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P20292 (AL5AP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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:
Arachidonate 5-lipoxygenase-activating protein
Alternative name(s):
FLAP
MK-886-binding protein
Gene names
Name:ALOX5AP
Synonyms:FLAP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length161 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes. Ref.1 Ref.6

Subunit structure

Homotrimer. Interacts with LTC4S and ALOX5. Ref.10 Ref.12

Subcellular location

Nucleus membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.6 Ref.7 Ref.10.

Domain

The C-terminal part after residue 140 is mostly unstructured. Ref.12

Involvement in disease

Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.8

Genetic variations in ALOX5AP may be associated with susceptibility to myocardial infarction. Involvement in myocardial infarction is however unclear: according to some authors (Ref.8), a 4-SNP haplotype in ALOX5AP confers risk of myocardial infarction, while according to other (Ref.9) ALOX5AP is not implicated in this condition.

Sequence similarities

Belongs to the MAPEG family.

Ontologies

Keywords
   Biological processLeukotriene biosynthesis
   Cellular componentEndoplasmic reticulum
Membrane
Nucleus
   DomainTransmembrane
Transmembrane helix
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processarachidonic acid metabolic process

Traceable author statement. Source: Reactome

cellular response to calcium ion

Inferred from direct assay Ref.1. Source: UniProtKB

leukotriene biosynthetic process

Inferred from direct assay Ref.1. Source: UniProtKB

leukotriene metabolic process

Traceable author statement. Source: Reactome

leukotriene production involved in inflammatory response

Inferred from electronic annotation. Source: Ensembl

lipoxin metabolic process

Traceable author statement. Source: Reactome

lipoxygenase pathway

Traceable author statement. Source: Reactome

positive regulation of acute inflammatory response

Inferred from electronic annotation. Source: Ensembl

protein homotrimerization

Inferred from physical interaction Ref.12. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from direct assay Ref.10. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nuclear envelope

Inferred from direct assay Ref.10. Source: UniProtKB

nuclear membrane

Inferred from direct assay Ref.7. Source: UniProtKB

   Molecular_functionarachidonic acid binding

Inferred from direct assay Ref.6. Source: UniProtKB

enzyme activator activity

Inferred from electronic annotation. Source: InterPro

protein N-terminus binding

Inferred from physical interaction Ref.10. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 161161Arachidonate 5-lipoxygenase-activating protein
PRO_0000217751

Regions

Topological domain1 – 88Lumenal Ref.12
Transmembrane9 – 3022Helical
Topological domain31 – 5222Cytoplasmic Ref.12
Transmembrane53 – 7725Helical
Topological domain78 – 803Lumenal Ref.12
Transmembrane81 – 10222Helical
Topological domain103 – 1075Cytoplasmic Ref.12
Intramembrane108 – 1158
Transmembrane116 – 12813Helical
Topological domain129 – 16133Lumenal Ref.12
Region20 – 278Inhibitor binding
Region112 – 12312Inhibitor binding

Experimental info

Mutagenesis201V → A: Increased affinity for the inhibitor MK-591. Ref.12
Mutagenesis271A → V: Strongly decreased affinity for the inhibitor MK-591. Ref.12
Mutagenesis301V → A: Strongly decreased affinity for the inhibitor MK-591. Ref.12
Mutagenesis621D → A: Decreased affinity for the inhibitor MK-591. Ref.12
Mutagenesis661T → A: Strongly decreased affinity for the inhibitor MK-591. Ref.12
Mutagenesis1121Y → A: Strongly decreased affinity for the inhibitor MK-591. Ref.12
Mutagenesis1131I → A: Increased affinity for the inhibitor MK-591. Ref.12
Mutagenesis1161K → A: Strongly increased affinity for the inhibitor MK-591. Ref.12
Mutagenesis1231F → A: Decreased affinity for the inhibitor MK-591. Ref.12
Sequence conflict1611P → S in CAA36441. Ref.1

Secondary structure

................. 161
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P20292 [UniParc].

Last modified December 1, 1992. Version 2.
Checksum: 2625F8081B9E1BAA

FASTA16118,157
        10         20         30         40         50         60 
MDQETVGNVV LLAIVTLISV VQNGFFAHKV EHESRTQNGR SFQRTGTLAF ERVYTANQNC 

        70         80         90        100        110        120 
VDAYPTFLAV LWSAGLLCSQ VPAAFAGLMY LFVRQKYFVG YLGERTQSTP GYIFGKRIIL 

       130        140        150        160 
FLFLMSVAGI FNYYLIFFFG SDFENYIKTI STTISPLLLI P 

« Hide

References

« Hide 'large scale' references
[1]"Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis."
Dixon R.A.F., Diehl R.E., Opas E., Rands E., Vickers P.J., Evans J.F., Gillard J.W., Miller D.K.
Nature 343:282-284(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[2]"Gene characterization and promoter analysis of the human 5-lipoxygenase-activating protein (FLAP)."
Kennedy B.P., Diehl R.E., Boie Y., Adam M., Dixon R.A.F.
J. Biol. Chem. 266:8511-8516(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]SeattleSNPs variation discovery resource
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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: Lymph.
[6]"5-lipoxygenase-activating protein is an arachidonate binding protein."
Mancini J.A., Abramovitz M., Cox M.E., Wong E., Charleson S., Perrier H., Wang Z., Prasit P., Vickers P.J.
FEBS Lett. 318:277-281(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]"5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes."
Woods J.W., Evans J.F., Ethier D., Scott S., Vickers P.J., Hearn L., Heibein J.A., Charleson S., Singer I.I.
J. Exp. Med. 178:1935-1946(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[8]"The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke."
Helgadottir A., Manolescu A., Thorleifsson G., Gretarsdottir S., Jonsdottir H., Thorsteinsdottir U., Samani N.J., Gudmundsson G., Grant S.F.A., Thorgeirsson G., Sveinbjornsdottir S., Valdimarsson E.M., Matthiasson S.E., Johannsson H., Gudmundsdottir O., Gurney M.E., Sainz J., Thorhallsdottir M. expand/collapse author list , Andresdottir M., Frigge M.L., Topol E.J., Kong A., Gudnason V., Hakonarson H., Gulcher J.R., Stefansson K.
Nat. Genet. 36:233-239(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUSCEPTIBILITY TO MYOCARDIAL INFARCTION, SUSCEPTIBILITY TO ISCHSTR.
[9]"No association of polymorphisms in the gene encoding 5-lipoxygenase-activating protein and myocardial infarction in a large central European population."
Koch W., Hoppmann P., Mueller J.C., Schomig A., Kastrati A.
Genet. Med. 9:123-129(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: LACK OF ASSOCIATION WITH MYOCARDIAL INFARCTION.
[10]"Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein."
Strid T., Svartz J., Franck N., Hallin E., Ingelsson B., Soederstroem M., Hammarstroem S.
Biochem. Biophys. Res. Commun. 381:518-522(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LTC4S AND ALOX5, SUBCELLULAR LOCATION.
[11]"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].
[12]"Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein."
Ferguson A.D., McKeever B.M., Xu S., Wisniewski D., Miller D.K., Yamin T.-T., Spencer R.H., Chu L., Ujjainwalla F., Cunningham B.R., Evans J.F., Becker J.W.
Science 317:510-512(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) IN COMPLEXES WITH LEUKOTRIENE BIOSYNTHESIS INHIBITOR MK-591, TOPOLOGY, SUBUNIT, MUTAGENESIS OF VAL-20; ALA-27; VAL-30; ASP-62; THR-66; TYR-112; ILE-113; LYS-116 AND PHE-123, DOMAIN.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X52195 mRNA. Translation: CAA36441.1.
M63262 expand/collapse EMBL AC list , M60470, M63259, M63260 Genomic DNA. Translation: AAA35845.1.
AY619687 Genomic DNA. Translation: AAT38104.1.
AL512642 Genomic DNA. Translation: CAH74084.1.
BC018538 mRNA. Translation: AAH18538.1.
PIRA39824.
RefSeqNP_001191335.1. NM_001204406.1.
NP_001620.2. NM_001629.3.
UniGeneHs.507658.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2Q7MX-ray4.25A/B/C/D/E/F1-161[»]
2Q7RX-ray4.00A/B/C/D/E/F1-161[»]
ProteinModelPortalP20292.
SMRP20292. Positions 1-147.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106742. 4 interactions.
IntActP20292. 1 interaction.
STRING9606.ENSP00000369858.

Chemistry

BindingDBP20292.
ChEMBLCHEMBL4550.

PTM databases

PhosphoSiteP20292.

Polymorphism databases

DMDM120267.

Proteomic databases

PaxDbP20292.
PRIDEP20292.

Protocols and materials databases

DNASU241.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380490; ENSP00000369858; ENSG00000132965.
GeneID241.
KEGGhsa:241.
UCSCuc001utf.2. human.

Organism-specific databases

CTD241.
GeneCardsGC13P031309.
HGNCHGNC:436. ALOX5AP.
HPAHPA026592.
MIM601367. phenotype.
603700. gene.
neXtProtNX_P20292.
PharmGKBPA47.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG79474.
HOGENOMHOG000116372.
HOVERGENHBG107295.
InParanoidP20292.
OMANCMDAYP.
OrthoDBEOG7GXPD5.
PhylomeDBP20292.
TreeFamTF105328.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

BgeeP20292.
CleanExHS_ALOX5AP.
GenevestigatorP20292.

Family and domain databases

Gene3D1.20.120.550. 1 hit.
InterProIPR001446. 5_LipOase_AP.
IPR018295. FLAP/GST2/LTC4S_CS.
IPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view]
PfamPF01124. MAPEG. 1 hit.
[Graphical view]
PRINTSPR00488. 5LPOXGNASEAP.
PROSITEPS01297. FLAP_GST2_LTC4S. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSALOX5AP. human.
EvolutionaryTraceP20292.
GeneWiki5-lipoxygenase-activating_protein.
GenomeRNAi241.
NextBio962.
PROP20292.
SOURCESearch...

Entry information

Entry nameAL5AP_HUMAN
AccessionPrimary (citable) accession number: P20292
Secondary accession number(s): Q5VV04
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: December 1, 1992
Last modified: April 16, 2014
This is version 125 of the entry and version 2 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 chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM