HAAO

Protein identityUniProt · HPA

UniProt accession

P46952

Gene

HAAO

Ensembl

ENSG00000162882

Chromosome

2

Canonical length

286 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

OverviewNCBI Gene

3-Hydroxyanthranilate 3,4-dioxygenase is a monomeric cytosolic protein belonging to the family of intramolecular dioxygenases containing nonheme ferrous iron. It is widely distributed in peripheral organs, such as liver and kidney, and is also present in low amounts in the central nervous system. HAAO catalyzes the synthesis of quinolinic acid (QUIN) from 3-hydroxyanthranilic acid. QUIN is an excitotoxin whose toxicity is mediated by its ability to activate glutamate N-methyl-D-aspartate receptors. Increased cerebral levels of QUIN may participate in the pathogenesis of neurologic and inflammatory disorders. HAAO has been suggested to play a role in disorders associated with altered tissue levels of QUIN. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

286 residues, UniProt reviewed canonical sequence.

>P46952|HAAO
     1  MERRLGVRAW VKENRGSFQP PVCNKLMHQE QLKVMFIGGP NTRKDYHIEE GEEVFYQLEG
    61  DMVLRVLEQG KHRDVVIRQG EIFLLPARVP HSPQRFANTV GLVVERRRLE TELDGLRYYV
   121  GDTMDVLFEK WFYCKDLGTQ LAPIIQEFFS SEQYRTGKPI PDQLLKEPPF PLSTRSIMEP
   181  MSLDAWLDSH HRELQAGTPL SLFGDTYETQ VIAYGQGSSE GLRQNVDVWL WQLEGSSVVT
   241  MGGRRLSLAP DDSLLVLAGT SYAWERTQGS VALSVTQDPA CKKPLG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HAAO 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)

0.25

Highest tissue expression

277 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HAAO.

Disease | AllUniProt

Conditions HAAO is implicated in, by any mechanism.

• Vertebral, cardiac, renal, and limb defects syndrome 1 (VCRL1) MIM:617660

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 82 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Vertebral, cardiac, renal, and limb defects syndrome 1
• Congenital NAD deficiency disorder
• Monogenic hearing loss

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)

1.14

gnomAD pLI

0

gnomAD missense Z

-0.18

DepMap mean gene effect

-0.11

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 'de novo' NAD+ biosynthetic process from L-tryptophan
• anthranilate metabolic process
• L-tryptophan catabolic process
• NAD+ biosynthetic process
• neuron cellular homeostasis
• quinolinate biosynthetic process
• response to cadmium ion
• response to zinc ion
• quinolinate metabolic process

Molecular functions

• electron transfer activity
• ferrous iron binding
• 3-hydroxyanthranilate 3,4-dioxygenase activity

Cellular components

• cytoplasm
• cytosol

Protein domainsUniProt · Pfam · InterPro

• RmlC-like cupin domain superfamily
• RmlC-like jelly roll fold
• 3-hydroxyanthranilic acid dioxygenase
• 3-hydroxyanthranilate 3, 4-dioxygenase, metazoan
• 3-hydroxyanthranilic acid dioxygenase

KeywordsUniProt

• Cytoplasm
• Dioxygenase
• Iron
• Metal-binding
• Oxidoreductase
• Pyridine nucleotide biosynthesis