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P20292

- AL5AP_HUMAN

UniProt

P20292 - AL5AP_HUMAN

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Protein

Arachidonate 5-lipoxygenase-activating protein

Gene

ALOX5AP

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  1. arachidonic acid binding Source: UniProtKB
  2. enzyme activator activity Source: InterPro
  3. protein N-terminus binding Source: UniProtKB

GO - Biological processi

  1. arachidonic acid metabolic process Source: Reactome
  2. cellular response to calcium ion Source: UniProtKB
  3. leukotriene biosynthetic process Source: UniProtKB
  4. leukotriene metabolic process Source: Reactome
  5. leukotriene production involved in inflammatory response Source: Ensembl
  6. lipoxin metabolic process Source: Reactome
  7. lipoxygenase pathway Source: Reactome
  8. positive regulation of acute inflammatory response Source: Ensembl
  9. protein homotrimerization Source: UniProtKB
  10. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Leukotriene biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000132965-MONOMER.
ReactomeiREACT_150209. Synthesis of 5-eicosatetraenoic acids.
REACT_150320. Synthesis of Lipoxins (LX).
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

Names & Taxonomyi

Protein namesi
Recommended name:
Arachidonate 5-lipoxygenase-activating protein
Alternative name(s):
FLAP
MK-886-binding protein
Gene namesi
Name:ALOX5AP
Synonyms:FLAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 13

Organism-specific databases

HGNCiHGNC:436. ALOX5AP.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Ensembl
  2. endoplasmic reticulum Source: UniProtKB
  3. integral component of membrane Source: UniProtKB-KW
  4. membrane Source: UniProtKB
  5. nuclear envelope Source: UniProtKB
  6. nuclear membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.
Genetic variations in ALOX5AP may be associated with susceptibility to myocardial infarction. Involvement in myocardial infarction is however unclear: according to some authors (PubMed:14770184), a 4-SNP haplotype in ALOX5AP confers risk of myocardial infarction, while according to other (PubMed:17304054) ALOX5AP is not implicated in this condition.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi20 – 201V → A: Increased affinity for the inhibitor MK-591. 1 Publication
Mutagenesisi27 – 271A → V: Strongly decreased affinity for the inhibitor MK-591. 1 Publication
Mutagenesisi30 – 301V → A: Strongly decreased affinity for the inhibitor MK-591. 1 Publication
Mutagenesisi62 – 621D → A: Decreased affinity for the inhibitor MK-591. 1 Publication
Mutagenesisi66 – 661T → A: Strongly decreased affinity for the inhibitor MK-591. 1 Publication
Mutagenesisi112 – 1121Y → A: Strongly decreased affinity for the inhibitor MK-591. 1 Publication
Mutagenesisi113 – 1131I → A: Increased affinity for the inhibitor MK-591. 1 Publication
Mutagenesisi116 – 1161K → A: Strongly increased affinity for the inhibitor MK-591. 1 Publication
Mutagenesisi123 – 1231F → A: Decreased affinity for the inhibitor MK-591. 1 Publication

Organism-specific databases

MIMi601367. phenotype.
PharmGKBiPA47.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 161161Arachidonate 5-lipoxygenase-activating proteinPRO_0000217751Add
BLAST

Proteomic databases

MaxQBiP20292.
PaxDbiP20292.
PRIDEiP20292.

PTM databases

PhosphoSiteiP20292.

Expressioni

Gene expression databases

BgeeiP20292.
CleanExiHS_ALOX5AP.
GenevestigatoriP20292.

Organism-specific databases

HPAiHPA026592.

Interactioni

Subunit structurei

Homotrimer. Interacts with LTC4S and ALOX5.2 Publications

Protein-protein interaction databases

BioGridi106742. 4 interactions.
IntActiP20292. 1 interaction.
STRINGi9606.ENSP00000369858.

Structurei

Secondary structure

1
161
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 75
Helixi10 – 2617
Turni27 – 304
Helixi31 – 366
Helixi50 – 6011
Helixi63 – 7614
Helixi80 – 10021
Beta strandi103 – 1064
Helixi116 – 13823

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2Q7MX-ray4.25A/B/C/D/E/F1-161[»]
2Q7RX-ray4.00A/B/C/D/E/F1-161[»]
ProteinModelPortaliP20292.
SMRiP20292. Positions 1-147.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20292.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 88Lumenal1 Publication
Topological domaini31 – 5222Cytoplasmic1 PublicationAdd
BLAST
Topological domaini78 – 803Lumenal1 Publication
Topological domaini103 – 1075Cytoplasmic1 Publication
Topological domaini129 – 16133Lumenal1 PublicationAdd
BLAST

Intramembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Intramembranei108 – 1158

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei9 – 3022HelicalAdd
BLAST
Transmembranei53 – 7725HelicalAdd
BLAST
Transmembranei81 – 10222HelicalAdd
BLAST
Transmembranei116 – 12813HelicalAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni20 – 278Inhibitor binding
Regioni112 – 12312Inhibitor bindingAdd
BLAST

Domaini

The C-terminal part after residue 140 is mostly unstructured.1 Publication

Sequence similaritiesi

Belongs to the MAPEG family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG79474.
GeneTreeiENSGT00430000030964.
HOGENOMiHOG000116372.
HOVERGENiHBG107295.
InParanoidiP20292.
OMAiNCMDAYP.
OrthoDBiEOG7GXPD5.
PhylomeDBiP20292.
TreeFamiTF105328.

Family and domain databases

Gene3Di1.20.120.550. 1 hit.
InterProiIPR001446. 5_LipOase_AP.
IPR018295. FLAP/GST2/LTC4S_CS.
IPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view]
PfamiPF01124. MAPEG. 1 hit.
[Graphical view]
PRINTSiPR00488. 5LPOXGNASEAP.
PROSITEiPS01297. FLAP_GST2_LTC4S. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P20292-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDQETVGNVV LLAIVTLISV VQNGFFAHKV EHESRTQNGR SFQRTGTLAF
60 70 80 90 100
ERVYTANQNC VDAYPTFLAV LWSAGLLCSQ VPAAFAGLMY LFVRQKYFVG
110 120 130 140 150
YLGERTQSTP GYIFGKRIIL FLFLMSVAGI FNYYLIFFFG SDFENYIKTI
160
STTISPLLLI P
Length:161
Mass (Da):18,157
Last modified:December 1, 1992 - v2
Checksum:i2625F8081B9E1BAA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti161 – 1611P → S in CAA36441. (PubMed:2300173)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X52195 mRNA. Translation: CAA36441.1.
M63262
, 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.
CCDSiCCDS9337.1.
PIRiA39824.
RefSeqiNP_001191335.1. NM_001204406.1.
NP_001620.2. NM_001629.3.
UniGeneiHs.507658.

Genome annotation databases

EnsembliENST00000380490; ENSP00000369858; ENSG00000132965.
GeneIDi241.
KEGGihsa:241.
UCSCiuc001utf.2. human.

Polymorphism databases

DMDMi120267.

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X52195 mRNA. Translation: CAA36441.1 .
M63262
, 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 .
CCDSi CCDS9337.1.
PIRi A39824.
RefSeqi NP_001191335.1. NM_001204406.1.
NP_001620.2. NM_001629.3.
UniGenei Hs.507658.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2Q7M X-ray 4.25 A/B/C/D/E/F 1-161 [» ]
2Q7R X-ray 4.00 A/B/C/D/E/F 1-161 [» ]
ProteinModelPortali P20292.
SMRi P20292. Positions 1-147.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 106742. 4 interactions.
IntActi P20292. 1 interaction.
STRINGi 9606.ENSP00000369858.

Chemistry

BindingDBi P20292.
ChEMBLi CHEMBL2111402.

PTM databases

PhosphoSitei P20292.

Polymorphism databases

DMDMi 120267.

Proteomic databases

MaxQBi P20292.
PaxDbi P20292.
PRIDEi P20292.

Protocols and materials databases

DNASUi 241.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000380490 ; ENSP00000369858 ; ENSG00000132965 .
GeneIDi 241.
KEGGi hsa:241.
UCSCi uc001utf.2. human.

Organism-specific databases

CTDi 241.
GeneCardsi GC13P031309.
HGNCi HGNC:436. ALOX5AP.
HPAi HPA026592.
MIMi 601367. phenotype.
603700. gene.
neXtProti NX_P20292.
PharmGKBi PA47.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG79474.
GeneTreei ENSGT00430000030964.
HOGENOMi HOG000116372.
HOVERGENi HBG107295.
InParanoidi P20292.
OMAi NCMDAYP.
OrthoDBi EOG7GXPD5.
PhylomeDBi P20292.
TreeFami TF105328.

Enzyme and pathway databases

BioCyci MetaCyc:ENSG00000132965-MONOMER.
Reactomei REACT_150209. Synthesis of 5-eicosatetraenoic acids.
REACT_150320. Synthesis of Lipoxins (LX).
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

Miscellaneous databases

ChiTaRSi ALOX5AP. human.
EvolutionaryTracei P20292.
GeneWikii 5-lipoxygenase-activating_protein.
GenomeRNAii 241.
NextBioi 962.
PROi P20292.
SOURCEi Search...

Gene expression databases

Bgeei P20292.
CleanExi HS_ALOX5AP.
Genevestigatori P20292.

Family and domain databases

Gene3Di 1.20.120.550. 1 hit.
InterProi IPR001446. 5_LipOase_AP.
IPR018295. FLAP/GST2/LTC4S_CS.
IPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view ]
Pfami PF01124. MAPEG. 1 hit.
[Graphical view ]
PRINTSi PR00488. 5LPOXGNASEAP.
PROSITEi PS01297. FLAP_GST2_LTC4S. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. 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.

Entry informationi

Entry nameiAL5AP_HUMAN
AccessioniPrimary (citable) accession number: P20292
Secondary accession number(s): Q5VV04
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: December 1, 1992
Last modified: October 29, 2014
This is version 131 of the entry and version 2 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3