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Protein

Arachidonate 5-lipoxygenase-activating protein

Gene

ALOX5AP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • arachidonic acid binding Source: UniProtKB
  • enzyme activator activity Source: InterPro
  • glutathione peroxidase activity Source: GO_Central
  • glutathione transferase activity Source: GO_Central
  • leukotriene-C4 synthase activity Source: GO_Central
  • protein N-terminus binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processLeukotriene biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000132965-MONOMER
ReactomeiR-HSA-2142688 Synthesis of 5-eicosatetraenoic acids
R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-2142700 Synthesis of Lipoxins (LX)

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
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000132965.9
HGNCiHGNC:436 ALOX5AP
MIMi603700 gene
neXtProtiNX_P20292

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 8Lumenal1 Publication8
Transmembranei9 – 30HelicalAdd BLAST22
Topological domaini31 – 52Cytoplasmic1 PublicationAdd BLAST22
Transmembranei53 – 77HelicalAdd BLAST25
Topological domaini78 – 80Lumenal1 Publication3
Transmembranei81 – 102HelicalAdd BLAST22
Topological domaini103 – 107Cytoplasmic1 Publication5
Intramembranei108 – 1158
Transmembranei116 – 128HelicalAdd BLAST13
Topological domaini129 – 161Lumenal1 PublicationAdd BLAST33

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Ischemic stroke (ISCHSTR)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:601367
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)DescriptionActionsGraphical viewLength
Mutagenesisi20V → A: Increased affinity for the inhibitor MK-591. 1 Publication1
Mutagenesisi27A → V: Strongly decreased affinity for the inhibitor MK-591. 1 Publication1
Mutagenesisi30V → A: Strongly decreased affinity for the inhibitor MK-591. 1 Publication1
Mutagenesisi62D → A: Decreased affinity for the inhibitor MK-591. 1 Publication1
Mutagenesisi66T → A: Strongly decreased affinity for the inhibitor MK-591. 1 Publication1
Mutagenesisi112Y → A: Strongly decreased affinity for the inhibitor MK-591. 1 Publication1
Mutagenesisi113I → A: Increased affinity for the inhibitor MK-591. 1 Publication1
Mutagenesisi116K → A: Strongly increased affinity for the inhibitor MK-591. 1 Publication1
Mutagenesisi123F → A: Decreased affinity for the inhibitor MK-591. 1 Publication1

Organism-specific databases

DisGeNETi241
MalaCardsiALOX5AP
MIMi601367 phenotype
OpenTargetsiENSG00000132965
PharmGKBiPA47

Chemistry databases

ChEMBLiCHEMBL4550
DrugBankiDB05225 AM103
DB04929 DG031

Polymorphism and mutation databases

BioMutaiALOX5AP
DMDMi120267

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002177511 – 161Arachidonate 5-lipoxygenase-activating proteinAdd BLAST161

Proteomic databases

MaxQBiP20292
PaxDbiP20292
PeptideAtlasiP20292
PRIDEiP20292
ProteomicsDBi53744
TopDownProteomicsiP20292

PTM databases

iPTMnetiP20292
PhosphoSitePlusiP20292

Expressioni

Gene expression databases

BgeeiENSG00000132965 Expressed in 194 organ(s), highest expression level in bone marrow
CleanExiHS_ALOX5AP
ExpressionAtlasiP20292 baseline and differential
GenevisibleiP20292 HS

Organism-specific databases

HPAiHPA026592

Interactioni

Subunit structurei

Homotrimer. Interacts with LTC4S and ALOX5.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106742, 6 interactors
IntActiP20292, 8 interactors
STRINGi9606.ENSP00000369858

Chemistry databases

BindingDBiP20292

Structurei

3D structure databases

ProteinModelPortaliP20292
SMRiP20292
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20292

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni20 – 27Inhibitor binding8
Regioni112 – 123Inhibitor bindingAdd BLAST12

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

eggNOGiENOG410IHE0 Eukaryota
ENOG4111T4I LUCA
GeneTreeiENSGT00430000030964
HOGENOMiHOG000116372
HOVERGENiHBG107295
InParanoidiP20292
KOiK20735
PhylomeDBiP20292
TreeFamiTF105328

Family and domain databases

Gene3Di1.20.120.550, 1 hit
InterProiView protein in InterPro
IPR001446 5_LipOase_AP
IPR018295 FLAP/GST2/LTC4S_CS
IPR023352 MAPEG-like_dom_sf
IPR001129 Membr-assoc_MAPEG
PfamiView protein in Pfam
PF01124 MAPEG, 1 hit
PRINTSiPR00488 5LPOXGNASEAP
SUPFAMiSSF161084 SSF161084, 1 hit
PROSITEiView protein in PROSITE
PS01297 FLAP_GST2_LTC4S, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WW23A0A087WW23_HUMAN
Arachidonate 5-lipoxygenase-activat...
ALOX5AP
218Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti161P → S in CAA36441 (PubMed:2300173).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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 No translation available.
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.3 human

Similar proteinsi

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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 No translation available.
BC018538 mRNA Translation: AAH18538.1
CCDSiCCDS9337.1
PIRiA39824
RefSeqiNP_001191335.1, NM_001204406.1
NP_001620.2, NM_001629.3
UniGeneiHs.507658

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Q7MX-ray4.25A/B/C/D/E/F1-161[»]
2Q7RX-ray4.00A/B/C/D/E/F1-161[»]
ProteinModelPortaliP20292
SMRiP20292
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106742, 6 interactors
IntActiP20292, 8 interactors
STRINGi9606.ENSP00000369858

Chemistry databases

BindingDBiP20292
ChEMBLiCHEMBL4550
DrugBankiDB05225 AM103
DB04929 DG031

PTM databases

iPTMnetiP20292
PhosphoSitePlusiP20292

Polymorphism and mutation databases

BioMutaiALOX5AP
DMDMi120267

Proteomic databases

MaxQBiP20292
PaxDbiP20292
PeptideAtlasiP20292
PRIDEiP20292
ProteomicsDBi53744
TopDownProteomicsiP20292

Protocols and materials databases

DNASUi241
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380490; ENSP00000369858; ENSG00000132965
GeneIDi241
KEGGihsa:241
UCSCiuc001utf.3 human

Organism-specific databases

CTDi241
DisGeNETi241
EuPathDBiHostDB:ENSG00000132965.9
GeneCardsiALOX5AP
HGNCiHGNC:436 ALOX5AP
HPAiHPA026592
MalaCardsiALOX5AP
MIMi601367 phenotype
603700 gene
neXtProtiNX_P20292
OpenTargetsiENSG00000132965
PharmGKBiPA47
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHE0 Eukaryota
ENOG4111T4I LUCA
GeneTreeiENSGT00430000030964
HOGENOMiHOG000116372
HOVERGENiHBG107295
InParanoidiP20292
KOiK20735
PhylomeDBiP20292
TreeFamiTF105328

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000132965-MONOMER
ReactomeiR-HSA-2142688 Synthesis of 5-eicosatetraenoic acids
R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-2142700 Synthesis of Lipoxins (LX)

Miscellaneous databases

ChiTaRSiALOX5AP human
EvolutionaryTraceiP20292
GeneWikii5-lipoxygenase-activating_protein
GenomeRNAii241
PROiPR:P20292
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000132965 Expressed in 194 organ(s), highest expression level in bone marrow
CleanExiHS_ALOX5AP
ExpressionAtlasiP20292 baseline and differential
GenevisibleiP20292 HS

Family and domain databases

Gene3Di1.20.120.550, 1 hit
InterProiView protein in InterPro
IPR001446 5_LipOase_AP
IPR018295 FLAP/GST2/LTC4S_CS
IPR023352 MAPEG-like_dom_sf
IPR001129 Membr-assoc_MAPEG
PfamiView protein in Pfam
PF01124 MAPEG, 1 hit
PRINTSiPR00488 5LPOXGNASEAP
SUPFAMiSSF161084 SSF161084, 1 hit
PROSITEiView protein in PROSITE
PS01297 FLAP_GST2_LTC4S, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAL5AP_HUMAN
AccessioniPrimary (citable) accession number: P20292
Secondary accession number(s): Q5VV04
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: December 1, 1992
Last modified: November 7, 2018
This is version 160 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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