Seroatlas · Human Serome Atlas

ALOXE3

Hydroperoxide isomerase ALOXE3

Also known as: E-LOX, eLOX3, LOXE3_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9BYJ1
Gene: ALOXE3
Ensembl: ENSG00000179148
Chromosome: 17
Canonical length: 711 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location: Plasma membrane,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

711 residues, UniProt reviewed canonical sequence.

>Q9BYJ1|ALOXE3
     1  MAVYRLCVTT GPYLRAGTLD NISVTLVGTC GESPKQRLDR MGRDFAPGSV QKYKVRCTAE
    61  LGELLLLRVH KERYAFFRKD SWYCSRICVT EPDGSVSHFP CYQWIEGYCT VELRPGTART
   121  ICQDSLPLLL DHRTRELRAR QECYRWKIYA PGFPCMVDVN SFQEMESDKK FALTKTTTCV
   181  DQGDSSGNRY LPGFPMKIDI PSLMYMEPNV RYSATKTISL LFNAIPASLG MKLRGLLDRK
   241  GSWKKLDDMQ NIFWCHKTFT TKYVTEHWCE DHFFGYQYLN GVNPVMLHCI SSLPSKLPVT
   301  NDMVAPLLGQ DTCLQTELER GNIFLADYWI LAEAPTHCLN GRQQYVAAPL CLLWLSPQGA
   361  LVPLAIQLSQ TPGPDSPIFL PTDSEWDWLL AKTWVRNSEF LVHENNTHFL CTHLLCEAFA
   421  MATLRQLPLC HPIYKLLLPH TRYTLQVNTI ARATLLNPEG LVDQVTSIGR QGLIYLMSTG
   481  LAHFTYTNFC LPDSLRARGV LAIPNYHYRD DGLKIWAAIE SFVSEIVGYY YPSDASVQQD
   541  SELQAWTGEI FAQAFLGRES SGFPSRLCTP GEMVKFLTAI IFNCSAQHAA VNSGQHDFGA
   601  WMPNAPSSMR QPPPQTKGTT TLKTYLDTLP EVNISCNNLL LFWLVSQEPK DQRPLGTYPD
   661  EHFTEEAPRR SIAAFQSRLA QISRDIQERN QGLALPYTYL DPPLIENSVS I

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ALOXE3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.21
Highest tissue expression: 54 nTPM

Expression across tissuesHPA

Tissue

skin: 54 nTPM
cerebellum: 2.3 nTPM
vagina: 1.7 nTPM
breast: 1.5 nTPM
cervix: 1.1 nTPM
tonsil: 1.1 nTPM

Single-cell type

oocytes: 65 nCPM
pdcs: 13 nCPM
suprabasal keratinocytes: 6.6 nCPM
endometrial glandular cells: 6.3 nCPM
pancreatic duct cells: 5.6 nCPM
esophageal suprabasal cells: 5.3 nCPM

Immune cell

naive CD4 T-cell: 0.5 nTPM
gdT-cell: 0.2 nTPM
basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
intermediate monocyte: 0 nTPM

Brain region

cerebral cortex: 4.7 nTPM
cerebellum: 4.5 nTPM
thalamus: 2.9 nTPM
pons: 2.6 nTPM
midbrain: 2.3 nTPM
white matter: 2 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ALOXE3.

Disease | AllUniProt

Conditions ALOXE3 is implicated in, by any mechanism.

Ichthyosis, congenital, autosomal recessive 3 (ARCI3) MIM:606545

Disease | GeneticClinVar

68 pathogenic / likely-pathogenic of 366 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Autosomal recessive congenital ichthyosis 3
Lamellar ichthyosis
Autosomal recessive congenital ichthyosis 2
ALOXE3-related disorder
Ichthyosis

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 1.06
gnomAD pLI: 0
gnomAD missense Z: 0.15
DepMap mean gene effect: -0.08
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

hydroperoxy icosatetraenoate dehydratase activity
hydroperoxy icosatetraenoate isomerase activity
iron ion binding
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
intramolecular hydroxytransferase activity

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ALOXE3 as an antibody target. Whether an autoantibody or antibody against ALOXE3 could matter depends on whether native ALOXE3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ALOXE3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label ALOXE3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Loading the interactive Seroatlas protein explorer...