O75342 · LX12B_HUMAN
- ProteinArachidonate 12-lipoxygenase, 12R-type
- GeneALOX12B
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids701 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the regio and stereo-specific incorporation of a single molecule of dioxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species (PubMed:21558561, PubMed:9618483, PubMed:9837935).
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 (PubMed:21558561).
Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss (PubMed:21558561).
May also play a role in the regulation of the expression of airway mucins (PubMed:22441738).
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 (PubMed:21558561).
Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss (PubMed:21558561).
May also play a role in the regulation of the expression of airway mucins (PubMed:22441738).
Catalytic activity
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12R)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoateThis reaction proceeds in the forward direction.
- N-[omega-(9Z,12Z)-octadecadienoyloxy]acyl-beta-D-glucosyl-(1<->1)-octadecasphing-4E-enine + O2 = N-[omega-(9R)-hydroperoxy-(10E,12Z)-octadecadienoyloxy]acyl-beta-D-glucosyl-(1<->1)-octadecasphing-4E-enineThis reaction proceeds in the forward direction.
- N-[omega-(9Z,12Z)-octadecadienoyloxy]-acylsphin-4-enine + O2 = N-acyl (9R)-hydroperoxy-(10E,12Z)-octadecadienoate octadecasphing-4E-enineThis reaction proceeds in the forward direction.
- (6Z,9Z,12Z)-octadecatrienoate + O2 = 10-hydroperoxy-(6Z,8E,12Z)-octadecatrienoateThis reaction proceeds in the forward direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = 14-hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoateThis reaction proceeds in the forward direction.
- (8Z,11Z,14Z)-eicosatrienoate + O2 = (8Z,10E,14Z)-12-hydroperoxyeicosatrienoateThis reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = (5Z,7Z,8Z,10E,14Z,17Z)-12-hydroperoxyeicosapentaenoateThis reaction proceeds in the forward direction.
- (6Z,9Z,12Z)-octadecatrienoate + O2 = 10R-hydroperoxy-(6Z,8E,12Z)-octadecatrienoateThis reaction proceeds in the forward direction.
- 1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-methyl (5Z,8Z,10E,12R,14Z)-hydroperoxyiecosatetraenoateThis reaction proceeds in the forward direction.
- 1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-methyl-8-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoateThis reaction proceeds in the forward direction.
- 1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-methyl-(8R)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- 1-O-methyl-(9Z,12Z)-octadecadienoate + O2 = 1-O-methyl-(9R)-hydroperoxy-(10E,12Z)-octadecadienoateThis reaction proceeds in the forward direction.
- 1-O-methyl-20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-methyl-8-hydroperoxy-20-hydroxy-(5Z,9E,11Z,14Z)-eicosatetraenoateThis reaction proceeds in the forward direction.
- 1-O-methyl-20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-methyl-12-hydroperoxy-20-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoateThis reaction proceeds in the forward direction.
- 1-O-methyl-20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-methyl-9-hydroperoxy-20-hydroxy-(5Z,7E,11Z,14Z)-eicosatetraenoateThis reaction proceeds in the forward direction.
- 1-O-methyl-(9Z,12Z)-octadecadienoate + O2 = 1-O-methyl-(13S)-hydroperoxy-(9Z,11E)-octadecadienoateThis reaction proceeds in the forward direction.
Cofactor
Note: Binds 1 Fe cation per subunit.
Activity regulation
Increased by calcium.
Pathway
Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.
Lipid metabolism; sphingolipid metabolism.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 398 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 403 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 578 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 582 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: N | ||||||
Binding site | 701 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: I |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameArachidonate 12-lipoxygenase, 12R-type
- EC number
- Short names12R-LOX; 12R-lipoxygenase
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO75342
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Ichthyosis, congenital, autosomal recessive 2 (ARCI2)
- Note
- 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 alsoMIM:242100
Natural variants in ARCI2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_069545 | 24 | L>P | in ARCI2; dbSNP:rs201575829 | |
VAR_069546 | 67 | I>F | in ARCI2; dbSNP:rs397514533 | |
VAR_069547 | 114 | R>W | in ARCI2; dbSNP:rs397514526 | |
VAR_069548 | 127 | P>S | in ARCI2; benign; dbSNP:rs72842957 | |
VAR_069549 | 195 | F>L | in ARCI2; complete loss of the enzyme activity; dbSNP:rs200516538 | |
VAR_069550 | 318 | Y>C | in ARCI2 | |
VAR_069551 | 382 | K>E | in ARCI2; complete loss of the enzyme activity; dbSNP:rs1567981916 | |
VAR_069552 | 383 | T>M | in ARCI2; dbSNP:rs760428119 | |
VAR_069553 | 416 | N>K | in ARCI2; dbSNP:rs1039399607 | |
VAR_015173 | 426 | L>P | in ARCI2; complete loss of the enzyme activity; dbSNP:rs137853023 | |
VAR_069554 | 462 | G>D | in ARCI2; dbSNP:rs774958790 | |
VAR_069555 | 488 | R>H | in ARCI2; complete loss of the enzyme activity; dbSNP:rs763468558 | |
VAR_069556 | 521 | Y>C | in ARCI2; dbSNP:rs199766569 | |
VAR_069557 | 527 | V>M | in ARCI2; dbSNP:rs199545653 | |
VAR_015174 | 578 | H>Q | in ARCI2; complete loss of the enzyme activity; dbSNP:rs137853024 | |
VAR_069558 | 597 | A>E | in ARCI2; dbSNP:rs752509098 | |
VAR_069559 | 664 | A>P | in ARCI2; complete loss of the enzyme activity | |
VAR_069560 | 679 | R>L | in ARCI2; dbSNP:rs397514528 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_069545 | 24 | in ARCI2; dbSNP:rs201575829 | |||
Sequence: L → P | ||||||
Natural variant | VAR_069546 | 67 | in ARCI2; dbSNP:rs397514533 | |||
Sequence: I → F | ||||||
Natural variant | VAR_050000 | 94 | in dbSNP:rs8077661 | |||
Sequence: G → S | ||||||
Natural variant | VAR_069547 | 114 | in ARCI2; dbSNP:rs397514526 | |||
Sequence: R → W | ||||||
Natural variant | VAR_069548 | 127 | in ARCI2; benign; dbSNP:rs72842957 | |||
Sequence: P → S | ||||||
Natural variant | VAR_069549 | 195 | in ARCI2; complete loss of the enzyme activity; dbSNP:rs200516538 | |||
Sequence: F → L | ||||||
Natural variant | VAR_069550 | 318 | in ARCI2 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_069551 | 382 | in ARCI2; complete loss of the enzyme activity; dbSNP:rs1567981916 | |||
Sequence: K → E | ||||||
Natural variant | VAR_069552 | 383 | in ARCI2; dbSNP:rs760428119 | |||
Sequence: T → M | ||||||
Natural variant | VAR_069553 | 416 | in ARCI2; dbSNP:rs1039399607 | |||
Sequence: N → K | ||||||
Natural variant | VAR_015173 | 426 | in ARCI2; complete loss of the enzyme activity; dbSNP:rs137853023 | |||
Sequence: L → P | ||||||
Natural variant | VAR_069554 | 462 | in ARCI2; dbSNP:rs774958790 | |||
Sequence: G → D | ||||||
Natural variant | VAR_069555 | 488 | in ARCI2; complete loss of the enzyme activity; dbSNP:rs763468558 | |||
Sequence: R → H | ||||||
Natural variant | VAR_069556 | 521 | in ARCI2; dbSNP:rs199766569 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_069557 | 527 | in ARCI2; dbSNP:rs199545653 | |||
Sequence: V → M | ||||||
Natural variant | VAR_015174 | 578 | in ARCI2; complete loss of the enzyme activity; dbSNP:rs137853024 | |||
Sequence: H → Q | ||||||
Natural variant | VAR_069558 | 597 | in ARCI2; dbSNP:rs752509098 | |||
Sequence: A → E | ||||||
Natural variant | VAR_069559 | 664 | in ARCI2; complete loss of the enzyme activity | |||
Sequence: A → P | ||||||
Natural variant | VAR_069560 | 679 | in ARCI2; dbSNP:rs397514528 | |||
Sequence: R → L |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 863 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000220689 | 1-701 | Arachidonate 12-lipoxygenase, 12R-type | |||
Sequence: MATYKVRVATGTDLLSGTRDSISLTIVGTQGESHKQLLNHFGRDFATGAVGQYTVQCPQDLGELIIIRLHKERYAFFPKDPWYCNYVQICAPNGRIYHFPAYQWMDGYETLALREATGKTTADDSLPVLLEHRKEEIRAKQDFYHWRVFLPGLPSYVHIPSYRPPVRRHRNPNRPEWNGYIPGFPILINFKATKFLNLNLRYSFLKTASFFVRLGPMALAFKVRGLLDCKHSWKRLKDIRKIFPGKKSVVSEYVAEHWAEDTFFGYQYLNGVNPGLIRRCTRIPDKFPVTDDMVAPFLGEGTCLQAELEKGNIYLADYRIMEGIPTVELSGRKQHHCAPLCLLHFGPEGKMMPIAIQLSQTPGPDCPIFLPSDSEWDWLLAKTWVRYAEFYSHEAIAHLLETHLIAEAFCLALLRNLPMCHPLYKLLIPHTRYTVQINSIGRAVLLNEGGLSAKGMSLGVEGFAGVMVRALSELTYDSLYLPNDFVERGVQDLPGYYYRDDSLAVWNALEKYVTEIITYYYPSDAAVEGDPELQSWVQEIFKECLLGRESSGFPRCLRTVPELIRYVTIVIYTCSAKHAAVNTGQMEFTAWMPNFPASMRNPPIQTKGLTTLETFMDTLPDVKTTCITLLVLWTLSREPDDRRPLGHFPDIHFVEEAPRRSIEAFRQRLNQISHDIRQRNKCLPIPYYYLDPVLIENSISI |
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in B-cells, hair follicles, foreskin keratinocytes and adult skin. Also expressed in psoriatic tissue.
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 2-119 | PLAT | ||||
Sequence: ATYKVRVATGTDLLSGTRDSISLTIVGTQGESHKQLLNHFGRDFATGAVGQYTVQCPQDLGELIIIRLHKERYAFFPKDPWYCNYVQICAPNGRIYHFPAYQWMDGYETLALREATGK | ||||||
Domain | 120-701 | Lipoxygenase | ||||
Sequence: TTADDSLPVLLEHRKEEIRAKQDFYHWRVFLPGLPSYVHIPSYRPPVRRHRNPNRPEWNGYIPGFPILINFKATKFLNLNLRYSFLKTASFFVRLGPMALAFKVRGLLDCKHSWKRLKDIRKIFPGKKSVVSEYVAEHWAEDTFFGYQYLNGVNPGLIRRCTRIPDKFPVTDDMVAPFLGEGTCLQAELEKGNIYLADYRIMEGIPTVELSGRKQHHCAPLCLLHFGPEGKMMPIAIQLSQTPGPDCPIFLPSDSEWDWLLAKTWVRYAEFYSHEAIAHLLETHLIAEAFCLALLRNLPMCHPLYKLLIPHTRYTVQINSIGRAVLLNEGGLSAKGMSLGVEGFAGVMVRALSELTYDSLYLPNDFVERGVQDLPGYYYRDDSLAVWNALEKYVTEIITYYYPSDAAVEGDPELQSWVQEIFKECLLGRESSGFPRCLRTVPELIRYVTIVIYTCSAKHAAVNTGQMEFTAWMPNFPASMRNPPIQTKGLTTLETFMDTLPDVKTTCITLLVLWTLSREPDDRRPLGHFPDIHFVEEAPRRSIEAFRQRLNQISHDIRQRNKCLPIPYYYLDPVLIENSISI |
Sequence similarities
Belongs to the lipoxygenase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length701
- Mass (Da)80,356
- Last updated1998-11-01 v1
- ChecksumC334075759F8B077
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3B3IRK2 | A0A3B3IRK2_HUMAN | ALOX12B | 389 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF038461 EMBL· GenBank· DDBJ | AAC39770.1 EMBL· GenBank· DDBJ | mRNA | ||
AF059250 EMBL· GenBank· DDBJ | AAC79680.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ305026 EMBL· GenBank· DDBJ | CAC34520.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ305027 EMBL· GenBank· DDBJ | CAC34520.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC041058 EMBL· GenBank· DDBJ | AAH41058.1 EMBL· GenBank· DDBJ | mRNA |