ID   AL5AP_MOUSE             Reviewed;         161 AA.
AC   P30355; Q9D138;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 2.
DT   24-JAN-2024, entry version 151.
DE   RecName: Full=Arachidonate 5-lipoxygenase-activating protein;
DE   AltName: Full=FLAP;
DE   AltName: Full=MK-886-binding protein;
GN   Name=Alox5ap; Synonyms=Flap;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Embryo;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-153.
RX   PubMed=1480129;
RA   Vickers P.J., O'Neill G.P., Mancini J.A., Charleson S., Abramovitz M.;
RT   "Cross-species comparison of 5-lipoxygenase-activating protein.";
RL   Mol. Pharmacol. 42:1014-1019(1992).
RN   [4]
RP   SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH ALOX5.
RX   PubMed=19075240; DOI=10.1073/pnas.0808211106;
RA   Mandal A.K., Jones P.B., Bair A.M., Christmas P., Miller D., Yamin T.-T.,
RA   Wisniewski D., Menke J., Evans J.F., Hyman B.T., Bacskai B., Chen M.,
RA   Lee D.M., Nikolic B., Soberman R.J.;
RT   "The nuclear membrane organization of leukotriene synthesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:20434-20439(2008).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Lung, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Required for leukotriene biosynthesis by ALOX5 (5-
CC       lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid,
CC       and could play an essential role in the transfer of arachidonic acid to
CC       ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of
CC       leukotrienes (By similarity). {ECO:0000250,
CC       ECO:0000269|PubMed:19075240}.
CC   -!- SUBUNIT: Homotrimer. Interacts with LTC4S and ALOX5.
CC       {ECO:0000269|PubMed:19075240}.
CC   -!- SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000269|PubMed:19075240};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:19075240}. Endoplasmic
CC       reticulum membrane {ECO:0000250}; Multi-pass membrane protein
CC       {ECO:0000250}.
CC   -!- DOMAIN: The C-terminal part after residue 140 is mostly disordered.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the MAPEG family. {ECO:0000305}.
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DR   EMBL; AK004002; BAB23117.1; -; mRNA.
DR   EMBL; BC026209; AAH26209.1; -; mRNA.
DR   EMBL; M96554; AAA37632.1; -; mRNA.
DR   CCDS; CCDS39407.1; -.
DR   RefSeq; NP_033793.1; NM_009663.2.
DR   AlphaFoldDB; P30355; -.
DR   SMR; P30355; -.
DR   BioGRID; 198077; 1.
DR   STRING; 10090.ENSMUSP00000071130; -.
DR   BindingDB; P30355; -.
DR   ChEMBL; CHEMBL3414408; -.
DR   PhosphoSitePlus; P30355; -.
DR   MaxQB; P30355; -.
DR   PaxDb; 10090-ENSMUSP00000071130; -.
DR   PeptideAtlas; P30355; -.
DR   ProteomicsDB; 296392; -.
DR   Pumba; P30355; -.
DR   Antibodypedia; 22770; 233 antibodies from 32 providers.
DR   DNASU; 11690; -.
DR   Ensembl; ENSMUST00000071130.5; ENSMUSP00000071130.4; ENSMUSG00000060063.10.
DR   GeneID; 11690; -.
DR   KEGG; mmu:11690; -.
DR   UCSC; uc009app.1; mouse.
DR   AGR; MGI:107505; -.
DR   CTD; 241; -.
DR   MGI; MGI:107505; Alox5ap.
DR   VEuPathDB; HostDB:ENSMUSG00000060063; -.
DR   eggNOG; ENOG502RZJB; Eukaryota.
DR   GeneTree; ENSGT00940000158706; -.
DR   HOGENOM; CLU_110291_0_0_1; -.
DR   InParanoid; P30355; -.
DR   OMA; QNVFFAQ; -.
DR   OrthoDB; 5343039at2759; -.
DR   PhylomeDB; P30355; -.
DR   TreeFam; TF105328; -.
DR   Reactome; R-MMU-2142688; Synthesis of 5-eicosatetraenoic acids.
DR   Reactome; R-MMU-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR   Reactome; R-MMU-2142700; Synthesis of Lipoxins (LX).
DR   BioGRID-ORCS; 11690; 3 hits in 79 CRISPR screens.
DR   PRO; PR:P30355; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; P30355; Protein.
DR   Bgee; ENSMUSG00000060063; Expressed in granulocyte and 208 other cell types or tissues.
DR   ExpressionAtlas; P30355; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR   GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0004051; F:arachidonate 5-lipoxygenase activity; IEA:Ensembl.
DR   GO; GO:0050544; F:arachidonic acid binding; ISS:UniProtKB.
DR   GO; GO:0008047; F:enzyme activator activity; IEA:InterPro.
DR   GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR   GO; GO:0004602; F:glutathione peroxidase activity; IBA:GO_Central.
DR   GO; GO:0004364; F:glutathione transferase activity; IBA:GO_Central.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0004464; F:leukotriene-C4 synthase activity; IBA:GO_Central.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0071277; P:cellular response to calcium ion; ISO:MGI.
DR   GO; GO:0019370; P:leukotriene biosynthetic process; IDA:MGI.
DR   GO; GO:0002540; P:leukotriene production involved in inflammatory response; IMP:MGI.
DR   GO; GO:0019372; P:lipoxygenase pathway; ISO:MGI.
DR   GO; GO:0002675; P:positive regulation of acute inflammatory response; ISO:MGI.
DR   GO; GO:0070207; P:protein homotrimerization; ISO:MGI.
DR   Gene3D; 1.20.120.550; Membrane associated eicosanoid/glutathione metabolism-like domain; 1.
DR   InterPro; IPR001446; 5_LipOase_AP.
DR   InterPro; IPR018295; FLAP/GST2/LTC4S_CS.
DR   InterPro; IPR023352; MAPEG-like_dom_sf.
DR   InterPro; IPR001129; Membr-assoc_MAPEG.
DR   PANTHER; PTHR10250:SF2; ARACHIDONATE 5-LIPOXYGENASE-ACTIVATING PROTEIN; 1.
DR   PANTHER; PTHR10250; MICROSOMAL GLUTATHIONE S-TRANSFERASE; 1.
DR   Pfam; PF01124; MAPEG; 1.
DR   PRINTS; PR00488; 5LPOXGNASEAP.
DR   SUPFAM; SSF161084; MAPEG domain-like; 1.
DR   PROSITE; PS01297; FLAP_GST2_LTC4S; 1.
DR   Genevisible; P30355; MM.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Leukotriene biosynthesis; Membrane; Nucleus;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..161
FT                   /note="Arachidonate 5-lipoxygenase-activating protein"
FT                   /id="PRO_0000217753"
FT   TOPO_DOM        1..8
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        9..30
FT                   /note="Helical"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        31..52
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        53..77
FT                   /note="Helical"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        78..80
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        81..102
FT                   /note="Helical"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        103..107
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        108..115
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        116..128
FT                   /note="Helical"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        129..161
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        142
FT                   /note="D -> Y (in Ref. 3; AAA37632)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   161 AA;  18136 MW;  28DA042AA18D17C8 CRC64;
     MDQEAVGNVV LLALVTLISV VQNAFFAHKV EHESKAHNGR SFQRTGTLAF ERVYTANQNC
     VDAYPTFLVV LWTAGLLCSQ VPAAFAGLMY LFVRQKYFVG YLGERTQSTP GYIFGKRIIL
     FLFLMSFAGI LNHYLIFFFG SDFENYIRTV STTISPLLLI P
//