EST4A_HUMAN
ID EST4A_HUMAN Reviewed; 561 AA.
AC Q5XG92; A8KAJ6; B7Z349; B7Z3L2; B7Z6R3; Q6UX55; Q8N9F4;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Carboxylesterase 4A;
DE EC=3.1.1.-;
DE Flags: Precursor;
GN Name=CES4A; Synonyms=CES8; ORFNames=UNQ440/PRO873;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4; 5 AND 6).
RC TISSUE=Hippocampus, Neuroepithelioma, Thalamus, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-561 (ISOFORM 7).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 38-561 (ISOFORM 2).
RC TISSUE=Blood;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Probable carboxylesterase. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=Q5XG92-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5XG92-2; Sequence=VSP_032483, VSP_032485;
CC Name=3;
CC IsoId=Q5XG92-4; Sequence=VSP_032480;
CC Name=4;
CC IsoId=Q5XG92-5; Sequence=VSP_040066, VSP_040067;
CC Name=5;
CC IsoId=Q5XG92-6; Sequence=VSP_040063;
CC Name=6;
CC IsoId=Q5XG92-7; Sequence=VSP_040063, VSP_040065, VSP_040066,
CC VSP_040067;
CC Name=7;
CC IsoId=Q5XG92-8; Sequence=VSP_040064, VSP_032483, VSP_040066,
CC VSP_040067;
CC -!- MISCELLANEOUS: [Isoform 2]: Inactive. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ88868.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};
CC Sequence=BAH12248.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK094783; BAC04422.1; -; mRNA.
DR EMBL; AK293061; BAF85750.1; -; mRNA.
DR EMBL; AK295483; BAH12085.1; -; mRNA.
DR EMBL; AK296064; BAH12248.1; ALT_INIT; mRNA.
DR EMBL; AK300792; BAH13349.1; -; mRNA.
DR EMBL; AC009084; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY358504; AAQ88868.1; ALT_SEQ; mRNA.
DR EMBL; BC084555; AAH84555.1; -; mRNA.
DR CCDS; CCDS42174.3; -. [Q5XG92-5]
DR CCDS; CCDS54024.1; -. [Q5XG92-6]
DR CCDS; CCDS54025.1; -. [Q5XG92-7]
DR RefSeq; NP_001177130.1; NM_001190201.1. [Q5XG92-6]
DR RefSeq; NP_001177131.1; NM_001190202.1. [Q5XG92-7]
DR RefSeq; NP_001305435.1; NM_001318506.1. [Q5XG92-4]
DR RefSeq; NP_776176.5; NM_173815.6. [Q5XG92-5]
DR AlphaFoldDB; Q5XG92; -.
DR SMR; Q5XG92; -.
DR BioGRID; 129682; 1.
DR STRING; 9606.ENSP00000444052; -.
DR ESTHER; human-CES4A; Carb_B_Chordata.
DR MEROPS; S09.959; -.
DR GlyGen; Q5XG92; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q5XG92; -.
DR PhosphoSitePlus; Q5XG92; -.
DR BioMuta; CES4A; -.
DR DMDM; 172045957; -.
DR MassIVE; Q5XG92; -.
DR MaxQB; Q5XG92; -.
DR PaxDb; Q5XG92; -.
DR PeptideAtlas; Q5XG92; -.
DR PRIDE; Q5XG92; -.
DR ProteomicsDB; 65816; -. [Q5XG92-1]
DR ProteomicsDB; 65817; -. [Q5XG92-2]
DR ProteomicsDB; 65818; -. [Q5XG92-4]
DR ProteomicsDB; 65819; -. [Q5XG92-5]
DR ProteomicsDB; 65820; -. [Q5XG92-6]
DR ProteomicsDB; 65822; -. [Q5XG92-8]
DR Antibodypedia; 48401; 76 antibodies from 14 providers.
DR DNASU; 283848; -.
DR Ensembl; ENST00000535696.1; ENSP00000441644.1; ENSG00000172824.16. [Q5XG92-7]
DR Ensembl; ENST00000540579.6; ENSP00000441907.1; ENSG00000172824.16. [Q5XG92-6]
DR Ensembl; ENST00000540947.6; ENSP00000444052.2; ENSG00000172824.16. [Q5XG92-5]
DR Ensembl; ENST00000648724.2; ENSP00000497868.2; ENSG00000172824.16. [Q5XG92-1]
DR GeneID; 283848; -.
DR KEGG; hsa:283848; -.
DR MANE-Select; ENST00000648724.3; ENSP00000497868.2; NM_001364782.1; NP_001351711.1.
DR UCSC; uc002eqy.4; human. [Q5XG92-1]
DR CTD; 283848; -.
DR GeneCards; CES4A; -.
DR HGNC; HGNC:26741; CES4A.
DR HPA; ENSG00000172824; Tissue enhanced (fallopian tube, skin).
DR neXtProt; NX_Q5XG92; -.
DR OpenTargets; ENSG00000172824; -.
DR PharmGKB; PA164717904; -.
DR VEuPathDB; HostDB:ENSG00000172824; -.
DR eggNOG; KOG1516; Eukaryota.
DR GeneTree; ENSGT00940000162924; -.
DR HOGENOM; CLU_006586_19_0_1; -.
DR InParanoid; Q5XG92; -.
DR OMA; QESWGQI; -.
DR OrthoDB; 754103at2759; -.
DR PhylomeDB; Q5XG92; -.
DR TreeFam; TF315470; -.
DR PathwayCommons; Q5XG92; -.
DR BioGRID-ORCS; 283848; 13 hits in 1067 CRISPR screens.
DR ChiTaRS; CES4A; human.
DR GenomeRNAi; 283848; -.
DR Pharos; Q5XG92; Tbio.
DR PRO; PR:Q5XG92; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q5XG92; protein.
DR Bgee; ENSG00000172824; Expressed in right uterine tube and 115 other tissues.
DR ExpressionAtlas; Q5XG92; baseline and differential.
DR Genevisible; Q5XG92; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Hydrolase;
KW Reference proteome; Secreted; Serine esterase; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..561
FT /note="Carboxylesterase 4A"
FT /id="PRO_0000325923"
FT ACT_SITE 221
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10039"
FT ACT_SITE 353
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 467
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 88..116
FT /evidence="ECO:0000250"
FT DISULFID 273..284
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..194
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_032480"
FT VAR_SEQ 1..98
FT /note="Missing (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040063"
FT VAR_SEQ 87
FT /note="G -> GWSLALSPGWSAVARSRLTATSASRVQASLLPQPLSVWGYR (in
FT isoform 7)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_040064"
FT VAR_SEQ 179
FT /note="S -> RWRGR (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040065"
FT VAR_SEQ 361..387
FT /note="Missing (in isoform 2 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_032483"
FT VAR_SEQ 439..481
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032485"
FT VAR_SEQ 439..468
FT /note="DAGLPVYLYEFEHHARGIIVKPRTDGADHG -> ETPMMGICPAGHATTRMK
FT STCSWILPQEWA (in isoform 4, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_040066"
FT VAR_SEQ 469..561
FT /note="Missing (in isoform 4, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_040067"
FT CONFLICT 254
FT /note="L -> P (in Ref. 1; BAC04422)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="K -> N (in Ref. 1; BAH12248)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 561 AA; 63529 MW; 27A4CFA5EBE0BC3A CRC64;
MRWILCWSLT LCLMAQTALG ALHTKRPQVV TKYGTLQGKQ MHVGKTPIQV FLGVPFSRPP
LGILRFAPPE PPEPWKGIRD ATTYPPGCLQ ESWGQLASMY VSTRERYKWL RFSEDCLYLN
VYAPARAPGD PQLPVMVWFP GGAFIVGAAS SYEGSDLAAR EKVVLVFLQH RLGIFGFLST
DDSHARGNWG LLDQMAALRW VQENIAAFGG DPGNVTLFGQ SAGAMSISGL MMSPLASGLF
HRAISQSGTA LFRLFITSNP LKVAKKVAHL AGCNHNSTQI LVNCLRALSG TKVMRVSNKM
RFLQLNFQRD PEEIIWSMSP VVDGVVIPDD PLVLLTQGKV SSVPYLLGVN NLEFNWLLPY
IMKFPLNRQA MRKETITKML WSTRTLLNIT KEQVPLVVEE YLDNVNEHDW KMLRNRMMDI
VQDATFVYAT LQTAHYHRDA GLPVYLYEFE HHARGIIVKP RTDGADHGDE MYFLFGGPFA
TGLSMGKEKA LSLQMMKYWA NFARTGNPND GNLPCWPRYN KDEKYLQLDF TTRVGMKLKE
KKMAFWMSLY QSQRPEKQRQ F
