P20292 (AL5AP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Arachidonate 5-lipoxygenase-activating protein

Alternative name(s):
FLAP
MK-886-binding protein

Gene names

Name:	ALOX5AP
Synonyms:	FLAP

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	161 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Leukotriene biosynthesis
Cellular component	Endoplasmic reticulum Membrane Nucleus
Domain	Transmembrane Transmembrane helix
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to calcium ion Inferred from direct assay Ref.1. Source: UniProtKB glutathione biosynthetic process Inferred from Biological aspect of Ancestor. Source: RefGenome leukotriene biosynthetic process Inferred from direct assay Ref.1. Source: UniProtKB leukotriene production involved in inflammatory response Inferred from electronic annotation. Source: Compara positive regulation of acute inflammatory response Inferred from electronic annotation. Source: Compara positive regulation of catalytic activity Inferred from electronic annotation. Source: GOC protein homotrimerization Inferred from physical interaction Ref.12. Source: UniProtKB
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from direct assay Ref.10. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nuclear membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	arachidonate 5-lipoxygenase activity Inferred from Biological aspect of Ancestor. Source: RefGenome arachidonic acid binding Inferred from direct assay Ref.6. Source: UniProtKB enzyme activator activity Inferred from electronic annotation. Source: InterPro glutathione peroxidase activity Inferred from Biological aspect of Ancestor. Source: RefGenome glutathione transferase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 161

161

Arachidonate 5-lipoxygenase-activating protein

PRO_0000217751

Regions

Topological domain

1 – 8

8

Lumenal Ref.12

Transmembrane

9 – 30

22

Helical

Topological domain

31 – 52

22

Cytoplasmic Ref.12

Transmembrane

53 – 77

25

Helical

Topological domain

78 – 80

3

Lumenal Ref.12

Transmembrane

81 – 102

22

Helical

Topological domain

103 – 107

5

Cytoplasmic Ref.12

Intramembrane

108 – 115

8

Transmembrane

116 – 128

13

Helical

Topological domain

129 – 161

33

Lumenal Ref.12

Region

20 – 27

8

Inhibitor binding

Region

112 – 123

12

Inhibitor binding

Experimental info

Mutagenesis

20

1

V → A: Increased affinity for the inhibitor MK-591. Ref.12

Mutagenesis

27

1

A → V: Strongly decreased affinity for the inhibitor MK-591. Ref.12

Mutagenesis

30

1

V → A: Strongly decreased affinity for the inhibitor MK-591. Ref.12

Mutagenesis

62

1

D → A: Decreased affinity for the inhibitor MK-591. Ref.12

Mutagenesis

66

1

T → A: Strongly decreased affinity for the inhibitor MK-591. Ref.12

Mutagenesis

112

1

Y → A: Strongly decreased affinity for the inhibitor MK-591. Ref.12

Mutagenesis

113

1

I → A: Increased affinity for the inhibitor MK-591. Ref.12

Mutagenesis

116

1

K → A: Strongly increased affinity for the inhibitor MK-591. Ref.12

Mutagenesis

123

1

F → A: Decreased affinity for the inhibitor MK-591. Ref.12

Sequence conflict

161

1

P → S in CAA36441. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

161

Helix Strand Turn

Details...

Helix

3 – 7

5

Helix

10 – 26

17

Turn

27 – 30

4

Helix

31 – 36

6

Helix

50 – 60

11

Helix

63 – 76

14

Helix

80 – 100

21

Beta strand

103 – 106

4

Helix

116 – 138

23

Sequences

	Sequence		Length	Mass (Da)
	P20292 [UniParc]. Last modified December 1, 1992. Version 2. Checksum: 2625F8081B9E1BAA	FASTA	161	18,157
	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

References

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

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00022975.

PIR

A39824.

RefSeq

NP_001191335.1. NM_001204406.1.
NP_001620.2. NM_001629.3.

UniGene

Hs.507658.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P20292.

ModBase

Search...

Protein-protein interaction databases

IntAct

P20292. 1 interaction.

STRING

9606.ENSP00000369858.

PTM databases

PhosphoSite

P20292.

Polymorphism databases

DMDM

120267.

Proteomic databases

PaxDb

P20292.

PRIDE

P20292.

Protocols and materials databases

DNASU

241.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380490; ENSP00000369858; ENSG00000132965.

GeneID

241.

KEGG

hsa:241.

UCSC

uc001utf.2. human.

Organism-specific databases

CTD

241.

GeneCards

GC13P031309.

HGNC

HGNC:436. ALOX5AP.

HPA

HPA026592.

MIM

601367. phenotype.
603700. gene.

neXtProt

NX_P20292.

PharmGKB

PA47.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG79474.

HOGENOM

HOG000116372.

HOVERGEN

HBG107295.

InParanoid

P20292.

OMA

LVMLWSA.

OrthoDB

EOG4229KX.

PhylomeDB

P20292.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

P20292.

CleanEx

HS_ALOX5AP.

Genevestigator

P20292.

GermOnline

ENSG00000132965. Homo sapiens.

Family and domain databases

Gene3D

1.20.120.550. 1 hit.

InterPro

IPR001446. 5_LipOase_AP.
IPR018295. FLAP/GST2/LTC4S_CS.
IPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view]

Pfam

PF01124. MAPEG. 1 hit.
[Graphical view]

PRINTS

PR00488. 5LPOXGNASEAP.

PROSITE

PS01297. FLAP_GST2_LTC4S. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P20292.

ChEMBL

CHEMBL4550.

ChiTaRS

ALOX5AP. human.

EvolutionaryTrace

P20292.

GenomeRNAi

241.

NextBio

962.

SOURCE

Search...

Entry information

Entry name

AL5AP_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 116 of the entry and version 2 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.