ID LOX12_HUMAN Reviewed; 663 AA. AC P18054; O95569; Q6ISF8; Q9UQM4; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 4. DT 31-MAY-2011, entry version 129. DE RecName: Full=Arachidonate 12-lipoxygenase, 12S-type; DE Short=12S-LOX; DE Short=12S-lipoxygenase; DE EC=1.13.11.31; DE AltName: Full=Platelet-type lipoxygenase 12; GN Name=ALOX12; Synonyms=LOG12; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-322. RX MEDLINE=90332636; PubMed=2377602; DOI=10.1073/pnas.87.15.5638; RA Funk C.D., Furci L., Fitzgerald G.A.; RT "Molecular cloning, primary structure, and expression of the human RT platelet/erythroleukemia cell 12-lipoxygenase."; RL Proc. Natl. Acad. Sci. U.S.A. 87:5638-5642(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-261. RX MEDLINE=91017529; PubMed=2217179; DOI=10.1073/pnas.87.19.7477; RA Izumi T., Hoshiko S., Raadmark O., Samuelsson B.; RT "Cloning of the cDNA for human 12-lipoxygenase."; RL Proc. Natl. Acad. Sci. U.S.A. 87:7477-7481(1990). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-322. RX MEDLINE=91058562; PubMed=2244907; DOI=10.1016/0006-291X(90)91580-L; RA Yoshimoto T., Yamamoto Y., Arakawa T., Suzuki H., Yamamoto S., RA Yokoyama C., Tanabe T., Toh H.; RT "Molecular cloning and expression of human arachidonate 12- RT lipoxygenase."; RL Biochem. Biophys. Res. Commun. 172:1230-1235(1990). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-261; SER-322 AND RP HIS-430. RG SeattleSNPs variation discovery resource; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-261. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-112. RX MEDLINE=93077582; PubMed=1447217; RA Yoshimoto T., Arakawa T., Hada T., Yamamoto S., Takahashi E.; RT "Structure and chromosomal localization of human arachidonate 12- RT lipoxygenase gene."; RL J. Biol. Chem. 267:24805-24809(1992). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45. RX MEDLINE=92237289; PubMed=1570320; DOI=10.1073/pnas.89.9.3962; RA Funk C.D., Funk L.B., Fitzgerald G.A., Samuelsson B.; RT "Characterization of human 12-lipoxygenase genes."; RL Proc. Natl. Acad. Sci. U.S.A. 89:3962-3966(1992). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 340-427. RC TISSUE=Skin; RX MEDLINE=94136572; PubMed=8304420; RA Hussain H., Shornick L.P., Shannon V.R., Wilson J.D., Funk C.D., RA Pentland A.P., Holtzman M.J.; RT "Epidermis contains platelet-type 12-lipoxygenase that is RT overexpressed in germinal layer keratinocytes in psoriasis."; RL Am. J. Physiol. 266:C243-C253(1994). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 531-663. RA Persson A.E., Lundeberg J., Uhlen M.; RT "EU-IMAGE: full-insert length sequencing of human cDNA clones."; RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases. RN [10] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 172-662 IN COMPLEX WITH IRON RP IONS. RG Structural genomics consortium (SGC); RT "Crystal structure of the lipoxygenase domain of human arachidonate RT 12-lipoxygenase, 12s-type."; RL Submitted (FEB-2009) to the PDB data bank. RN [11] RP VARIANT ARG-261. RX PubMed=15308583; DOI=10.1093/carcin/bgh260; RA Goodman J.E., Bowman E.D., Chanock S.J., Alberg A.J., Harris C.C.; RT "Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) RT polymorphisms and colon cancer risk."; RL Carcinogenesis 25:2467-2472(2004). CC -!- FUNCTION: Oxygenase and 14,15-leukotriene A4 synthase activity. CC -!- CATALYTIC ACTIVITY: Arachidonate + O(2) = (5Z,8Z,10E,14Z)-(12S)- CC 12-hydroperoxyicosa-5,8,10,14-tetraenoate. CC -!- COFACTOR: Binds 1 iron ion per subunit. CC -!- PATHWAY: Lipid metabolism; leukotriene D4 biosynthesis. CC -!- INTERACTION: CC P16144:ITGB4; NbExp=2; IntAct=EBI-1633210, EBI-948678; CC P13647:KRT5; NbExp=3; IntAct=EBI-1633210, EBI-702187; CC P02545:LMNA; NbExp=3; IntAct=EBI-1633210, EBI-351935; CC Q96RU8:TRIB1; NbExp=2; IntAct=EBI-1633210, EBI-492555; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- SIMILARITY: Belongs to the lipoxygenase family. CC -!- SIMILARITY: Contains 1 lipoxygenase domain. CC -!- SIMILARITY: Contains 1 PLAT domain. CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/alox12/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/ALOX12ID620ch17p13.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M35418; AAA60056.1; -; mRNA. DR EMBL; M58704; AAA59523.1; -; mRNA. DR EMBL; M62982; AAA51533.1; -; mRNA. DR EMBL; AY527817; AAS00094.1; -; Genomic_DNA. DR EMBL; BC069557; AAH69557.1; -; mRNA. DR EMBL; D12638; BAA02162.1; -; Genomic_DNA. DR EMBL; M87004; AAA51587.1; -; Genomic_DNA. DR EMBL; S68587; AAD14020.1; -; mRNA. DR EMBL; AF143883; AAD32700.1; -; mRNA. DR IPI; IPI00218915; -. DR PIR; A38283; A38283. DR RefSeq; NP_000688.2; NM_000697.2. DR UniGene; Hs.654431; -. DR PDB; 2ABU; Model; -; A=2-663. DR PDB; 3D3L; X-ray; 2.60 A; A/B=172-662. DR PDBsum; 2ABU; -. DR PDBsum; 3D3L; -. DR ProteinModelPortal; P18054; -. DR SMR; P18054; 2-663. DR IntAct; P18054; 15. DR MINT; MINT-1206406; -. DR STRING; P18054; -. DR PhosphoSite; P18054; -. DR PRIDE; P18054; -. DR Ensembl; ENST00000251535; ENSP00000251535; ENSG00000108839. DR GeneID; 239; -. DR KEGG; hsa:239; -. DR NMPDR; fig|9606.3.peg.12986; -. DR UCSC; uc002gdx.2; human. DR CTD; 239; -. DR GeneCards; GC17P006840; -. DR H-InvDB; HIX0039067; -. DR HGNC; HGNC:429; ALOX12. DR HPA; CAB019287; -. DR HPA; HPA010691; -. DR MIM; 152391; gene. DR neXtProt; NX_P18054; -. DR PharmGKB; PA45; -. DR eggNOG; prNOG13991; -. DR HOGENOM; HBG443995; -. DR HOVERGEN; HBG005150; -. DR InParanoid; P18054; -. DR OMA; HHKEKYF; -. DR OrthoDB; EOG4W0XCM; -. DR PhylomeDB; P18054; -. DR NextBio; 952; -. DR ArrayExpress; P18054; -. DR Bgee; P18054; -. DR CleanEx; HS_ALOX12; -. DR Genevestigator; P18054; -. DR GermOnline; ENSG00000108839; Homo sapiens. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB. DR GO; GO:0004052; F:arachidonate 12-lipoxygenase activity; IDA:UniProtKB. DR GO; GO:0047977; F:hepoxilin-epoxide hydrolase activity; ISS:UniProtKB. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0016165; F:lipoxygenase activity; IEA:InterPro. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0006916; P:anti-apoptosis; IMP:UniProtKB. DR GO; GO:0006928; P:cellular component movement; IMP:UniProtKB. DR GO; GO:0019395; P:fatty acid oxidation; IMP:UniProtKB. DR GO; GO:0019370; P:leukotriene biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB. DR GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB. DR GO; GO:0042554; P:superoxide anion generation; NAS:UniProtKB. DR InterPro; IPR008976; Lipase_LipOase. DR InterPro; IPR000907; LipOase. DR InterPro; IPR013819; LipOase_C. DR InterPro; IPR020834; LipOase_CS. DR InterPro; IPR020833; LipOase_Fe_BS. DR InterPro; IPR001024; LipOase_LH2. DR InterPro; IPR001885; LipOase_mml. DR Gene3D; G3DSA:2.60.60.20; Lipase_LipOase; 1. DR PANTHER; PTHR11771; LipOase; 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; SSF49723; Lipase_LipOase; 1. DR SUPFAM; SSF48484; Lipoxygenase; 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 3D-structure; Complete proteome; Cytoplasm; Dioxygenase; Iron; KW Leukotriene biosynthesis; Metal-binding; Oxidoreductase; Polymorphism. FT INIT_MET 1 1 Removed (By similarity). FT CHAIN 2 663 Arachidonate 12-lipoxygenase, 12S-type. FT /FTId=PRO_0000220682. FT DOMAIN 2 114 PLAT. FT DOMAIN 115 663 Lipoxygenase. FT METAL 360 360 Iron; catalytic. FT METAL 365 365 Iron; catalytic. FT METAL 540 540 Iron; catalytic. FT METAL 544 544 Iron; catalytic (By similarity). FT METAL 663 663 Iron; via carboxylate; catalytic (By FT similarity). FT VARIANT 259 259 E -> K (in dbSNP:rs4987104). FT /FTId=VAR_030471. FT VARIANT 261 261 Q -> R (in dbSNP:rs1126667). FT /FTId=VAR_018743. FT VARIANT 298 298 A -> T. FT /FTId=VAR_004279. FT VARIANT 322 322 N -> S (in dbSNP:rs434473). FT /FTId=VAR_018744. FT VARIANT 430 430 R -> H (in dbSNP:rs11571342). FT /FTId=VAR_018745. FT CONFLICT 189 192 RVYT -> PCLH (in Ref. 3; AAA51533). FT CONFLICT 345 345 S -> C (in Ref. 3; AAA51533). FT CONFLICT 389 389 L -> P (in Ref. 1; AAA60056). FT HELIX 183 195 FT STRAND 198 200 FT HELIX 203 207 FT HELIX 213 221 FT HELIX 225 230 FT TURN 231 233 FT HELIX 258 269 FT STRAND 273 277 FT HELIX 279 281 FT STRAND 300 306 FT STRAND 311 319 FT STRAND 325 327 FT HELIX 337 357 FT HELIX 358 364 FT HELIX 365 378 FT HELIX 384 389 FT HELIX 390 392 FT HELIX 426 434 FT TURN 438 441 FT HELIX 443 449 FT HELIX 459 475 FT HELIX 479 482 FT HELIX 486 489 FT HELIX 493 503 FT HELIX 510 512 FT HELIX 522 536 FT HELIX 538 544 FT HELIX 548 551 FT HELIX 554 556 FT STRAND 567 571 FT HELIX 574 577 FT HELIX 584 597 FT HELIX 619 643 FT HELIX 654 656 FT STRAND 657 660 SQ SEQUENCE 663 AA; 75694 MW; C4D6D5B320666A77 CRC64; MGRYRIRVAT GAWLFSGSYN RVQLWLVGTR GEAELELQLR PARGEEEEFD HDVAEDLGLL QFVRLRKHHW LVDDAWFCDR ITVQGPGACA EVAFPCYRWV QGEDILSLPE GTARLPGDNA LDMFQKHREK ELKDRQQIYC WATWKEGLPL TIAADRKDDL PPNMRFHEEK RLDFEWTLKA GALEMALKRV YTLLSSWNCL EDFDQIFWGQ KSALAEKVRQ CWQDDELFSY QFLNGANPML LRRSTSLPSR LVLPSGMEEL QAQLEKELQN GSLFEADFIL LDGIPANVIR GEKQYLAAPL VMLKMEPNGK LQPMVIQIQP PNPSSPTPTL FLPSDPPLAW LLAKSWVRNS DFQLHEIQYH LLNTHLVAEV IAVATMRCLP GLHPIFKFLI PHIRYTMEIN TRARTQLISD GGIFDKAVST GGGGHVQLLR RAAAQLTYCS LCPPDDLADR GLLGLPGALY AHDALRLWEI IARYVEGIVH LFYQRDDIVK GDPELQAWCR EITEVGLCQA QDRGFPVSFQ SQSQLCHFLT MCVFTCTAQH AAINQGQLDW YAWVPNAPCT MRMPPPTTKE DVTMATVMGS LPDVRQACLQ MAISWHLSRR QPDMVPLGHH KEKYFSGPKP KAVLNQFRTD LEKLEKEITA RNEQLDWPYE YLKPSCIENS VTI //