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Q13093 (PAFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Platelet-activating factor acetylhydrolase

Short name=PAF acetylhydrolase
EC=3.1.1.47
Alternative name(s):
1-alkyl-2-acetylglycerophosphocholine esterase
2-acetyl-1-alkylglycerophosphocholine esterase
Group-VIIA phospholipase A2
Short name=gVIIA-PLA2
LDL-associated phospholipase A2
Short name=LDL-PLA(2)
PAF 2-acylhydrolase
Gene names
Name:PLA2G7
Synonyms:PAFAH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length441 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Modulates the action of platelet-activating factor (PAF) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. Has a specificity for substrates with a short residue at the sn-2 position. It is inactive against long-chain phospholipids.

Catalytic activity

1-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-alkyl-sn-glycero-3-phosphocholine + acetate.

Subcellular location

Secretedextracellular space.

Tissue specificity

Plasma.

Involvement in disease

Platelet-activating factor acetylhydrolase deficiency (PAFAD) [MIM:614278]: An enzymatic deficiency that results in exacerbated bodily response to inflammatory agents. It can be associated with several disease states including inflammatory gastrointestinal disorders, asthma and atopy. Asthmatic individuals with PAFAD may manifest aggravated respiratory symptoms.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Asthma (ASTHMA) [MIM:600807]: The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.15

Atopic hypersensitivity (ATOPY) [MIM:147050]: A condition characterized by predisposition to develop hypersensitivity reactions. Atopic individuals can develop eczema, allergic rhinitis and allergic asthma.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.15

Sequence similarities

Belongs to the AB hydrolase superfamily. Lipase family.

Ontologies

Keywords
   Biological processLipid degradation
Lipid metabolism
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseAsthma
Disease mutation
   DomainSignal
   Molecular functionHydrolase
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular protein metabolic process

Traceable author statement. Source: Reactome

lipid catabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

lipid oxidation

Inferred from direct assay Ref.2. Source: BHF-UCL

low-density lipoprotein particle remodeling

Inferred from direct assay Ref.2. Source: BHF-UCL

plasma lipoprotein particle oxidation

Inferred from direct assay Ref.2. Source: BHF-UCL

positive regulation of inflammatory response

Traceable author statement Ref.2. Source: BHF-UCL

positive regulation of monocyte chemotaxis

Inferred from direct assay Ref.2. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular region

Traceable author statement. Source: Reactome

low-density lipoprotein particle

Inferred from direct assay Ref.2. Source: BHF-UCL

   Molecular_function1-alkyl-2-acetylglycerophosphocholine esterase activity

Inferred from electronic annotation. Source: UniProtKB-EC

calcium-independent phospholipase A2 activity

Inferred from direct assay Ref.2. Source: BHF-UCL

phospholipid binding

Inferred from direct assay Ref.2. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121
Chain22 – 441420Platelet-activating factor acetylhydrolase
PRO_0000017833

Sites

Active site2731Nucleophile Ref.8
Active site2961Charge relay system Ref.8
Active site3511Charge relay system Ref.8

Amino acid modifications

Glycosylation4231N-linked (GlcNAc...) Potential
Glycosylation4331N-linked (GlcNAc...)

Natural variations

Natural variant451L → P. Ref.3
Corresponds to variant rs45521937 [ dbSNP | Ensembl ].
VAR_047970
Natural variant921R → H Common polymorphism. Ref.3 Ref.15
Corresponds to variant rs1805017 [ dbSNP | Ensembl ].
VAR_011583
Natural variant1911K → N. Ref.3
Corresponds to variant rs45454695 [ dbSNP | Ensembl ].
VAR_047971
Natural variant1981I → T Common polymorphism; associated with asthma and atopy. Ref.3 Ref.15
Corresponds to variant rs1805018 [ dbSNP | Ensembl ].
VAR_011584
Natural variant2791V → F in PAFAD; loss of function; risk factor for coronary arthery disease and stroke. Ref.10 Ref.12 Ref.13 Ref.14
Corresponds to variant rs16874954 [ dbSNP | Ensembl ].
VAR_004268
Natural variant2811Q → R in PAFAD; loss of function. Ref.11
VAR_011585
Natural variant3791V → A Common polymorphism. Ref.3 Ref.5 Ref.6 Ref.15
Corresponds to variant rs1051931 [ dbSNP | Ensembl ].
VAR_011586

Experimental info

Mutagenesis1081S → A: Activity is higher than wild-type.
Mutagenesis2731S → A: Loss of activity.
Mutagenesis2861D → A: Almost no activity.
Mutagenesis2861D → N: Diminishes activity.
Mutagenesis2961D → A: Loss of activity.
Mutagenesis2961D → N: Loss of activity.
Mutagenesis3041D → A: No change in activity.
Mutagenesis3381D → A: Activity is higher than wild-type.
Mutagenesis3511H → A: Loss of activity.

Secondary structure

............................................................... 441
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q13093 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 3BA9EEA9E8094A57

FASTA44150,077
        10         20         30         40         50         60 
MVPPKLHVLF CLCGCLAVVY PFDWQYINPV AHMKSSAWVN KIQVLMAAAS FGQTKIPRGN 

        70         80         90        100        110        120 
GPYSVGCTDL MFDHTNKGTF LRLYYPSQDN DRLDTLWIPN KEYFWGLSKF LGTHWLMGNI 

       130        140        150        160        170        180 
LRLLFGSMTT PANWNSPLRP GEKYPLVVFS HGLGAFRTLY SAIGIDLASH GFIVAAVEHR 

       190        200        210        220        230        240 
DRSASATYYF KDQSAAEIGD KSWLYLRTLK QEEETHIRNE QVRQRAKECS QALSLILDID 

       250        260        270        280        290        300 
HGKPVKNALD LKFDMEQLKD SIDREKIAVI GHSFGGATVI QTLSEDQRFR CGIALDAWMF 

       310        320        330        340        350        360 
PLGDEVYSRI PQPLFFINSE YFQYPANIIK MKKCYSPDKE RKMITIRGSV HQNFADFTFA 

       370        380        390        400        410        420 
TGKIIGHMLK LKGDIDSNVA IDLSNKASLA FLQKHLGLHK DFDQWDCLIE GDDENLIPGT 

       430        440 
NINTTNQHIM LQNSSGIEKY N 

« Hide

References

« Hide 'large scale' references
[1]"Anti-inflammatory properties of a platelet-activating factor acetylhydrolase."
Tjoelker L.W., Wilder C., Eberhardt C., Stafforini D.M., Dietsch G., Schimpf B., Hooper S., le Trong H., Cousens L.S., Zimmerman G.A., Yamada Y., McIntyre T.M., Prescott S.M., Gray P.W.
Nature 374:549-553(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 42-57.
Tissue: Myeloid.
[2]"Purification, properties, sequencing, and cloning of a lipoprotein-associated, serine-dependent phospholipase involved in the oxidative modification of low-density lipoproteins."
Tew D.G., Southan C., Rice S.Q.J., Lawrence M.P., Li H., Boyd H.F., Moores K., Gloger I.S., Macphee C.H.
Arterioscler. Thromb. Vasc. Biol. 16:591-599(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Lymphoma.
[3]SeattleSNPs variation discovery resource
Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-45; HIS-92; ASN-191; THR-198 AND ALA-379.
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-379.
[6]"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], VARIANT ALA-379.
Tissue: Blood.
[7]"Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad."
Tjoelker L.W., Eberhardt C., Unger J., le Trong H., Zimmerman G.A., McIntyre T.M., Stafforini D.M., Prescott S.M., Gray P.W.
J. Biol. Chem. 270:25481-25487(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[8]"Crystal structure of human plasma platelet-activating factor acetylhydrolase: structural implication to lipoprotein binding and catalysis."
Samanta U., Bahnson B.J.
J. Biol. Chem. 283:31617-31624(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 47-429 ALONE AND IN COMPLEX WITH PARAOXON, ACTIVE SITE.
[9]"Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes."
Samanta U., Kirby S.D., Srinivasan P., Cerasoli D.M., Bahnson B.J.
Biochem. Pharmacol. 78:420-429(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 47-429 IN COMPLEX WITH ORGANOPHOSPHORUS NERVE AGENTS.
[10]"Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase."
Stafforini D.M., Satoh K., Atkinson D.L., Tjoelker L.W., Eberhardt C., Yoshida H., Imaizumi T., Takamatsu S., Zimmerman G.A., McIntyre T.M., Gray P.W., Prescott S.M.
J. Clin. Invest. 97:2784-2791(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PAFAD PHE-279.
[11]"Loss of activity of plasma platelet-activating factor acetylhydrolase due to a novel Gln281-->Arg mutation."
Yamada Y., Yokota M.
Biochem. Biophys. Res. Commun. 236:772-775(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PAFAD ARG-281.
[12]"A mutation in plasma platelet-activating factor acetylhydrolase (Val279-->Phe) is a genetic risk factor for stroke."
Hiramoto M., Yoshida H., Imaizumi T., Yoshimizu N., Satoh K.
Stroke 28:2417-2420(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PAFAD PHE-279.
[13]"Identification of the G994--> T missense in exon 9 of the plasma platelet-activating factor acetylhydrolase gene as an independent risk factor for coronary artery disease in Japanese men."
Yamada Y., Ichihara S., Fujimura T., Yokota M.
Metabolism 47:177-181(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PAFAD PHE-279.
[14]"A mutation in plasma platelet-activating factor acetylhydrolase (Val279Phe) is a genetic risk factor for cerebral hemorrhage but not for hypertension."
Yoshida H., Imaizumi T., Fujimoto K., Itaya H., Hiramoto M., Yoshimizu N., Fukushi K., Satoh K.
Thromb. Haemost. 80:372-375(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PAFAD PHE-279.
[15]"The Ile198Thr and Ala379Val variants of plasmatic PAF-acetylhydrolase impair catalytical activities and are associated with atopy and asthma."
Kruse S., Mao X.-Q., Heinzmann A., Blattmann S., Roberts M.H., Braun S., Gao P.-S., Forster J., Kuehr J., Hopkin J.M., Shirakawa T., Deichmann K.A.
Am. J. Hum. Genet. 66:1522-1530(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-92; THR-198 AND ALA-379, INVOLVEMENT IN ASTHMA AND ATOPY.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U20157 mRNA. Translation: AAC50126.1.
U24577 mRNA. Translation: AAB04170.1.
EF568110 Genomic DNA. Translation: ABQ01234.1.
AL591242 Genomic DNA. Translation: CAH73907.1.
CH471081 Genomic DNA. Translation: EAX04301.1.
BC038452 mRNA. Translation: AAH38452.1.
PIRS60247.
RefSeqNP_001161829.1. NM_001168357.1.
NP_005075.3. NM_005084.3.
XP_005249465.1. XM_005249408.2.
UniGeneHs.584823.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3D59X-ray1.50A/B47-429[»]
3D5EX-ray2.10A/B47-429[»]
3F96X-ray2.10A/B47-429[»]
3F97X-ray1.70A/B47-429[»]
3F98X-ray1.70A/B/C47-429[»]
3F9CX-ray2.30A/B47-429[»]
ProteinModelPortalQ13093.
SMRQ13093. Positions 54-427.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113667. 1 interaction.
IntActQ13093. 3 interactions.
STRING9606.ENSP00000274793.

Chemistry

BindingDBQ13093.
ChEMBLCHEMBL3514.
GuidetoPHARMACOLOGY1432.

Polymorphism databases

DMDM2497687.

Proteomic databases

PaxDbQ13093.
PRIDEQ13093.

Protocols and materials databases

DNASU7941.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000274793; ENSP00000274793; ENSG00000146070.
ENST00000537365; ENSP00000445666; ENSG00000146070.
GeneID7941.
KEGGhsa:7941.
UCSCuc010jzf.3. human.

Organism-specific databases

CTD7941.
GeneCardsGC06M046719.
HGNCHGNC:9040. PLA2G7.
HPAHPA035915.
MIM147050. phenotype.
600807. phenotype.
601690. gene.
614278. phenotype.
neXtProtNX_Q13093.
PharmGKBPA33368.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4188.
HOGENOMHOG000008053.
HOVERGENHBG001322.
InParanoidQ13093.
KOK01062.
OMAWLMGNIL.
OrthoDBEOG7MSMQ5.
PhylomeDBQ13093.
TreeFamTF313831.

Enzyme and pathway databases

BRENDA3.1.1.4. 2681.
ReactomeREACT_17015. Metabolism of proteins.
SABIO-RKQ13093.

Gene expression databases

ArrayExpressQ13093.
BgeeQ13093.
CleanExHS_PLA2G7.
GenevestigatorQ13093.

Family and domain databases

InterProIPR005065. PAF_acetylhydro.
IPR016715. PAF_acetylhydro_eukaryote.
[Graphical view]
PANTHERPTHR10272. PTHR10272. 1 hit.
PfamPF03403. PAF-AH_p_II. 1 hit.
[Graphical view]
PIRSFPIRSF018169. PAF_acetylhydrolase. 1 hit.
PROSITEPS00120. LIPASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13093.
GeneWikiLipoprotein-associated_phospholipase_A2.
GenomeRNAi7941.
NextBio30458.
PROQ13093.
SOURCESearch...

Entry information

Entry namePAFA_HUMAN
AccessionPrimary (citable) accession number: Q13093
Secondary accession number(s): A5HTT5 expand/collapse secondary AC list , Q15692, Q5VTT1, Q8IVA2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM