LX12B_HUMAN
ID LX12B_HUMAN Reviewed; 701 AA.
AC O75342;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Arachidonate 12-lipoxygenase, 12R-type {ECO:0000305};
DE Short=12R-LOX;
DE Short=12R-lipoxygenase;
DE EC=1.13.11.- {ECO:0000269|PubMed:21558561, ECO:0000269|PubMed:9618483, ECO:0000269|PubMed:9837935};
DE AltName: Full=Epidermis-type lipoxygenase 12;
GN Name=ALOX12B {ECO:0000312|HGNC:HGNC:430};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND CATALYTIC
RP ACTIVITY.
RC TISSUE=Hair follicle;
RX PubMed=9618483; DOI=10.1073/pnas.95.12.6744;
RA Boeglin W.E., Kim R.B., Brash A.R.;
RT "A 12R-lipoxygenase in human skin: mechanistic evidence, molecular cloning,
RT and expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:6744-6749(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=B-cell;
RX PubMed=9837935; DOI=10.1074/jbc.273.50.33540;
RA Sun D., McDonnell M., Chen X.-S., Lakkis M.M., Li H., Isaacs S.N.,
RA Elsea S.H., Patel P.I., Funk C.D.;
RT "Human 12(R)-lipoxygenase and the mouse ortholog. Molecular cloning,
RT expression, and gene chromosomal assignment.";
RL J. Biol. Chem. 273:33540-33547(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11350124; DOI=10.1006/geno.2001.6519;
RA Krieg P., Marks F., Fuerstenberger G.;
RT "A gene cluster encoding human epidermis-type lipoxygenases at chromosome
RT 17p13.1: cloning, physical mapping, and expression.";
RL Genomics 73:323-330(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=21558561; DOI=10.1074/jbc.m111.251496;
RA Zheng Y., Yin H., Boeglin W.E., Elias P.M., Crumrine D., Beier D.R.,
RA Brash A.R.;
RT "Lipoxygenases mediate the effect of essential fatty acid in skin barrier
RT formation: a proposed role in releasing omega-hydroxyceramide for
RT construction of the corneocyte lipid envelope.";
RL J. Biol. Chem. 286:24046-24056(2011).
RN [6]
RP FUNCTION IN MUCUS PRODUCTION.
RX PubMed=22441738; DOI=10.1183/09031936.00023111;
RA Garcia-Verdugo I., BenMohamed F., Tattermusch S., Leduc D., Charpigny G.,
RA Chignard M., Ollero M., Touqui L.;
RT "A role for 12R-lipoxygenase in MUC5AC expression by respiratory epithelial
RT cells.";
RL Eur. Respir. J. 40:714-723(2012).
RN [7]
RP VARIANTS ARCI2 PRO-426 AND GLN-578.
RX PubMed=11773004; DOI=10.1093/hmg/11.1.107;
RA Jobard F., Lefevre C., Karaduman A., Blanchet-Bardon C., Emre S.,
RA Weissenbach J., Ozguc M., Lathrop M., Prud'homme J.-F., Fischer J.;
RT "Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in
RT non-bullous congenital ichthyosiform erythroderma (NCIE) linked to
RT chromosome 17p13.1.";
RL Hum. Mol. Genet. 11:107-113(2002).
RN [8]
RP CHARACTERIZATION OF VARIANTS ARCI2 PRO-426 AND GLN-578.
RX PubMed=15629692; DOI=10.1016/j.bbalip.2004.10.007;
RA Yu Z., Schneider C., Boeglin W.E., Brash A.R.;
RT "Mutations associated with a congenital form of ichthyosis (NCIE)
RT inactivate the epidermal lipoxygenases 12R-LOX and eLOX3.";
RL Biochim. Biophys. Acta 1686:238-247(2005).
RN [9]
RP VARIANTS ARCI2 PRO-24; TRP-114; SER-127; CYS-318; MET-383; LYS-416;
RP HIS-488; CYS-521; PRO-664 AND LEU-679, AND CHARACTERIZATION OF VARIANTS
RP ARCI2 HIS-488 AND PRO-664.
RX PubMed=16116617; DOI=10.1002/humu.20236;
RA Eckl K.M., Krieg P., Kuester W., Traupe H., Andre F., Wittstruck N.,
RA Fuerstenberger G., Hennies H.C.;
RT "Mutation spectrum and functional analysis of epidermis-type lipoxygenases
RT in patients with autosomal recessive congenital ichthyosis.";
RL Hum. Mutat. 26:351-361(2005).
RN [10]
RP VARIANTS ARCI2 LEU-195 AND GLU-382, AND CHARACTERIZATION OF VARIANTS ARCI2
RP LEU-195 AND GLU-382.
RX PubMed=19131948; DOI=10.1038/jid.2008.409;
RA Eckl K.M., de Juanes S., Kurtenbach J., Naetebus M., Lugassy J., Oji V.,
RA Traupe H., Preil M.L., Martinez F., Smolle J., Harel A., Krieg P.,
RA Sprecher E., Hennies H.C.;
RT "Molecular analysis of 250 patients with autosomal recessive congenital
RT ichthyosis: evidence for mutation hotspots in ALOXE3 and allelic
RT heterogeneity in ALOX12B.";
RL J. Invest. Dermatol. 129:1421-1428(2009).
RN [11]
RP VARIANTS ARCI2 PHE-67; ASP-462; CYS-521; MET-527 AND GLU-597.
RX PubMed=19890349; DOI=10.1038/jid.2009.346;
RA Vahlquist A., Bygum A., Gaanemo A., Virtanen M., Hellstroem-Pigg M.,
RA Strauss G., Brandrup F., Fischer J.;
RT "Genotypic and clinical spectrum of self-improving collodion ichthyosis:
RT ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients.";
RL J. Invest. Dermatol. 130:438-443(2010).
CC -!- FUNCTION: Catalyzes the regio and stereo-specific incorporation of a
CC single molecule of dioxygen into free and esterified polyunsaturated
CC fatty acids generating lipid hydroperoxides that can be further reduced
CC to the corresponding hydroxy species (PubMed:9837935, PubMed:9618483,
CC PubMed:21558561). In the skin, acts upstream of ALOXE3 on the lineolate
CC moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to
CC produce an epoxy-ketone derivative, a crucial step in the conjugation
CC of omega-hydroxyceramide to membrane proteins (PubMed:21558561).
CC Therefore plays a crucial role in the synthesis of corneocytes lipid
CC envelope and the establishment of the skin barrier to water loss
CC (PubMed:21558561). May also play a role in the regulation of the
CC expression of airway mucins (PubMed:22441738).
CC {ECO:0000269|PubMed:21558561, ECO:0000269|PubMed:22441738,
CC ECO:0000269|PubMed:9618483, ECO:0000269|PubMed:9837935}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12R)-hydroperoxy-
CC (5Z,8Z,10E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:41336,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:75230;
CC Evidence={ECO:0000269|PubMed:9618483, ECO:0000269|PubMed:9837935};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41337;
CC Evidence={ECO:0000305|PubMed:9837935};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-[omega-(9Z,12Z)-octadecadienoyloxy]acyl-beta-D-glucosyl-
CC (1<->1)-octadecasphing-4E-enine + O2 = N-[omega-(9R)-hydroperoxy-
CC (10E,12Z)-octadecadienoyloxy]acyl-beta-D-glucosyl-(1<->1)-
CC octadecasphing-4E-enine; Xref=Rhea:RHEA:40495, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:134621, ChEBI:CHEBI:134624;
CC Evidence={ECO:0000269|PubMed:21558561};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40496;
CC Evidence={ECO:0000305|PubMed:21558561};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-acyl (9Z,12Z)-octadecadienoate octadecasphin-4E-enine + O2 =
CC N-acyl (9R)-hydroperoxy-(10E,12Z)-octadecadienoate octadecasphing-4E-
CC enine; Xref=Rhea:RHEA:41239, ChEBI:CHEBI:15379, ChEBI:CHEBI:77888,
CC ChEBI:CHEBI:77889; Evidence={ECO:0000269|PubMed:21558561};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41240;
CC Evidence={ECO:0000305|PubMed:21558561};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6Z,9Z,12Z)-octadecatrienoate + O2 = 10-hydroperoxy-
CC (6Z,8E,12Z)-octadecatrienoate; Xref=Rhea:RHEA:43476,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32391, ChEBI:CHEBI:83342;
CC Evidence={ECO:0000269|PubMed:9837935};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43477;
CC Evidence={ECO:0000305|PubMed:9837935};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = 14-
CC hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:43472, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:83336; Evidence={ECO:0000269|PubMed:9837935};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43473;
CC Evidence={ECO:0000305|PubMed:9837935};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-eicosatrienoate + O2 = (8Z,10E,14Z)-12-
CC hydroperoxyeicosatrienoate; Xref=Rhea:RHEA:43468, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:71589, ChEBI:CHEBI:83334;
CC Evidence={ECO:0000269|PubMed:9837935};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43469;
CC Evidence={ECO:0000305|PubMed:9837935};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 =
CC (5Z,7Z,8Z,10E,14Z,17Z)-12-hydroperoxyeicosapentaenoate;
CC Xref=Rhea:RHEA:41344, ChEBI:CHEBI:15379, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:78078; Evidence={ECO:0000269|PubMed:9837935};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41345;
CC Evidence={ECO:0000305|PubMed:9837935};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6Z,9Z,12Z)-octadecatrienoate + O2 = 10R-hydroperoxy-
CC (6Z,8E,12Z)-octadecatrienoate; Xref=Rhea:RHEA:41340,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32391, ChEBI:CHEBI:78070;
CC Evidence={ECO:0000269|PubMed:9837935};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41341;
CC Evidence={ECO:0000305|PubMed:9837935};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-methyl
CC (5Z,8Z,10E,12R,14Z)-hydroperoxyiecosatetraenoate;
CC Xref=Rhea:RHEA:41311, ChEBI:CHEBI:15379, ChEBI:CHEBI:78033,
CC ChEBI:CHEBI:78034; Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41312;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-
CC methyl-8-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate;
CC Xref=Rhea:RHEA:43480, ChEBI:CHEBI:15379, ChEBI:CHEBI:78033,
CC ChEBI:CHEBI:83344; Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43481;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-
CC methyl-(8R)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:61868, ChEBI:CHEBI:15379, ChEBI:CHEBI:78033,
CC ChEBI:CHEBI:78180; Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61869;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(9Z,12Z)-octadecadienoate + O2 = 1-O-methyl-(9R)-
CC hydroperoxy-(10E,12Z)-octadecadienoate; Xref=Rhea:RHEA:61872,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:69080, ChEBI:CHEBI:145036;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61873;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 =
CC 1-O-methyl-8-hydroperoxy-20-hydroxy-(5Z,9E,11Z,14Z)-
CC eicosatetraenoate; Xref=Rhea:RHEA:61876, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:145032, ChEBI:CHEBI:145033;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61877;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 =
CC 1-O-methyl-12-hydroperoxy-20-hydroxy-(5Z,8Z,10E,14Z)-
CC eicosatetraenoate; Xref=Rhea:RHEA:61880, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:145032, ChEBI:CHEBI:145034;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61881;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 =
CC 1-O-methyl-9-hydroperoxy-20-hydroxy-(5Z,7E,11Z,14Z)-
CC eicosatetraenoate; Xref=Rhea:RHEA:61884, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:145032, ChEBI:CHEBI:145035;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61885;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(9Z,12Z)-octadecadienoate + O2 = 1-O-methyl-(13S)-
CC hydroperoxy-(9Z,11E)-octadecadienoate; Xref=Rhea:RHEA:41756,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:69080, ChEBI:CHEBI:78040;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41757;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00726};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00726};
CC -!- ACTIVITY REGULATION: Increased by calcium.
CC {ECO:0000250|UniProtKB:O70582}.
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis. {ECO:0000269|PubMed:21558561}.
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:21558561}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00726}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:9837935}.
CC -!- TISSUE SPECIFICITY: Expressed in B-cells, hair follicles, foreskin
CC keratinocytes and adult skin. Also expressed in psoriatic tissue.
CC {ECO:0000269|PubMed:9618483}.
CC -!- DISEASE: Ichthyosis, congenital, autosomal recessive 2 (ARCI2)
CC [MIM:242100]: A form of autosomal recessive congenital ichthyosis, a
CC disorder of keratinization with abnormal differentiation and
CC desquamation of the epidermis, resulting in abnormal skin scaling over
CC the whole body. The main skin phenotypes are lamellar ichthyosis (LI)
CC and non-bullous congenital ichthyosiform erythroderma (NCIE), although
CC phenotypic overlap within the same patient or among patients from the
CC same family can occur. Lamellar ichthyosis is a condition often
CC associated with an embedment in a collodion-like membrane at birth;
CC skin scales later develop, covering the entire body surface. Non-
CC bullous congenital ichthyosiform erythroderma characterized by fine
CC whitish scaling on an erythrodermal background; larger brownish scales
CC are present on the buttocks, neck and legs.
CC {ECO:0000269|PubMed:11773004, ECO:0000269|PubMed:15629692,
CC ECO:0000269|PubMed:16116617, ECO:0000269|PubMed:19131948,
CC ECO:0000269|PubMed:19890349}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=about water - Issue 153 of
CC September 2013;
CC URL="https://web.expasy.org/spotlight/back_issues/153/";
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DR EMBL; AF038461; AAC39770.1; -; mRNA.
DR EMBL; AF059250; AAC79680.1; -; mRNA.
DR EMBL; AJ305026; CAC34520.1; -; Genomic_DNA.
DR EMBL; AJ305027; CAC34520.1; JOINED; Genomic_DNA.
DR EMBL; BC041058; AAH41058.1; -; mRNA.
DR CCDS; CCDS11129.1; -.
DR RefSeq; NP_001130.1; NM_001139.2.
DR AlphaFoldDB; O75342; -.
DR SMR; O75342; -.
DR BioGRID; 106743; 137.
DR IntAct; O75342; 19.
DR MINT; O75342; -.
DR STRING; 9606.ENSP00000315167; -.
DR BindingDB; O75342; -.
DR DrugCentral; O75342; -.
DR SwissLipids; SLP:000000655; -.
DR GlyGen; O75342; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75342; -.
DR PhosphoSitePlus; O75342; -.
DR BioMuta; ALOX12B; -.
DR MassIVE; O75342; -.
DR MaxQB; O75342; -.
DR PaxDb; O75342; -.
DR PeptideAtlas; O75342; -.
DR PRIDE; O75342; -.
DR ProteomicsDB; 49910; -.
DR Antibodypedia; 12404; 102 antibodies from 19 providers.
DR DNASU; 242; -.
DR Ensembl; ENST00000647874.1; ENSP00000497784.1; ENSG00000179477.11.
DR GeneID; 242; -.
DR KEGG; hsa:242; -.
DR MANE-Select; ENST00000647874.1; ENSP00000497784.1; NM_001139.3; NP_001130.1.
DR UCSC; uc002gjy.1; human.
DR CTD; 242; -.
DR DisGeNET; 242; -.
DR GeneCards; ALOX12B; -.
DR GeneReviews; ALOX12B; -.
DR HGNC; HGNC:430; ALOX12B.
DR HPA; ENSG00000179477; Tissue enriched (skin).
DR MalaCards; ALOX12B; -.
DR MIM; 242100; phenotype.
DR MIM; 603741; gene.
DR neXtProt; NX_O75342; -.
DR OpenTargets; ENSG00000179477; -.
DR Orphanet; 79394; Congenital non-bullous ichthyosiform erythroderma.
DR Orphanet; 313; Lamellar ichthyosis.
DR Orphanet; 281122; Self-improving collodion baby.
DR PharmGKB; PA24722; -.
DR VEuPathDB; HostDB:ENSG00000179477; -.
DR eggNOG; ENOG502SJSP; Eukaryota.
DR GeneTree; ENSGT00940000162032; -.
DR HOGENOM; CLU_004282_3_3_1; -.
DR InParanoid; O75342; -.
DR OMA; RCRNPNR; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; O75342; -.
DR TreeFam; TF105320; -.
DR BRENDA; 1.13.11.31; 2681.
DR PathwayCommons; O75342; -.
DR Reactome; R-HSA-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR SignaLink; O75342; -.
DR UniPathway; UPA00222; -.
DR UniPathway; UPA00881; -.
DR BioGRID-ORCS; 242; 10 hits in 1064 CRISPR screens.
DR GeneWiki; ALOX12B; -.
DR GenomeRNAi; 242; -.
DR Pharos; O75342; Tbio.
DR PRO; PR:O75342; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O75342; protein.
DR Bgee; ENSG00000179477; Expressed in skin of leg and 105 other tissues.
DR ExpressionAtlas; O75342; baseline and differential.
DR Genevisible; O75342; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0106237; F:arachidonate 12(R)-lipoxygenase activity; IEA:RHEA.
DR GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; IMP:UniProtKB.
DR GO; GO:0047677; F:arachidonate 8(R)-lipoxygenase activity; IEA:Ensembl.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:1990136; F:linoleate 9S-lipoxygenase activity; ISS:UniProtKB.
DR GO; GO:0016829; F:lyase activity; 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; IDA:UniProtKB.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IMP:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR GO; GO:0051122; P:hepoxilin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central.
DR GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0070257; P:positive regulation of mucus secretion; IMP:UniProtKB.
DR GO; GO:0006497; P:protein lipidation; ISS:UniProtKB.
DR GO; GO:0006665; P:sphingolipid metabolic process; IDA: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 Cytoplasm; Dioxygenase; Disease variant; Fatty acid metabolism; Ichthyosis;
KW Iron; Isomerase; Lipid metabolism; Lyase; Metal-binding; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..701
FT /note="Arachidonate 12-lipoxygenase, 12R-type"
FT /id="PRO_0000220689"
FT DOMAIN 2..119
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DOMAIN 120..701
FT /note="Lipoxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 398
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 403
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 578
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 582
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 701
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT VARIANT 24
FT /note="L -> P (in ARCI2; dbSNP:rs201575829)"
FT /evidence="ECO:0000269|PubMed:16116617"
FT /id="VAR_069545"
FT VARIANT 67
FT /note="I -> F (in ARCI2; dbSNP:rs397514533)"
FT /evidence="ECO:0000269|PubMed:19890349"
FT /id="VAR_069546"
FT VARIANT 94
FT /note="G -> S (in dbSNP:rs8077661)"
FT /id="VAR_050000"
FT VARIANT 114
FT /note="R -> W (in ARCI2; dbSNP:rs397514526)"
FT /evidence="ECO:0000269|PubMed:16116617"
FT /id="VAR_069547"
FT VARIANT 127
FT /note="P -> S (in ARCI2; dbSNP:rs72842957)"
FT /evidence="ECO:0000269|PubMed:16116617"
FT /id="VAR_069548"
FT VARIANT 195
FT /note="F -> L (in ARCI2; complete loss of the enzyme
FT activity; dbSNP:rs200516538)"
FT /evidence="ECO:0000269|PubMed:19131948"
FT /id="VAR_069549"
FT VARIANT 318
FT /note="Y -> C (in ARCI2)"
FT /evidence="ECO:0000269|PubMed:16116617"
FT /id="VAR_069550"
FT VARIANT 382
FT /note="K -> E (in ARCI2; complete loss of the enzyme
FT activity; dbSNP:rs1567981916)"
FT /evidence="ECO:0000269|PubMed:19131948"
FT /id="VAR_069551"
FT VARIANT 383
FT /note="T -> M (in ARCI2; dbSNP:rs760428119)"
FT /evidence="ECO:0000269|PubMed:16116617"
FT /id="VAR_069552"
FT VARIANT 416
FT /note="N -> K (in ARCI2; dbSNP:rs1039399607)"
FT /evidence="ECO:0000269|PubMed:16116617"
FT /id="VAR_069553"
FT VARIANT 426
FT /note="L -> P (in ARCI2; complete loss of the enzyme
FT activity; dbSNP:rs137853023)"
FT /evidence="ECO:0000269|PubMed:11773004,
FT ECO:0000269|PubMed:15629692"
FT /id="VAR_015173"
FT VARIANT 462
FT /note="G -> D (in ARCI2; dbSNP:rs774958790)"
FT /evidence="ECO:0000269|PubMed:19890349"
FT /id="VAR_069554"
FT VARIANT 488
FT /note="R -> H (in ARCI2; complete loss of the enzyme
FT activity; dbSNP:rs763468558)"
FT /evidence="ECO:0000269|PubMed:16116617"
FT /id="VAR_069555"
FT VARIANT 521
FT /note="Y -> C (in ARCI2; dbSNP:rs199766569)"
FT /evidence="ECO:0000269|PubMed:16116617,
FT ECO:0000269|PubMed:19890349"
FT /id="VAR_069556"
FT VARIANT 527
FT /note="V -> M (in ARCI2; dbSNP:rs199545653)"
FT /evidence="ECO:0000269|PubMed:19890349"
FT /id="VAR_069557"
FT VARIANT 578
FT /note="H -> Q (in ARCI2; complete loss of the enzyme
FT activity; dbSNP:rs137853024)"
FT /evidence="ECO:0000269|PubMed:11773004,
FT ECO:0000269|PubMed:15629692"
FT /id="VAR_015174"
FT VARIANT 597
FT /note="A -> E (in ARCI2; dbSNP:rs752509098)"
FT /evidence="ECO:0000269|PubMed:19890349"
FT /id="VAR_069558"
FT VARIANT 664
FT /note="A -> P (in ARCI2; complete loss of the enzyme
FT activity)"
FT /evidence="ECO:0000269|PubMed:16116617"
FT /id="VAR_069559"
FT VARIANT 679
FT /note="R -> L (in ARCI2; dbSNP:rs397514528)"
FT /evidence="ECO:0000269|PubMed:16116617"
FT /id="VAR_069560"
SQ SEQUENCE 701 AA; 80356 MW; C334075759F8B077 CRC64;
MATYKVRVAT GTDLLSGTRD SISLTIVGTQ GESHKQLLNH FGRDFATGAV GQYTVQCPQD
LGELIIIRLH KERYAFFPKD PWYCNYVQIC APNGRIYHFP AYQWMDGYET LALREATGKT
TADDSLPVLL EHRKEEIRAK QDFYHWRVFL PGLPSYVHIP SYRPPVRRHR NPNRPEWNGY
IPGFPILINF KATKFLNLNL RYSFLKTASF FVRLGPMALA FKVRGLLDCK HSWKRLKDIR
KIFPGKKSVV SEYVAEHWAE DTFFGYQYLN GVNPGLIRRC TRIPDKFPVT DDMVAPFLGE
GTCLQAELEK GNIYLADYRI MEGIPTVELS GRKQHHCAPL CLLHFGPEGK MMPIAIQLSQ
TPGPDCPIFL PSDSEWDWLL AKTWVRYAEF YSHEAIAHLL ETHLIAEAFC LALLRNLPMC
HPLYKLLIPH TRYTVQINSI GRAVLLNEGG LSAKGMSLGV EGFAGVMVRA LSELTYDSLY
LPNDFVERGV QDLPGYYYRD DSLAVWNALE KYVTEIITYY YPSDAAVEGD PELQSWVQEI
FKECLLGRES SGFPRCLRTV PELIRYVTIV IYTCSAKHAA VNTGQMEFTA WMPNFPASMR
NPPIQTKGLT TLETFMDTLP DVKTTCITLL VLWTLSREPD DRRPLGHFPD IHFVEEAPRR
SIEAFRQRLN QISHDIRQRN KCLPIPYYYL DPVLIENSIS I
