiae and human inorganic pyrophosphatases for differential screening of compounds for antifungal activity." Rumsfeld J., Ziegelbauer K., Spaltmann F. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-286.
[9]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 10-18; 26-41; 58-70; 80-88; 110-128; 140-191; 193-221 AND 239-253, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[10]	"Partial sequence of the human inorganic pyrophosphatase." Lacroix J., Vigneron M., Kedinger C. Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 83-196.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-57 AND LYS-228, MASS SPECTROMETRY.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-57.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF154065 mRNA. Translation: AAD34643.1. AB026723 mRNA. Translation: BAA84702.1. AF217186 mRNA. Translation: AAG36780.1. AF092439 mRNA. Translation: AAP97214.1. AF119665 mRNA. Translation: AAF17222.1. AL731540 Genomic DNA. Translation: CAI13692.1. BC001022 mRNA. Translation: AAH01022.3. BC061581 mRNA. Translation: AAH61581.2. BC105034 mRNA. Translation: AAI05035.1. BC105036 mRNA. Translation: AAI05037.1. BC107882 mRNA. Translation: AAI07883.1. AF108211 mRNA. Translation: AAD24964.1. Z48605 mRNA. Translation: CAA88494.1.
IPI	IPI00015018.
RefSeq	NP_066952.1. NM_021129.3.
UniGene	Hs.437403.
3D structure databases
ProteinModelPortal	Q15181.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15181. 9 interactions.
STRING	9606.ENSP00000362329.
PTM databases
PhosphoSite	Q15181.
Polymorphism databases
DMDM	8247940.
2D gel databases
REPRODUCTION-2DPAGE	IPI00015018.
Proteomic databases
PaxDb	Q15181.
PeptideAtlas	Q15181.
PRIDE	Q15181.
Protocols and materials databases
DNASU	5464.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373232; ENSP00000362329; ENSG00000180817.
GeneID	5464.
KEGG	hsa:5464.
UCSC	uc001jqv.1. human.
Organism-specific databases
CTD	5464.
GeneCards	GC10M071962.
H-InvDB	HIX0032502.
HGNC	HGNC:9226. PPA1.
HPA	HPA019878. HPA020096.
MIM	179030. gene.
neXtProt	NX_Q15181.
PharmGKB	PA33550.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0221.
HOGENOM	HOG000195569.
HOVERGEN	HBG000491.
InParanoid	Q15181.
KO	K01507.
OMA	WEDPGHS.
OrthoDB	EOG4KPTBC.
PhylomeDB	Q15181.
Enzyme and pathway databases
BRENDA	3.6.1.1. 2681.
Reactome	REACT_21259. Pyrophosphate hydrolysis. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q15181.
Bgee	Q15181.
CleanEx	HS_PPA1.
Genevestigator	Q15181.
GermOnline	ENSG00000180817. Homo sapiens.
Family and domain databases
Gene3D	3.90.80.10. 1 hit.
InterPro	IPR008162. Pyrophosphatase. [Graphical view]
PANTHER	PTHR10286. PTHR10286. 1 hit.
Pfam	PF00719. Pyrophosphatase. 1 hit. [Graphical view]
SUPFAM	SSF50324. Pyrophosphatase. 1 hit.
PROSITE	PS00387. PPASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PPA1. human.
GenomeRNAi	5464.
NextBio	21148.
SOURCE	Search...

Entry information

Entry name

IPYR_HUMAN

Accession

Primary (citable) accession number: Q15181
Secondary accession number(s): Q2M348 , Q5SQT7, Q6P7P4, Q9UQJ5, Q9Y5B1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 30, 2000
Last modified:	May 1, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.