Gene_locus Report for: human-CMBL

Q8TED6 Q96DG6 2aa diff

(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E

A85-EsteraseD-FGH : human-ESD Homo sapiens (Human) esterase D (EC 3.1.1.1) formylglutathione hydrolase.
ABHD6-Lip : human-ABHD6 Homo sapiens (Human) ABHD6 Monoacylglycerol lipase EC: 3.1.1.23.
ABHD8 : human-ABHD8Homo sapiens (Human) Abhydrolase domain containing 8 (ABHD8) cDNA FLJ11743 fis, clone HEMBA1005517.
ABHD10 : human-ABHD10Homo sapiens (Human) ABHDA ABHD10 Abhydrolase domain-containing protein 10, Mycophenolic acid acyl-glucuronide esterase, mitochondrial.
ABHD11-Acetyl_transferase : human-ABHD11Homo sapiens (Human) (EC 3.3.2.3) Abhydrolase domain-containing protein 11 williams-beuren syndrome critical region protein 21.
ABHD12-PHARC : human-ABHD12Homo sapiens (Human) abhydrolase domain-containing protein 12. Protein C20orf22, flj90542, CT022, 2-arachidonoylglycerol hydrolase, Monoacylglycerol lipase, human-ABHD12BHomo sapiens (Human) Abhydrolase domain-containing protein 12B ABHD12B protein c14orf29.
ABHD13-BEM46 : human-ABHD13Homo sapiens (Human) C13orf6 Q7L211 ABHDD_HUMAN ABHD13 Abhydrolase domain-containing protein 13.
ABHD16 : human-ABHD16AHomo sapiens (Human) Abhydrolase domain-containing protein 16A BAT5 (HLA-B-associated transcript 5) (NG26 protein) (G5) (PP199), human-ABHD16BHomo sapiens (Human) ABHD16B PS-PLA1 lipase activity.
ABHD17-depalmitoylase : human-ABHD17AHomo sapiens (Human) Abhydrolase domain-containing protein FAM108A1, C19orf27 ABHD17A, human-ABHD17BHomo sapiens (Human) CGI-67 C9orf77 FAM108B1 protein Abhydrolase domain-containing protein FAM108B1, human-ABHD17CHomo sapiens (Human) Abhydrolase domain-containing protein FAM108C1 Q6PCB6 F108C_HUMAN.
ABHD18 : human-ABHD18Homo sapiens (Human) ABHD18 C4orf29 CD029 hypothetical protein.
abh_upf0017 : human-ABHD1Homo sapiens (Human) lung alpha/beta hydrolase 1, human-ABHD2Homo sapiens (Human) Monoacylglycerol lipase ABHD2 LABH2 LBH2 protein phps1-2, human-ABHD3Homo sapiens (Human) hypothetical 49.3 kda protein, human-ABHD15Homo sapiens (Human) ABH15 Abhydrolase domain-containing protein 15 hypothetical protein.
ACHE : human-ACHE Homo sapiens (Human) acetylcholinesterase.
Acidic_Lipase : human-LIPA Homo sapiens (Human) lysosomal acid lipase LICH_HUMAN gene LIPA, Lysosomal acid lipase/cholesteryl ester hydrolase (EC:3.1.1.13) LAL cholesterol esterase (wolman disease) Sebelipase, human-LIPF Homo sapiens (Human) human gastric lipase, human-LIPJHomo sapiens (Human) Lipase member J lipase-like, ab-hydrolase domain containing 1, human-LIPKHomo sapiens (Human) Lipase member K lipase-like, ab-hydrolase domain containing 2 LIPL2, human-LIPMHomo sapiens (Human) LIPM LIPL3 ba304i5.1, human-LIPNHomo sapiens (Human) lipase-like, Lipase-like abhydrolase domain-containing protein 4.
ACPH_Peptidase_S9 : human-APEHHomo sapiens (Human) acylamino acid-releasing enzyme APH APEH.
Acyl-CoA_Thioesterase : human-ACOT1Homo sapiens (Human) Inducible cytosolic acyl-coenzyme A thioester hydrolase Long chain Acyl-CoA hydrolase) (cte-i) (cte-ib), human-ACOT2 Homo sapiens (Human) peroxisomal long-chain Acyl-CoA thioesterase 2 (zap128) (protein for mgc:3983) mitochondrial (EC 3.1.2.2) CTE-1a, human-ACOT4 Homo sapiens (Human) Q8N9L9 Acyl-coenzyme A thioesterase 4, inducible (EC 3.1.2.2), human-ACOT6Homo sapiens (Human) Acyl-CoA thioesterase 6 (EC 3.1.2.2), human-BAATHomo sapiens (Human) bile acid CoA: amino acid n-acyltransferase (EC 3.1.2.2).
Arb2_FAM172A : human-f172aHomo sapiens (Human).Cotranscriptional regulator Protein FAM172A.
Arylacetamide_deacetylase : human-AADACHomo sapiens (Human) arylacetamide deacetylase, human-AADACL2Homo sapiens (Human) similar to arylacetamide deacetylase (aadac), human-AADACL3Homo sapiens (Human) AADACL3 arylacetamide deacetylase-like 3 ADCL3, human-AADACL4Homo sapiens (Human) Arylacetamide deacetylase-like 4, human-NCEH1Homo sapiens (Human) NCEH1 KIAA1363 AADACL1 neutral cholesterol ester hydrolase 1.
BCHE : human-BCHE Homo sapiens (Human) butyrylcholinesterase.
Carboxypeptidase_S10 : human-CPVLHomo sapiens (Human) carboxypeptidase, vitellogenic-like CP-Mac ou CPVL carboxypeptidase WUG, human-CTSA Homo sapiens (Human) protective protein associated with lysosomal beta-galactosidase ppt2 protein CTSA Cathepsin A, PPGB, human-SCPEP1Homo sapiens (Human) serine Retinoid-inducible serine carboxypeptidase RISC SCP1 (EC 3.4.16.-).
Carb_B_Chordata : human-CES1 Homo sapiens (Human) carboxylesterase CES1 hCE1 & for monocyte/macrophage serine-esterase 1 egasyn, human-CES2Homo sapiens (Human) carboxylesterase hCE-2,iCE, hiCE, CES2 gene cDNA FLJ76104 Cocaine esterase, human-CES3Homo sapiens (Human) Carboxylesterase 3 (Brain) Liver carboxylesterase 31 homolog, human-CES4AHomo sapiens (Human) Carboxylesterase 4A Carboxylesterase 8, human-CES5AHomo sapiens (Human) est5a CES7 Cauxin Carboxylesterase-like urinary excreted protein homolog.
CGI-58_ABHD5_ABHD4 : human-ABHD4Homo sapiens (Human) abhydrolase domain-containing protein 4 FLJ12816 similar to 2-hydroxymuconic semialdehyde hydrolase (EC 3.1.1.-), human-ABHD5 Homo sapiens (Human) 39.1 kDa Comparative gene identification 58 (CGI-58)/Alpha Beta Hydrolase Domain 5 (ABHD5).
Cholesterol_esterase : human-CEL Homo sapiens (Human) bile-salt-activated lipase, BSSL BAL CEL CEH carboxyl ester lipase chr 9.
CIB-CCG1-interacting-factor-B : human-ABHD14AHomo sapiens (Human) Abhydrolase domain-containing protein 14A srsq1913, human-CIB Homo sapiens (Human) Ccg1/TafII250-Interacting Factor B CIB MGC15429 Abhydrolase domain-containing protein 14B ABHD14B. lysine deacetylase.
DPP4N_Peptidase_S9 : human-DPP4 Homo sapiens (Human) dipeptidyl peptidase IV (DPP4), T-cell activation antigen CD26, human-DPP6 Homo sapiens (Human) (dipeptidylpeptidase VI) (dppx), human-DPP8 Homo sapiens (Human) dipeptidyl peptidase 8 (DPP8), human-DPP9 Homo sapiens (Human) dipeptidyl peptidase 9 DPP9 DPRP2, human-DPP10 Homo sapiens (Human) DPP-10 Dipeptidyl peptidase IV-related protein-3 KIAA1492 protein (fragment), human-FAP Homo sapiens (Human) fibroblast activation protein alpha FAPalpha, integral membrane serine protease seprase FAPA, FAP, SEPR.
Duf_676 : human-FAM135AHomo sapiens (Human) F135A DKFZp781H2319 FLJ20176 fis KIAA1411 previously human-F135A, human-FAM135BHomo sapiens (Human) F135B loc51059 c8orfk32 protein.
Duf_726 : human-TMCO4Homo sapiens (Human) Transmembrane and coiled-coil domain-containing protein 4.
Duf_829 : human-TMEM53Homo sapiens (Human) Transmembrane protein 53, FLJ22353, NET4.
Epoxide_hydrolase : human-EPHX1Homo sapiens (Human) microsomal epoxide hydrolase HYEP mEH, epoxide hydratase EPHX1, human-EPHX2 Homo sapiens (Human) epoxide hydrolase 2, Bifunctional epoxide hydrolase 2 cytosolic (EPHX2) (EC 3.3.2.3) Lipid-phosphate phosphatase (EC 3.1.3.76), human-EPHX3Homo sapiens (Human) Epoxide hydrolase 3 (EPHX3) Abhydrolase domain-containing protein 9 (ABHD9) FLJ22408, human-EPHX4Homo sapiens (Human) Epoxide hydrolase 4 EPHX4 ABHD7 EPHXRP Abhydrolase domain-containing protein 7.
FSH1 : human-OVCA2Homo sapiens (Human) Candidate tumor suppressor in ovarian cancer.
Hepatic_Lipase : human-LIPCHomo sapiens (Human) LIPC hepatic triacylglycerol lipase HTGL.
Hormone-sensitive_lipase_like : human-LIPEHuman mRNA (Human) hormone sensitive lipase HSL.
Hydrolase_RBBP9_YdeN : human-RBBP9 Homo sapiens (Human) Retinoblastoma-binding protein 9 and 10 (rbbp-10) (b5t overexpressed gene protein) (bog protein).
Kynurenine-formamidase : human-AFMIDHomo sapiens (Human) Kynurenine formamidase.
LIDHydrolase : human-LDAHHomo sapiens (Human) lipid droplet-associated hydrolase (LDAH) C2orf43.
Lipase_3 : human-DAGLAHomo sapiens (Human) DAGLA Sn1-specific diacylglycerol lipase alpha DGL-alpha, neural stem cell-derived dendrite regulator KIAA0659, human-DAGLBHomo sapiens (Human) DAGLB Sn1-specific diacylglycerol lipase beta kccr13l FLJ36639.
Lipoprotein_Lipase : human-LIPGHomo sapiens (Human) endothelial lipase LIPE_HUMAN flj43354, human-LPL Homo sapiens (Human) Lipoprotein lipase LPL, LIPD.
LYsophospholipase_carboxylesterase : human-LYPLA1 Homo sapiens (Human) lysophospholipase I (LYPLA1) APT1, acyl-protein thioesterase 1 S-depalmitoylase, human-LYPLA2 Homo sapiens (Human) acyl-protein thioesterase dJ886K2.4 lysophospholipase II APT2, human-LYPLAL1 Homo sapiens (Human) LYPLAL1 26.3 kda protein lysophospholipase-like 1.
Maspardin-ACP33-SPG21_like : human-SPG21Homo sapiens (Human) Maspardin spg21 acid cluster protein 33 ACP33 sbm-019 (gl010)flj24010 Maspardin.
MEST-like : human-MESTHomo sapiens (Human) MEST mesoderm-specific transcript.
Monoglyceridelipase_lysophospholip : human-MGLL Homo sapiens (Human) Monoglyceride lipase (MAGL) lysophospholipase homolog.
Ndr_family : human-NDRG1 Homo sapiens (Human) N-myc downstream-regulated gene 1 protein (cap43,rit42, ndr1 DRG1, PROXY1, RTP, TDD5), human-NDRG2 Homo sapiens (Human) ndrg2 protein N-myc downstream-regulated gene 2 protein (syld709613 protein) ndr1-related protein 2, human-NDRG3 Homo sapiens (Human) ndrg3 protein ndr1-related development protein ndr3 otthump00000030883 otthump00000030882, human-NDRG4Homo sapiens (Human) NDRG4, N-myc downstream-regulated gene 4 protein (smap-8) flj42011 flj16174 flj44611.
Neuroligin : human-NLGN1 Homo sapiens (Human) Neuroligin 1 KIAA1070 protein, human-NLGN2 Homo sapiens (Human) neuroligin 2 (KIAA1366), human-NLGN3Homo sapiens (Human) Neuroligin 3 KIAA1480, human-NLGN4X Homo sapiens (Human) Neuroligin-4, X-linked (HNLX) Neuroligin4 KIAA0951, human-NLGN4YHomo sapiens (Human) Neuroligin-4, Y-linked precursor (Neuroligin Y) KIAA0951.
NLS3-Tex30 : human-KANSL3Homo sapiens (Human) KAT8 regulatory NSL complex subunit 3, Testis development protein PRTD, KIAA1310, PRTD, SI1, FLJ10081, NSL3, Rcd1, human-TEX30Homo sapiens (Human) testis expressed 30 C13orf27 chromosome 13 open reading frame 27.
PAF-Acetylhydrolase : human-PAFAH2Homo sapiens (Human) (EC 3.1.1.47) platelet-activating factor acetylhydrolase 2, cytoplasmic (serine dependent phospholipase a2) (hsd-pla2), PAFAH2, PAFA2 PAF-AH, human-PLA2G7 Homo sapiens (Human) plasma PAF acetylhydrolase Phospholipase A2 groupe 7 PLA2G7 PAFAH PAF-AH Lp-PLA(2).
Palmitoyl-protein_thioesterase : human-PPT1 Homo sapiens (Human) palmitoyl-protein thioesterase (PPT), human-PPT2 Homo sapiens (Human) 34.9 kda protein (palmitoyl-protein thioesterase-2).
Pancreatic_lipase : human-PNLIP Homo sapiens (Human) triacylglycerol lipase (pancreatic lipase), human-PNLIPRP1 Homo sapiens (Human) pancreatic lipase related protein 1, human-PNLIPRP2 Homo sapiens (Human) pancreatic lipase related protein 2, human-PNLIPRP3Homo sapiens (Human) Pancreatic lipase-related protein 3.
PC-sterol_acyltransferase : human-LCAT Homo sapiens (Human) phosphatidylcholine-sterol acyltransferase. Lecithin-cholesterol acyltransferase, human-PLA2G15 Homo sapiens (Human) Group XV phospholipase A2 lcat-like lysophospholipase (llpl) (unq341/pro540).
Pectinacetylesterase-Notum : human-NOTUM Homo sapiens (Human) Protein notum homolog.
PGAP1 : human-PGAP1Homo sapiens (Human)GPI inositol-deacylase PGAP1 117.8 kd protein in ste2-frs2 intergenic region, human-SERAC1Homo sapiens (Human) Protein SERAC1.
Phospholipase : human-LIPHHomo sapiens (Human) membrane-bound phosphatidic acid-selective phospholipase a1-alpha, LPD lipase-related protein mPA-PLA1 alpha, human-LIPIHomo sapiens (Human) membrane-associated phosphatidic acid-selective phospholipase a1 beta mPA-PLA1 beta (LPD lipase) Cancer/testis antigen 17 CT17, human-PLA1AHomo sapiens (Human) Phospholipase A1 member A, phosphatidylserine-specific phospholipase A1 deltaC.
PPase_methylesterase_euk : human-PPME1 Homo sapiens (Human) protein phosphatase PP2A methylesterase-1 (EC 3.1.1.-) (pme-1).
Prolylcarboxypeptidase : human-DPP7 Homo sapiens (Human), Dipeptidyl peptidase 2, quiescent cell proline dipeptidase precursor, DPP7, DPP2, QPP, human-PRCP Homo sapiens (Human) Lysosomal Pro-X carboxypeptidase C prolylcarboxypeptidase , Angiotensinase C, Proline carboxypeptidase (EC3.4.16.2), human-PRSS16Homo sapiens (Human) PRSS16 protease, serine, 16 (thymus) TSSP thymus-specific serine protease precursor (EC 3.4.-.-).
S9N_PPCE_Peptidase_S9 : human-PREP Homo sapiens (Human) Prolyl endopeptidase PE, Post-proline cleaving enzyme PPCE, prolyl oligopeptidase POP.
S9N_PREPL_Peptidase_S9 : human-PREPL Homo sapiens (Human) PREPL Prolylendopeptidase-like KIAA0436.
SERHL : human-SERHL2Homo sapiens (Human) serine hydrolase-like protein 2 SERHL2 chomosome 22.
Thioesterase : human-FASN Homo sapiens (Human) FAS FASN Fatty acid synthase Thioesterase domain (EC 2.3.1.85), human-OLAH Homo sapiens (Human) s-acyl fatty acid synthase thioesterase, medium chain OLAH THEDC1 SAST (EC 3.1.2.14).
Thyroglobulin : human-TG Homo sapiens (Human) Thyroglobulin TG Tg.
Valacyclovir-hydrolase : human-BPHL Homo sapiens (Human) biphenyl hydrolase-like DJ40E16.6.3, breast epithelial mucin-associated antigen AG BPHL (mcnaa), Valacyclovir hydrolase VACVase

Title: Interindividual variability of carboxymethylenebutenolidase homolog, a novel olmesartan medoxomil hydrolase, in the human liver and intestine
Ishizuka T, Rozehnal V, Fischer T, Kato A, Endo S, Yoshigae Y, Kurihara A, Izumi T
Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, 41:1156, 2013 : PubMed
Abstract


ESTHER: Ishizuka_2013_Drug.Metab.Dispos_41_1156
PubMedSearch: Ishizuka 2013 Drug.Metab.Dispos 41 1156
PubMedID: 23471504
Gene_locus related to this paper: human-CMBL

Abstract

Olmesartan medoxomil (OM) is a prodrug-type angiotensin II type 1 receptor antagonist. OM is rapidly converted into its active metabolite olmesartan by multiple hydrolases in humans, and we recently identified carboxymethylenebutenolidase homolog (CMBL) as one of the OM bioactivating hydrolases. In the present study, we further investigated the interindividual variability of mRNA and protein expression of CMBL and OM-hydrolase activity using 40 individual human liver and 30 intestinal specimens. In the intestinal samples, OM-hydrolase activity strongly correlated with the CMBL protein expression, clearly indicating that CMBL is a major contributor to the prodrug bioactivation in human intestine. The protein and activity were highly distributed in the proximal region (duodenum and jejunum) and decreased to the distal region of the intestine. Although there was high interindividual variability (16-fold) in both the protein and activity in the intestinal segments from the duodenum to colon, the interindividual variability in the duodenum and jejunum was relatively small (3.0- and 2.4-fold, respectively). In the liver samples, the interindividual variability in the protein and activity was 4.1- and 6.8-fold, respectively. No sex differences in the protein and activity were shown in the human liver or intestine. A genetically engineered Y155C mutant of CMBL, which was caused by a single nucleotide polymorphism rs35489000, showed significantly lower OM-hydrolase activity than the wild-type protein although no minor allele was genotyped in the 40 individual liver specimens.



        

Title: Human carboxymethylenebutenolidase as a bioactivating hydrolase of olmesartan medoxomil in liver and intestine
Ishizuka T, Fujimori I, Kato M, Noji-Sakikawa C, Saito M, Yoshigae Y, Kubota K, Kurihara A, Izumi T and Okazaki O <1 more author(s)> Ishizuka T, Fujimori I, Kato M, Noji-Sakikawa C, Saito M, Yoshigae Y, Kubota K, Kurihara A, Izumi T, Ikeda T, Okazaki O (- 1)
Ref: Journal of Biological Chemistry, 285:11892, 2010 : PubMed
Abstract


ESTHER: Ishizuka_2010_J.Biol.Chem_285_11892
PubMedSearch: Ishizuka 2010 J.Biol.Chem 285 11892
PubMedID: 20177059
Gene_locus related to this paper: human-CMBL

Abstract

Olmesartan medoxomil (OM) is a prodrug type angiotensin II type 1 receptor antagonist widely prescribed as an antihypertensive agent. Herein, we describe the identification and characterization of the OM bioactivating enzyme that hydrolyzes the prodrug and converts to its pharmacologically active metabolite olmesartan in human liver and intestine. The protein was purified from human liver cytosol by successive column chromatography and was identified by mass spectrometry to be a carboxymethylenebutenolidase (CMBL) homolog. Human CMBL, whose endogenous function has still not been reported, is a human homolog of Pseudomonas dienelactone hydrolase involved in the bacterial halocatechol degradation pathway. The ubiquitous expression of human CMBL gene transcript in various tissues was observed. The recombinant human CMBL expressed in mammalian cells was clearly shown to activate OM. By comparing the enzyme kinetics and chemical inhibition properties between the recombinant protein and human tissue preparations, CMBL was demonstrated to be the primary OM bioactivating enzyme in the liver and intestine. The recombinant CMBL also converted other prodrugs having the same ester structure as OM, faropenem medoxomil and lenampicillin, to their active metabolites. CMBL exhibited a unique sensitivity to chemical inhibitors, thus, being distinguishable from other known esterases. Site-directed mutagenesis on the putative active residue Cys(132) of the recombinant CMBL caused a drastic reduction of the OM-hydrolyzing activity. We report for the first time that CMBL serves as a key enzyme in the bioactivation of OM, hydrolyzing the ester bond of the prodrug type xenobiotics.



        

Title: The sequence of the human genome
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA and Zhu X <264 more author(s)> Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (- 264)
Ref: Science, 291:1304, 2001 : PubMed
Abstract


ESTHER: Venter_2001_Science_291_1304
PubMedSearch: Venter 2001 Science 291 1304
PubMedID: 11181995
Gene_locus related to this paper: human-AADAC, human-ABHD1, human-ABHD10, human-ABHD11, human-ACHE, human-BCHE, human-LDAH, human-ABHD18, human-CMBL, human-ABHD17A, human-KANSL3, human-LIPA, human-LYPLAL1, human-NDRG2, human-NLGN3, human-NLGN4X, human-NLGN4Y, human-PAFAH2, human-PREPL, human-RBBP9, human-SPG21

Abstract

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.