Gene/Proteome Database (LMPD)
LMPD ID
LMP000947
Gene ID
Species
Homo sapiens (Human)
Gene Name
arachidonate lipoxygenase 3
Gene Symbol
Synonyms
ARCI3; E-LOX; eLOX-3; eLOX3
Alternate Names
hydroperoxide isomerase ALOXE3; e-LOX-3; epidermal LOX-3; epidermal lipoxygenase; epidermis-type lipoxygenase 3; hydroperoxy icosatetraenoate dehydratase
Chromosome
17
Map Location
17p13.1
EC Number
5.4.4.7
Summary
This gene is a member of the lipoxygenase family, which are catabolized by arachidonic acid-derived compounds. The encoded enzyme is a hydroperoxide isomerase that synthesizes a unique type of epoxy alcohol (8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid) from 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). This epoxy alcohol can activate the the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha), which is implicated in epidermal differentiation. Loss of function of the enzyme encoded by this gene results in ichthyosis, implicating the function of this gene in the differentiation of human skin. This gene is part of a cluster of lipoxygenase genes on 17p13.1. Mutations in this gene result in nonbullous congenital ichthyosiform erythroderma (NCIE). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
Orthologs
Proteins
| hydroperoxide isomerase ALOXE3 isoform 1 precursor | |
|---|---|
| Refseq ID | NP_001159432 |
| Protein GI | 260166612 |
| UniProt ID | Q9BYJ1 |
| mRNA ID | NM_001165960 |
| Length | 843 |
| RefSeq Status | REVIEWED |
| MPRGAFRPCLPALYFAFLTCPTPEQRMSGTQAPDIHLGEPARGTGCVRGKQTSIRVQDCGRREEARAASRELRREKAQEHPRESWAHPQPYPAPQPLALRPETQPCPACRSSPPGRLLLRPALPGHPFLLPIMAVYRLCVTTGPYLRAGTLDNISVTLVGTCGESPKQRLDRMGRDFAPGSVQKYKVRCTAELGELLLLRVHKERYAFFRKDSWYCSRICVTEPDGSVSHFPCYQWIEGYCTVELRPGTARTICQDSLPLLLDHRTRELRARQECYRWKIYAPGFPCMVDVNSFQEMESDKKFALTKTTTCVDQGDSSGNRYLPGFPMKIDIPSLMYMEPNVRYSATKTISLLFNAIPASLGMKLRGLLDRKGSWKKLDDMQNIFWCHKTFTTKYVTEHWCEDHFFGYQYLNGVNPVMLHCISSLPSKLPVTNDMVAPLLGQDTCLQTELERGNIFLADYWILAEAPTHCLNGRQQYVAAPLCLLWLSPQGALVPLAIQLSQTPGPDSPIFLPTDSEWDWLLAKTWVRNSEFLVHENNTHFLCTHLLCEAFAMATLRQLPLCHPIYKLLLPHTRYTLQVNTIARATLLNPEGLVDQVTSIGRQGLIYLMSTGLAHFTYTNFCLPDSLRARGVLAIPNYHYRDDGLKIWAAIESFVSEIVGYYYPSDASVQQDSELQAWTGEIFAQAFLGRESSGFPSRLCTPGEMVKFLTAIIFNCSAQHAAVNSGQHDFGAWMPNAPSSMRQPPPQTKGTTTLKTYLDTLPEVNISCNNLLLFWLVSQEPKDQRPLGTYPDEHFTEEAPRRSIAAFQSRLAQISRDIQERNQGLALPYTYLDPPLIENSVSI | |
| hydroperoxide isomerase ALOXE3 isoform 2 | |
|---|---|
| Refseq ID | NP_067641 |
| Protein GI | 182765464 |
| UniProt ID | Q9BYJ1 |
| mRNA ID | NM_021628 |
| Length | 711 |
| RefSeq Status | REVIEWED |
| MAVYRLCVTTGPYLRAGTLDNISVTLVGTCGESPKQRLDRMGRDFAPGSVQKYKVRCTAELGELLLLRVHKERYAFFRKDSWYCSRICVTEPDGSVSHFPCYQWIEGYCTVELRPGTARTICQDSLPLLLDHRTRELRARQECYRWKIYAPGFPCMVDVNSFQEMESDKKFALTKTTTCVDQGDSSGNRYLPGFPMKIDIPSLMYMEPNVRYSATKTISLLFNAIPASLGMKLRGLLDRKGSWKKLDDMQNIFWCHKTFTTKYVTEHWCEDHFFGYQYLNGVNPVMLHCISSLPSKLPVTNDMVAPLLGQDTCLQTELERGNIFLADYWILAEAPTHCLNGRQQYVAAPLCLLWLSPQGALVPLAIQLSQTPGPDSPIFLPTDSEWDWLLAKTWVRNSEFLVHENNTHFLCTHLLCEAFAMATLRQLPLCHPIYKLLLPHTRYTLQVNTIARATLLNPEGLVDQVTSIGRQGLIYLMSTGLAHFTYTNFCLPDSLRARGVLAIPNYHYRDDGLKIWAAIESFVSEIVGYYYPSDASVQQDSELQAWTGEIFAQAFLGRESSGFPSRLCTPGEMVKFLTAIIFNCSAQHAAVNSGQHDFGAWMPNAPSSMRQPPPQTKGTTTLKTYLDTLPEVNISCNNLLLFWLVSQEPKDQRPLGTYPDEHFTEEAPRRSIAAFQSRLAQISRDIQERNQGLALPYTYLDPPLIENSVSI | |
| sig_peptide: 1..3 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 403 peptide sequence: MPR | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005737 | IEA:UniProtKB-KW | C | cytoplasm |
| GO:0051120 | IDA:UniProtKB | F | hepoxilin A3 synthase activity |
| GO:0005506 | IEA:InterPro | F | iron ion binding |
| GO:0016829 | IEA:UniProtKB-KW | F | lyase activity |
| GO:0016702 | IDA:UniProtKB | F | oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen |
| GO:0019369 | IDA:UniProtKB | P | arachidonic acid metabolic process |
| GO:0046513 | ISS:UniProtKB | P | ceramide biosynthetic process |
| GO:0061436 | ISS:UniProtKB | P | establishment of skin barrier |
| GO:0045444 | ISS:UniProtKB | P | fat cell differentiation |
| GO:0051122 | IDA:UniProtKB | P | hepoxilin biosynthetic process |
| GO:0043651 | IDA:UniProtKB | P | linoleic acid metabolic process |
| GO:0019372 | IDA:UniProtKB | P | lipoxygenase pathway |
| GO:0035357 | ISS:UniProtKB | P | peroxisome proliferator activated receptor signaling pathway |
| GO:0019233 | ISS:UniProtKB | P | sensory perception of pain |
| GO:0006665 | IDA:UniProtKB | P | sphingolipid metabolic process |
Domain Information
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9BYJ1-1; Sequence=Displayed; Name=2; IsoId=Q9BYJ1-2; Sequence=VSP_043287; Note=No experimental confirmation available.; |
| Biophysicochemical Properties | Kinetic parameters: KM=46 uM for (12R)-HPETE {ECO |
| Catalytic Activity | A hydroperoxy icosatetraenoate = a hydroxy epoxy icosatrienoate. |
| Catalytic Activity | A hydroperoxy icosatetraenoate = an oxoicosatetraenoate + H(2)O. |
| Cofactor | Name=Fe cation; Xref=ChEBI |
| Disease | Ichthyosis, congenital, autosomal recessive 3 (ARCI3) [MIM |
| Function | Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced dioxygenase activity compared to other lipoxygenases. The hydroperoxide isomerase activity catalyzes the isomerization of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into hepoxilin-type epoxyalcohols. The dioxygenase activity requires a step of activation of the enzyme by molecular oxygen. In presence of oxygen, oxygenates polyunsaturated fatty acids, including arachidonic acid, to produce fatty acid hydroperoxides. In the skin, acts downstream of ALOX12B on the linoleate 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. In parallel, it may have a signaling function in barrier formation through the production of hepoxilins metabolites. Plays also a role in adipocyte differentiation through hepoxilin A3 and hepoxilin B3 production which in turn activate PPARG. Through the production of hepoxilins in the spinal cord, it may regulate inflammatory tactile allodynia. {ECO |
| Interaction | O75342:ALOX12B; NbExp=2; IntAct=EBI-6925949, EBI-6925925; |
| Pathway | Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis. |
| Pathway | Lipid metabolism; sphingolipid metabolism. |
| Similarity | Belongs to the lipoxygenase family. |
| Similarity | Contains 1 PLAT domain. {ECO |
| Similarity | Contains 1 lipoxygenase domain. {ECO |
| Subcellular Location | Cytoplasm {ECO |
| Tissue Specificity | Predominantly expressed in skin. |
| Web Resource | Name=Protein Spotlight; Note=about water - Issue 153 of September 2013; URL="http://web.expasy.org/spotlight/back_issues/153/"; |
Identical and Related Proteins
Unique RefSeq proteins for LMP000947 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 260166612 | RefSeq | NP_001159432 | 843 | hydroperoxide isomerase ALOXE3 isoform 1 precursor |
| 182765464 | RefSeq | NP_067641 | 711 | hydroperoxide isomerase ALOXE3 isoform 2 |
Identical Sequences to LMP000947 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:182765464 | DBBJ | BAG36428.1 | 711 | unnamed protein product [Homo sapiens] |
| GI:260166612 | DBBJ | BAH12346.1 | 843 | unnamed protein product [Homo sapiens] |
| GI:182765464 | GenBank | AAI01939.1 | 711 | Arachidonate lipoxygenase 3 [Homo sapiens] |
| GI:182765464 | GenBank | AAI01940.1 | 711 | Arachidonate lipoxygenase 3 [Homo sapiens] |
| GI:182765464 | GenBank | AAI04725.1 | 711 | Arachidonate lipoxygenase 3 [Homo sapiens] |
| GI:182765464 | GenBank | ABL58827.1 | 711 | Sequence 2 from patent US 7144730 |
| GI:260166612 | GenBank | EAW90094.1 | 843 | arachidonate lipoxygenase 3, isoform CRA_b [Homo sapiens] |
| GI:182765464 | GenBank | AIC52066.1 | 711 | ALOXE3, partial [synthetic construct] |
Related Sequences to LMP000947 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:182765464 | DBBJ | BAH12346.1 | 843 | unnamed protein product [Homo sapiens] |
| GI:182765464 | GenBank | AAQ42236.1 | 867 | Sequence 24 from patent US 6582957 |
| GI:182765464 | GenBank | ABL58838.1 | 867 | Sequence 24 from patent US 7144730 |
| GI:260166612 | GenBank | ABL58838.1 | 867 | Sequence 24 from patent US 7144730 |
| GI:182765464 | GenBank | EAW90093.1 | 867 | arachidonate lipoxygenase 3, isoform CRA_a [Homo sapiens] |
| GI:182765464 | GenBank | EAW90094.1 | 843 | arachidonate lipoxygenase 3, isoform CRA_b [Homo sapiens] |
| GI:260166612 | RefSeq | XP_002808161.1 | 843 | PREDICTED: LOW QUALITY PROTEIN: epidermis-type lipoxygenase 3-like [Macaca mulatta] |
| GI:260166612 | RefSeq | XP_003818100.1 | 879 | PREDICTED: hydroperoxide isomerase ALOXE3 isoform X1 [Pan paniscus] |
| GI:260166612 | RefSeq | XP_004058585.1 | 879 | PREDICTED: epidermis-type lipoxygenase 3 isoform 1 [Gorilla gorilla gorilla] |
| GI:260166612 | RefSeq | XP_005256802.1 | 867 | PREDICTED: hydroperoxide isomerase ALOXE3 isoform X1 [Homo sapiens] |
| GI:182765464 | RefSeq | XP_005256802.1 | 867 | PREDICTED: hydroperoxide isomerase ALOXE3 isoform X1 [Homo sapiens] |
| GI:260166612 | RefSeq | XP_005582878.1 | 843 | PREDICTED: LOW QUALITY PROTEIN: epidermis-type lipoxygenase 3 [Macaca fascicularis] |