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Protein

Arachidonate 5-lipoxygenase-activating protein

Gene

ALOX5AP

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

  • arachidonic acid binding Source: UniProtKB
  • enzyme activator activity Source: InterPro
  • protein N-terminus binding Source: UniProtKB

GO - Biological processi

  • cellular response to calcium ion Source: UniProtKB
  • leukotriene biosynthetic process Source: UniProtKB
  • leukotriene metabolic process Source: Reactome
  • lipoxin metabolic process Source: Reactome
  • lipoxygenase pathway Source: Reactome
  • protein homotrimerization Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Leukotriene biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000132965-MONOMER.
ZFISH: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

HGNCiHGNC:436. ALOX5AP.

Subcellular locationi

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

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • nuclear envelope Source: UniProtKB
  • nuclear membrane Source: UniProtKB
Complete GO annotation...

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.

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.

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.
TopDownProteomicsiP20292.

PTM databases

iPTMnetiP20292.
PhosphoSitePlusiP20292.

Expressioni

Gene expression databases

BgeeiENSG00000132965.
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 N-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi106742. 5 interactors.
IntActiP20292. 1 interactor.
STRINGi9606.ENSP00000369858.

Chemistry databases

BindingDBiP20292.

Structurei

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...

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.
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)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. 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.3. human.

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. 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.

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. 5 interactors.
IntActiP20292. 1 interactor.
STRINGi9606.ENSP00000369858.

Chemistry databases

BindingDBiP20292.
ChEMBLiCHEMBL4550.

PTM databases

iPTMnetiP20292.
PhosphoSitePlusiP20292.

Polymorphism and mutation databases

BioMutaiALOX5AP.
DMDMi120267.

Proteomic databases

MaxQBiP20292.
PaxDbiP20292.
PeptideAtlasiP20292.
PRIDEiP20292.
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.
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.
ZFISH: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.
PROiP20292.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000132965.
CleanExiHS_ALOX5AP.
ExpressionAtlasiP20292. baseline and differential.
GenevisibleiP20292. HS.

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]
ProtoNetiSearch...

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: November 30, 2016
This is version 147 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.