LTA4H
entrez
4048
canonical
uniprot
P09960
canonical
ensembl
ENSG00000111144
resolver
ensp
ENSP00000228740
resolver
ensp
ENSP00000395051
resolver
ensp
ENSP00000449958
resolver
ensp
ENSP00000631704
resolver
ensp
ENSP00000631706
resolver
ensp
ENSP00000675250
resolver
ensp
ENSP00000675252
resolver
ensp
ENSP00000739314
resolver
genesymbol
LTA4H
resolver
genesymbol_syn
LTA4
resolver
hgnc
HGNC:6710
resolver
uniprot
A0A140VK27
resolver
uniprot
B4DNQ9
resolver
uniprot
F8VV40
resolver
uniprot
Q6IAT6
resolver
uniprot
Q9UCT7
resolver
uniprot_entry
A0A140VK27_HUMAN
resolver
uniprot_entry
LKHA4_HUMAN
resolver
uniprot_sec
B4DNQ9
resolver
uniprot_sec
F8VV40
resolver
uniprot_sec
Q6IAT6
resolver
uniprot_sec
Q9UCT7
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by bestatin (PubMed:11175901). The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379 (PubMed:7667299). 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity (PubMed:24591641). {ECO:0000269|PubMed:11175901, ECO:0000269|PubMed:24591641, ECO:0000269|PubMed:7667299}.
uniprot
proteins
amino_acid_sequence
MPEIVDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRSLVLDTKDLTIEKVVINGQEVKYALGERQSYKGSPMEISLPIALSKNQEIVIEISFETSPKSSALQWLTPEQTSGKEHPYLFSQCQAIHCRAILPCQDTPSVKLTYTAEVSVPKELVALMSAIRDGETPDPEDPSRKIYKFIQKVPIPCYLIALVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETESMLKIAEDLGGPYVWGQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISHSWTGNLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFNALGGWGELQNSVKTFGETHPFTKLVVDLTDIDPDVAYSSVPYEKGFALLFYLEQLLGGPEIFLGFLKAYVEKFSYKSITTDDWKDFLYSYFKDKVDVLNQVDWNAWLYSPGLPPIKPNYDMTLTNACIALSQRWITAKEDDLNSFNATDLKDLSSHQLNEFLAQTLQRAPLPLGHIKRMQEVYNFNAINNSEIRFRWLRLCIQSKWEDAIPLALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKASMHPVTAMLVGKDLKVD
uniprot
proteins
ec_number
3.3.2.6
uniprot
proteins
ec_number
3.4.11.4
uniprot
proteins
function
FUNCTION: Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory mediator leukotriene B4 (LTB4) (PubMed:11917124, PubMed:12207002, PubMed:15078870, PubMed:18804029, PubMed:1897988, PubMed:1975494, PubMed:2244921, PubMed:2996528). Can utilize LTA5 less effectively as a substrate than LTA4, and produce LTB5 (PubMed:2996528). Also has aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (PubMed:18804029, PubMed:20813919). In addition to its pro-inflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL) (PubMed:20813919, PubMed:24591641). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (PubMed:21206090). {ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:1897988, ECO:0000269|PubMed:1975494, ECO:0000269|PubMed:20813919, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:2244921, ECO:0000269|PubMed:24591641, ECO:0000269|PubMed:2996528}.
uniprot
proteins
mass_dalton
69285
uniprot
proteins
mutagenesis
MUTAGEN 135; /note="Q->A,L: Srongly increased epoxide hydrolase activity."; /evidence="ECO:0000269|PubMed:11917124"; MUTAGEN 135; /note="Q->A: Strongly reduced aminopeptidase activity. Strongly decreased affinity for leukotriene. Abolishes epoxide hydrolase activity."; /evidence="ECO:0000269|PubMed:11917124"; MUTAGEN 137; /note="Q->A: No loss of activity."; /evidence="ECO:0000269|PubMed:11675384"; MUTAGEN 137; /note="Q->L: Aminopeptidase activity strongly impaired, but keeps LTA4 activity."; /evidence="ECO:0000269|PubMed:11675384"; MUTAGEN 137; /note="Q->N: Aminopeptidase activity almost absent, but keeps LTA4 activity."; /evidence="ECO:0000269|PubMed:11675384"; MUTAGEN 140; /note="H->Q: Aminopeptidase activity almost absent, but keeps LTA4 activity."; /evidence="ECO:0000269|PubMed:11917124"; MUTAGEN 269; /note="G->A: No loss of activity."; /evidence="ECO:0000269|PubMed:1881903"; MUTAGEN 270; /note="G->A: No loss of activity."; /evidence="ECO:0000269|PubMed:11675384"; MUTAGEN 271; /note="M->L: No loss of activity."; /evidence="ECO:0000269|PubMed:11675384"; MUTAGEN 272; /note="E->A,D: Complete loss of epoxide hydrolase activity and aminopeptidase activity."; /evidence="ECO:0000269|PubMed:11675384"; MUTAGEN 272; /note="E->Q: Loss of LTA4 hydrolase activity, and aminopeptidase activity strongly impaired."; /evidence="ECO:0000269|PubMed:11675384"; MUTAGEN 273; /note="N->A: No loss of epoxide hydrolase activity and aminopeptidase activity."; /evidence="ECO:0000269|PubMed:11675384"; MUTAGEN 296; /note="H->Y: Complete loss of LTA4 hydrolase and peptidase enzyme activities."; /evidence="ECO:0000269|PubMed:1881903"; MUTAGEN 297; /note="E->A: Loss of epoxide hydrolase and aminopeptidase activities."; /evidence="ECO:0000269|PubMed:1357660, ECO:0000269|PubMed:1516710, ECO:0000269|PubMed:18804029"; MUTAGEN 297; /note="E->K: Loss of epoxide hydrolase and aminopeptidase activities."; /evidence="ECO:0000269|PubMed:1357660, ECO:0000269|PubMed:1516710, ECO:0000269|PubMed:18804029"; MUTAGEN 297; /note="E->Q: Loss of aminopeptidase activity, but keeps LTA4 hydrolase activity."; /evidence="ECO:0000269|PubMed:1357660, ECO:0000269|PubMed:1516710, ECO:0000269|PubMed:18804029"; MUTAGEN 300; /note="H->L: Complete loss of LTA4 hydrolase and peptidase enzyme activities."; /evidence="ECO:0000269|PubMed:1881903"; MUTAGEN 319; /note="E->A: Complete loss of LTA4 hydrolase and peptidase enzyme activities."; /evidence="ECO:0000269|PubMed:1881903"; MUTAGEN 372; /note="D->N: No loss of activity."; /evidence="ECO:0000269|PubMed:11917124"; MUTAGEN 374; /note="D->N: No loss of activity."; /evidence="ECO:0000269|PubMed:11917124"; MUTAGEN 376; /note="D->A: Strongly reduced hydrolysis of peptides starting with Arg. Small effect on hydrolysis of peptides starting with Ala. Abolishes epoxide hydrolase activity."; /evidence="ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:18804029"; MUTAGEN 376; /note="D->E: Strongly reduced aminopeptidase activity. Abolishes epoxide hydrolase activity."; /evidence="ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:18804029"; MUTAGEN 376; /note="D->N: Abolishes aminopeptidase activity. Decreased epoxide hydrolase activity."; /evidence="ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:18804029"; MUTAGEN 385; /note="E->Q: Reduced aminopeptidase activity. Minor effect on epoxide hydrolase activity."; /evidence="ECO:0000269|PubMed:11917124"; MUTAGEN 564; /note="R->A,K,M: Abolishes epoxide hydrolase activity. Reduced aminopeptidase activity."; /evidence="ECO:0000269|PubMed:15078870"; MUTAGEN 566; /note="K->A,M: Strongly reduced affinity for peptide substrates. Reduced epoxide hydrolase and aminopeptidase activity."; /evidence="ECO:0000269|PubMed:15078870"; MUTAGEN 566; /note="K->R: No effect on epoxide hydrolase and aminopeptidase activity."; /evidence="ECO:0000269|PubMed:15078870
uniprot
proteins
pathway_participation
PATHWAY: Lipid metabolism; leukotriene B4 biosynthesis. {ECO:0000269|PubMed:11917124}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-416 inhibits leukotriene-A4 hydrolase activity. {ECO:0000269|PubMed:9395533}.
uniprot
proteins
protein_family
Peptidase M1 family
uniprot
proteins
pubmed
11175901
uniprot
proteins
pubmed
11675384
uniprot
proteins
pubmed
11917124
uniprot
proteins
pubmed
12207002
uniprot
proteins
pubmed
1357660
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15078870
uniprot
proteins
pubmed
1516710
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18804029
uniprot
proteins
pubmed
1881903
uniprot
proteins
pubmed
1897988
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19618939
uniprot
proteins
pubmed
1975494
uniprot
proteins
pubmed
20813919
uniprot
proteins
pubmed
21206090
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
2244921
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24591641
uniprot
proteins
pubmed
2821541
uniprot
proteins
pubmed
2996528
uniprot
proteins
pubmed
3654641
uniprot
proteins
pubmed
6490615
uniprot
proteins
pubmed
7628486
uniprot
proteins
pubmed
7667299
uniprot
proteins
pubmed
8615763
uniprot
proteins
pubmed
9395533
uniprot
proteins
sequence_length
611
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:6490615}.
uniprot
proteins