Q13093 (PAFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	441 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Secreted › extracellular 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 weezing 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 process	Lipid degradation Lipid metabolism
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Asthma Disease mutation
Domain	Signal
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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_component	low-density lipoprotein particle Inferred from direct assay Ref.2. Source: BHF-UCL
Molecular_function	1-alkyl-2-acetylglycerophosphocholine esterase activity Inferred from electronic annotation. Source: 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Chain

22 – 441

420

Platelet-activating factor acetylhydrolase

PRO_0000017833

Sites

Active site

273

1

Nucleophile Ref.8

Active site

296

1

Charge relay system Ref.8

Active site

351

1

Charge relay system Ref.8

Amino acid modifications

Glycosylation

423

1

N-linked (GlcNAc...) Potential

Glycosylation

433

1

N-linked (GlcNAc...)

Natural variations

Natural variant

45

1

L → P. Ref.3
Corresponds to variant rs45521937 [ dbSNP | Ensembl ].

VAR_047970

Natural variant

92

1

R → H Common polymorphism. Ref.3 Ref.15
Corresponds to variant rs1805017 [ dbSNP | Ensembl ].

VAR_011583

Natural variant

191

1

K → N. Ref.3
Corresponds to variant rs45454695 [ dbSNP | Ensembl ].

VAR_047971

Natural variant

198

1

I → T Common polymorphism; associated with asthma and atopy. Ref.3 Ref.15
Corresponds to variant rs1805018 [ dbSNP | Ensembl ].

VAR_011584

Natural variant

279

1

V → 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 variant

281

1

Q → R in PAFAD; loss of function. Ref.11

VAR_011585

Natural variant

379

1

V → A Common polymorphism. Ref.3 Ref.5 Ref.6 Ref.15
Corresponds to variant rs1051931 [ dbSNP | Ensembl ].

VAR_011586

Experimental info

Mutagenesis

108

1

S → A: Activity is higher than wild-type.

Mutagenesis

273

1

S → A: Loss of activity.

Mutagenesis

286

1

D → A: Almost no activity.

Mutagenesis

286

1

D → N: Diminishes activity.

Mutagenesis

296

1

D → A: Loss of activity.

Mutagenesis

296

1

D → N: Loss of activity.

Mutagenesis

304

1

D → A: No change in activity.

Mutagenesis

338

1

D → A: Activity is higher than wild-type.

Mutagenesis

351

1

H → A: Loss of activity.

Secondary structure

1

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441

Helix Strand Turn

Details...

Beta strand

54 – 56

3

Beta strand

61 – 75

15

Beta strand

78 – 88

11

Beta strand

95 – 98

4

Helix

101 – 111

11

Helix

115 – 125

11

Beta strand

129 – 134

6

Beta strand

144 – 150

7

Turn

157 – 160

4

Helix

161 – 169

9

Beta strand

173 – 177

5

Beta strand

184 – 189

6

Helix

193 – 198

6

Beta strand

202 – 205

4

Helix

211 – 213

3

Helix

214 – 240

27

Helix

255 – 258

4

Beta strand

262 – 272

11

Helix

274 – 285

12

Beta strand

291 – 296

6

Helix

304 – 308

5

Beta strand

314 – 319

6

Turn

320 – 322

3

Helix

325 – 332

8

Beta strand

337 – 339

3

Beta strand

341 – 346

6

Helix

351 – 354

4

Helix

356 – 359

4

Helix

363 – 368

6

Helix

377 – 396

20

Helix

402 – 405

4

Helix

406 – 409

4

Beta strand

416 – 419

4

Sequences

	Sequence		Length	Mass (Da)
	Q13093 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 3BA9EEA9E8094A57	FASTA	441	50,077
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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

SeattleSNPs

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.

IPI

IPI00011588.

PIR

S60247.

RefSeq

NP_001161829.1. NM_001168357.1.
NP_005075.3. NM_005084.3.

UniGene

Hs.584823.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3D59	X-ray	1.50	A/B	47-429	[»]
3D5E	X-ray	2.10	A/B	47-429	[»]
3F96	X-ray	2.10	A/B	47-429	[»]
3F97	X-ray	1.70	A/B	47-429	[»]
3F98	X-ray	1.70	A/B/C	47-429	[»]
3F9C	X-ray	2.30	A/B	47-429	[»]

ProteinModelPortal

Q13093.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13093. 3 interactions.

STRING

9606.ENSP00000274793.

Polymorphism databases

DMDM

2497687.

Proteomic databases

PaxDb

Q13093.

PRIDE

Q13093.

Protocols and materials databases

DNASU

7941.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000274793; ENSP00000274793; ENSG00000146070.
ENST00000537365; ENSP00000445666; ENSG00000146070.

GeneID

7941.

KEGG

hsa:7941.

UCSC

uc010jzf.3. human.

Organism-specific databases

CTD

7941.

GeneCards

GC06M046719.

HGNC

HGNC:9040. PLA2G7.

HPA

HPA035915.

MIM

147050. phenotype.
600807. phenotype.
601690. gene.
614278. phenotype.

neXtProt

NX_Q13093.

PharmGKB

PA33368.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4188.

HOGENOM

HOG000008053.

HOVERGEN

HBG001322.

InParanoid

Q13093.

KO

K01062.

OMA

RERKMIT.

OrthoDB

EOG4QC156.

PhylomeDB

Q13093.

Enzyme and pathway databases

BRENDA

3.1.1.4. 2681.

Pathway_Interaction_DB

lis1pathway. Lissencephaly gene (LIS1) in neuronal migration and development.

Reactome

REACT_116125. Disease.

SABIO-RK

Q13093.

Gene expression databases

ArrayExpress

Q13093.

Bgee

Q13093.

CleanEx

HS_PLA2G7.

Genevestigator

Q13093.

GermOnline

ENSG00000146070. Homo sapiens.

Family and domain databases

InterPro

IPR016715. Ac_Ohase_PAF.
IPR005065. PAF_acetylhydro.
[Graphical view]

PANTHER

PTHR10272. PTHR10272. 1 hit.

Pfam

PF03403. PAF-AH_p_II. 1 hit.
[Graphical view]

PIRSF

PIRSF018169. PAF_acetylhydrolase. 1 hit.

PROSITE

PS00120. LIPASE_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q13093.

ChEMBL

CHEMBL3514.

EvolutionaryTrace

Q13093.

GenomeRNAi

7941.

NextBio

30458.

SOURCE

Search...

Entry information

Entry name

PAFA_HUMAN

Accession

Primary (citable) accession number: Q13093
Secondary accession number(s): A5HTT5 , Q15692, Q5VTT1, Q8IVA2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 128 of the entry and version 1 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.