Overview
| Uniprot ID | P09960 |
|---|
| Protein Name | Leukotriene A-4 hydrolase |
|---|
| Gene Name | LTA4H |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 414 |
FLKAYVEKFSYKSIT |
| 580 |
KDLAAFDKSHDQAVR |
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)
Protein Sequence
10
MPEIVDTCSL
20
ASPASVCRTK
30
HLHLRCSVDF
40
TRRTLTGTAA
50
LTVQSQEDNL
60
RSLVLDTKDL
70
TIEKVVINGQ
80
EVKYALGERQ
90
SYKGSPMEIS
100
LPIALSKNQE
110
IVIEISFETS
120
PKSSALQWLT
130
PEQTSGKEHP
140
YLFSQCQAIH
150
CRAILPCQDT
160
PSVKLTYTAE
170
VSVPKELVAL
180
MSAIRDGETP
190
DPEDPSRKIY
200
KFIQKVPIPC
210
YLIALVVGAL
220
ESRQIGPRTL
230
VWSEKEQVEK
240
SAYEFSETES
250
MLKIAEDLGG
260
PYVWGQYDLL
270
VLPPSFPYGG
280
MENPCLTFVT
290
PTLLAGDKSL
300
SNVIAHEISH
310
SWTGNLVTNK
320
TWDHFWLNEG
330
HTVYLERHIC
340
GRLFGEKFRH
350
FNALGGWGEL
360
QNSVKTFGET
370
HPFTKLVVDL
380
TDIDPDVAYS
390
SVPYEKGFAL
400
LFYLEQLLGG
410
PEIFLGFLKA
420
YVEKFSYKSI
430
TTDDWKDFLY
440
SYFKDKVDVL
450
NQVDWNAWLY
460
SPGLPPIKPN
470
YDMTLTNACI
480
ALSQRWITAK
490
EDDLNSFNAT
500
DLKDLSSHQL
510
NEFLAQTLQR
520
APLPLGHIKR
530
MQEVYNFNAI
540
NNSEIRFRWL
550
RLCIQSKWED
560
AIPLALKMAT
570
EQGRMKFTRP
580
LFKDLAAFDK
590
SHDQAVRTYQ
600
EHKASMHPVT
610
AMLVGKDLKV
D
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005829 |
cytosol |
| Molecular Function |
GO:0003723 |
RNA binding |
| Molecular Function |
GO:0045148 |
tripeptide aminopeptidase activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0019370 |
leukotriene biosynthetic process |
| Biological Process |
GO:0006629 |
lipid metabolic process |
| Biological Process |
GO:0043171 |
peptide catabolic process |
| Biological Process |
GO:0006508 |
proteolysis |
| Biological Process |
GO:0043434 |
response to peptide hormone |
| Biological Process |
GO:0010043 |
response to zinc ion |
| Biological Process |
GO:0060509 |
type I pneumocyte differentiation |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0005576 |
extracellular region |
| Cellular Component |
GO:1904813 |
ficolin-1-rich granule lumen |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:1904724 |
tertiary granule lumen |
| Molecular Function |
GO:0004177 |
aminopeptidase activity |
| Molecular Function |
GO:0004301 |
epoxide hydrolase activity |
| Molecular Function |
GO:0004463 |
leukotriene-A4 hydrolase activity |
| Molecular Function |
GO:0070006 |
metalloaminopeptidase activity |
| Molecular Function |
GO:0008233 |
peptidase activity |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.