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P39655 (LOX12_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Arachidonate 12-lipoxygenase, 12S-type

Short name=12S-LOX
Short name=12S-lipoxygenase
EC=1.13.11.31
Alternative name(s):
Lipoxin synthase 12-LO
EC=3.3.2.-
Platelet-type lipoxygenase 12
Short name=P-12LO
Gene names
Name:Alox12
Synonyms:Alox12p
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length663 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7

Catalytic activity

Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate. Ref.1

(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (5S,6R,15S)-trihydroxy-(7E,9E,11Z,13E)-eicosatetraenoate. Ref.1

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

Cofactor

Binds 1 iron ion per subunit.

Enzyme regulation

Activated by EGF By similarity.

Pathway

Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.

Subcellular location

Cytoplasmcytosol. Membrane By similarity. Note: Membrane association is stimulated by EGF By similarity. Ref.6

Tissue specificity

Found primarily in platelets and in microsomal and cytosolic fractions of the epidermis (at protein level). Ref.1 Ref.7 Ref.8

Disruption phenotype

Mice are fertile and appear to exhibit no gross abnormalities. However, they display increased aggregation of platelets in response to ADP. They also display a mild basal transepidermal water loss. Ref.7 Ref.8

Sequence similarities

Belongs to the lipoxygenase family.

Contains 1 lipoxygenase domain.

Contains 1 PLAT domain.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
   Cellular componentCytoplasm
Membrane
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Hydrolase
Oxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

arachidonic acid metabolic process

Inferred from direct assay Ref.1. Source: UniProtKB

cellular component movement

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to lipid

Inferred from electronic annotation. Source: Ensembl

establishment of skin barrier

Inferred from mutant phenotype Ref.8. Source: UniProtKB

fatty acid oxidation

Inferred from sequence or structural similarity. Source: UniProtKB

hepoxilin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

leukotriene A4 metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

linoleic acid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

lipoxin A4 biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

lipoxin B4 biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

lipoxygenase pathway

Inferred from direct assay Ref.1. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 15161019. Source: UniProtKB

negative regulation of muscle cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of platelet aggregation

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 15161019. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of mitochondrial depolarization

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasodilation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay Ref.6. Source: UniProtKB

cytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

sarcolemma

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionarachidonate 12-lipoxygenase activity

Inferred from direct assay Ref.1. Source: UniProtKB

hepoxilin-epoxide hydrolase activity

Inferred from sequence or structural similarity. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

linoleate 13S-lipoxygenase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 663663Arachidonate 12-lipoxygenase, 12S-type
PRO_0000220683

Regions

Domain2 – 114113PLAT
Domain115 – 663549Lipoxygenase

Sites

Metal binding3601Iron; catalytic By similarity
Metal binding3651Iron; catalytic By similarity
Metal binding5401Iron; catalytic By similarity
Metal binding5441Iron; catalytic By similarity
Metal binding6631Iron; via carboxylate; catalytic By similarity

Experimental info

Mutagenesis6631I → D, R, K or G: Loss of activity. Ref.1
Mutagenesis6631I → S or N: Little activity (8-15%). Ref.1
Mutagenesis6631I → V: Nearly full activity. Ref.1
Sequence conflict31R → A in AAA20659. Ref.1
Sequence conflict1121T → Q in AAA20659. Ref.1
Sequence conflict1121T → Q in AAB36013. Ref.2
Sequence conflict4031S → T in AAA20659. Ref.1
Sequence conflict4031S → T in AAB36013. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P39655 [UniParc].

Last modified September 11, 2007. Version 4.
Checksum: 205BE32BE2CF3E87

FASTA66375,390
        10         20         30         40         50         60 
MGRYRVRVVT GAWLFSGSLN LVRLWLVGEH REAKLELQLR PARGKEEEFD FDVPEDLGPL 

        70         80         90        100        110        120 
QFVKLHKQHT VVDDAWFCNL ITVQGPGTSA EAVFPCYRWV QGEGILSLPE GTARLAGDNA 

       130        140        150        160        170        180 
LDVFQKYREK ELKERQQTYC WATWKEGLPQ TIAADCKDDL PPNMRFHEEK RLDFEWTLKA 

       190        200        210        220        230        240 
GVLEMGLKRV YTLLRSWNHL EDFDQIFWGQ KSALAEKVHQ CWQEDELFGY QFLNGANPML 

       250        260        270        280        290        300 
LRRSTSLPSR LVLPSGMEEL QAQLEKELKN GSLFEADFIL LDGIPANVIR GEPQYLAAPL 

       310        320        330        340        350        360 
VMLRMDPGGK LLPMAIQIQP PNPSSPAPTL FLPSDPPLAW LLAKIWVRNS DFQLQELQFH 

       370        380        390        400        410        420 
LLNTHLVAEV IAVATMRCLP GLHPIFKLLV PHIRYTMEIN TRSRTQLISD GGIFDQVVST 

       430        440        450        460        470        480 
GGGGHVQLLT RAVAQLTYHS LCPPDDLANR GLLRIPSALY ARDALQLWEV TARYVKGMVH 

       490        500        510        520        530        540 
LFYQSDDIVR GDPELQAWCR EITEVGLCHA QDRGFPVSFQ SRAQLCHFLT MCVFTCTAQH 

       550        560        570        580        590        600 
AAINQGQLDW YGWVPNAPCT MRMPPPTSKD DVTMETVMGS LPDVQKACLQ MTITWHLGRL 

       610        620        630        640        650        660 
QPDMVPLGHH TEKYFSDPRT KAVLSQFQAD LDNLEKEITA RNEQLDLPYE YLKPSRIENS 


ITI 

« Hide

References

« Hide 'large scale' references
[1]"cDNA cloning, expression, mutagenesis of C-terminal isoleucine, genomic structure, and chromosomal localizations of murine 12-lipoxygenases."
Chen X.-S., Kurre U., Jenkins N.A., Copeland N.G., Funk C.D.
J. Biol. Chem. 269:13979-13987(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-663, TISSUE SPECIFICITY.
Strain: C57BL/6 and ICR.
Tissue: Spleen.
[2]"12-lipoxygenase isoenzymes in mouse skin tumor development."
Krieg P., Kinzig A., Ress-Loschke M., Vogel S., Vanlandingham B., Stephan M., Lehmann W.D., Marks F., Furstenberger G.
Mol. Carcinog. 14:118-129(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Ovary and Vagina.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"12-lipoxygenase in Lewis lung carcinoma cells: molecular identity, intracellular distribution of activity and protein, and Ca(2+)-dependent translocation from cytosol to membranes."
Hagmann W., Gao X., Zacharek A., Wojciechowski L.A., Honn K.V.
Prostaglandins 49:49-62(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 126-218.
Tissue: Lung.
[6]"Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase in mouse blood cells."
Nakamura M., Ueda N., Kishimoto K., Yoshimoto T., Yamamoto S., Ishimura K.
J. Histochem. Cytochem. 43:237-244(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenase."
Johnson E.N., Brass L.F., Funk C.D.
Proc. Natl. Acad. Sci. U.S.A. 95:3100-3105(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PLATELET ACTIVATION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[8]"Basal transepidermal water loss is increased in platelet-type 12-lipoxygenase deficient mice."
Johnson E.N., Nanney L.B., Virmani J., Lawson J.A., Funk C.D.
J. Invest. Dermatol. 112:861-865(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U04334 mRNA. Translation: AAA20659.1.
S80446 mRNA. Translation: AAB36013.1.
AK036898 mRNA. Translation: BAC29629.1.
AK087724 mRNA. Translation: BAC39981.1.
AL669869 Genomic DNA. Translation: CAI35235.1.
S77511 mRNA. Translation: AAB34667.1.
PIRA54075.
RefSeqNP_031466.2. NM_007440.4.
UniGeneMm.12286.

3D structure databases

ProteinModelPortalP39655.
SMRP39655. Positions 2-663.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP39655.
ChEMBLCHEMBL3225.

PTM databases

PhosphoSiteP39655.

Proteomic databases

PaxDbP39655.
PRIDEP39655.

Protocols and materials databases

DNASU11684.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000000329; ENSMUSP00000000329; ENSMUSG00000000320.
GeneID11684.
KEGGmmu:11684.
UCSCuc007juj.1. mouse.

Organism-specific databases

CTD239.
MGIMGI:87998. Alox12.

Phylogenomic databases

eggNOGNOG69653.
GeneTreeENSGT00550000074415.
HOGENOMHOG000234358.
HOVERGENHBG005150.
InParanoidP39655.
KOK00458.
OMAQNQLCHF.
OrthoDBEOG7B05CG.
PhylomeDBP39655.
TreeFamTF105320.

Enzyme and pathway databases

UniPathwayUPA00881.

Gene expression databases

ArrayExpressP39655.
BgeeP39655.
CleanExMM_ALOX12.
GenevestigatorP39655.

Family and domain databases

Gene3D2.60.60.20. 1 hit.
InterProIPR008976. Lipase_LipOase.
IPR000907. LipOase.
IPR013819. LipOase_C.
IPR020834. LipOase_CS.
IPR020833. LipOase_Fe_BS.
IPR001885. LipOase_mml.
IPR001024. PLAT/LH2_dom.
[Graphical view]
PANTHERPTHR11771. PTHR11771. 1 hit.
PfamPF00305. Lipoxygenase. 1 hit.
PF01477. PLAT. 1 hit.
[Graphical view]
PRINTSPR00087. LIPOXYGENASE.
PR00467. MAMLPOXGNASE.
SMARTSM00308. LH2. 1 hit.
[Graphical view]
SUPFAMSSF48484. SSF48484. 1 hit.
SSF49723. SSF49723. 1 hit.
PROSITEPS00711. LIPOXYGENASE_1. 1 hit.
PS00081. LIPOXYGENASE_2. 1 hit.
PS51393. LIPOXYGENASE_3. 1 hit.
PS50095. PLAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio279319.
PROP39655.
SOURCESearch...

Entry information

Entry nameLOX12_MOUSE
AccessionPrimary (citable) accession number: P39655
Secondary accession number(s): Q8BHG4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: September 11, 2007
Last modified: April 16, 2014
This is version 122 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot