ID LKHA4_RAT Reviewed; 610 AA.
AC P30349;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 01-MAY-2013, entry version 106.
DE RecName: Full=Leukotriene A-4 hydrolase;
DE Short=LTA-4 hydrolase;
DE EC=3.3.2.6;
DE AltName: Full=Leukotriene A(4) hydrolase;
GN Name=Lta4h;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1544505; DOI=10.1016/0014-5793(92)80130-9;
RA Makita N., Funk C.D., Imai E., Hoover R.L., Badr K.F.;
RT "Molecular cloning and functional expression of rat leukotriene A4
RT hydrolase using the polymerase chain reaction.";
RL FEBS Lett. 299:273-277(1992).
CC -!- FUNCTION: Epoxide hydrolase that catalyzes the final step in the
CC biosynthesis of the proinflammatory mediator leukotriene B4. Has
CC also aminopeptidase activity.
CC -!- CATALYTIC ACTIVITY: (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-
CC 7,9,11,14-tetraenoate + H(2)O = (6Z,8E,10E,14Z)-(5S,12R)-5,12-
CC dihydroxyicosa-6,8,10,14-tetraenoate.
CC -!- COFACTOR: Binds 1 zinc ion per subunit (By similarity).
CC -!- ENZYME REGULATION: Inhibited by bestatin. Subject to suicide
CC inhibition by leukotriene A4 (By similarity).
CC -!- PATHWAY: Lipid metabolism; leukotriene B4 biosynthesis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: Phosphorylation at Ser-415 inhibits enzymatic activity (By
CC similarity).
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
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DR EMBL; S87522; AAB21778.1; -; mRNA.
DR IPI; IPI00207947; -.
DR PIR; S20444; S20444.
DR UniGene; Rn.104990; -.
DR ProteinModelPortal; P30349; -.
DR SMR; P30349; 2-610.
DR STRING; 10116.ENSRNOP00000005930; -.
DR MEROPS; M01.004; -.
DR PaxDb; P30349; -.
DR PRIDE; P30349; -.
DR UCSC; RGD:1311333; rat.
DR RGD; 1311333; Lta4h.
DR eggNOG; COG0308; -.
DR HOVERGEN; HBG001274; -.
DR InParanoid; P30349; -.
DR OrthoDB; EOG40GCQC; -.
DR BRENDA; 3.3.2.6; 5301.
DR UniPathway; UPA00878; -.
DR BindingDB; P30349; -.
DR ChEMBL; CHEMBL2400; -.
DR ArrayExpress; P30349; -.
DR Genevestigator; P30349; -.
DR GermOnline; ENSRNOG00000004494; Rattus norvegicus.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0004177; F:aminopeptidase activity; ISS:UniProtKB.
DR GO; GO:0004301; F:epoxide hydrolase activity; ISS:UniProtKB.
DR GO; GO:0004463; F:leukotriene-A4 hydrolase activity; IDA:RGD.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0019370; P:leukotriene biosynthetic process; ISS:UniProtKB.
DR GO; GO:0043171; P:peptide catabolic process; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0043434; P:response to peptide hormone stimulus; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
DR GO; GO:0060509; P:Type I pneumocyte differentiation; IEP:RGD.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR012777; Leukotriene_A4_hydrolase.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR015211; Peptidase_M1_C.
DR InterPro; IPR014782; Peptidase_M1_N.
DR PANTHER; PTHR11533; PTHR11533; 1.
DR Pfam; PF09127; Leuk-A4-hydro_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SUPFAM; SSF48371; ARM-type_fold; 1.
DR TIGRFAMs; TIGR02411; leuko_A4_hydro; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Complete proteome; Cytoplasm; Hydrolase;
KW Leukotriene biosynthesis; Metal-binding; Metalloprotease;
KW Phosphoprotein; Protease; Reference proteome; Zinc.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 610 Leukotriene A-4 hydrolase.
FT /FTId=PRO_0000095126.
FT REGION 135 137 Substrate binding (By similarity).
FT REGION 266 271 Substrate binding (By similarity).
FT REGION 563 565 Substrate binding (By similarity).
FT ACT_SITE 296 296 Proton acceptor (By similarity).
FT ACT_SITE 383 383 Proton donor (By similarity).
FT METAL 295 295 Zinc; catalytic (By similarity).
FT METAL 299 299 Zinc; catalytic (By similarity).
FT METAL 318 318 Zinc; catalytic (By similarity).
FT SITE 375 375 Essential for epoxide hydrolase activity,
FT but not for aminopeptidase activity (By
FT similarity).
FT SITE 378 378 Covalently modified during suicide
FT inhibition by leukotrienes (By
FT similarity).
FT MOD_RES 73 73 N6-acetyllysine (By similarity).
FT MOD_RES 336 336 N6-acetyllysine (By similarity).
FT MOD_RES 413 413 N6-acetyllysine (By similarity).
FT MOD_RES 415 415 Phosphoserine (By similarity).
FT MOD_RES 572 572 N6-acetyllysine (By similarity).
SQ SEQUENCE 610 AA; 69176 MW; 1A1F8DBE20293887 CRC64;
MPEVEDTCSL ASPASVCRTQ HLHLRCSVDF ARRALTGTAA LTVQSQEDNL RTLTLDTKDL
TIEKVVINGQ EVKYTLGESQ GYKGSPMEIS LPIALSKNQE VVIEISFETS PKSSALQWLT
PEQTSGKQHP YLFSQWEAIH CRAILPCQDT SVKLTYTAEV SVPKELVALM SAIRDGEAPD
PEDPSRKIYR FNQRVPIPCY LIALVVGALE SRQIGPRTLV WSEKEQVEKS AYEFSETESM
LKIAEDLGGP YVWGQYDLLV LPPSFPYGGM ENPCLTFVTP TLLAGDKSLS NVIAHEISHS
WTGNLVTNKT WDHFWLNEGH TVYLERHICG RLFGEKFRHF HALGGWGELQ NTIKTFGESH
PFTKLVVDLK DVDPDVAYSS IPYEKGFALL FYLEQLLGGP EVFLGFLKAY VEKFSYQSVT
TDDWKSFLYA HFKDKVDLLN QVDWNAWLYA PGLPPVKPNY DVTLTNACIA LSQRWVTAKE
EDLNSFSIED LKDLSSHQLN EFLAQVLQRA PLPLGHIKRM QEVYNFNAIN NSEIRFRWLR
LCIQSKWEEA IPLALKMATE QGRMKFTRPL FKDLAAFDKS HDQAVRTYQE HKACMHPVTA
MLVGKDLKVD
//
