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Protein

Arachidonate 12-lipoxygenase, 12R-type

Gene

ALOX12B

Organism
Homo sapiens (Human)
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 (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.3 Publications

Catalytic activityi

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

Cofactori

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

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.

Pathwayi: sphingolipid metabolism

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi398Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi403Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi578Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi582Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi701Iron; via carboxylate; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • arachidonic acid metabolic process Source: UniProtKB
  • ceramide biosynthetic process Source: UniProtKB
  • establishment of skin barrier Source: UniProtKB
  • hepoxilin biosynthetic process Source: UniProtKB
  • linoleic acid metabolic process Source: UniProtKB
  • lipoxygenase pathway Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of mucus secretion Source: UniProtKB
  • protein lipidation Source: UniProtKB
  • sphingolipid metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

Fatty acid metabolism, Lipid metabolism

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000179477-MONOMER.
BRENDAi1.13.11.31. 2681.
ReactomeiR-HSA-2142712. Synthesis of 12-eicosatetraenoic acid derivatives.
UniPathwayiUPA00222.
UPA00881.

Chemistry databases

SwissLipidsiSLP:000000655.

Names & Taxonomyi

Protein namesi
Recommended name:
Arachidonate 12-lipoxygenase, 12R-type (EC:1.13.11.-)
Short name:
12R-LOX
Short name:
12R-lipoxygenase
Alternative name(s):
Epidermis-type lipoxygenase 12
Gene namesi
Name:ALOX12B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:430. ALOX12B.

Subcellular locationi

  • Cytoplasm PROSITE-ProRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Ichthyosis, congenital, autosomal recessive 2 (ARCI2)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:242100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06954524L → P in ARCI2. 1 PublicationCorresponds to variant rs201575829dbSNPEnsembl.1
Natural variantiVAR_06954667I → F in ARCI2. 1 PublicationCorresponds to variant rs397514533dbSNPEnsembl.1
Natural variantiVAR_069547114R → W in ARCI2. 1 PublicationCorresponds to variant rs397514526dbSNPEnsembl.1
Natural variantiVAR_069548127P → S in ARCI2. 1 PublicationCorresponds to variant rs72842957dbSNPEnsembl.1
Natural variantiVAR_069549195F → L in ARCI2; complete loss of the enzyme activity. 1 PublicationCorresponds to variant rs200516538dbSNPEnsembl.1
Natural variantiVAR_069550318Y → C in ARCI2. 1 Publication1
Natural variantiVAR_069551382K → E in ARCI2; complete loss of the enzyme activity. 1 Publication1
Natural variantiVAR_069552383T → M in ARCI2. 1 PublicationCorresponds to variant rs760428119dbSNPEnsembl.1
Natural variantiVAR_069553416N → K in ARCI2. 1 Publication1
Natural variantiVAR_015173426L → P in ARCI2; complete loss of the enzyme activity. 2 PublicationsCorresponds to variant rs137853023dbSNPEnsembl.1
Natural variantiVAR_069554462G → D in ARCI2. 1 PublicationCorresponds to variant rs774958790dbSNPEnsembl.1
Natural variantiVAR_069555488R → H in ARCI2; complete loss of the enzyme activity. 1 PublicationCorresponds to variant rs763468558dbSNPEnsembl.1
Natural variantiVAR_069556521Y → C in ARCI2. 2 PublicationsCorresponds to variant rs199766569dbSNPEnsembl.1
Natural variantiVAR_069557527V → M in ARCI2. 1 PublicationCorresponds to variant rs199545653dbSNPEnsembl.1
Natural variantiVAR_015174578H → Q in ARCI2; complete loss of the enzyme activity. 2 PublicationsCorresponds to variant rs137853024dbSNPEnsembl.1
Natural variantiVAR_069558597A → E in ARCI2. 1 PublicationCorresponds to variant rs752509098dbSNPEnsembl.1
Natural variantiVAR_069559664A → P in ARCI2; complete loss of the enzyme activity. 1 Publication1
Natural variantiVAR_069560679R → L in ARCI2. 1 PublicationCorresponds to variant rs397514528dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Ichthyosis

Organism-specific databases

DisGeNETi242.
MalaCardsiALOX12B.
MIMi242100. phenotype.
OpenTargetsiENSG00000179477.
Orphaneti79394. Congenital non-bullous ichthyosiform erythroderma.
313. Lamellar ichthyosis.
281122. Self-healing collodion baby.
PharmGKBiPA24722.

Polymorphism and mutation databases

BioMutaiALOX12B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002206891 – 701Arachidonate 12-lipoxygenase, 12R-typeAdd BLAST701

Proteomic databases

MaxQBiO75342.
PaxDbiO75342.
PeptideAtlasiO75342.
PRIDEiO75342.

PTM databases

iPTMnetiO75342.
PhosphoSitePlusiO75342.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000179477.
CleanExiHS_ALOX12B.
GenevisibleiO75342. HS.

Organism-specific databases

HPAiHPA024002.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ALOXE3Q9BYJ12EBI-6925925,EBI-6925949

Protein-protein interaction databases

BioGridi106743. 16 interactors.
IntActiO75342. 3 interactors.
STRINGi9606.ENSP00000315167.

Chemistry databases

BindingDBiO75342.

Structurei

3D structure databases

ProteinModelPortaliO75342.
SMRiO75342.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 119PLATPROSITE-ProRule annotationAdd BLAST118
Domaini120 – 701LipoxygenasePROSITE-ProRule annotationAdd BLAST582

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.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiO75342.
KOiK08021.
OMAiHWTEDSF.
OrthoDBiEOG091G04A4.
PhylomeDBiO75342.
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.

O75342-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATYKVRVAT GTDLLSGTRD SISLTIVGTQ GESHKQLLNH FGRDFATGAV
60 70 80 90 100
GQYTVQCPQD LGELIIIRLH KERYAFFPKD PWYCNYVQIC APNGRIYHFP
110 120 130 140 150
AYQWMDGYET LALREATGKT TADDSLPVLL EHRKEEIRAK QDFYHWRVFL
160 170 180 190 200
PGLPSYVHIP SYRPPVRRHR NPNRPEWNGY IPGFPILINF KATKFLNLNL
210 220 230 240 250
RYSFLKTASF FVRLGPMALA FKVRGLLDCK HSWKRLKDIR KIFPGKKSVV
260 270 280 290 300
SEYVAEHWAE DTFFGYQYLN GVNPGLIRRC TRIPDKFPVT DDMVAPFLGE
310 320 330 340 350
GTCLQAELEK GNIYLADYRI MEGIPTVELS GRKQHHCAPL CLLHFGPEGK
360 370 380 390 400
MMPIAIQLSQ TPGPDCPIFL PSDSEWDWLL AKTWVRYAEF YSHEAIAHLL
410 420 430 440 450
ETHLIAEAFC LALLRNLPMC HPLYKLLIPH TRYTVQINSI GRAVLLNEGG
460 470 480 490 500
LSAKGMSLGV EGFAGVMVRA LSELTYDSLY LPNDFVERGV QDLPGYYYRD
510 520 530 540 550
DSLAVWNALE KYVTEIITYY YPSDAAVEGD PELQSWVQEI FKECLLGRES
560 570 580 590 600
SGFPRCLRTV PELIRYVTIV IYTCSAKHAA VNTGQMEFTA WMPNFPASMR
610 620 630 640 650
NPPIQTKGLT TLETFMDTLP DVKTTCITLL VLWTLSREPD DRRPLGHFPD
660 670 680 690 700
IHFVEEAPRR SIEAFRQRLN QISHDIRQRN KCLPIPYYYL DPVLIENSIS

I
Length:701
Mass (Da):80,356
Last modified:November 1, 1998 - v1
Checksum:iC334075759F8B077
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06954524L → P in ARCI2. 1 PublicationCorresponds to variant rs201575829dbSNPEnsembl.1
Natural variantiVAR_06954667I → F in ARCI2. 1 PublicationCorresponds to variant rs397514533dbSNPEnsembl.1
Natural variantiVAR_05000094G → S.Corresponds to variant rs8077661dbSNPEnsembl.1
Natural variantiVAR_069547114R → W in ARCI2. 1 PublicationCorresponds to variant rs397514526dbSNPEnsembl.1
Natural variantiVAR_069548127P → S in ARCI2. 1 PublicationCorresponds to variant rs72842957dbSNPEnsembl.1
Natural variantiVAR_069549195F → L in ARCI2; complete loss of the enzyme activity. 1 PublicationCorresponds to variant rs200516538dbSNPEnsembl.1
Natural variantiVAR_069550318Y → C in ARCI2. 1 Publication1
Natural variantiVAR_069551382K → E in ARCI2; complete loss of the enzyme activity. 1 Publication1
Natural variantiVAR_069552383T → M in ARCI2. 1 PublicationCorresponds to variant rs760428119dbSNPEnsembl.1
Natural variantiVAR_069553416N → K in ARCI2. 1 Publication1
Natural variantiVAR_015173426L → P in ARCI2; complete loss of the enzyme activity. 2 PublicationsCorresponds to variant rs137853023dbSNPEnsembl.1
Natural variantiVAR_069554462G → D in ARCI2. 1 PublicationCorresponds to variant rs774958790dbSNPEnsembl.1
Natural variantiVAR_069555488R → H in ARCI2; complete loss of the enzyme activity. 1 PublicationCorresponds to variant rs763468558dbSNPEnsembl.1
Natural variantiVAR_069556521Y → C in ARCI2. 2 PublicationsCorresponds to variant rs199766569dbSNPEnsembl.1
Natural variantiVAR_069557527V → M in ARCI2. 1 PublicationCorresponds to variant rs199545653dbSNPEnsembl.1
Natural variantiVAR_015174578H → Q in ARCI2; complete loss of the enzyme activity. 2 PublicationsCorresponds to variant rs137853024dbSNPEnsembl.1
Natural variantiVAR_069558597A → E in ARCI2. 1 PublicationCorresponds to variant rs752509098dbSNPEnsembl.1
Natural variantiVAR_069559664A → P in ARCI2; complete loss of the enzyme activity. 1 Publication1
Natural variantiVAR_069560679R → L in ARCI2. 1 PublicationCorresponds to variant rs397514528dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF038461 mRNA. Translation: AAC39770.1.
AF059250 mRNA. Translation: AAC79680.1.
AJ305026, AJ305027 Genomic DNA. Translation: CAC34520.1.
BC041058 mRNA. Translation: AAH41058.1.
CCDSiCCDS11129.1.
RefSeqiNP_001130.1. NM_001139.2.
UniGeneiHs.136574.

Genome annotation databases

EnsembliENST00000319144; ENSP00000315167; ENSG00000179477.
GeneIDi242.
KEGGihsa:242.
UCSCiuc002gjy.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Protein Spotlight

about water - Issue 153 of September 2013

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF038461 mRNA. Translation: AAC39770.1.
AF059250 mRNA. Translation: AAC79680.1.
AJ305026, AJ305027 Genomic DNA. Translation: CAC34520.1.
BC041058 mRNA. Translation: AAH41058.1.
CCDSiCCDS11129.1.
RefSeqiNP_001130.1. NM_001139.2.
UniGeneiHs.136574.

3D structure databases

ProteinModelPortaliO75342.
SMRiO75342.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106743. 16 interactors.
IntActiO75342. 3 interactors.
STRINGi9606.ENSP00000315167.

Chemistry databases

BindingDBiO75342.
SwissLipidsiSLP:000000655.

PTM databases

iPTMnetiO75342.
PhosphoSitePlusiO75342.

Polymorphism and mutation databases

BioMutaiALOX12B.

Proteomic databases

MaxQBiO75342.
PaxDbiO75342.
PeptideAtlasiO75342.
PRIDEiO75342.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000319144; ENSP00000315167; ENSG00000179477.
GeneIDi242.
KEGGihsa:242.
UCSCiuc002gjy.1. human.

Organism-specific databases

CTDi242.
DisGeNETi242.
GeneCardsiALOX12B.
GeneReviewsiALOX12B.
HGNCiHGNC:430. ALOX12B.
HPAiHPA024002.
MalaCardsiALOX12B.
MIMi242100. phenotype.
603741. gene.
neXtProtiNX_O75342.
OpenTargetsiENSG00000179477.
Orphaneti79394. Congenital non-bullous ichthyosiform erythroderma.
313. Lamellar ichthyosis.
281122. Self-healing collodion baby.
PharmGKBiPA24722.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF0U. Eukaryota.
ENOG410YN4N. LUCA.
GeneTreeiENSGT00550000074415.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiO75342.
KOiK08021.
OMAiHWTEDSF.
OrthoDBiEOG091G04A4.
PhylomeDBiO75342.
TreeFamiTF105320.

Enzyme and pathway databases

UniPathwayiUPA00222.
UPA00881.
BioCyciZFISH:ENSG00000179477-MONOMER.
BRENDAi1.13.11.31. 2681.
ReactomeiR-HSA-2142712. Synthesis of 12-eicosatetraenoic acid derivatives.

Miscellaneous databases

GeneWikiiALOX12B.
GenomeRNAii242.
PROiO75342.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000179477.
CleanExiHS_ALOX12B.
GenevisibleiO75342. HS.

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...

Entry informationi

Entry nameiLX12B_HUMAN
AccessioniPrimary (citable) accession number: O75342
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 1, 1998
Last modified: November 2, 2016
This is version 151 of the entry and version 1 of the sequence. [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

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. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. 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.