Alox12b

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.4 Publications

Miscellaneous

Mummy, a recessive ethylnitrosurea-induced mutant has a nonsense mutation in the catalytic domain of Lox12b, resulting in truncation of the protein by 68 amino acids. The affected mice are born with red, shiny skin that dessicates and appears scaly. They probably die of dehydration like mice with targeted disruption of the gene (PubMed:17429434).1 Publication

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.
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.
View all proteins of this organism that are known to be involved in the pathway sphingolipid metabolism and in Lipid metabolism.

Sites

Feature key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	398	Iron; catalyticPROSITE-ProRule annotation	1
Metal bindingⁱ	403	Iron; catalyticPROSITE-ProRule annotation	1
Metal bindingⁱ	578	Iron; catalyticPROSITE-ProRule annotation	1
Metal bindingⁱ	582	Iron; catalyticPROSITE-ProRule annotation	1
Metal bindingⁱ	701	Iron; via carboxylate; catalyticPROSITE-ProRule annotation	1

GO - Molecular functionⁱ

arachidonate 12-lipoxygenase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 16129665
catalytic activity
Source: MGI
Inferred from direct assayⁱ
- 10366447
iron ion binding Source: InterPro
linoleate 9S-lipoxygenase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 16129665
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: MGI

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

arachidonic acid metabolic process
Source: UniProtKB
Inferred from direct assayⁱ
- 16129665
ceramide biosynthetic process
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 17403930
establishment of skin barrier
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 17403930
- 21558561
hepoxilin biosynthetic process Source: UniProtKB
linoleic acid metabolic process
Source: UniProtKB
Inferred from direct assayⁱ
- 16129665
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
Inferred from mutant phenotypeⁱ
- 21558561
sphingolipid metabolic process Source: UniProtKB

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Dioxygenase, Oxidoreductase
Biological process	Fatty acid metabolism, Lipid metabolism
Ligand	Iron, Metal-binding

Enzyme and pathway databases

BRENDAⁱ	1.13.11.31 3474
Reactomeⁱ	R-MMU-2142712 Synthesis of 12-eicosatetraenoic acid derivatives
UniPathwayⁱ	UPA00222 UPA00881

Chemistry databases

SwissLipidsⁱ	SLP:000000658 SLP:000000942

SwissLipidsⁱ

SLP:000000658
SLP:000000942

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 Epidermis-type lipoxygenase 2 Short name: e-LOX 2
Gene namesⁱ	Name:Alox12b Synonyms:Aloxe2
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 11

Organism-specific databases

MGIⁱ	MGI:1274782 Alox12b

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Disruption phenotypeⁱ

Mice die within 3 to 5 hours after birth due to defective skin barrier function loosing around 30% of body weight within 3 hours. Dehydration through the skin is increased 8 folds. The outside-in barrier acquisition is also affected, the skin remaining permeable at E18.5 while it is impermeable in wild-type mice. The stratum corneum is more tightly packed while other layers are unaffected. Processing of filaggrin/FG is aberrant and the skin displays structural abnormalities. The cornified envelope is more fragile and the ceramide composition of the epidermis is altered.2 Publications

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	390	F → A: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. 1 Publication	1
Mutagenesisⁱ	390	F → W: Loss of enzymatic activity. 1 Publication	1
Mutagenesisⁱ	441	G → A: Reduced enzymatic activity and changed stereoselectivity of the oxygenation reaction. 1 Publication	1
Mutagenesisⁱ	441	G → V: Loss of enzymatic activity. 1 Publication	1
Mutagenesisⁱ	455	A → I or W: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. 1 Publication	1
Mutagenesisⁱ	631	V → A or G: Increased enzymatic activity and changed stereoselectivity of the oxygenation reaction to produce (11R)-HPETE preferentially instead of (12R)-HPETE. 1 Publication	1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000220690	1 – 701	Arachidonate 12-lipoxygenase, 12R-typeAdd BLAST		701

Proteomic databases

PaxDbⁱ	O70582
PRIDEⁱ	O70582

PTM databases

PhosphoSitePlusⁱ	O70582

PhosphoSitePlusⁱ

O70582

Expressionⁱ

Tissue specificityⁱ

Expressed in skin epidermis and other stratified epithelia including tongue and forestomach. Low levels of expression are found in trachea, brain and lung. Not expressed in intestine, liver, kidney, adipose tissue, muscle or hematopoietic cells.1 Publication

Developmental stageⁱ

In the embryo, expression begins at day 15.5.1 Publication

Gene expression databases

Bgeeⁱ	ENSMUSG00000032807 Expressed in 42 organ(s), highest expression level in esophagus
CleanExⁱ	MM_ALOX12B
ExpressionAtlasⁱ	O70582 baseline and differential
Genevisibleⁱ	O70582 MM

Interactionⁱ

Protein-protein interaction databases

STRINGⁱ	10090.ENSMUSP00000035250

STRINGⁱ

10090.ENSMUSP00000035250

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	O70582
SMRⁱ	O70582
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	2 – 119	PLATPROSITE-ProRule annotationAdd BLAST		118
Domainⁱ	120 – 701	LipoxygenasePROSITE-ProRule annotationAdd BLAST		582

Sequence similaritiesⁱ

Belongs to the lipoxygenase family.Curated

Phylogenomic databases

eggNOGⁱ	ENOG410IF0U Eukaryota ENOG410YN4N LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00550000074415
HOGENOMⁱ	HOG000234358
HOVERGENⁱ	HBG005150
InParanoidⁱ	O70582
KEGG Orthology (KO) More...KOⁱ	K08021
OMAⁱ	TQGESHK
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G04A4
PhylomeDBⁱ	O70582
TreeFamⁱ	TF105320

Family and domain databases

InterProⁱ	View 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
PANTHERⁱ	PTHR11771 PTHR11771, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00305 Lipoxygenase, 1 hit PF01477 PLAT, 1 hit
PRINTSⁱ	PR00087 LIPOXYGENASE PR00467 MAMLPOXGNASE
SMARTⁱ	View protein in SMART SM00308 LH2, 1 hit
SUPFAMⁱ	SSF48484 SSF48484, 1 hit SSF49723 SSF49723, 1 hit
PROSITEⁱ	View 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.

O70582-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MATYKVKVAT GTDFFSGTLD SISLTIVGTQ GESHKQRLNH FGRDFATGAV 
        60         70         80         90        100
DDYTVQCQQD LGELIIIRLH KEPHSFLAKD PWYCNYVQIC APDCRVYHFP 
       110        120        130        140        150
AYQWMDGYET LALREATGKI TADDTLPILL EHRQEEIRAK KDFYHWRVFV 
       160        170        180        190        200
PGLPNYVDIP SYHPPPRRCR NPNRPEWDGY IPGFPILINI KATRFLNSNL 
       210        220        230        240        250
RFSFVKTASF FYRLGPMALA FKLRGLVDRK RSWKRLKDIK NIFPATKSVV 
       260        270        280        290        300
SEYVAEHWTE DSFFGYQYLN GINPGLIRRC TQIPDKFPVT DEMVAPFLGE 
       310        320        330        340        350
GTCLQAELER GNIYLADYRI LDGIPTVELN GQQQHHCAPM CLLHFGPDGN 
       360        370        380        390        400
MMPIAIQLSQ TPGPDCPIFL PNDSEWDWLL AKTWVRYAEF YSHEAVAHLL 
       410        420        430        440        450
ESHLIGEAFC LALLRNLPMC HPLYKLLIPH TRYNVQINSI GRALLLNKGG 
       460        470        480        490        500
LSARAMSLGL EGFAQVMVRG LSELTYKSLC IPNDFVERGV QDLPGYYFRD 
       510        520        530        540        550
DSLAVWYAME RYVTEIITYY YPNDAAVEGD PELQCWVQEI FKECLLGRES 
       560        570        580        590        600
SGFPTCLRTI PELIEYVTMV MYTCSARHAA VNSGQLEYTS WMPNFPSSMR 
       610        620        630        640        650
NPPMQTKGLT TLQTYMDTLP DVKTTCIVLL VLWTLCREPD DRRPLGHFPD 
       660        670        680        690        700
IHFVEEGPRR SIEAFRQNLN QISHNIRQRN KCLTLPYYYL DPVLIENSIS 

I

Length:701

Mass (Da):80,578

Last modified:August 1, 1998 - v1

Checksum:ⁱFAE3A3B8D2AA142E

GO

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱ	9	A → V in strain: C57BL/6 X SJL.	1
Natural variantⁱ	351	M → V in strain: C57BL/6 X SJL.	1
Natural variantⁱ	361	T → I in strain: C57BL/6 X SJL.	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	Y14334 mRNA Translation: CAA74714.1 AF059251 mRNA Translation: AAC79681.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS24885.1
NCBI Reference Sequences More...RefSeqⁱ	NP_033789.1, NM_009659.2
UniGeneⁱ	Mm.340329

Genome annotation databases

Ensemblⁱ	ENSMUST00000036424; ENSMUSP00000035250; ENSMUSG00000032807
GeneIDⁱ	11686
KEGGⁱ	mmu:11686
UCSC genome browser More...UCSCⁱ	uc007jpk.1 mouse

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
O70582	Arachidonate 12-lipoxygenase, 12R type		MOUSE		701	UniRef100_O70582
Uncharacterized protein		MOUSE		133

Protein	Similar proteins		Species	Score	Length	Source
O70582	Arachidonate 12-lipoxygenase, 12R-type		RAT		701	UniRef90_O70582
Arachidonate 12-lipoxygenase, 12R type		MOUSE		701
arachidonate 12-lipoxygenase, 12R-type		MESAU		701
arachidonate 12-lipoxygenase, 12R-type		DIPOR		701
UPI00042AB679		PERMB		701
+11

Protein	Similar proteins		Species	Score	Length	Source
O70582	Arachidonate 12-lipoxygenase, 12R-type		HUMAN		701	UniRef50_O75342
Arachidonate 12-lipoxygenase, 12R-type		RAT		701
Uncharacterized protein		CALJA		701
Uncharacterized protein		MACNE		701
Uncharacterized protein		RHIRO		701
+120

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	Y14334 mRNA Translation: CAA74714.1 AF059251 mRNA Translation: AAC79681.1
CCDSⁱ	CCDS24885.1
RefSeqⁱ	NP_033789.1, NM_009659.2
UniGeneⁱ	Mm.340329

3D structure databases

ProteinModelPortalⁱ	O70582
SMRⁱ	O70582
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

STRINGⁱ	10090.ENSMUSP00000035250

STRINGⁱ

10090.ENSMUSP00000035250

Chemistry databases

SwissLipidsⁱ	SLP:000000658 SLP:000000942

SwissLipidsⁱ

SLP:000000658
SLP:000000942

PTM databases

PhosphoSitePlusⁱ	O70582

PhosphoSitePlusⁱ

O70582

Proteomic databases

PaxDbⁱ	O70582
PRIDEⁱ	O70582

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000036424; ENSMUSP00000035250; ENSMUSG00000032807
GeneIDⁱ	11686
KEGGⁱ	mmu:11686
UCSCⁱ	uc007jpk.1 mouse

Organism-specific databases

CTDⁱ	242
MGIⁱ	MGI:1274782 Alox12b

Phylogenomic databases

eggNOGⁱ	ENOG410IF0U Eukaryota ENOG410YN4N LUCA
GeneTreeⁱ	ENSGT00550000074415
HOGENOMⁱ	HOG000234358
HOVERGENⁱ	HBG005150
InParanoidⁱ	O70582
KOⁱ	K08021
OMAⁱ	TQGESHK
OrthoDBⁱ	EOG091G04A4
PhylomeDBⁱ	O70582
TreeFamⁱ	TF105320

Enzyme and pathway databases

UniPathwayⁱ	UPA00222 UPA00881
BRENDAⁱ	1.13.11.31 3474
Reactomeⁱ	R-MMU-2142712 Synthesis of 12-eicosatetraenoic acid derivatives

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:O70582
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000032807 Expressed in 42 organ(s), highest expression level in esophagus
CleanExⁱ	MM_ALOX12B
ExpressionAtlasⁱ	O70582 baseline and differential
Genevisibleⁱ	O70582 MM

Family and domain databases

InterProⁱ	View 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
PANTHERⁱ	PTHR11771 PTHR11771, 1 hit
Pfamⁱ	View protein in Pfam PF00305 Lipoxygenase, 1 hit PF01477 PLAT, 1 hit
PRINTSⁱ	PR00087 LIPOXYGENASE PR00467 MAMLPOXGNASE
SMARTⁱ	View protein in SMART SM00308 LH2, 1 hit
SUPFAMⁱ	SSF48484 SSF48484, 1 hit SSF49723 SSF49723, 1 hit
PROSITEⁱ	View protein in PROSITE PS00711 LIPOXYGENASE_1, 1 hit PS00081 LIPOXYGENASE_2, 1 hit PS51393 LIPOXYGENASE_3, 1 hit PS50095 PLAT, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	LX12B_MOUSE
Accessionⁱ	O70582Primary (citable) accession number: O70582
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
	Last sequence update:	August 1, 1998
	Last modified:	November 7, 2018
	This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
PATHWAY comments
Index of metabolic and biosynthesis pathways

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Supporting data

UniProtKB - O70582 (LX12B_MOUSE)

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Arachidonate 12-lipoxygenase, 12R-type

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: hydroperoxy eicosatetraenoic acid biosynthesis

Pathwayi: sphingolipid metabolism

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Chemistry databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Other locations

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

Pathwayⁱ: hydroperoxy eicosatetraenoic acid biosynthesis

Pathwayⁱ: sphingolipid metabolism

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ