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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi398 – 3981Iron; catalyticPROSITE-ProRule annotation
Metal bindingi403 – 4031Iron; catalyticPROSITE-ProRule annotation
Metal bindingi578 – 5781Iron; catalyticPROSITE-ProRule annotation
Metal bindingi582 – 5821Iron; catalyticPROSITE-ProRule annotation
Metal bindingi701 – 7011Iron; via carboxylate; catalyticPROSITE-ProRule annotation

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

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

Chemistry

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti24 – 241L → P in ARCI2. 1 Publication
Corresponds to variant rs201575829 [ dbSNP | Ensembl ].
VAR_069545
Natural varianti67 – 671I → F in ARCI2. 1 Publication
Corresponds to variant rs397514533 [ dbSNP | Ensembl ].
VAR_069546
Natural varianti114 – 1141R → W in ARCI2. 1 Publication
Corresponds to variant rs397514526 [ dbSNP | Ensembl ].
VAR_069547
Natural varianti127 – 1271P → S in ARCI2. 1 Publication
Corresponds to variant rs72842957 [ dbSNP | Ensembl ].
VAR_069548
Natural varianti195 – 1951F → L in ARCI2; complete loss of the enzyme activity. 1 Publication
Corresponds to variant rs200516538 [ dbSNP | Ensembl ].
VAR_069549
Natural varianti318 – 3181Y → C in ARCI2. 1 Publication
VAR_069550
Natural varianti382 – 3821K → E in ARCI2; complete loss of the enzyme activity. 1 Publication
VAR_069551
Natural varianti383 – 3831T → M in ARCI2. 1 Publication
Corresponds to variant rs760428119 [ dbSNP | Ensembl ].
VAR_069552
Natural varianti416 – 4161N → K in ARCI2. 1 Publication
VAR_069553
Natural varianti426 – 4261L → P in ARCI2; complete loss of the enzyme activity. 2 Publications
Corresponds to variant rs137853023 [ dbSNP | Ensembl ].
VAR_015173
Natural varianti462 – 4621G → D in ARCI2. 1 Publication
Corresponds to variant rs774958790 [ dbSNP | Ensembl ].
VAR_069554
Natural varianti488 – 4881R → H in ARCI2; complete loss of the enzyme activity. 1 Publication
Corresponds to variant rs763468558 [ dbSNP | Ensembl ].
VAR_069555
Natural varianti521 – 5211Y → C in ARCI2. 2 Publications
Corresponds to variant rs199766569 [ dbSNP | Ensembl ].
VAR_069556
Natural varianti527 – 5271V → M in ARCI2. 1 Publication
Corresponds to variant rs199545653 [ dbSNP | Ensembl ].
VAR_069557
Natural varianti578 – 5781H → Q in ARCI2; complete loss of the enzyme activity. 2 Publications
Corresponds to variant rs137853024 [ dbSNP | Ensembl ].
VAR_015174
Natural varianti597 – 5971A → E in ARCI2. 1 Publication
Corresponds to variant rs752509098 [ dbSNP | Ensembl ].
VAR_069558
Natural varianti664 – 6641A → P in ARCI2; complete loss of the enzyme activity. 1 Publication
VAR_069559
Natural varianti679 – 6791R → L in ARCI2. 1 Publication
Corresponds to variant rs397514528 [ dbSNP | Ensembl ].
VAR_069560

Keywords - Diseasei

Disease mutation, Ichthyosis

Organism-specific databases

MalaCardsiALOX12B.
MIMi242100. phenotype.
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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 701701Arachidonate 12-lipoxygenase, 12R-typePRO_0000220689Add
BLAST

Proteomic databases

MaxQBiO75342.
PaxDbiO75342.
PeptideAtlasiO75342.
PRIDEiO75342.

PTM databases

iPTMnetiO75342.
PhosphoSiteiO75342.

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 interactions.
IntActiO75342. 3 interactions.
STRINGi9606.ENSP00000315167.

Chemistry

BindingDBiO75342.

Structurei

3D structure databases

ProteinModelPortaliO75342.
SMRiO75342. Positions 2-701.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 119118PLATPROSITE-ProRule annotationAdd
BLAST
Domaini120 – 701582LipoxygenasePROSITE-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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti24 – 241L → P in ARCI2. 1 Publication
Corresponds to variant rs201575829 [ dbSNP | Ensembl ].
VAR_069545
Natural varianti67 – 671I → F in ARCI2. 1 Publication
Corresponds to variant rs397514533 [ dbSNP | Ensembl ].
VAR_069546
Natural varianti94 – 941G → S.
Corresponds to variant rs8077661 [ dbSNP | Ensembl ].
VAR_050000
Natural varianti114 – 1141R → W in ARCI2. 1 Publication
Corresponds to variant rs397514526 [ dbSNP | Ensembl ].
VAR_069547
Natural varianti127 – 1271P → S in ARCI2. 1 Publication
Corresponds to variant rs72842957 [ dbSNP | Ensembl ].
VAR_069548
Natural varianti195 – 1951F → L in ARCI2; complete loss of the enzyme activity. 1 Publication
Corresponds to variant rs200516538 [ dbSNP | Ensembl ].
VAR_069549
Natural varianti318 – 3181Y → C in ARCI2. 1 Publication
VAR_069550
Natural varianti382 – 3821K → E in ARCI2; complete loss of the enzyme activity. 1 Publication
VAR_069551
Natural varianti383 – 3831T → M in ARCI2. 1 Publication
Corresponds to variant rs760428119 [ dbSNP | Ensembl ].
VAR_069552
Natural varianti416 – 4161N → K in ARCI2. 1 Publication
VAR_069553
Natural varianti426 – 4261L → P in ARCI2; complete loss of the enzyme activity. 2 Publications
Corresponds to variant rs137853023 [ dbSNP | Ensembl ].
VAR_015173
Natural varianti462 – 4621G → D in ARCI2. 1 Publication
Corresponds to variant rs774958790 [ dbSNP | Ensembl ].
VAR_069554
Natural varianti488 – 4881R → H in ARCI2; complete loss of the enzyme activity. 1 Publication
Corresponds to variant rs763468558 [ dbSNP | Ensembl ].
VAR_069555
Natural varianti521 – 5211Y → C in ARCI2. 2 Publications
Corresponds to variant rs199766569 [ dbSNP | Ensembl ].
VAR_069556
Natural varianti527 – 5271V → M in ARCI2. 1 Publication
Corresponds to variant rs199545653 [ dbSNP | Ensembl ].
VAR_069557
Natural varianti578 – 5781H → Q in ARCI2; complete loss of the enzyme activity. 2 Publications
Corresponds to variant rs137853024 [ dbSNP | Ensembl ].
VAR_015174
Natural varianti597 – 5971A → E in ARCI2. 1 Publication
Corresponds to variant rs752509098 [ dbSNP | Ensembl ].
VAR_069558
Natural varianti664 – 6641A → P in ARCI2; complete loss of the enzyme activity. 1 Publication
VAR_069559
Natural varianti679 – 6791R → L in ARCI2. 1 Publication
Corresponds to variant rs397514528 [ dbSNP | Ensembl ].
VAR_069560

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. Positions 2-701.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106743. 16 interactions.
IntActiO75342. 3 interactions.
STRINGi9606.ENSP00000315167.

Chemistry

BindingDBiO75342.
SwissLipidsiSLP:000000655.

PTM databases

iPTMnetiO75342.
PhosphoSiteiO75342.

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.
GeneCardsiALOX12B.
GeneReviewsiALOX12B.
HGNCiHGNC:430. ALOX12B.
HPAiHPA024002.
MalaCardsiALOX12B.
MIMi242100. phenotype.
603741. gene.
neXtProtiNX_O75342.
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.
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: September 7, 2016
This is version 149 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.