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O75342 (LX12B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

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

Short name=12R-LOX
Short name=12R-lipoxygenase
EC=1.13.11.-
Alternative name(s):
Epidermis-type lipoxygenase 12
Gene names
Name:ALOX12B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length701 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 (12R)-hydroperoxyeicosatetraenoic acid/(12R)-HPETE and minor stereoisomers. In the skin, acts upstream of ALOXE3 on the lineolate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins. Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss. May also play a role in the regulation of the expression of airway mucins. Ref.1 Ref.5 Ref.6

Catalytic activity

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

Cofactor

Binds 1 iron ion per subunit By similarity.

Pathway

Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis. Ref.5

Lipid metabolism; sphingolipid metabolism. Ref.5

Subcellular location

Cytoplasm By similarity.

Tissue specificity

Expressed in B-cells, hair follicles, foreskin keratinocytes and adult skin. Also expressed in psoriatic tissue. Ref.1

Involvement in disease

Ichthyosis, congenital, autosomal recessive 2 (ARCI2) [MIM:242100]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

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
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Ichthyosis
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processarachidonic acid metabolic process

Inferred from mutant phenotype Ref.8. Source: UniProtKB

ceramide biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

establishment of skin barrier

Inferred from sequence or structural similarity. Source: UniProtKB

hepoxilin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

linoleic acid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

lipoxygenase pathway

Inferred from direct assay Ref.5. Source: UniProtKB

oxidation-reduction process

Inferred from direct assay Ref.5. Source: UniProtKB

positive regulation of MAPK cascade

Inferred from direct assay Ref.6. Source: UniProtKB

positive regulation of gene expression

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of mucus secretion

Inferred from mutant phenotype Ref.6. Source: UniProtKB

protein lipidation

Inferred from sequence or structural similarity. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Inferred from direct assay Ref.5. Source: UniProtKB

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functionarachidonate 12-lipoxygenase activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

linoleate 9S-lipoxygenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ALOXE3Q9BYJ12EBI-6925925,EBI-6925949

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 701701Arachidonate 12-lipoxygenase, 12R-type
PRO_0000220689

Regions

Domain2 – 119118PLAT
Domain120 – 701582Lipoxygenase

Sites

Metal binding3981Iron; catalytic By similarity
Metal binding4031Iron; catalytic By similarity
Metal binding5781Iron; catalytic By similarity
Metal binding5821Iron; catalytic By similarity
Metal binding7011Iron; via carboxylate; catalytic By similarity

Natural variations

Natural variant241L → P in ARCI2. Ref.9
VAR_069545
Natural variant671I → F in ARCI2. Ref.11
VAR_069546
Natural variant941G → S.
Corresponds to variant rs8077661 [ dbSNP | Ensembl ].
VAR_050000
Natural variant1141R → W in ARCI2. Ref.9
VAR_069547
Natural variant1271P → S in ARCI2. Ref.9
VAR_069548
Natural variant1951F → L in ARCI2; complete loss of the enzyme activity. Ref.10
VAR_069549
Natural variant3181Y → C in ARCI2. Ref.9
VAR_069550
Natural variant3821K → E in ARCI2; complete loss of the enzyme activity. Ref.10
VAR_069551
Natural variant3831T → M in ARCI2. Ref.9
VAR_069552
Natural variant4161N → K in ARCI2. Ref.9
VAR_069553
Natural variant4261L → P in ARCI2; complete loss of the enzyme activity. Ref.7 Ref.8
VAR_015173
Natural variant4621G → D in ARCI2. Ref.11
VAR_069554
Natural variant4881R → H in ARCI2; complete loss of the enzyme activity. Ref.9
VAR_069555
Natural variant5211Y → C in ARCI2. Ref.9 Ref.11
VAR_069556
Natural variant5271V → M in ARCI2. Ref.11
VAR_069557
Natural variant5781H → Q in ARCI2; complete loss of the enzyme activity. Ref.7 Ref.8
VAR_015174
Natural variant5971A → E in ARCI2. Ref.11
VAR_069558
Natural variant6641A → P in ARCI2; complete loss of the enzyme activity. Ref.9
VAR_069559
Natural variant6791R → L in ARCI2. Ref.9
VAR_069560

Sequences

Sequence LengthMass (Da)Tools
O75342 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: C334075759F8B077

FASTA70180,356
        10         20         30         40         50         60 
MATYKVRVAT GTDLLSGTRD SISLTIVGTQ GESHKQLLNH FGRDFATGAV GQYTVQCPQD 

        70         80         90        100        110        120 
LGELIIIRLH KERYAFFPKD PWYCNYVQIC APNGRIYHFP AYQWMDGYET LALREATGKT 

       130        140        150        160        170        180 
TADDSLPVLL EHRKEEIRAK QDFYHWRVFL PGLPSYVHIP SYRPPVRRHR NPNRPEWNGY 

       190        200        210        220        230        240 
IPGFPILINF KATKFLNLNL RYSFLKTASF FVRLGPMALA FKVRGLLDCK HSWKRLKDIR 

       250        260        270        280        290        300 
KIFPGKKSVV SEYVAEHWAE DTFFGYQYLN GVNPGLIRRC TRIPDKFPVT DDMVAPFLGE 

       310        320        330        340        350        360 
GTCLQAELEK GNIYLADYRI MEGIPTVELS GRKQHHCAPL CLLHFGPEGK MMPIAIQLSQ 

       370        380        390        400        410        420 
TPGPDCPIFL PSDSEWDWLL AKTWVRYAEF YSHEAIAHLL ETHLIAEAFC LALLRNLPMC 

       430        440        450        460        470        480 
HPLYKLLIPH TRYTVQINSI GRAVLLNEGG LSAKGMSLGV EGFAGVMVRA LSELTYDSLY 

       490        500        510        520        530        540 
LPNDFVERGV QDLPGYYYRD DSLAVWNALE KYVTEIITYY YPSDAAVEGD PELQSWVQEI 

       550        560        570        580        590        600 
FKECLLGRES SGFPRCLRTV PELIRYVTIV IYTCSAKHAA VNTGQMEFTA WMPNFPASMR 

       610        620        630        640        650        660 
NPPIQTKGLT TLETFMDTLP DVKTTCITLL VLWTLSREPD DRRPLGHFPD IHFVEEAPRR 

       670        680        690        700 
SIEAFRQRLN QISHDIRQRN KCLPIPYYYL DPVLIENSIS I 

« Hide

References

« Hide 'large scale' references
[1]"A 12R-lipoxygenase in human skin: mechanistic evidence, molecular cloning, and expression."
Boeglin W.E., Kim R.B., Brash A.R.
Proc. Natl. Acad. Sci. U.S.A. 95:6744-6749(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
Tissue: Hair follicle.
[2]"Human 12(R)-lipoxygenase and the mouse ortholog. Molecular cloning, expression, and gene chromosomal assignment."
Sun D., McDonnell M., Chen X.-S., Lakkis M.M., Li H., Isaacs S.N., Elsea S.H., Patel P.I., Funk C.D.
J. Biol. Chem. 273:33540-33547(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
Tissue: B-cell.
[3]"A gene cluster encoding human epidermis-type lipoxygenases at chromosome 17p13.1: cloning, physical mapping, and expression."
Krieg P., Marks F., Fuerstenberger G.
Genomics 73:323-330(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation: a proposed role in releasing omega-hydroxyceramide for construction of the corneocyte lipid envelope."
Zheng Y., Yin H., Boeglin W.E., Elias P.M., Crumrine D., Beier D.R., Brash A.R.
J. Biol. Chem. 286:24046-24056(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY.
[6]"A role for 12R-lipoxygenase in MUC5AC expression by respiratory epithelial cells."
Garcia-Verdugo I., BenMohamed F., Tattermusch S., Leduc D., Charpigny G., Chignard M., Ollero M., Touqui L.
Eur. Respir. J. 40:714-723(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MUCUS PRODUCTION.
[7]"Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1."
Jobard F., Lefevre C., Karaduman A., Blanchet-Bardon C., Emre S., Weissenbach J., Ozguc M., Lathrop M., Prud'homme J.-F., Fischer J.
Hum. Mol. Genet. 11:107-113(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARCI2 PRO-426 AND GLN-578.
[8]"Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3."
Yu Z., Schneider C., Boeglin W.E., Brash A.R.
Biochim. Biophys. Acta 1686:238-247(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS ARCI2 PRO-426 AND GLN-578.
[9]"Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis."
Eckl K.M., Krieg P., Kuester W., Traupe H., Andre F., Wittstruck N., Fuerstenberger G., Hennies H.C.
Hum. Mutat. 26:351-361(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARCI2 PRO-24; TRP-114; SER-127; CYS-318; MET-383; LYS-416; HIS-488; CYS-521; PRO-664 AND LEU-679, CHARACTERIZATION OF VARIANTS ARCI2 HIS-488 AND PRO-664.
[10]"Molecular analysis of 250 patients with autosomal recessive congenital ichthyosis: evidence for mutation hotspots in ALOXE3 and allelic heterogeneity in ALOX12B."
Eckl K.M., de Juanes S., Kurtenbach J., Naetebus M., Lugassy J., Oji V., Traupe H., Preil M.L., Martinez F., Smolle J., Harel A., Krieg P., Sprecher E., Hennies H.C.
J. Invest. Dermatol. 129:1421-1428(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARCI2 LEU-195 AND GLU-382, CHARACTERIZATION OF VARIANTS ARCI2 LEU-195 AND GLU-382.
[11]"Genotypic and clinical spectrum of self-improving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients."
Vahlquist A., Bygum A., Gaanemo A., Virtanen M., Hellstroem-Pigg M., Strauss G., Brandrup F., Fischer J.
J. Invest. Dermatol. 130:438-443(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARCI2 PHE-67; ASP-462; CYS-521; MET-527 AND GLU-597.
+Additional computationally mapped references.

Web resources

GeneReviews
Protein Spotlight

about water - Issue 153 of September 2013

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF038461 mRNA. Translation: AAC39770.1.
AF059250 mRNA. Translation: AAC79680.1.
AJ305026, AJ305027 Genomic DNA. Translation: CAC34520.1.
BC041058 mRNA. Translation: AAH41058.1.
RefSeqNP_001130.1. NM_001139.2.
UniGeneHs.136574.

3D structure databases

ProteinModelPortalO75342.
SMRO75342. Positions 2-701.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO75342. 2 interactions.
STRING9606.ENSP00000315167.

Chemistry

BindingDBO75342.

PTM databases

PhosphoSiteO75342.

Proteomic databases

PaxDbO75342.
PRIDEO75342.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000319144; ENSP00000315167; ENSG00000179477.
GeneID242.
KEGGhsa:242.
UCSCuc002gjy.1. human.

Organism-specific databases

CTD242.
GeneCardsGC17M007975.
HGNCHGNC:430. ALOX12B.
HPAHPA024002.
MIM242100. phenotype.
603741. gene.
neXtProtNX_O75342.
Orphanet79394. Congenital non-bullous ichthyosiform erythroderma.
313. Lamellar ichthyosis.
281122. Self-healing collodion baby.
PharmGKBPA24722.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG69653.
HOGENOMHOG000234358.
HOVERGENHBG005150.
InParanoidO75342.
KOK08021.
OMAYHFPAYQ.
OrthoDBEOG7V49XR.
PhylomeDBO75342.
TreeFamTF105320.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00222.
UPA00881.

Gene expression databases

BgeeO75342.
CleanExHS_ALOX12B.
GenevestigatorO75342.

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

GeneWikiALOX12B.
GenomeRNAi242.
NextBio966.
PROO75342.
SOURCESearch...

Entry information

Entry nameLX12B_HUMAN
AccessionPrimary (citable) accession number: O75342
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM