ALOX8_MOUSE
ID ALOX8_MOUSE Reviewed; 677 AA.
AC O35936; B1ASX5;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Polyunsaturated fatty acid lipoxygenase ALOX8 {ECO:0000305};
DE AltName: Full=15-lipoxygenase 2 {ECO:0000250|UniProtKB:O15296};
DE Short=15-LOX-2 {ECO:0000250|UniProtKB:O15296};
DE AltName: Full=Arachidonate 15-lipoxygenase B;
DE Short=15-LOX-B;
DE AltName: Full=Arachidonate 8S-lipoxygenase;
DE Short=8-LOX;
DE Short=8S-LOX;
DE EC=1.13.11.- {ECO:0000269|PubMed:10625675, ECO:0000269|PubMed:10965849, ECO:0000269|PubMed:15558016, ECO:0000269|PubMed:16112079, ECO:0000269|PubMed:16143298, ECO:0000269|PubMed:9305900, ECO:0000305|PubMed:27435673};
DE AltName: Full=Linoleate 9S-lipoxygenase ALOX8 {ECO:0000305};
DE EC=1.13.11.58 {ECO:0000269|PubMed:15558016, ECO:0000269|PubMed:9305900, ECO:0000305|PubMed:27435673};
GN Name=Alox8 {ECO:0000312|MGI:MGI:1098228}; Synonyms=Alox15b;
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 [MRNA], FUNCTION IN ARACHIDONATE AND LINOLEATE
RP METABOLISM, INDUCTION BY PHORBOL ESTER, TISSUE SPECIFICITY, AND CATALYTIC
RP ACTIVITY.
RC TISSUE=Epidermis;
RX PubMed=9305900; DOI=10.1074/jbc.272.39.24410;
RA Jisaka M., Kim R.B., Boeglin W.E., Nanney L.B., Brash A.R.;
RT "Molecular cloning and functional expression of a phorbol ester-inducible
RT 8S-lipoxygenase from mouse skin.";
RL J. Biol. Chem. 272:24410-24416(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=NMRI; TISSUE=Epidermis;
RX PubMed=9518531; DOI=10.1016/s0005-2760(97)00214-2;
RA Krieg P., Kinzig A., Heidt M., Marks F., Fuerstenberger G.;
RT "cDNA cloning of a 8-lipoxygenase and a novel epidermis-type lipoxygenase
RT from phorbol ester-treated mouse skin.";
RL Biochim. Biophys. Acta 1391:7-12(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [6]
RP FUNCTION IN KERATINOCYTE DIFFERENTIATION, AND CATALYTIC ACTIVITY.
RX PubMed=10965849;
RA Muga S.J., Thuillier P., Pavone A., Rundhaug J.E., Boeglin W.E., Jisaka M.,
RA Brash A.R., Fischer S.M.;
RT "8S-lipoxygenase products activate peroxisome proliferator-activated
RT receptor alpha and induce differentiation in murine keratinocytes.";
RL Cell Growth Differ. 11:447-454(2000).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-603 AND HIS-604.
RX PubMed=10625675; DOI=10.1074/jbc.275.2.1287;
RA Jisaka M., Kim R.B., Boeglin W.E., Brash A.R.;
RT "Identification of amino acid determinants of the positional specificity of
RT mouse 8S-lipoxygenase and human 15S-lipoxygenase-2.";
RL J. Biol. Chem. 275:1287-1293(2000).
RN [8]
RP MUTAGENESIS OF SER-558.
RX PubMed=11368335; DOI=10.1006/abbi.2000.2175;
RA Jisaka M., Boeglin W.E., Kim R.B., Brash A.R.;
RT "Site-directed mutagenesis studies on a putative fifth iron ligand of mouse
RT 8S-lipoxygenase: retention of catalytic activity on mutation of serine-558
RT to asparagine, histidine, or alanine.";
RL Arch. Biochem. Biophys. 386:136-142(2001).
RN [9]
RP FUNCTION AS A 8S-LIPOXYGENASE, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP HIS-374.
RX PubMed=16143298; DOI=10.1016/j.bbrc.2005.08.099;
RA Kawajiri H., Piao Y., Takahashi Y., Murakami T., Hamanaka N., Yoshimoto T.;
RT "Synthesis of 8,9-leukotriene A4 by murine 8-lipoxygenase.";
RL Biochem. Biophys. Res. Commun. 338:144-148(2005).
RN [10]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, KINETIC PARAMETERS, AND
RP FUNCTION.
RX PubMed=16112079; DOI=10.1016/j.bbrc.2005.08.029;
RA Jisaka M., Iwanaga C., Takahashi N., Goto T., Kawada T., Yamamoto T.,
RA Ikeda I., Nishimura K., Nagaya T., Fushiki T., Yokota K.;
RT "Double dioxygenation by mouse 8S-lipoxygenase: specific formation of a
RT potent peroxisome proliferator-activated receptor alpha agonist.";
RL Biochem. Biophys. Res. Commun. 338:136-143(2005).
RN [11]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=15558016; DOI=10.1038/sj.onc.1208269;
RA Kim E., Rundhaug J.E., Benavides F., Yang P., Newman R.A., Fischer S.M.;
RT "An antitumorigenic role for murine 8S-lipoxygenase in skin
RT carcinogenesis.";
RL Oncogene 24:1174-1187(2005).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=27435673; DOI=10.1074/jbc.m116.741454;
RA Bender G., Schexnaydre E.E., Murphy R.C., Uhlson C., Newcomer M.E.;
RT "Membrane-dependent Activities of Human 15-LOX-2 and Its Murine
RT Counterpart: IMPLICATIONS FOR MURINE MODELS OF ATHEROSCLEROSIS.";
RL J. Biol. Chem. 291:19413-19424(2016).
CC -!- FUNCTION: Non-heme iron-containing dioxygenase that catalyzes the
CC stereo-specific peroxidation of free and esterified polyunsaturated
CC fatty acids generating a spectrum of bioactive lipid mediators
CC (PubMed:9305900, PubMed:10965849, PubMed:10625675, PubMed:16143298,
CC PubMed:16112079, PubMed:15558016, PubMed:27435673). Catalyzes the
CC peroxidation of arachidonate and linoleate into (8S)-HPETE and (9S)-
CC HPODE respectively (PubMed:9305900, PubMed:10965849, PubMed:10625675,
CC PubMed:16143298, PubMed:16112079, PubMed:15558016, PubMed:27435673). In
CC addition to generate (8S)-HPETE from free arachidonic acid (AA), may
CC produce other HETE isomers from phospholipid-esterified polyunsaturated
CC fatty acids and minor products derived from (8S)-HPETE itself that may
CC include leukotriene A4 and 8,15-diHPETE (PubMed:16143298,
CC PubMed:16112079, PubMed:27435673). With free arachidonate as substrate,
CC has no detectable 15S-lipoxygenase activity and only displays a 8S-
CC lipoxygenase activity (PubMed:10625675, PubMed:16112079,
CC PubMed:16143298, PubMed:15558016, PubMed:10965849, PubMed:9305900).
CC However may have a 15S-lipoxygenase activity with (8S)-HPETE to produce
CC (8S,15S)-diHPETE and when oxidizes directly arachidonic acid esterified
CC to membrane-bound phospholipids to produce a phospholipid-esterified
CC 15-HpETE (PubMed:27435673, PubMed:16112079, PubMed:16143298). May also
CC catalyze (15S)-HPETE peroxidation to produce 8,15-diHPETE
CC (PubMed:16112079). May play a role in keratinocyte differentiation
CC through activation of the peroxisome proliferator activated receptor
CC signaling pathway (PubMed:10965849). {ECO:0000269|PubMed:10625675,
CC ECO:0000269|PubMed:10965849, ECO:0000269|PubMed:15558016,
CC ECO:0000269|PubMed:16112079, ECO:0000269|PubMed:16143298,
CC ECO:0000269|PubMed:27435673, ECO:0000269|PubMed:9305900}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate + O2 = (9S)-hydroperoxy-(10E,12Z)-
CC octadecadienoate; Xref=Rhea:RHEA:30291, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:60955; EC=1.13.11.58;
CC Evidence={ECO:0000269|PubMed:15558016, ECO:0000269|PubMed:9305900,
CC ECO:0000305|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30292;
CC Evidence={ECO:0000305|PubMed:9305900};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy-
CC (5Z,9E,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:38675,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:75322;
CC Evidence={ECO:0000269|PubMed:10625675, ECO:0000269|PubMed:10965849,
CC ECO:0000269|PubMed:15558016, ECO:0000269|PubMed:16112079,
CC ECO:0000269|PubMed:16143298, ECO:0000269|PubMed:9305900,
CC ECO:0000305|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38676;
CC Evidence={ECO:0000305|PubMed:16112079};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + O2 =
CC (8S,15S)-dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate;
CC Xref=Rhea:RHEA:50972, ChEBI:CHEBI:15379, ChEBI:CHEBI:57446,
CC ChEBI:CHEBI:133899; Evidence={ECO:0000269|PubMed:16112079};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50973;
CC Evidence={ECO:0000305|PubMed:16112079};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate + O2 =
CC (8S,15S)-dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate;
CC Xref=Rhea:RHEA:50932, ChEBI:CHEBI:15379, ChEBI:CHEBI:75322,
CC ChEBI:CHEBI:133899; Evidence={ECO:0000269|PubMed:16112079,
CC ECO:0000269|PubMed:16143298};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50933;
CC Evidence={ECO:0000305|PubMed:16112079};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphocholine + O2 = 1-octadecanoyl-2-(15-hydroperoxy-
CC 5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phosphocholine;
CC Xref=Rhea:RHEA:63264, ChEBI:CHEBI:15379, ChEBI:CHEBI:74965,
CC ChEBI:CHEBI:146283; Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63265;
CC Evidence={ECO:0000305|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-
CC phospho-(1D-myo-inositol) + O2 = a 1-acyl-2-(15-hydroperoxy-
CC 5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-
CC inositol); Xref=Rhea:RHEA:63276, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:75243, ChEBI:CHEBI:146285;
CC Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63277;
CC Evidence={ECO:0000305|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phospho-
CC (1D-myo-inositol) + O2 = a 1-acyl-2-(15-hydroperoxy-8Z,11Z,13E-
CC eicosatrienoyl)-sn-glycero-3-phospho-(1D-myo-inositol);
CC Xref=Rhea:RHEA:63280, ChEBI:CHEBI:15379, ChEBI:CHEBI:146286,
CC ChEBI:CHEBI:146287; Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63281;
CC Evidence={ECO:0000305|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 9-hydroperoxy-
CC (5Z,7E,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:63288,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:146289;
CC Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63289;
CC Evidence={ECO:0000269|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 11-hydroperoxy-
CC (5Z,8Z,12E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:63308,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:146291;
CC Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63309;
CC Evidence={ECO:0000269|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-eicosatrienoate + O2 = 15-hydroperoxy-
CC (8Z,11Z,13E)-eicosatrienoate; Xref=Rhea:RHEA:63312,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:71589, ChEBI:CHEBI:146292;
CC Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63313;
CC Evidence={ECO:0000269|PubMed:27435673};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:O15296,
CC ECO:0000255|PROSITE-ProRule:PRU00726};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000250|UniProtKB:O15296,
CC ECO:0000255|PROSITE-ProRule:PRU00726};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.2 uM for arachidonate (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:16112079};
CC KM=2.1 uM for (8S)-HPETE (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:16112079};
CC KM=5.7 uM for (8S)-HETE (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:16112079};
CC KM=39 uM for (15S)-HPETE (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:16112079};
CC KM=15 uM for (15S)-HETE (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:16112079};
CC KM=2.86 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:27435673};
CC KM=0.964 uM for (8Z,11Z,14Z)-eicosatrienoate
CC {ECO:0000269|PubMed:27435673};
CC Note=The highest catalytic efficiency is observed with arachidonate
CC followed by (8S)-HPETE and(15S)-HPETE with similar efficiencies
CC (PubMed:16112079). kcat is 0.22 sec(-1) for (5Z,8Z,11Z,14Z)-
CC eicosatetraenoate. kcat is 0.045 sec(-1) for (8Z,11Z,14Z)-
CC eicosatrienoate (PubMed:27435673). {ECO:0000269|PubMed:16112079,
CC ECO:0000269|PubMed:27435673};
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis. {ECO:0000269|PubMed:9305900}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O15296}. Membrane
CC {ECO:0000250|UniProtKB:O15296}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O15296}. Note=Predominantly cytosolic; becomes
CC enriched at membranes upon calcium binding.
CC {ECO:0000250|UniProtKB:O15296}.
CC -!- TISSUE SPECIFICITY: Expressed in epidermis and brain (PubMed:9305900,
CC PubMed:9518531). No expression found in heart, spleen, liver, skeletal
CC muscle, kidney or testis. {ECO:0000269|PubMed:9305900,
CC ECO:0000269|PubMed:9518531}.
CC -!- INDUCTION: By phorbol ester. {ECO:0000269|PubMed:9305900}.
CC -!- DOMAIN: The PLAT domain can bind calcium ions; this promotes
CC association with membranes. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
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DR EMBL; U93277; AAC53356.1; -; mRNA.
DR EMBL; Y14696; CAA75003.1; -; mRNA.
DR EMBL; AK028724; BAC26085.1; -; mRNA.
DR EMBL; AL645527; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015253; AAH15253.1; -; mRNA.
DR CCDS; CCDS24886.1; -.
DR RefSeq; NP_033791.1; NM_009661.4.
DR AlphaFoldDB; O35936; -.
DR SMR; O35936; -.
DR STRING; 10090.ENSMUSP00000021262; -.
DR SwissLipids; SLP:000000650; -.
DR SwissLipids; SLP:000000742; -.
DR PhosphoSitePlus; O35936; -.
DR PaxDb; O35936; -.
DR PRIDE; O35936; -.
DR ProteomicsDB; 296100; -.
DR Antibodypedia; 12373; 298 antibodies from 31 providers.
DR DNASU; 11688; -.
DR Ensembl; ENSMUST00000021262; ENSMUSP00000021262; ENSMUSG00000020891.
DR GeneID; 11688; -.
DR KEGG; mmu:11688; -.
DR UCSC; uc007jpl.1; mouse.
DR CTD; 11688; -.
DR MGI; MGI:1098228; Alox8.
DR VEuPathDB; HostDB:ENSMUSG00000020891; -.
DR eggNOG; ENOG502QVKD; Eukaryota.
DR GeneTree; ENSGT00940000161510; -.
DR HOGENOM; CLU_004282_3_3_1; -.
DR InParanoid; O35936; -.
DR OMA; LALPYPY; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; O35936; -.
DR TreeFam; TF105320; -.
DR Reactome; R-MMU-2142770; Synthesis of 15-eicosatetraenoic acid derivatives.
DR UniPathway; UPA00881; -.
DR BioGRID-ORCS; 11688; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Alox8; mouse.
DR PRO; PR:O35936; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O35936; protein.
DR Bgee; ENSMUSG00000020891; Expressed in lip and 35 other tissues.
DR ExpressionAtlas; O35936; baseline and differential.
DR Genevisible; O35936; MM.
DR GO; GO:0005912; C:adherens junction; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0036403; F:arachidonate 8(S)-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR GO; GO:0005506; F:iron ion binding; ISO:MGI.
DR GO; GO:0016165; F:linoleate 13S-lipoxygenase activity; ISO:MGI.
DR GO; GO:1990136; F:linoleate 9S-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IBA:GO_Central.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:1901696; P:cannabinoid biosynthetic process; ISO:MGI.
DR GO; GO:0071926; P:endocannabinoid signaling pathway; ISO:MGI.
DR GO; GO:0051122; P:hepoxilin biosynthetic process; ISO:MGI.
DR GO; GO:0043651; P:linoleic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; ISO:MGI.
DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central.
DR GO; GO:2001303; P:lipoxin A4 biosynthetic process; ISO:MGI.
DR GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045926; P:negative regulation of growth; ISO:MGI.
DR GO; GO:0006644; P:phospholipid metabolic process; IDA:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; ISO:MGI.
DR GO; GO:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; IMP:UniProtKB.
DR CDD; cd01753; PLAT_LOX; 1.
DR InterPro; IPR000907; LipOase.
DR InterPro; IPR013819; LipOase_C.
DR InterPro; IPR036226; LipOase_C_sf.
DR InterPro; IPR020834; LipOase_CS.
DR InterPro; IPR020833; LipOase_Fe_BS.
DR InterPro; IPR001885; LipOase_mml.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR042062; PLAT_LOX_verte.
DR PANTHER; PTHR11771; PTHR11771; 1.
DR Pfam; PF00305; Lipoxygenase; 1.
DR Pfam; PF01477; PLAT; 1.
DR PRINTS; PR00087; LIPOXYGENASE.
DR PRINTS; PR00467; MAMLPOXGNASE.
DR SMART; SM00308; LH2; 1.
DR SUPFAM; SSF48484; SSF48484; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR PROSITE; PS00711; LIPOXYGENASE_1; 1.
DR PROSITE; PS00081; LIPOXYGENASE_2; 1.
DR PROSITE; PS51393; LIPOXYGENASE_3; 1.
DR PROSITE; PS50095; PLAT; 1.
PE 1: Evidence at protein level;
KW Calcium; Cytoplasm; Dioxygenase; Iron; Lipid metabolism; Lipid-binding;
KW Membrane; Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..677
FT /note="Polyunsaturated fatty acid lipoxygenase ALOX8"
FT /id="PRO_0000220701"
FT DOMAIN 2..125
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DOMAIN 126..677
FT /note="Lipoxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 15
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O15296"
FT BINDING 17
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O15296"
FT BINDING 39
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O15296"
FT BINDING 40
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O15296"
FT BINDING 42
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O15296"
FT BINDING 44
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O15296"
FT BINDING 86
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O15296"
FT BINDING 87
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O15296"
FT BINDING 374
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 379
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 554
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 677
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT VARIANT 32
FT /note="E -> G (in clone K12)"
FT VARIANT 38
FT /note="L -> M (in clone G2)"
FT VARIANT 58
FT /note="P -> R (in clone K12)"
FT VARIANT 76
FT /note="V -> A (in clones G2, G5, G11 and K1)"
FT VARIANT 413
FT /note="I -> V (in clone K7)"
FT VARIANT 536
FT /note="R -> Q (in clones G2, G5 and G11)"
FT MUTAGEN 374
FT /note="H->L: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:16143298"
FT MUTAGEN 558
FT /note="S->A,H,N: Retains catalytic activity indicating it
FT is not required for iron ligand-binding."
FT /evidence="ECO:0000269|PubMed:11368335"
FT MUTAGEN 603
FT /note="Y->D: Changes the stereoselectivity of the
FT oxygenation reaction to produce (15S)-HPETE instead of
FT (8S)-HPETE. Completely changes the stereoselectivity; when
FT associated with V-604."
FT /evidence="ECO:0000269|PubMed:10625675"
FT MUTAGEN 604
FT /note="H->V: Changes the stereoselectivity of the
FT oxygenation reaction to produce (15S)-HPETE instead of
FT (8S)-HPETE. Completely changes the stereoselectivity; when
FT associated with D-603."
FT /evidence="ECO:0000269|PubMed:10625675"
SQ SEQUENCE 677 AA; 76230 MW; 78DB1AC9C2F68399 CRC64;
MAKCRVRVST GEACGAGTWD KVSVSIVGTH GESPLVPLDH LGKEFSAGAE EDFEVTLPQD
VGTVLMLRVH KAPPEVSLPL MSFRSDAWFC RWFELEWLPG AALHFPCYQW LEGAGELVLR
EGAAKVSWQD HHPTLQDQRQ KELESRQKMY SWKTYIEGWP RCLDHETVKD LDLNIKYSAM
KNAKLFFKAH SAYTELKVKG LLDRTGLWRS LREMRRLFNF RKTPAAEYVF AHWQEDAFFA
SQFLNGINPV LIRRCHSLPN NFPVTDEMVA PVLGPGTSLQ AELEKGSLFL VDHGILSGVH
TNILNGKPQF SAAPMTLLHQ SSGSGPLLPI AIQLKQTPGP DNPIFLPSDD TWDWLLAKTW
VRNSEFYIHE AVTHLLHAHL IPEVFALATL RQLPRCHPLF KLLIPHIRYT LHINTLAREL
LVAPGKLIDK STGLGTGGFS DLIKRNMEQL NYSVLCLPED IRARGVEDIP GYYYRDDGMQ
IWGAIKSFVS EIVSIYYPSD TSVQDDQELQ AWVREIFSEG FLGRESSGMP SLLDTREALV
QYITMVIFTC SAKHAAVSSG QFDSCVWMPN LPPTMQLPPP TSKGQARPES FIATLPAVNS
SSYHIIALWL LSAEPGDQRP LGHYPDEHFT EDAPRRSVAA FQRKLIQISK GIRERNRGLA
LPYTYLDPPL IENSVSI
