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Protein

Arachidonate 12-lipoxygenase, 12S-type

Gene

Alox12

Organism
Mus musculus (Mouse)
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.1 Publication

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 cationNote: Binds 1 Fe cation per subunit.

Enzyme regulationi

Activated by EGF.By similarity

Pathwayi

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

  1. arachidonate 12-lipoxygenase activity Source: UniProtKB
  2. hepoxilin-epoxide hydrolase activity Source: UniProtKB
  3. iron ion binding Source: InterPro
  4. linoleate 13S-lipoxygenase activity Source: MGI

GO - Biological processi

  1. aging Source: Ensembl
  2. arachidonic acid metabolic process Source: UniProtKB
  3. cellular response to lipid Source: Ensembl
  4. establishment of skin barrier Source: UniProtKB
  5. fatty acid oxidation Source: UniProtKB
  6. hepoxilin biosynthetic process Source: UniProtKB
  7. leukotriene A4 metabolic process Source: UniProtKB
  8. linoleic acid metabolic process Source: UniProtKB
  9. lipoxin A4 biosynthetic process Source: UniProtKB
  10. lipoxin B4 biosynthetic process Source: UniProtKB
  11. lipoxygenase pathway Source: UniProtKB
  12. movement of cell or subcellular component Source: UniProtKB
  13. negative regulation of apoptotic process Source: UniProtKB
  14. negative regulation of muscle cell apoptotic process Source: UniProtKB
  15. negative regulation of platelet aggregation Source: UniProtKB
  16. positive regulation of angiogenesis Source: UniProtKB
  17. positive regulation of apoptotic process Source: UniProtKB
  18. positive regulation of cell adhesion Source: UniProtKB
  19. positive regulation of cell growth Source: UniProtKB
  20. positive regulation of cell migration Source: UniProtKB
  21. positive regulation of cell proliferation Source: UniProtKB
  22. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  23. positive regulation of endothelial cell differentiation Source: Ensembl
  24. positive regulation of endothelial cell migration Source: Ensembl
  25. positive regulation of gene expression Source: Ensembl
  26. positive regulation of mitochondrial depolarization Source: Ensembl
  27. positive regulation of smooth muscle cell proliferation Source: Ensembl
  28. positive regulation of vasodilation Source: Ensembl
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

ReactomeiREACT_280918. Synthesis of Lipoxins (LX).
REACT_325938. Synthesis of 12-eicosatetraenoic acid derivatives.
REACT_346992. Synthesis of Hepoxilins (HX) and Trioxilins (TrX).
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
Short name:
P-12LO
Gene namesi
Name:Alox12
Synonyms:Alox12p
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:87998. Alox12.

Subcellular locationi

  1. Cytoplasmcytosol 1 Publication
  2. Membrane By similarity

  3. Note: Membrane association is stimulated by EGF.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: MGI
  3. extracellular vesicular exosome Source: MGI
  4. membrane Source: UniProtKB
  5. sarcolemma Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi663 – 6631I → D, R, K or G: Loss of activity. 1 Publication
Mutagenesisi663 – 6631I → S or N: Little activity (8-15%). 1 Publication
Mutagenesisi663 – 6631I → V: Nearly full activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 663663Arachidonate 12-lipoxygenase, 12S-typePRO_0000220683Add
BLAST

Proteomic databases

MaxQBiP39655.
PaxDbiP39655.
PRIDEiP39655.

PTM databases

PhosphoSiteiP39655.

Expressioni

Tissue specificityi

Found primarily in platelets and in microsomal and cytosolic fractions of the epidermis (at protein level).3 Publications

Gene expression databases

BgeeiP39655.
CleanExiMM_ALOX12.
ExpressionAtlasiP39655. baseline and differential.
GenevestigatoriP39655.

Interactioni

Structurei

3D structure databases

ProteinModelPortaliP39655.
SMRiP39655. Positions 2-663.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 114113PLATPROSITE-ProRule annotationAdd
BLAST
Domaini115 – 663549LipoxygenasePROSITE-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

eggNOGiNOG69653.
GeneTreeiENSGT00550000074415.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiP39655.
KOiK00458.
OMAiRQACLQM.
OrthoDBiEOG7B05CG.
PhylomeDBiP39655.
TreeFamiTF105320.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR008976. Lipase_LipOase.
IPR000907. 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.

P39655-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRYRVRVVT GAWLFSGSLN LVRLWLVGEH REAKLELQLR PARGKEEEFD
60 70 80 90 100
FDVPEDLGPL QFVKLHKQHT VVDDAWFCNL ITVQGPGTSA EAVFPCYRWV
110 120 130 140 150
QGEGILSLPE GTARLAGDNA LDVFQKYREK ELKERQQTYC WATWKEGLPQ
160 170 180 190 200
TIAADCKDDL PPNMRFHEEK RLDFEWTLKA GVLEMGLKRV YTLLRSWNHL
210 220 230 240 250
EDFDQIFWGQ KSALAEKVHQ CWQEDELFGY QFLNGANPML LRRSTSLPSR
260 270 280 290 300
LVLPSGMEEL QAQLEKELKN GSLFEADFIL LDGIPANVIR GEPQYLAAPL
310 320 330 340 350
VMLRMDPGGK LLPMAIQIQP PNPSSPAPTL FLPSDPPLAW LLAKIWVRNS
360 370 380 390 400
DFQLQELQFH LLNTHLVAEV IAVATMRCLP GLHPIFKLLV PHIRYTMEIN
410 420 430 440 450
TRSRTQLISD GGIFDQVVST GGGGHVQLLT RAVAQLTYHS LCPPDDLANR
460 470 480 490 500
GLLRIPSALY ARDALQLWEV TARYVKGMVH LFYQSDDIVR GDPELQAWCR
510 520 530 540 550
EITEVGLCHA QDRGFPVSFQ SRAQLCHFLT MCVFTCTAQH AAINQGQLDW
560 570 580 590 600
YGWVPNAPCT MRMPPPTSKD DVTMETVMGS LPDVQKACLQ MTITWHLGRL
610 620 630 640 650
QPDMVPLGHH TEKYFSDPRT KAVLSQFQAD LDNLEKEITA RNEQLDLPYE
660
YLKPSRIENS ITI
Length:663
Mass (Da):75,390
Last modified:September 11, 2007 - v4
Checksum:i205BE32BE2CF3E87
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 31R → A in AAA20659 (PubMed:8188678).Curated
Sequence conflicti112 – 1121T → Q in AAA20659 (PubMed:8188678).Curated
Sequence conflicti112 – 1121T → Q in AAB36013 (PubMed:7576099).Curated
Sequence conflicti403 – 4031S → T in AAA20659 (PubMed:8188678).Curated
Sequence conflicti403 – 4031S → T in AAB36013 (PubMed:7576099).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24942.1.
PIRiA54075.
RefSeqiNP_031466.2. NM_007440.4.
UniGeneiMm.12286.

Genome annotation databases

EnsembliENSMUST00000000329; ENSMUSP00000000329; ENSMUSG00000000320.
GeneIDi11684.
KEGGimmu:11684.
UCSCiuc007juj.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24942.1.
PIRiA54075.
RefSeqiNP_031466.2. NM_007440.4.
UniGeneiMm.12286.

3D structure databases

ProteinModelPortaliP39655.
SMRiP39655. Positions 2-663.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiP39655.
ChEMBLiCHEMBL3225.

PTM databases

PhosphoSiteiP39655.

Proteomic databases

MaxQBiP39655.
PaxDbiP39655.
PRIDEiP39655.

Protocols and materials databases

DNASUi11684.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000000329; ENSMUSP00000000329; ENSMUSG00000000320.
GeneIDi11684.
KEGGimmu:11684.
UCSCiuc007juj.1. mouse.

Organism-specific databases

CTDi239.
MGIiMGI:87998. Alox12.

Phylogenomic databases

eggNOGiNOG69653.
GeneTreeiENSGT00550000074415.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiP39655.
KOiK00458.
OMAiRQACLQM.
OrthoDBiEOG7B05CG.
PhylomeDBiP39655.
TreeFamiTF105320.

Enzyme and pathway databases

UniPathwayiUPA00881.
ReactomeiREACT_280918. Synthesis of Lipoxins (LX).
REACT_325938. Synthesis of 12-eicosatetraenoic acid derivatives.
REACT_346992. Synthesis of Hepoxilins (HX) and Trioxilins (TrX).

Miscellaneous databases

NextBioi279319.
PROiP39655.
SOURCEiSearch...

Gene expression databases

BgeeiP39655.
CleanExiMM_ALOX12.
ExpressionAtlasiP39655. baseline and differential.
GenevestigatoriP39655.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR008976. Lipase_LipOase.
IPR000907. 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. "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. 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.
    , 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. 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.

Entry informationi

Entry nameiLOX12_MOUSE
AccessioniPrimary (citable) accession number: P39655
Secondary accession number(s): Q8BHG4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: September 11, 2007
Last modified: April 1, 2015
This is version 132 of the entry and version 4 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.