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Protein

Leukotriene A-4 hydrolase

Gene

Lta4h

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.

Catalytic activityi

(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Inhibited by bestatin. Subject to suicide inhibition by leukotriene A4 (By similarity).By similarity

Pathwayi: leukotriene B4 biosynthesis

This protein is involved in the pathway leukotriene B4 biosynthesis, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway leukotriene B4 biosynthesis and in Lipid metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi295 – 2951Zinc; catalyticPROSITE-ProRule annotation
Active sitei296 – 2961Proton acceptorPROSITE-ProRule annotation
Metal bindingi299 – 2991Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi318 – 3181Zinc; catalyticPROSITE-ProRule annotation
Sitei375 – 3751Essential for epoxide hydrolase activity, but not for aminopeptidase activityBy similarity
Sitei378 – 3781Covalently modified during suicide inhibition by leukotrienesBy similarity
Active sitei383 – 3831Proton donorPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • leukotriene biosynthetic process Source: UniProtKB
  • leukotriene metabolic process Source: RGD
  • peptide catabolic process Source: UniProtKB
  • response to peptide hormone Source: RGD
  • response to zinc ion Source: RGD
  • Type I pneumocyte differentiation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Leukotriene biosynthesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.3.2.6. 5301.
UniPathwayiUPA00878.

Protein family/group databases

MEROPSiM01.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Leukotriene A-4 hydrolase (EC:3.3.2.6)
Short name:
LTA-4 hydrolase
Alternative name(s):
Leukotriene A(4) hydrolase
Gene namesi
Name:Lta4h
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1311333. Lta4h.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2400.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 610609Leukotriene A-4 hydrolasePRO_0000095126Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei73 – 731N6-acetyllysineBy similarity
Modified residuei336 – 3361N6-acetyllysineBy similarity
Modified residuei413 – 4131N6-acetyllysineBy similarity
Modified residuei415 – 4151PhosphoserineBy similarity
Modified residuei572 – 5721N6-acetyllysineBy similarity

Post-translational modificationi

Phosphorylation at Ser-415 inhibits enzymatic activity.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP30349.
PRIDEiP30349.

PTM databases

iPTMnetiP30349.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000005930.

Structurei

3D structure databases

ProteinModelPortaliP30349.
SMRiP30349. Positions 2-610.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni135 – 1373Substrate bindingBy similarity
Regioni266 – 2716Substrate bindingBy similarity
Regioni563 – 5653Substrate bindingBy similarity

Sequence similaritiesi

Belongs to the peptidase M1 family.Curated

Phylogenomic databases

eggNOGiKOG1047. Eukaryota.
COG0308. LUCA.
HOVERGENiHBG001274.
InParanoidiP30349.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR012777. Leukotriene_A4_hydrolase.
IPR001930. Peptidase_M1.
IPR015211. Peptidase_M1_C.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 1 hit.
PfamiPF09127. Leuk-A4-hydro_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
SMARTiSM01263. Leuk-A4-hydro_C. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
TIGRFAMsiTIGR02411. leuko_A4_hydro. 1 hit.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P30349-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPEVEDTCSL ASPASVCRTQ HLHLRCSVDF ARRALTGTAA LTVQSQEDNL
60 70 80 90 100
RTLTLDTKDL TIEKVVINGQ EVKYTLGESQ GYKGSPMEIS LPIALSKNQE
110 120 130 140 150
VVIEISFETS PKSSALQWLT PEQTSGKQHP YLFSQWEAIH CRAILPCQDT
160 170 180 190 200
SVKLTYTAEV SVPKELVALM SAIRDGEAPD PEDPSRKIYR FNQRVPIPCY
210 220 230 240 250
LIALVVGALE SRQIGPRTLV WSEKEQVEKS AYEFSETESM LKIAEDLGGP
260 270 280 290 300
YVWGQYDLLV LPPSFPYGGM ENPCLTFVTP TLLAGDKSLS NVIAHEISHS
310 320 330 340 350
WTGNLVTNKT WDHFWLNEGH TVYLERHICG RLFGEKFRHF HALGGWGELQ
360 370 380 390 400
NTIKTFGESH PFTKLVVDLK DVDPDVAYSS IPYEKGFALL FYLEQLLGGP
410 420 430 440 450
EVFLGFLKAY VEKFSYQSVT TDDWKSFLYA HFKDKVDLLN QVDWNAWLYA
460 470 480 490 500
PGLPPVKPNY DVTLTNACIA LSQRWVTAKE EDLNSFSIED LKDLSSHQLN
510 520 530 540 550
EFLAQVLQRA PLPLGHIKRM QEVYNFNAIN NSEIRFRWLR LCIQSKWEEA
560 570 580 590 600
IPLALKMATE QGRMKFTRPL FKDLAAFDKS HDQAVRTYQE HKACMHPVTA
610
MLVGKDLKVD
Length:610
Mass (Da):69,176
Last modified:January 23, 2007 - v2
Checksum:i1A1F8DBE20293887
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S87522 mRNA. Translation: AAB21778.1.
PIRiS20444.
UniGeneiRn.104990.

Genome annotation databases

UCSCiRGD:1311333. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S87522 mRNA. Translation: AAB21778.1.
PIRiS20444.
UniGeneiRn.104990.

3D structure databases

ProteinModelPortaliP30349.
SMRiP30349. Positions 2-610.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000005930.

Chemistry

ChEMBLiCHEMBL2400.

Protein family/group databases

MEROPSiM01.004.

PTM databases

iPTMnetiP30349.

Proteomic databases

PaxDbiP30349.
PRIDEiP30349.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:1311333. rat.

Organism-specific databases

RGDi1311333. Lta4h.

Phylogenomic databases

eggNOGiKOG1047. Eukaryota.
COG0308. LUCA.
HOVERGENiHBG001274.
InParanoidiP30349.

Enzyme and pathway databases

UniPathwayiUPA00878.
BRENDAi3.3.2.6. 5301.

Miscellaneous databases

PROiP30349.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR012777. Leukotriene_A4_hydrolase.
IPR001930. Peptidase_M1.
IPR015211. Peptidase_M1_C.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 1 hit.
PfamiPF09127. Leuk-A4-hydro_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
SMARTiSM01263. Leuk-A4-hydro_C. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
TIGRFAMsiTIGR02411. leuko_A4_hydro. 1 hit.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Molecular cloning and functional expression of rat leukotriene A4 hydrolase using the polymerase chain reaction."
    Makita N., Funk C.D., Imai E., Hoover R.L., Badr K.F.
    FEBS Lett. 299:273-277(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiLKHA4_RAT
AccessioniPrimary (citable) accession number: P30349
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2007
Last modified: May 11, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.