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Protein

Arachidonate 12-lipoxygenase, 12S-type

Gene

Alox12

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Mainly converts arachidonic acid to (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE but can also metabolize linoleic acid. Has a dual activity since it also converts leukotriene A4/LTA4 into both the bioactive lipoxin A4/LXA4 and lipoxin B4/LXB4. Through the production of specific bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. It also probably positively regulates angiogenesis through regulation of the expression of the vascular endothelial growth factor. Plays a role in apoptotic process, promoting the survival of vascular smooth muscle cells for instance. May also play a role in the control of cell migration and proliferation.2 Publications

Catalytic activityi

Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate.1 Publication
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (5S,6R,15S)-trihydroxy-(7E,9E,11Z,13E)-eicosatetraenoate.1 Publication
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (5S,14R,15S)-trihydroxy-(6E,8Z,10E,12E)-eicosatetraenoate.1 Publication

Cofactori

Fe cationPROSITE-ProRule annotationNote: Binds 1 Fe cation per subunit.PROSITE-ProRule annotation

Enzyme regulationi

Activated by EGF.By similarity

Pathwayi: hydroperoxy eicosatetraenoic acid biosynthesis

This protein is involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis, which is part of Lipid metabolism.1 Publication
View all proteins of this organism that are known to be involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis and in Lipid metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi360 – 3601Iron; catalyticPROSITE-ProRule annotation
Metal bindingi365 – 3651Iron; catalyticPROSITE-ProRule annotation
Metal bindingi540 – 5401Iron; catalyticPROSITE-ProRule annotation
Metal bindingi544 – 5441Iron; catalyticPROSITE-ProRule annotation
Metal bindingi663 – 6631Iron; via carboxylate; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

  • arachidonate 12-lipoxygenase activity Source: RGD
  • hydrolase activity Source: UniProtKB-KW
  • iron ion binding Source: InterPro
  • linoleate 13S-lipoxygenase activity Source: Ensembl

GO - Biological processi

  • aging Source: RGD
  • arachidonic acid metabolic process Source: UniProtKB
  • cellular response to lipid Source: RGD
  • establishment of skin barrier Source: UniProtKB
  • fatty acid oxidation Source: Ensembl
  • hepoxilin biosynthetic process Source: UniProtKB
  • leukotriene A4 metabolic process Source: UniProtKB
  • linoleic acid metabolic process Source: UniProtKB
  • lipoxin A4 biosynthetic process Source: UniProtKB
  • lipoxin B4 biosynthetic process Source: UniProtKB
  • lipoxygenase pathway Source: UniProtKB
  • negative regulation of apoptotic process Source: RGD
  • negative regulation of muscle cell apoptotic process Source: UniProtKB
  • negative regulation of platelet aggregation Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of cell adhesion Source: Ensembl
  • positive regulation of cell death Source: RGD
  • positive regulation of cell growth Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: RGD
  • positive regulation of endothelial cell differentiation Source: RGD
  • positive regulation of endothelial cell migration Source: RGD
  • positive regulation of gene expression Source: RGD
  • positive regulation of mitochondrial depolarization Source: RGD
  • positive regulation of smooth muscle cell proliferation Source: RGD
  • positive regulation of vasodilation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Hydrolase, Oxidoreductase

Keywords - Biological processi

Fatty acid metabolism, Lipid metabolism

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

ReactomeiR-RNO-2142696. Synthesis of Hepoxilins (HX) and Trioxilins (TrX).
R-RNO-2142700. Synthesis of Lipoxins (LX).
R-RNO-2142712. Synthesis of 12-eicosatetraenoic acid derivatives.
UniPathwayiUPA00881.

Names & Taxonomyi

Protein namesi
Recommended name:
Arachidonate 12-lipoxygenase, 12S-type (EC:1.13.11.31)
Short name:
12S-LOX
Short name:
12S-lipoxygenase
Alternative name(s):
Lipoxin synthase 12-LO (EC:3.3.2.-)
Platelet-type lipoxygenase 12
Gene namesi
Name:Alox12
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi1311159. Alox12.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: RGD
  • extracellular exosome Source: Ensembl
  • membrane Source: UniProtKB
  • sarcolemma Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 663663Arachidonate 12-lipoxygenase, 12S-typePRO_0000423852Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei246 – 2461PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiF1LQ70.

PTM databases

iPTMnetiF1LQ70.

Expressioni

Gene expression databases

ExpressionAtlasiF1LQ70. baseline and differential.
GenevisibleiF1LQ70. RN.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000034009.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 114113PLATPROSITE-ProRule annotationAdd
BLAST
Domaini114 – 663550LipoxygenasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the lipoxygenase family.Curated
Contains 1 lipoxygenase domain.PROSITE-ProRule annotation
Contains 1 PLAT domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IF0U. Eukaryota.
ENOG410YN4N. LUCA.
GeneTreeiENSGT00550000074415.
InParanoidiF1LQ70.
OMAiADCKDDL.
OrthoDBiEOG7B05CG.
TreeFamiTF105320.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR000907. LipOase.
IPR013819. LipOase_C.
IPR020834. LipOase_CS.
IPR020833. LipOase_Fe_BS.
IPR001885. LipOase_mml.
IPR001024. PLAT/LH2_dom.
[Graphical view]
PANTHERiPTHR11771. PTHR11771. 1 hit.
PfamiPF00305. Lipoxygenase. 1 hit.
PF01477. PLAT. 1 hit.
[Graphical view]
PRINTSiPR00087. LIPOXYGENASE.
PR00467. MAMLPOXGNASE.
SMARTiSM00308. LH2. 1 hit.
[Graphical view]
SUPFAMiSSF48484. SSF48484. 1 hit.
SSF49723. SSF49723. 1 hit.
PROSITEiPS00711. LIPOXYGENASE_1. 1 hit.
PS00081. LIPOXYGENASE_2. 1 hit.
PS51393. LIPOXYGENASE_3. 1 hit.
PS50095. PLAT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

F1LQ70-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRYRVRVVT GAWLFSGSVN LVRLWLVGAH REARLELQLR PARGKEEEFD
60 70 80 90 100
FDVAEDLGPL QFVKLHKEHT VVDDAWFCNL ITVQGPGMSA EAVFPCYRWV
110 120 130 140 150
QGEGILRLPE GTARLAGDNA LDVFQKHREK ELKERQQTYR WATWKQGLPQ
160 170 180 190 200
TIAADCKDDL PPNMRFHEEK RLDFEWTLKA GVLEMGLKRV YTLLRSWNRL
210 220 230 240 250
EDFDQIFWGQ KSALAEKVHR CWQEDELFGY QFLNGANPML LRRSTSLPSR
260 270 280 290 300
LVLPPGTEEL QAQLEKELKD GCLFEADFIL LDGIPANVIR GEQQYLAAPL
310 320 330 340 350
VMLRMDPSGK LLPMAIQIQP PNPSSPAPTL FLPSDPPLAW LLAKIWVRNS
360 370 380 390 400
DFQLQELQFH LLNTHLVAEV IAVATMRCLP GLHPIFKLLV PHIRYTMEIN
410 420 430 440 450
TRSRTQLISD GGIFDQVVST GGGGHVQLLT RAVAQLTYCS LCPPDDLATR
460 470 480 490 500
GLLRVPSALY AQDALQLWEV TARYVNGMVH LFYQSDDIVR GDPELQAWCR
510 520 530 540 550
EITEVGLCHA QDRGFPVSFQ SRAQLCHFLT MCVFTCTSQH AAINQGQLDW
560 570 580 590 600
YGWVPNAPCT MRMPPPTSKD DVTMETIMGS LPDVQKSCLQ MTITWHLGRL
610 620 630 640 650
QPDMVPLGHH KEKYFSDPRT KAVLSQFQAD LENLEKEITA RNQQLDLPYE
660
YLKPSRIENS ITI
Length:663
Mass (Da):75,534
Last modified:May 3, 2011 - v1
Checksum:i2DC11842CDA025CA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06064404 Genomic DNA. No translation available.
UniGeneiRn.66513.

Genome annotation databases

EnsembliENSRNOT00000033098; ENSRNOP00000034009; ENSRNOG00000027037.
UCSCiRGD:1311159. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06064404 Genomic DNA. No translation available.
UniGeneiRn.66513.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000034009.

PTM databases

iPTMnetiF1LQ70.

Proteomic databases

PaxDbiF1LQ70.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000033098; ENSRNOP00000034009; ENSRNOG00000027037.
UCSCiRGD:1311159. rat.

Organism-specific databases

RGDi1311159. Alox12.

Phylogenomic databases

eggNOGiENOG410IF0U. Eukaryota.
ENOG410YN4N. LUCA.
GeneTreeiENSGT00550000074415.
InParanoidiF1LQ70.
OMAiADCKDDL.
OrthoDBiEOG7B05CG.
TreeFamiTF105320.

Enzyme and pathway databases

UniPathwayiUPA00881.
ReactomeiR-RNO-2142696. Synthesis of Hepoxilins (HX) and Trioxilins (TrX).
R-RNO-2142700. Synthesis of Lipoxins (LX).
R-RNO-2142712. Synthesis of 12-eicosatetraenoic acid derivatives.

Miscellaneous databases

PROiF1LQ70.

Gene expression databases

ExpressionAtlasiF1LQ70. baseline and differential.
GenevisibleiF1LQ70. RN.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR000907. LipOase.
IPR013819. LipOase_C.
IPR020834. LipOase_CS.
IPR020833. LipOase_Fe_BS.
IPR001885. LipOase_mml.
IPR001024. PLAT/LH2_dom.
[Graphical view]
PANTHERiPTHR11771. PTHR11771. 1 hit.
PfamiPF00305. Lipoxygenase. 1 hit.
PF01477. PLAT. 1 hit.
[Graphical view]
PRINTSiPR00087. LIPOXYGENASE.
PR00467. MAMLPOXGNASE.
SMARTiSM00308. LH2. 1 hit.
[Graphical view]
SUPFAMiSSF48484. SSF48484. 1 hit.
SSF49723. SSF49723. 1 hit.
PROSITEiPS00711. LIPOXYGENASE_1. 1 hit.
PS00081. LIPOXYGENASE_2. 1 hit.
PS51393. LIPOXYGENASE_3. 1 hit.
PS50095. PLAT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
    Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
    , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
    Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  2. "Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by beta-amyloid peptide."
    Lebeau A., Terro F., Rostene W., Pelaprat D.
    Cell Death Differ. 11:875-884(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN APOPTOSIS.
  3. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  4. "Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical role for spinal eLOX3 hepoxilin synthase activity in inflammatory hyperalgesia."
    Gregus A.M., Dumlao D.S., Wei S.C., Norris P.C., Catella L.C., Meyerstein F.G., Buczynski M.W., Steinauer J.J., Fitzsimmons B.L., Yaksh T.L., Dennis E.A.
    FASEB J. 27:1939-1949(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY.

Entry informationi

Entry nameiLOX12_RAT
AccessioniPrimary (citable) accession number: F1LQ70
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 16, 2013
Last sequence update: May 3, 2011
Last modified: June 8, 2016
This is version 39 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.