UniProt: P42357 (HUTH_HUMAN); gene HAL (syn. HIS); HGNC:4806; GeneID 3034;
chromosome 12q. 657 aa. EC 4.3.1.3. Evidence at protein level (PE 1).
Molecular function. Histidine ammonia-lyase (histidase): catalyzes the
non-oxidative deamination of L-histidine to trans-urocanate + ammonia.
[file:human/HAL/HAL-uniprot.txt "RecName: Full=Histidine ammonia-lyase;"]
[file:human/HAL/HAL-uniprot.txt "Reaction=L-histidine = trans-urocanate + NH4(+); Xref=Rhea:RHEA:21232,"]
Core MF term = GO:0004397 histidine ammonia-lyase activity (label verified
current in local go.db; MF branch confirmed via entailed ancestors).
Catalytic mechanism. Uses an autocatalytically formed MIO
(4-methylideneimidazol-5-one) prosthetic group, made by cyclization/dehydration
of an internal Ala-Ser-Gly tripeptide (crosslink FT 253..255; MOD_RES 254
2,3-didehydroalanine).
[file:human/HAL/HAL-uniprot.txt "Contains an active site 4-methylidene-imidazol-5-one (MIO), which"]
Pathway / BP. First step (step 1/3) of L-histidine degradation to
L-glutamate.
[file:human/HAL/HAL-uniprot.txt "glutamate; N-formimidoyl-L-glutamate from L-histidine: step 1/3."]
Core BP term = GO:0006548 L-histidine catabolic process (current; BP branch
confirmed). Note: UniProt DR lines also carry GO:0019556 / GO:0019557
("...to glutamate and formamide/formate"), but both are now obsolete in
go.db and are NOT in the GOA-seeded existing_annotations, so not used.
Location. Soluble cytosolic enzyme (homotetramer). Reactome localizes to
cytosol. Core CC = GO:0005829 cytosol (CC branch confirmed); the InterPro
IEA "cytoplasm" (GO:0005737) is the less-specific parent.
[Reactome:R-HSA-70899 "Cytosolic histidine ammonia lyase (HAL) catalyzes the reaction of histidine to form urocanate and NH4+"]
Expression. Group-enriched in liver and skin.
[file:human/HAL/HAL-uniprot.txt "Group enriched (liver, skin)"] Epidermal
urocanate (the product) is a major UV chromophore of the stratum corneum
(background biology, not separately quoted).
Family. PAL/histidase (aromatic amino acid ammonia-lyase) family; shares
the MIO mechanism with phenylalanine ammonia-lyase.
[file:human/HAL/HAL-uniprot.txt "Belongs to the PAL/histidase family."]
Disease. Histidinemia (HISTID; MIM 235800), autosomal recessive, caused by
HAL loss of function; elevated histidine, decreased urocanate.
[file:human/HAL/HAL-uniprot.txt "Histidinemia (HISTID) [MIM:235800]: Autosomal recessive"]
PMID:15806399
Four disease missense mutations (R322P, P259L, R206T, R208L) in the human HAL
gene were the first coding-region mutations reported.
PMID:15806399
Actions (13 existing annotations):
- ACCEPT (7): GO:0004397 IBA, GO:0004397 IEA, GO:0004397 EXP (core MF);
GO:0006548 IBA, GO:0006548 IEA, GO:0006548 TAS (core BP); GO:0005829 cytosol TAS
(core CC).
- MARK_AS_OVER_ANNOTATED (5): GO:0003824 catalytic activity IEA (root),
GO:0016841 ammonia-lyase activity IEA (parent of specific MF), GO:0005515
protein binding IPI x2 (RPS19BP1/Q86WX3 high-throughput), GO:0031670 cellular
response to nutrient IEA (ortholog-transferred, vague/non-core).
- MODIFY (1): GO:0005737 cytoplasm IEA -> GO:0005829 cytosol (more specific;
matches Reactome CC).
Note per curation policy: the two GO:0005515 "protein binding" IPI annotations
are experimental (IPI) — marked OVER_ANNOTATED, not REMOVED. The single interactor
in both screens is RPS19BP1 (Q86WX3), matching the UniProt INTERACTION line
(NbExp=2). No established biological role for a HAL-RPS19BP1 interaction.