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Protein

Arachidonate 12-lipoxygenase, 12S-type

Gene

ALOX12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.5 Publications

Catalytic activityi

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

Cofactori

Fe cationNote: Binds 1 Fe cation per subunit.

Enzyme regulationi

Activated by EGF.1 Publication

Kineticsi

  1. KM=8 µM for arachidonate (at pH 7.0 and 37 degrees Celsius)1 Publication
  2. KM=10 µM for arachidonate (at pH 8.0 and 25 degrees Celsius)1 Publication
  3. KM=6.2 µM for arachidonate (at pH 7.4)1 Publication
  4. KM=9 µM for linoleate (at pH 8.0 and 25 degrees Celsius)1 Publication
  5. KM=7.9 µM for leukotriene A4 (at pH 7.4)1 Publication
  6. KM=3 µM for eicosa-5,8,11,14,17-pentaenoate (at pH 7.0 and 37 degrees Celsius)1 Publication
  7. KM=35 µM for eicosa-8,11,14-trienoate (at pH 7.0 and 37 degrees Celsius)1 Publication
  8. KM=14.3 µM for 5,6-epoxy-8,11,14-eicosatrienoate (at pH 7.4)1 Publication
  1. Vmax=3 µmol/min/mg enzyme with arachidonate as substrate (at pH 8.0 and 25 degrees Celsius)1 Publication
  2. Vmax=1.057 µmol/min/mg enzyme with arachidonate as substrate (at pH 7.4)1 Publication
  3. Vmax=0.0375 µmol/min/mg enzyme with linoleate as substrate (at pH 8.0 and 25 degrees Celsius)1 Publication
  4. Vmax=0.025 µmol/min/mg enzyme with leukotriene A4 as substrate (at pH 7.4)1 Publication
  5. Vmax=0.985 µmol/min/mg enzyme with 5,6-epoxy-8,11,14-eicosatrienoate as substrate (at pH 7.4)1 Publication

pH dependencei

Optimum pH is 7.5-8.0 (for arachidonate 12-lipoxygenase activity).2 Publications

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)DescriptionActionsGraphical viewLength
Metal bindingi360Iron; catalytic1
Metal bindingi365Iron; catalytic1
Metal bindingi540Iron; catalytic1
Metal bindingi544Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi663Iron; via carboxylate; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • arachidonic acid metabolic process Source: UniProtKB
  • establishment of skin barrier Source: UniProtKB
  • fatty acid oxidation Source: UniProtKB
  • hepoxilin biosynthetic process Source: UniProtKB
  • hepoxilin metabolic process Source: Reactome
  • leukotriene A4 metabolic process Source: UniProtKB
  • linoleic acid metabolic process Source: UniProtKB
  • lipoxin A4 biosynthetic process Source: UniProtKB
  • lipoxin B4 biosynthetic process Source: UniProtKB
  • lipoxin biosynthetic process Source: Reactome
  • lipoxygenase pathway Source: UniProtKB
  • long-chain fatty acid biosynthetic process Source: Reactome
  • negative regulation of muscle cell apoptotic process Source: UniProtKB
  • negative regulation of platelet aggregation Source: UniProtKB
  • superoxide anion generation Source: UniProtKB

Keywordsi

Molecular functionDioxygenase, Hydrolase, Oxidoreductase
Biological processFatty acid metabolism, Lipid metabolism
LigandIron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS03167-MONOMER
BRENDAi1.13.11.31 2681
ReactomeiR-HSA-2142696 Synthesis of Hepoxilins (HX) and Trioxilins (TrX)
R-HSA-2142700 Synthesis of Lipoxins (LX)
R-HSA-2142712 Synthesis of 12-eicosatetraenoic acid derivatives
R-HSA-9018677 Biosynthesis of DHA-derived SPMs
R-HSA-9025106 Biosynthesis of DPAn-6 SPMs
R-HSA-9026290 Biosynthesis of DPAn-3-derived maresins
SABIO-RKiP18054
UniPathwayiUPA00881

Chemistry databases

SwissLipidsiSLP:000000670

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
Synonyms:12LO, LOG12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108839.11
HGNCiHGNC:429 ALOX12
MIMi152391 gene
neXtProtiNX_P18054

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Esophageal cancer (ESCR)1 Publication
Disease susceptibility may be associated with variations affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to esophageal cancer (PubMed:17460548).1 Publication
Disease descriptionA malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage.
See also OMIM:133239
Colorectal cancer (CRC)1 Publication
Disease susceptibility may be associated with variations affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to colorectal cancer (PubMed:17460548).1 Publication
Disease descriptionA complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
See also OMIM:114500

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi355H → Q: No effect on catalytic activity. 1 Publication1
Mutagenesisi360H → Q or Y: Complete loss of catalytic activity. 1 Publication1
Mutagenesisi365H → Q: Complete loss of catalytic activity. 1 Publication1
Mutagenesisi383H → Q: Altered catalytic activity and protein expression. 1 Publication1
Mutagenesisi392H → Q: No effect on catalytic activity. 1 Publication1
Mutagenesisi416K → Q: Reduced catalytic activity. No effect on the stereoselectivity of the oxygenation reaction. 1 Publication1
Mutagenesisi417A → I: Reduced catalytic activity. Alters the stereoselectivity of the oxygenation reaction. 1 Publication1
Mutagenesisi418V → M: No effect on catalytic activity. No effect on the stereoselectivity of the oxygenation reaction. 1 Publication1
Mutagenesisi540H → Q: Complete loss of catalytic activity. 1 Publication1

Organism-specific databases

DisGeNETi239
MIMi114500 phenotype
133239 phenotype
OpenTargetsiENSG00000108839
PharmGKBiPA45

Chemistry databases

ChEMBLiCHEMBL3687
GuidetoPHARMACOLOGYi1387

Polymorphism and mutation databases

BioMutaiALOX12
DMDMi125987838

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002206821 – 663Arachidonate 12-lipoxygenase, 12S-typeAdd BLAST663

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei246PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP18054
PeptideAtlasiP18054
PRIDEiP18054
ProteomicsDBi53540

PTM databases

iPTMnetiP18054
PhosphoSitePlusiP18054

Expressioni

Tissue specificityi

Expressed in vascular smooth muscle cells.1 Publication

Inductioni

Down-regulated upon starvation, by UV-irradiation and 15-lipoxygenase metabolites.2 Publications

Gene expression databases

BgeeiENSG00000108839
CleanExiHS_ALOX12
ExpressionAtlasiP18054 baseline and differential
GenevisibleiP18054 HS

Organism-specific databases

HPAiCAB019287
HPA010691

Interactioni

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi106740, 8 interactors
IntActiP18054, 4 interactors
MINTiP18054
STRINGi9606.ENSP00000251535

Chemistry databases

BindingDBiP18054

Structurei

Secondary structure

1663
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi182 – 195Combined sources14
Beta strandi198 – 200Combined sources3
Helixi203 – 207Combined sources5
Helixi213 – 221Combined sources9
Helixi225 – 234Combined sources10
Helixi258 – 269Combined sources12
Beta strandi273 – 277Combined sources5
Helixi279 – 281Combined sources3
Beta strandi300 – 305Combined sources6
Beta strandi311 – 319Combined sources9
Beta strandi325 – 327Combined sources3
Helixi337 – 357Combined sources21
Helixi358 – 364Combined sources7
Helixi365 – 378Combined sources14
Helixi384 – 389Combined sources6
Helixi390 – 392Combined sources3
Helixi426 – 434Combined sources9
Turni438 – 441Combined sources4
Helixi443 – 449Combined sources7
Helixi459 – 482Combined sources24
Helixi486 – 491Combined sources6
Helixi493 – 503Combined sources11
Turni504 – 508Combined sources5
Helixi510 – 512Combined sources3
Helixi522 – 536Combined sources15
Helixi538 – 544Combined sources7
Helixi547 – 551Combined sources5
Helixi554 – 556Combined sources3
Beta strandi567 – 571Combined sources5
Helixi574 – 580Combined sources7
Helixi584 – 597Combined sources14
Helixi618 – 643Combined sources26
Helixi654 – 656Combined sources3
Beta strandi657 – 660Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ABUmodel-A2-663[»]
3D3LX-ray2.60A/B172-663[»]
ProteinModelPortaliP18054
SMRiP18054
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP18054

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 114PLATPROSITE-ProRule annotationAdd BLAST113
Domaini115 – 663LipoxygenasePROSITE-ProRule annotationAdd BLAST549

Sequence similaritiesi

Belongs to the lipoxygenase family.Curated

Phylogenomic databases

eggNOGiENOG410IF0U Eukaryota
ENOG410YN4N LUCA
GeneTreeiENSGT00550000074415
HOGENOMiHOG000234358
HOVERGENiHBG005150
InParanoidiP18054
KOiK00458
OMAiMTITWHL
OrthoDBiEOG091G04A4
PhylomeDBiP18054
TreeFamiTF105320

Family and domain databases

InterProiView protein in InterPro
IPR000907 LipOase
IPR013819 LipOase_C
IPR036226 LipOase_C_sf
IPR020834 LipOase_CS
IPR020833 LipOase_Fe_BS
IPR001885 LipOase_mml
IPR001024 PLAT/LH2_dom
IPR036392 PLAT/LH2_dom_sf
PANTHERiPTHR11771 PTHR11771, 1 hit
PfamiView protein in Pfam
PF00305 Lipoxygenase, 1 hit
PF01477 PLAT, 1 hit
PRINTSiPR00087 LIPOXYGENASE
PR00467 MAMLPOXGNASE
SMARTiView protein in SMART
SM00308 LH2, 1 hit
SUPFAMiSSF48484 SSF48484, 1 hit
SSF49723 SSF49723, 1 hit
PROSITEiView protein in PROSITE
PS00711 LIPOXYGENASE_1, 1 hit
PS00081 LIPOXYGENASE_2, 1 hit
PS51393 LIPOXYGENASE_3, 1 hit
PS50095 PLAT, 1 hit

Sequencei

Sequence statusi: Complete.

P18054-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRYRIRVAT GAWLFSGSYN RVQLWLVGTR GEAELELQLR PARGEEEEFD
60 70 80 90 100
HDVAEDLGLL QFVRLRKHHW LVDDAWFCDR ITVQGPGACA EVAFPCYRWV
110 120 130 140 150
QGEDILSLPE GTARLPGDNA LDMFQKHREK ELKDRQQIYC WATWKEGLPL
160 170 180 190 200
TIAADRKDDL PPNMRFHEEK RLDFEWTLKA GALEMALKRV YTLLSSWNCL
210 220 230 240 250
EDFDQIFWGQ KSALAEKVRQ CWQDDELFSY QFLNGANPML LRRSTSLPSR
260 270 280 290 300
LVLPSGMEEL QAQLEKELQN GSLFEADFIL LDGIPANVIR GEKQYLAAPL
310 320 330 340 350
VMLKMEPNGK LQPMVIQIQP PNPSSPTPTL FLPSDPPLAW LLAKSWVRNS
360 370 380 390 400
DFQLHEIQYH LLNTHLVAEV IAVATMRCLP GLHPIFKFLI PHIRYTMEIN
410 420 430 440 450
TRARTQLISD GGIFDKAVST GGGGHVQLLR RAAAQLTYCS LCPPDDLADR
460 470 480 490 500
GLLGLPGALY AHDALRLWEI IARYVEGIVH LFYQRDDIVK GDPELQAWCR
510 520 530 540 550
EITEVGLCQA QDRGFPVSFQ SQSQLCHFLT MCVFTCTAQH AAINQGQLDW
560 570 580 590 600
YAWVPNAPCT MRMPPPTTKE DVTMATVMGS LPDVRQACLQ MAISWHLSRR
610 620 630 640 650
QPDMVPLGHH KEKYFSGPKP KAVLNQFRTD LEKLEKEITA RNEQLDWPYE
660
YLKPSCIENS VTI
Length:663
Mass (Da):75,694
Last modified:February 6, 2007 - v4
Checksum:iC4D6D5B320666A77
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti189 – 192RVYT → PCLH in AAA51533 (PubMed:2244907).Curated4
Sequence conflicti345S → C in AAA51533 (PubMed:2244907).Curated1
Sequence conflicti389L → P in AAA60056 (PubMed:2377602).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030471259E → K. Corresponds to variant dbSNP:rs4987104Ensembl.1
Natural variantiVAR_018743261Q → R6 PublicationsCorresponds to variant dbSNP:rs1126667Ensembl.1
Natural variantiVAR_004279298A → T. 1
Natural variantiVAR_018744322N → S3 PublicationsCorresponds to variant dbSNP:rs434473Ensembl.1
Natural variantiVAR_018745430R → H1 PublicationCorresponds to variant dbSNP:rs11571342Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M62982 mRNA Translation: AAA51533.1
M35418 mRNA Translation: AAA60056.1
M58704 mRNA Translation: AAA59523.1
AY527817 Genomic DNA Translation: AAS00094.1
AC040977 Genomic DNA No translation available.
BC069557 mRNA Translation: AAH69557.1
D12638 Genomic DNA Translation: BAA02162.1
M87004 Genomic DNA Translation: AAA51587.1
S68587 mRNA Translation: AAD14020.1
AF143883 mRNA Translation: AAD32700.1
CCDSiCCDS11084.1
PIRiA38283
RefSeqiNP_000688.2, NM_000697.2
UniGeneiHs.654431

Genome annotation databases

EnsembliENST00000251535; ENSP00000251535; ENSG00000108839
GeneIDi239
KEGGihsa:239
UCSCiuc002gdx.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLOX12_HUMAN
AccessioniPrimary (citable) accession number: P18054
Secondary accession number(s): O95569, Q6ISF8, Q9UQM4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: February 6, 2007
Last modified: June 20, 2018
This is version 195 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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