EST2A_RAT
ID EST2A_RAT Reviewed; 558 AA.
AC Q8K3R0; F7F3M3;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Pyrethroid hydrolase Ces2a {ECO:0000305};
DE EC=3.1.1.88 {ECO:0000250|UniProtKB:Q8QZR3};
DE AltName: Full=Carboxylic ester hydrolase {ECO:0000255|RuleBase:RU361235};
DE EC=3.1.1.- {ECO:0000255|RuleBase:RU361235};
DE Flags: Precursor;
GN Name=Ces2a {ECO:0000312|RGD:708353};
GN Synonyms=Ces6 {ECO:0000312|RGD:708353}, LOC246252 {ECO:0000312|RGD:708353};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|EMBL:AAK61610.1};
RN [1] {ECO:0000312|EMBL:AAK61610.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, FUNCTION,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAK61610.1};
RC TISSUE=Liver {ECO:0000312|EMBL:AAK61610.1};
RX PubMed=12230550; DOI=10.1046/j.1432-1033.2002.03121.x;
RA Sanghani S.P., Davis W.I., Dumaual N.G., Mahrenholz A., Bosron W.F.;
RT "Identification of microsomal rat liver carboxylesterases and their
RT activity with retinyl palmitate.";
RL Eur. J. Biochem. 269:4387-4398(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
CC -!- FUNCTION: Carboxylesterases that catalyzes the hydrolysis of
CC pyrethroids pesticides. Hydrolyzes permethrin faster than cypermethrin
CC (By similarity). Hydrolyzes retinyl esters (PubMed:12230550).
CC {ECO:0000250|UniProtKB:Q8QZR3, ECO:0000269|PubMed:12230550}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinyl hexadecanoate + H2O = all-trans-retinol +
CC H(+) + hexadecanoate; Xref=Rhea:RHEA:13933, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17616; Evidence={ECO:0000269|PubMed:12230550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934;
CC Evidence={ECO:0000305|PubMed:12230550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(-)-trans-permethrin + H2O = (1S,3R)-3-(2,2-dichlorovinyl)-
CC 2,2-dimethylcyclopropanecarboxylate + (3-phenoxyphenyl)methanol +
CC H(+); Xref=Rhea:RHEA:30283, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:62523, ChEBI:CHEBI:62527, ChEBI:CHEBI:62531; EC=3.1.1.88;
CC Evidence={ECO:0000250|UniProtKB:Q8QZR3};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=kcat is 0.05 min(-1) with retinyl palmitate as substrate.
CC {ECO:0000269|PubMed:12230550};
CC -!- SUBCELLULAR LOCATION: Microsome {ECO:0000269|PubMed:12230550}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K3R0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K3R0-2; Sequence=VSP_060584;
CC -!- TISSUE SPECIFICITY: Expressed in liver, stomach, small intestine and
CC kidney. {ECO:0000269|PubMed:12230550}.
CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC {ECO:0000255, ECO:0000255|RuleBase:RU361235}.
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DR EMBL; AY034877; AAK61610.1; -; mRNA.
DR EMBL; AABR07042570; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_653344.1; NM_144743.1. [Q8K3R0-1]
DR AlphaFoldDB; Q8K3R0; -.
DR SMR; Q8K3R0; -.
DR IntAct; Q8K3R0; 1.
DR STRING; 10116.ENSRNOP00000015451; -.
DR SwissLipids; SLP:000001456; -.
DR ESTHER; ratno-LOC246252; Carb_B_Chordata.
DR MEROPS; S09.953; -.
DR PRIDE; Q8K3R0; -.
DR GeneID; 246252; -.
DR KEGG; rno:246252; -.
DR UCSC; RGD:708353; rat. [Q8K3R0-1]
DR CTD; 102022; -.
DR RGD; 708353; Ces2a.
DR VEuPathDB; HostDB:ENSRNOG00000011330; -.
DR eggNOG; KOG1516; Eukaryota.
DR HOGENOM; CLU_006586_4_0_1; -.
DR OMA; GINTDEC; -.
DR OrthoDB; 754103at2759; -.
DR PhylomeDB; Q8K3R0; -.
DR TreeFam; TF315470; -.
DR BRENDA; 3.1.1.1; 5301.
DR PRO; PR:Q8K3R0; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000011330; Expressed in duodenum and 9 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0047376; F:all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity; IEA:RHEA.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IDA:RGD.
DR GO; GO:0102209; F:trans-permethrin hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0001523; P:retinoid metabolic process; TAS:RGD.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR002018; CarbesteraseB.
DR InterPro; IPR019826; Carboxylesterase_B_AS.
DR InterPro; IPR019819; Carboxylesterase_B_CS.
DR Pfam; PF00135; COesterase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00122; CARBOXYLESTERASE_B_1; 1.
DR PROSITE; PS00941; CARBOXYLESTERASE_B_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Endoplasmic reticulum; Hydrolase;
KW Microsome; Reference proteome; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255|RuleBase:RU361235"
FT CHAIN 27..558
FT /note="Pyrethroid hydrolase Ces2a"
FT /evidence="ECO:0000255|RuleBase:RU361235"
FT /id="PRO_5005144506"
FT ACT_SITE 227
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10039"
FT ACT_SITE 344
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT ACT_SITE 456
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT MOD_RES 296
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8QZR3"
FT DISULFID 95..122
FT /evidence="ECO:0000250|UniProtKB:Q99K10"
FT DISULFID 279..290
FT /evidence="ECO:0000250|UniProtKB:Q99K10"
FT VAR_SEQ 411..558
FT /note="Missing (in isoform 2)"
FT /id="VSP_060584"
SQ SEQUENCE 558 AA; 61802 MW; FB267DDD19581106 CRC64;
MPLARLPGWL YVVACGLLLL LQHVHGQDSA SPIRNTHTGQ VRGSFVHVKD TKSGIHTFLG
IPFAKPPVGP LRFAPPEDPE PWSGVRDATS QPAMCLQTDI MNLDGIKEMK LTVHPTPMSE
DCLYLNIYTP AHAREGSNLP VMVWIHGGGL VLGSASMNDA STLAATEEIV IVSIQYRLGV
LGFFSTGDQN ARGNWGYLDQ VAALRWVQQN IAYFGGNHGK VTIFGGSAGG TSVSSHVVSP
MSKGLFHGAI MQSGVALLPD LISDKSEVVY KTVANLSGCE APDSEALIRC LRAKSKQEIL
AINQVFKMIP GVVDGKFLPK HPQELLASGD FHPVPSIIGI NTDECGWGIP VFLGLDHIIK
KITRETLPTV LKSTAAQMML PPECIDLIME EYMGDTENPE TLQEQFRHML GDFMFVIPAL
QVAHFQRSQA PVYFYEFQHL PSFIKQVRPS HVKADHGDDI LFVFGSYLWG MTFDLTEEEE
LLKRRVMKYW ANFARTGNPN GEDLPHWPVL DHDEQYLQLN TQPAVGRALK ARRLQFWTKT
LPQKIQELKG SQSKHAEL
