RBCC

Full text data of ACHE

ACHE [Confidence: high (a blood group or CD marker)]
Acetylcholinesterase; AChE; 3.1.1.7; Flags: Precursor

hRBCD IPI00026103
IPI00026103 Splice isoform 1 of P22303 Acetylcholinesterase precursor Splice isoform 1 of P22303 Acetylcholinesterase precursor membrane n/a 1 2 4 5 n/a 5 1 n/a n/a 1 1 1 1 n/a n/a 1 n/a 2 1 integral membrane protein n/a found at its expected molecular weight found at molecular weight

BGMUT yt
718 yt ACHE ACHE 3698-3700del YT 3698-3700del 3698-3700del (292-294 nt upstream of intron 5-exon 6 jn) none rare 7814634 L42812 Camp et al. Blumenfeld OO,curator 2008-09-30 20:19:13.323 NA

Comments
Isoform P22303-4 was detected.

UniProt P22303
ID ACES_HUMAN Reviewed; 614 AA.
AC P22303; A4D2E2; B7ZKZ0; D6W5X7; Q16169; Q29S23; Q2M324; Q504V3;
read moreAC Q53F46; Q86TM9; Q86YX9; Q9BXP7;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 22-JAN-2014, entry version 155.
DE RecName: Full=Acetylcholinesterase;
DE Short=AChE;
DE EC=3.1.1.7;
DE Flags: Precursor;
GN Name=ACHE;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM T).
RX PubMed=2263619; DOI=10.1073/pnas.87.24.9688;
RA Soreq H., Ben-Aziz R., Prody C.A., Seidman S., Gnatt A., Neville L.,
RA Lieman-Hurwitz J., Lev-Lehman E., Ginzberg D., Lipidot-Lifson Y.,
RA Zakut H.;
RT "Molecular cloning and construction of the coding region for human
RT acetylcholinesterase reveals a G + C-rich attenuating structure.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9688-9692(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS H; R AND T).
RX PubMed=8299725; DOI=10.1006/excr.1994.1039;
RA Karpel R., Ben Aziz-Aloya R., Sternfeld M., Ehrlich G., Ginzberg D.,
RA Tarroni P., Clementi F., Zakut H., Soreq H.;
RT "Expression of three alternative acetylcholinesterase messenger RNAs
RT in human tumor cell lines of different tissue origins.";
RL Exp. Cell Res. 210:268-277(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA Yang L., Zhang X.J.;
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM T).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM T).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-34; ALA-135 AND
RP ASN-353.
RG SeattleSNPs variation discovery resource;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM H), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-546 (ISOFORMS H/R/T).
RC TISSUE=Cerebellum, and Hippocampus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 521-614.
RX PubMed=11239002; DOI=10.1093/nar/29.6.1352;
RA Wilson M.D., Riemer C., Martindale D.W., Schnupf P., Boright A.P.,
RA Cheung T.L., Hardy D.M., Schwartz S., Scherer S.W., Tsui L.-C.,
RA Miller W., Koop B.F.;
RT "Comparative analysis of the gene-dense ACHE/TFR2 region on human
RT chromosome 7q22 with the orthologous region on mouse chromosome 5.";
RL Nucleic Acids Res. 29:1352-1365(2001).
RN [11]
RP PROTEIN SEQUENCE OF 256-273; 306-326; 396-422; 465-480 AND 528-551,
RP FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Erythrocyte;
RX PubMed=2714437; DOI=10.1016/0014-5793(89)81352-3;
RA Chhajlani V., Derr D., Earles B., Schmell E., August T.;
RT "Purification and partial amino acid sequence analysis of human
RT erythrocyte acetylcholinesterase.";
RL FEBS Lett. 247:279-282(1989).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-611.
RX PubMed=1748670;
RA Velan B., Grosfeld H., Kronman C., Leitner M., Gozes Y., Lazar A.,
RA Flashner Y., Marcus D., Cohen S., Shafferman A.;
RT "The effect of elimination of intersubunit disulfide bonds on the
RT activity, assembly, and secretion of recombinant human
RT acetylcholinesterase. Expression of acetylcholinesterase Cys-580-->Ala
RT mutant.";
RL J. Biol. Chem. 266:23977-23984(1991).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF ASP-206; SER-234; GLU-365; ASP-435 AND
RP HIS-478.
RX PubMed=1517212;
RA Shafferman A., Kronman C., Flashner Y., Leitner M., Grosfeld H.,
RA Ordentlich A., Gozes Y., Cohen S., Ariel N., Barak D.;
RT "Mutagenesis of human acetylcholinesterase. Identification of residues
RT involved in catalytic activity and in polypeptide folding.";
RL J. Biol. Chem. 267:17640-17648(1992).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11985878; DOI=10.1016/S0168-0102(02)00005-6;
RA Yang L., He H.Y., Zhang X.J.;
RT "Increased expression of intranuclear AChE involved in apoptosis of
RT SK-N-SH cells.";
RL Neurosci. Res. 42:261-268(2002).
RN [15]
RP 3D-STRUCTURE MODELING OF 35-574.
RX PubMed=9640563; DOI=10.1016/S1093-3263(98)00005-9;
RA Felder C.E., Botti S.A., Lifson S., Silman I., Sussman J.L.;
RT "External and internal electrostatic potentials of cholinesterase
RT models.";
RL J. Mol. Graph. Model. 15:318-327(1997).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 32-614 IN COMPLEX WITH
RP FASCICULIN-2, AND GLYCOSYLATION AT ASN-381 AND ASN-495.
RX PubMed=11053835; DOI=10.1107/S0907444900010659;
RA Kryger G., Harel M., Giles K., Toker L., Velan B., Lazar A.,
RA Kronman C., Barak D., Ariel N., Shafferman A., Silman I.,
RA Sussman J.L.;
RT "Structures of recombinant native and E202Q mutant human
RT acetylcholinesterase complexed with the snake-venom toxin fasciculin-
RT II.";
RL Acta Crystallogr. D 56:1385-1394(2000).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 575-614 IN COMPLEX WITH
RP COLQ.
RX PubMed=15526038; DOI=10.1038/sj.emboj.7600425;
RA Dvir H., Harel M., Bon S., Liu W.-Q., Vidal M., Garbay C.,
RA Sussman J.L., Massoulie J., Silman I.;
RT "The synaptic acetylcholinesterase tetramer assembles around a
RT polyproline II helix.";
RL EMBO J. 23:4394-4405(2004).
RN [18]
RP VARIANT BLOOD GROUP YT(B) ASN-353.
RX PubMed=8488842;
RA Bartels C.F., Zelinski T., Lockridge O.;
RT "Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene
RT accounts for YT blood group polymorphism.";
RL Am. J. Hum. Genet. 52:928-936(1993).
CC -!- FUNCTION: Terminates signal transduction at the neuromuscular
CC junction by rapid hydrolysis of the acetylcholine released into
CC the synaptic cleft. Role in neuronal apoptosis.
CC -!- CATALYTIC ACTIVITY: Acetylcholine + H(2)O = choline + acetate.
CC -!- SUBUNIT: Interacts with PRIMA1. The interaction with PRIMA1 is
CC required to anchor it to the basal lamina of cells and organize
CC into tetramers (By similarity). Isoform H generates GPI-anchored
CC dimers; disulfide linked. Isoform T generates multiple structures,
CC ranging from monomers and dimers to collagen-tailed and
CC hydrophobic-tailed forms, in which catalytic tetramers are
CC associated with anchoring proteins that attach them to the basal
CC lamina or to cell membranes. In the collagen-tailed forms, isoform
CC T subunits are associated with a specific collagen, COLQ, which
CC triggers the formation of isoform T tetramers, from monomers and
CC dimers. Isoform R may be monomeric.
CC -!- INTERACTION:
CC Q9Y215:COLQ; NbExp=2; IntAct=EBI-1637793, EBI-1637847;
CC P06733:ENO1; NbExp=2; IntAct=EBI-1637793, EBI-353877;
CC P63244:GNB2L1; NbExp=2; IntAct=EBI-1637793, EBI-296739;
CC -!- SUBCELLULAR LOCATION: Cell junction, synapse. Secreted (By
CC similarity). Cell membrane; Peripheral membrane protein (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Isoform T: Nucleus. Note=Only observed in
CC apoptotic nuclei.
CC -!- SUBCELLULAR LOCATION: Isoform H: Cell membrane; Lipid-anchor, GPI-
CC anchor; Extracellular side (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=T; Synonyms=ACHE-S, synaptic;
CC IsoId=P22303-1; Sequence=Displayed;
CC Name=H; Synonyms=ACHE-E, erythrocytic, E4-E5;
CC IsoId=P22303-2; Sequence=VSP_001457;
CC Note=GPI-anchor amidated glycine on Gly-588. Ref.9 (AAI43470)
CC sequence is in conflict in position: 592:P->R;
CC Name=R; Synonyms=ACHE-R, readthrough;
CC IsoId=P22303-4; Sequence=VSP_035569, VSP_035570;
CC Name=4;
CC IsoId=P22303-3; Sequence=VSP_035568;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Isoform H is highly expressed in erythrocytes.
CC -!- POLYMORPHISM: ACHE is responsible for the Yt blood group system
CC [MIM:112100]. The molecular basis of the Yt(a)=Yt1/Yt(b)=Yt2 blood
CC group antigens is a single variation in position 353; His-353
CC corresponds to Yt(a) and the rare variant with Asn-353 to Yt(b).
CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC mutation database;
CC URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system;=yt";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Acetylcholinesterase entry;
CC URL="http://en.wikipedia.org/wiki/Acetylcholinesterase";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ache/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ACHEID44317ch7q22.html";
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DR EMBL; M55040; AAA68151.1; -; mRNA.
DR EMBL; S71129; AAC60618.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AF334270; AAO32948.1; -; mRNA.
DR EMBL; AK291321; BAF84010.1; -; mRNA.
DR EMBL; AK223443; BAD97163.1; -; mRNA.
DR EMBL; AY750146; AAU43801.1; -; Genomic_DNA.
DR EMBL; AC011895; AAP22364.1; -; Genomic_DNA.
DR EMBL; AC011895; AAP22365.1; -; Genomic_DNA.
DR EMBL; CH236956; EAL23812.1; -; Genomic_DNA.
DR EMBL; CH236956; EAL23813.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76461.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76463.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76462.1; -; Genomic_DNA.
DR EMBL; BC036813; AAH36813.1; -; mRNA.
DR EMBL; BC105060; AAI05061.1; -; mRNA.
DR EMBL; BC105062; AAI05063.1; -; mRNA.
DR EMBL; BC143469; AAI43470.1; -; mRNA.
DR EMBL; AF312032; AAK21003.1; -; Genomic_DNA.
DR PIR; A39256; A39256.
DR RefSeq; NP_000656.1; NM_000665.3.
DR RefSeq; NP_001269378.1; NM_001282449.1.
DR RefSeq; NP_056646.1; NM_015831.2.
DR RefSeq; XP_005250414.1; XM_005250357.1.
DR RefSeq; XP_005250415.1; XM_005250358.1.
DR UniGene; Hs.154495; -.
DR PDB; 1B41; X-ray; 2.76 A; A=36-574.
DR PDB; 1F8U; X-ray; 2.90 A; A=32-614.
DR PDB; 1PUV; Model; -; A=37-574.
DR PDB; 1PUW; Model; -; A=37-574.
DR PDB; 1VZJ; X-ray; 2.35 A; A/B/C/D/E/F/G/H=575-614.
DR PDB; 2CLJ; Model; -; A=32-574.
DR PDB; 2X8B; X-ray; 2.95 A; A=32-614.
DR PDB; 3LII; X-ray; 3.20 A; A/B=35-574.
DR PDB; 4BDT; X-ray; 3.10 A; A=32-614.
DR PDB; 4EY4; X-ray; 2.16 A; A/B=33-574.
DR PDB; 4EY5; X-ray; 2.30 A; A/B=33-574.
DR PDB; 4EY6; X-ray; 2.40 A; A/B=33-574.
DR PDB; 4EY7; X-ray; 2.35 A; A/B=33-574.
DR PDB; 4EY8; X-ray; 2.60 A; A=33-574.
DR PDB; 4M0E; X-ray; 2.00 A; A/B=33-574.
DR PDB; 4M0F; X-ray; 2.30 A; A/B=33-574.
DR PDBsum; 1B41; -.
DR PDBsum; 1F8U; -.
DR PDBsum; 1PUV; -.
DR PDBsum; 1PUW; -.
DR PDBsum; 1VZJ; -.
DR PDBsum; 2CLJ; -.
DR PDBsum; 2X8B; -.
DR PDBsum; 3LII; -.
DR PDBsum; 4BDT; -.
DR PDBsum; 4EY4; -.
DR PDBsum; 4EY5; -.
DR PDBsum; 4EY6; -.
DR PDBsum; 4EY7; -.
DR PDBsum; 4EY8; -.
DR PDBsum; 4M0E; -.
DR PDBsum; 4M0F; -.
DR ProteinModelPortal; P22303; -.
DR SMR; P22303; 36-608.
DR DIP; DIP-1119N; -.
DR IntAct; P22303; 8.
DR MINT; MINT-149019; -.
DR BindingDB; P22303; -.
DR ChEMBL; CHEMBL2095233; -.
DR DrugBank; DB01122; Ambenonium.
DR DrugBank; DB00572; Atropine.
DR DrugBank; DB00122; Choline.
DR DrugBank; DB01245; Decamethonium.
DR DrugBank; DB00944; Demecarium bromide.
DR DrugBank; DB00843; Donepezil.
DR DrugBank; DB01010; Edrophonium.
DR DrugBank; DB01364; Ephedrine.
DR DrugBank; DB00674; Galantamine.
DR DrugBank; DB00483; Gallamine Triethiodide.
DR DrugBank; DB00677; Isoflurophate.
DR DrugBank; DB01400; Neostigmine.
DR DrugBank; DB00981; Physostigmine.
DR DrugBank; DB00545; Pyridostigmine.
DR DrugBank; DB00989; Rivastigmine.
DR DrugBank; DB00382; Tacrine.
DR DrugBank; DB01199; Tubocurarine.
DR GuidetoPHARMACOLOGY; 2465; -.
DR MEROPS; S09.979; -.
DR PhosphoSite; P22303; -.
DR DMDM; 113037; -.
DR SWISS-2DPAGE; P22303; -.
DR PaxDb; P22303; -.
DR PRIDE; P22303; -.
DR Ensembl; ENST00000241069; ENSP00000241069; ENSG00000087085.
DR Ensembl; ENST00000302913; ENSP00000303211; ENSG00000087085.
DR Ensembl; ENST00000411582; ENSP00000404865; ENSG00000087085.
DR Ensembl; ENST00000412389; ENSP00000394976; ENSG00000087085.
DR Ensembl; ENST00000419336; ENSP00000403474; ENSG00000087085.
DR Ensembl; ENST00000428317; ENSP00000414858; ENSG00000087085.
DR GeneID; 43; -.
DR KEGG; hsa:43; -.
DR UCSC; uc003uxd.3; human.
DR CTD; 43; -.
DR GeneCards; GC07M100487; -.
DR HGNC; HGNC:108; ACHE.
DR HPA; HPA019704; -.
DR MIM; 100740; gene+phenotype.
DR MIM; 112100; phenotype.
DR neXtProt; NX_P22303; -.
DR PharmGKB; PA20; -.
DR eggNOG; COG2272; -.
DR HOVERGEN; HBG008839; -.
DR KO; K01049; -.
DR OMA; RPPWCPL; -.
DR OrthoDB; EOG789C9R; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_17015; Metabolism of proteins.
DR SABIO-RK; P22303; -.
DR EvolutionaryTrace; P22303; -.
DR GeneWiki; Acetylcholinesterase; -.
DR GenomeRNAi; 43; -.
DR NextBio; 173; -.
DR PRO; PR:P22303; -.
DR ArrayExpress; P22303; -.
DR Bgee; P22303; -.
DR Genevestigator; P22303; -.
DR GO; GO:0031225; C:anchored to membrane; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IBA:RefGenome.
DR GO; GO:0005605; C:basal lamina; NAS:HGNC.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IBA:RefGenome.
DR GO; GO:0030425; C:dendrite; IBA:RefGenome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IBA:RefGenome.
DR GO; GO:0005615; C:extracellular space; IBA:RefGenome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HGNC.
DR GO; GO:0031594; C:neuromuscular junction; IBA:RefGenome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:HGNC.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:RefGenome.
DR GO; GO:0042734; C:presynaptic membrane; IBA:RefGenome.
DR GO; GO:0042166; F:acetylcholine binding; NAS:UniProtKB.
DR GO; GO:0003990; F:acetylcholinesterase activity; IMP:UniProtKB.
DR GO; GO:0001540; F:beta-amyloid binding; TAS:UniProtKB.
DR GO; GO:0005518; F:collagen binding; IDA:HGNC.
DR GO; GO:0043236; F:laminin binding; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; NAS:UniProtKB.
DR GO; GO:0017171; F:serine hydrolase activity; IDA:HGNC.
DR GO; GO:0001507; P:acetylcholine catabolic process in synaptic cleft; NAS:UniProtKB.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; TAS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; TAS:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; TAS:UniProtKB.
DR GO; GO:0019695; P:choline metabolic process; IBA:RefGenome.
DR GO; GO:0006260; P:DNA replication; TAS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; TAS:UniProtKB.
DR GO; GO:0032223; P:negative regulation of synaptic transmission, cholinergic; IC:HGNC.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; TAS:Reactome.
DR GO; GO:0045212; P:neurotransmitter receptor biosynthetic process; IEA:Ensembl.
DR GO; GO:0002076; P:osteoblast development; IEP:HGNC.
DR GO; GO:0006656; P:phosphatidylcholine biosynthetic process; TAS:Reactome.
DR GO; GO:0050714; P:positive regulation of protein secretion; TAS:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; IEA:Ensembl.
DR GO; GO:0031623; P:receptor internalization; IEA:Ensembl.
DR GO; GO:0050770; P:regulation of axonogenesis; IBA:RefGenome.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IBA:RefGenome.
DR GO; GO:0001919; P:regulation of receptor recycling; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; TAS:UniProtKB.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0007416; P:synapse assembly; TAS:UniProtKB.
DR InterPro; IPR014788; AChE_tetra.
DR InterPro; IPR002018; CarbesteraseB.
DR InterPro; IPR019826; Carboxylesterase_B_AS.
DR InterPro; IPR019819; Carboxylesterase_B_CS.
DR InterPro; IPR000997; Cholinesterase.
DR Pfam; PF08674; AChE_tetra; 1.
DR Pfam; PF00135; COesterase; 1.
DR PRINTS; PR00878; CHOLNESTRASE.
DR ProDom; PD415333; AChE_tetra; 1.
DR PROSITE; PS00122; CARBOXYLESTERASE_B_1; 1.
DR PROSITE; PS00941; CARBOXYLESTERASE_B_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood group antigen;
KW Cell junction; Cell membrane; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; GPI-anchor;
KW Hydrolase; Lipoprotein; Membrane; Neurotransmitter degradation;
KW Nucleus; Polymorphism; Reference proteome; Secreted; Serine esterase;
KW Signal; Synapse.
FT SIGNAL 1 31 Potential.
FT CHAIN 32 614 Acetylcholinesterase.
FT /FTId=PRO_0000008587.
FT ACT_SITE 234 234 Acyl-ester intermediate.
FT ACT_SITE 365 365 Charge relay system.
FT ACT_SITE 478 478 Charge relay system.
FT CARBOHYD 296 296 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 381 381 N-linked (GlcNAc...).
FT CARBOHYD 495 495 N-linked (GlcNAc...).
FT DISULFID 100 127
FT DISULFID 288 303
FT DISULFID 440 560
FT DISULFID 611 611 Interchain.
FT VAR_SEQ 357 444 Missing (in isoform 4).
FT /FTId=VSP_035568.
FT VAR_SEQ 575 614 DTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL
FT -> ASEAPSTCPGFTHGEAAPRPGLPLPLLLLHQLLLLFLS
FT HLRRL (in isoform H).
FT /FTId=VSP_001457.
FT VAR_SEQ 575 603 DTLDEAERQWKAEFHRWSSYMVHWKNQFD -> GMQGPAGS
FT AGRRGVGARQCNPSLLPLASE (in isoform R).
FT /FTId=VSP_035569.
FT VAR_SEQ 604 614 Missing (in isoform R).
FT /FTId=VSP_035570.
FT VARIANT 34 34 R -> Q (in dbSNP:rs17881553).
FT /FTId=VAR_021325.
FT VARIANT 135 135 P -> A (in dbSNP:rs17885778).
FT /FTId=VAR_021326.
FT VARIANT 333 333 V -> E (in dbSNP:rs8286).
FT /FTId=VAR_011934.
FT VARIANT 353 353 H -> N (in Yt(b) antigen;
FT dbSNP:rs1799805).
FT /FTId=VAR_002359.
FT MUTAGEN 206 206 D->N: Misfolding, absence of secretion.
FT MUTAGEN 234 234 S->A: Loss of activity.
FT MUTAGEN 365 365 E->A: Loss of activity.
FT MUTAGEN 435 435 D->N: Misfolding, absence of secretion.
FT MUTAGEN 478 478 H->A: Loss of activity.
FT MUTAGEN 611 611 C->A: Impairment of interchain disulfide
FT bridge formation.
FT CONFLICT 279 279 A -> T (in Ref. 5; BAD97163).
FT CONFLICT 415 415 D -> G (in Ref. 5; BAD97163).
FT CONFLICT 486 486 F -> L (in Ref. 9; AAI43470).
FT HELIX 37 39
FT STRAND 40 43
FT STRAND 46 49
FT STRAND 51 53
FT STRAND 60 67
FT HELIX 74 76
FT STRAND 88 92
FT STRAND 99 101
FT HELIX 112 115
FT STRAND 123 125
FT STRAND 129 137
FT STRAND 143 149
FT TURN 153 155
FT HELIX 162 164
FT HELIX 167 173
FT STRAND 176 180
FT HELIX 185 189
FT STRAND 196 198
FT HELIX 202 217
FT HELIX 218 221
FT STRAND 223 233
FT HELIX 235 244
FT HELIX 247 250
FT STRAND 254 260
FT TURN 266 268
FT HELIX 272 285
FT HELIX 297 305
FT HELIX 309 315
FT HELIX 316 319
FT STRAND 320 323
FT STRAND 333 341
FT HELIX 343 348
FT STRAND 356 362
FT STRAND 364 366
FT HELIX 367 370
FT TURN 371 373
FT STRAND 379 381
FT HELIX 387 397
FT HELIX 403 413
FT HELIX 422 437
FT HELIX 439 451
FT STRAND 455 461
FT HELIX 472 474
FT TURN 478 481
FT HELIX 482 485
FT HELIX 488 490
FT STRAND 492 494
FT HELIX 498 517
FT STRAND 526 528
FT TURN 536 538
FT STRAND 540 547
FT STRAND 550 553
FT HELIX 557 564
FT HELIX 566 572
FT HELIX 580 601
SQ SEQUENCE 614 AA; 67796 MW; B9AA84C77831C302 CRC64;
MRPPQCLLHT PSLASPLLLL LLWLLGGGVG AEGREDAELL VTVRGGRLRG IRLKTPGGPV
SAFLGIPFAE PPMGPRRFLP PEPKQPWSGV VDATTFQSVC YQYVDTLYPG FEGTEMWNPN
RELSEDCLYL NVWTPYPRPT SPTPVLVWIY GGGFYSGASS LDVYDGRFLV QAERTVLVSM
NYRVGAFGFL ALPGSREAPG NVGLLDQRLA LQWVQENVAA FGGDPTSVTL FGESAGAASV
GMHLLSPPSR GLFHRAVLQS GAPNGPWATV GMGEARRRAT QLAHLVGCPP GGTGGNDTEL
VACLRTRPAQ VLVNHEWHVL PQESVFRFSF VPVVDGDFLS DTPEALINAG DFHGLQVLVG
VVKDEGSYFL VYGAPGFSKD NESLISRAEF LAGVRVGVPQ VSDLAAEAVV LHYTDWLHPE
DPARLREALS DVVGDHNVVC PVAQLAGRLA AQGARVYAYV FEHRASTLSW PLWMGVPHGY
EIEFIFGIPL DPSRNYTAEE KIFAQRLMRY WANFARTGDP NEPRDPKAPQ WPPYTAGAQQ
YVSLDLRPLE VRRGLRAQAC AFWNRFLPKL LSATDTLDEA ERQWKAEFHR WSSYMVHWKN
QFDHYSKQDR CSDL
//

MIM 100740
*RECORD*
*FIELD* NO
100740
*FIELD* TI
*100740 ACETYLCHOLINESTERASE; ACHE
;;ACETYLCHOLINE ACETYLHYDROLASE;;
YT
*FIELD* TX
read more
DESCRIPTION

Acetylcholinesterase (ACHE; EC 3.1.1.7) controls synaptic and
neurohumoral cholinergic activity by hydrolyzing the neurotransmitter
acetylcholine. ACHE function relies on precise regulation of its
expression and localization. In particular, alternative splicing of the
3-prime region of ACHE results in ACHE isoforms with distinct C-terminal
peptides that determine posttranslational maturation and oligomeric
assembly (summary by Xie et al., 2010).

CLONING

Soreq et al. (1990) obtained several ACHE cDNA clones truncated at the
5-prime end from adult and fetal human tissues, and they obtained the
5-prime end of ACHE from a genomic DNA library. The 5-prime end of the
coding region contains a GC-rich region. The deduced 614-amino acid
protein has a 25-amino acid N-terminal signal sequence, 3 potential
N-glycosylation sites, and 7 cysteines. Six of the cysteines are
predicted to form 3 intrasubunit disulfide bonds, and the free cysteine,
cys611, is predicted to be involved in ACHE dimerization. The mature
protein is predicted to begin with glu32 and to contain 583 amino acids.

Li et al. (1991) obtained mouse and human genomic DNA clones for ACHE,
as well as several mouse cDNA clones, and they extensively characterized
the mouse clones. They identified 3 alternative splicing events at the
3-prime end of Ache. All Ache variants use the first 3 exons, which
encode the N-terminal signal peptide and the first 535 amino acids of
the mature protein. Alternative usage of the next exon alters the
reading frame and introduces structural divergence in the C termini of
the catalytic subunits. mRNA protection studies showed that an Ache
transcript encoding a hydrophilic catalytic subunit was the dominant
species in mouse brain and muscle. This isoform is found as soluble
dimers and tetramers and is also disulfide linked to the
lipid-associated noncatalytic subunit and the collagen-tail noncatalytic
subunits. Two other Ache splice variants, one including intronic
sequence and the other including a novel 5-prime exon after the common
exons, were expressed in mouse hematopoietic cells. These variants were
predicted to produce a monomeric Ache isoform and a
glycophospholipid-linked Ache isoform, respectively.

Using Northern blot and RT-PCR analyses, Karpel et al. (1994) identified
3 ACHE splice variants in human brain and tumor cell lines. All 3
variants include exons 1 through 4 and differ through alternative
splicing at their 3-prime ends. An ACHE variant containing alternative
exon 6 was expressed in adult brain and was predicted to encode the
mature 583-amino acid globular hydrophilic subunit. This isoform forms
homotetramers that can be 'tailed' to the membrane through interaction
with other subunits. Two ACHE variants, one including alternative exon 5
and the other including unspliced intron 4 and exon 5, designated the
read-through variant, were present in tumor tissues and cells, but not
brain. These variants were predicted to encode hydrophobic
phosphoinositide-linked ACHE isoforms that diverge from the mature
583-amino acid tailed isoform after amino acid 543. The novel C termini
of both of these isoforms include a free cysteine, a consensus HG
element for phosphoinositide linkage, and a 29-amino acid hydrophobic
cleavable peptide. The mature proteins encoded by the exon 5- and intron
4/exon 5-containing variants (i.e., excluding the C-terminal cleavable
peptide) contain 557 and 583 amino acids, respectively. Karpel et al.
(1994) noted that intron 4 of rodent Ache contains a stop codon not
present in human intron 4, indicating that the rodent read-through
transcript produces a shorter isoform incapable of
phosphoinositide-linkage.

Santos et al. (2007) stated that all 3 ACHE variants generated by
3-prime alternative splicing contain exons 1 through 4. Synaptic ACHE
(ACHE-S), also called tailed ACHE (ACHE-T), includes exon 6 and is the
most frequent splice variant in brain and muscle cells. Erythrocyte ACHE
(ACHE-E), also called hydrophobic ACHE (ACHE-H), includes exon 5, and
read-through ACHE (ACHE-R) includes intron 4 and exon 5. All 3 isoforms
show catalytic activity, but they differ in their noncatalytic
activities. Santos et al. (2007) noted that 5-prime alternative splicing
of ACHE also occurs. Using RT-PCR, Santos et al. (2007) detected ACHE-S
expression in all cell types examined, including human umbilical vein
endothelial cells (HUVECs). ACHE-E was detected in Jurkat T-cell
leukemia cells, K562 erythroleukemia cells, and HUVECs, while ACHE-R was
detected only in Jurkat cells. Western blot analysis detected an ACHE
protein with an apparent molecular mass of 70 kD in both cytoplasmic and
nuclear fractions and both soluble and insoluble fractions of HUVECs and
cardiac microvascular endothelial cells (HMECs). An ACHE protein with an
apparent molecular mass of 55 kD was detected by an antibody directed
against the ACHE N terminus, but its expression was restricted to
nuclear and insoluble fractions of HUVECs and HMECs.

GENE STRUCTURE

Li et al. (1991) identified 5 coding exons in the ACHE gene, with the
ACHE coding region spanning about 5 kb.

Karpel et al. (1994) determined that the ACHE gene contains 6 exons and
spans about 7 kb.

MAPPING

It has been demonstrated that the Yt erythrocyte blood group antigen
system (112100) resides on the acetylcholinesterase molecule. Since this
blood group system has been mapped to the long arm of chromosome 7 in
the proximity of the COL1A2 (120160) locus, one can conclude that this
is the site of the acetylcholinesterase gene. That such was the case was
demonstrated by Getman et al. (1992). By chromosomal in situ suppression
hybridization analysis, they showed that a single gene is located at
chromosome 7q22 and confirmed the results by PCR analysis of genomic DNA
from a human/hamster somatic cell hybrid containing a single human
chromosome 7. Thus the gene maps to the same region that is frequently
the site of nonrandom deletion in leukemias of myeloid cell precursors
known to express acetylcholinesterase during normal differentiation.

Ehrlich et al. (1992) mapped the ACHE gene to chromosome 7q22 by
fluorescence in situ hybridization and by selective PCR amplification
from a somatic hybrid cell panel and chromosome-sorted DNA libraries.
This conforms well with the previous assignment of the YT blood group to
chromosome 7q21-q22. Ehrlich et al. (1992) suggested that the assignment
of the gene to chromosome 7q22 may provide an explanation of the in vivo
amplification of the ACHE gene observed in ovarian tumors and leukemias
and the phenomenon of tumor-related breakage in chromosome 7q.

By analysis of a RFLP in recombinant inbred (RI) strains, Rachinsky et
al. (1992) demonstrated that the Ache gene is located on distal mouse
chromosome 5.

GENE FUNCTION

Soreq et al. (1990) microinjected human ACHE cDNA into Xenopus oocytes
and observed catalytic activity. ACHE had a marked preference for
acetylthiocholine over butyrylthiocholine as substrate, and it was
specifically sensitive to an ACHE inhibitor.

Karpel et al. (1994) showed that the ACHE splice variant containing
intron 4 was fully functional following microinjection into Xenopus
oocytes.

To explore neuronal mechanisms underlying long-term consequences of
stress, Meshorer et al. (2002) studied stress-induced changes in the
neuritic translocation of acetylcholinesterase splice variants. Meshorer
et al. (2002) found AChE-S mRNA and protein in neurites under normal
conditions. Corticosterone, anticholinesterases, and forced swim each
facilitated a rapid (minutes), yet long-lasting (weeks), shift from
AChE-S to the normally rare AChE-R mRNA, promoted AChE-R mRNA
translocation into neurites, and induced enzyme secretion. Weeks after
stress, electrophysiologic measurements in hippocampus slices displayed
apparently normal evoked synaptic responses but extreme hypersensitivity
to both anticholinesterases and atropine. Meshorer et al. (2002)
concluded that their findings suggest that neuronal hypersensitivity
under stress involves neuritic replacement of AChE-S with AChE-R.

By expressing cDNAs encoding mouse Prima (PRIMA1; 613851) and rat Ache
in mammalian cell lines and Xenopus oocytes, Perrier et al. (2002)
showed that Prima directed cell surface expression of enzymatically
active Ache tetramers. Mutation analysis revealed that the C-terminal
domain of Ache interacted with the proline-rich attachment domain of
Prima. Extraction of cholinesterases from mouse brain and skeletal
muscle revealed that Prima associated with most endogenous Ache
tetramers in mouse brain and with most endogenous Ache and Bche
tetramers in skeletal muscle.

Perrier et al. (2003) found that Ache activity in mouse brain better
correlated with expression of Prima transcripts that with expression of
Ache transcripts. Coexpression of the 2 Prima variants with Ache in COS
cells showed that both Prima I and Prima II produced amphiphilic Ache
tetramers at the cell surface. Immunodepletion of Prima I from mouse
brain extracts depleted the major part of Ache activity, suggesting that
Prima I predominates in Ache tetramer formation.

Santos et al. (2007) found that VEGF (VEGFA; 192240) downregulated
expression of the 55-kD ACHE protein, but not the 70-kD protein, in
HUVECs.

Xie et al. (2009) showed that overexpression of an active mutant of Raf
(RAF1; 164760) induced expression of both Prima and Ache-T transcripts
in cultured rat neurons. Quantitative PCR analysis revealed upregulation
of both Prima and Ache-T transcripts with differentiation in rat
cortical neurons, with concomitant increase in Ache activity.
Coexpression of Prima with Ache-T was required to induce formation of
active Ache-T tetramers.

Xie et al. (2010) showed that Prima integrated Ache tetramers into
membrane rafts in rat brain. The fraction of membrane-bound Ache in
rafts was markedly higher in low rather than high detergent
concentration. The proportion of detergent-resistant ACHE in rafts
increased during brain development. In cultured rodent neuroblastoma
cells, association of Ache with membrane rafts required both cholesterol
and the cholesterol-binding motif of transfected mouse Prima. Both Prima
isoforms could recruit Ache tetramers to membrane rafts, but Prima I
directed a more stable association of Ache with membrane rafts.

MOLECULAR GENETICS

Hypersensitivity to acetylcholinesterase inhibitors (anti-AChEs) causes
severe nervous system symptoms under low dose exposure. Shapira et al.
(2000) found a 4-bp deletion located 17 kb upstream of the transcription
start site that abolished 1 of 2 adjacent HNF3 (see 602294) binding
sites. The allele frequency was 0.012, with a strong linkage between the
deletion and the biochemically neutral his322-to-asn polymorphism
(100740.0001). Heterozygous carriers of the deletion included a proband
who presented with acute hypersensitivity to the anti-AChE
pyridostigmine and another with unexplained excessive vomiting during a
fourth pregnancy following 3 spontaneous abortions. Electromobility
shift assays, transfection studies, and measurements of AChE levels in
immortalized lymphocytes and peripheral blood demonstrated increased
AChE expression from the mutant allele, probably caused by alleviation
of competition between the 2 hepatocyte nuclear factor-3 binding sites.
Moreover, AChE-overexpressing transgenic mice, unlike normal FVB/N mice,
displayed anti-AChE hypersensitivity and failed to transcriptionally
induce AChE production following exposure to anti-AChEs. The authors
concluded that promoter polymorphism(s) in the ACHE gene are dominant
susceptibility factor(s) for adverse responses to exposure or to
treatment with anti-AChEs.

ANIMAL MODEL

Feng et al. (1999) generated ColQ (603033) -/- mice to study the roles
played by ColQ and AChE in synapses and elsewhere. Such mice failed to
thrive and most died before reaching maturity. They completely lacked
asymmetric AChE in skeletal and cardiac muscles, specifically at the
neuromuscular junction and in the brain. Nonetheless, neuromuscular
function was present. A compensatory mechanism appeared to be a partial
ensheathment of nerve terminals by Schwann cells. Such mice also lacked
the asymmetric forms of Bche. Surprisingly, globular AChE tetramers were
absent as well, suggesting a role for the ColQ gene in assembly or
stabilization of AChE forms that do not contain a collagenous subunit.

Volpicelli-Daley et al. (2003) noted that the use of AChE inhibitors to
enhance cholinergic transmission is a main treatment of Alzheimer
disease (AD; 104300), but that AChE inhibitors only modestly improve
symptoms, suggesting the existence of adaptive mechanisms that
downregulate the neuronal response to elevated ACh levels. In AChE
knockout mice (-/-), Volpicelli-Daley et al. (2003) found drastic
reductions in expression of several muscarinic ACh receptors in brain
regions associated with learning and memory, and diminished ability of
the receptors to initiate signaling cascades. The authors suggested that
AChR downregulation may contribute to the limited efficacy of chronic
treatment with AChE inhibitors in AD.

HISTORY

Coates and Simpson (1972) concluded that 3 phenotypic variants of
acetylcholinesterase result from 2 codominant alleles at a single locus.

Chen et al. (1978) studied 3 strains of human fibroblasts that were
trisomic for chromosome 2 and had an average level of AChE activity over
28 times higher than the average fibroblasts. The mean
pseudocholinesterase level of the trisomy 2 strains was normal. The 19
control strains comprised 10 trisomic for other autosomes and 9 euploid
strains. The AChE activity of control fibroblasts did not differ
significantly from zero. Despite the unusual elevation of AChE activity
in trisomy 2 fibroblasts, the level, expressed in terms of micrograms of
DNA, was only 1.5% of that in cerebral cortex. Two other enzymes,
xanthine oxidase and choline acetyltransferase, which, like AChE, have a
restricted distribution in human tissues, were absent from all 22
strains of fibroblasts. The results were interpreted as evidence for a
gene on chromosome 2 involved in regulation of AChE.

Rotundo et al. (1988) showed that all the forms of acetylcholinesterase
observed in avian nerves and muscle are encoded by a single autosomal
gene. Differences in assembly and localization of the multiple synaptic
forms of acetylcholinesterase are thought to arise through
posttranscriptional events.

Lapidot-Lifson et al. (1989) used acetylcholinesterase clones to study
coamplification of acetylcholinesterase and pseudocholinesterase, or
butyrylcholinesterase (BCHE; 177400). Their coamplification in certain
leukemias and in disorders of platelet formation suggested that the 2
loci may be linked. The pseudocholinesterase gene is located at
chromosome 3q25.2. Whereas pseudocholinesterase is a soluble plasma
enzyme presumed to be produced by the liver but also present in muscle
and brain, acetylcholinesterase or 'true' cholinesterase is involved in
the signal transmission at neuromuscular junctions and is also intensely
expressed in the human central nervous system and the erythrocyte
membrane.

*FIELD* AV
.0001
YT BLOOD GROUP POLYMORPHISM
ACHE, HIS322ASN

Bartels et al. (1993) demonstrated that the wildtype sequence of the
ACHE gene, which corresponds to the YT1 blood group antigen (112100),
has histidine at codon 322 (CAC) and that the rare variant, the YT2
blood group antigen, has asparagine (AAC) at that position.

*FIELD* SA
Telen and Whitsett (1992)
*FIELD* RF
1. Bartels, C. F.; Zelinski, T.; Lockridge, O.: Mutation at codon
322 in the human acetylcholinesterase (ACHE) gene accounts for YT
blood group polymorphism. Am. J. Hum. Genet. 52: 928-936, 1993.

2. Chen, Y.-T.; Worthy, T. E.; Krooth, R. S.: Evidence for a striking
increase in acetylcholinesterase activity in cultured human fibroblasts
which are trisomic for chromosome two. Somat. Cell Genet. 4: 265-298,
1978.

3. Coates, P. M.; Simpson, N. E.: Genetic variation in human erythrocyte
acetylcholinesterase. Science 175: 1466-1467, 1972.

4. Ehrlich, G.; Viegas-Pequignot, E.; Ginzberg, D.; Sindel, L.; Soreq,
H.; Zakut, H.: Mapping the human acetylcholinesterase gene to chromosome
7q22 by fluorescent in situ hybridization coupled with selective PCR
amplification from a somatic hybrid cell panel and chromosome-sorted
DNA libraries. Genomics 13: 1192-1197, 1992.

5. Feng, G.; Krejci, E.; Molgo, J.; Cunningham, J. M.; Massoulie,
J.; Sanes, J. R.: Genetic analysis of collagen Q: roles in acetylcholinesterase
and butyrylcholinesterase assembly and in synaptic structure and function. J.
Cell Biol. 144: 1349-1360, 1999.

6. Getman, D. K.; Eubanks, J. H.; Camp, S.; Evans, G. A.; Taylor,
P.: The human gene encoding acetylcholinesterase is located on the
long arm of chromosome 7. Am. J. Hum. Genet. 51: 170-177, 1992.

7. Karpel, R.; Ben Aziz-Alova, R.; Sternfeld, M.; Ehrlich, G.; Ginzberg,
D.; Tarroni, P.; Clementi, F.; Zakut, H.; Soreq, H.: Expression of
three alternative acetylcholinesterase messenger RNAs in human tumor
cell lines of different tissue origins. Exp. Cell Res. 210: 268-277,
1994.

8. Lapidot-Lifson, Y.; Prody, C. A.; Ginzberg, D.; Meytes, D.; Zakut,
H.; Soreq, H.: Coamplification of human acetylcholinesterase and
butyrylcholinesterase genes in blood cells: correlation with various
leukemias and abnormal megakaryocytopoiesis. Proc. Nat. Acad. Sci. 86:
4715-4719, 1989.

9. Li, Y.; Camp, S.; Rachinsky, T. L.; Getman, D.; Taylor, P.: Gene
structure of mammalian acetylcholinesterase: alternative exons dictate
tissue-specific expression. J. Biol. Chem. 266: 23083-23090, 1991.

10. Meshorer, E.; Erb, C.; Gazit, R.; Pavlovsky, L.; Kaufer, D.; Friedman,
A.; Glick, D.; Ben-Arie, N.; Soreq, H.: Alternative splicing and
neuritic mRNA translocation under long-term neuronal hypersensitivity. Science 295:
508-512, 2002.

11. Perrier, A. L.; Massoulie, J.; Krejci, E.: PRiMA: the membrane
anchor of acetylcholinesterase in the brain. Neuron 33: 275-285,
2002.

12. Perrier, N. A.; Kherif, S.; Perrier, A. L.; Dumas, S.; Mallet,
J.; Massoulie, J.: Expression of PRiMA in the mouse brain: membrane
anchoring and accumulation of 'tailed' acetylcholinesterase. Europ.
J. Neurosci. 18: 1837-1847, 2003.

13. Rachinsky, T. L.; Crenshaw, E. B., III; Taylor, P.: Assignment
of the gene for acetylcholinesterase to distal mouse chromosome 5. Genomics 14:
511-514, 1992.

14. Rotundo, R. L.; Gomez, A. M.; Fernandez-Valle, C.; Randall, W.
R.: Allelic variants of acetylcholinesterase: genetic evidence that
all acetylcholinesterase forms in avian nerves and muscles are encoded
by a single gene. Proc. Nat. Acad. Sci. 85: 7805-7809, 1988.

15. Santos, S. C. R.; Vala, I.; Miguel, C.; Barata, J. T.; Garcao,
P.; Agostinho, P.; Mendes, M.; Coelho, A. V.; Calado, A.; Oliveira,
C. R.; Silva, J. M.; Saldanha, C.: Expression and subcellular localization
of a novel nuclear acetylcholinesterase protein. J. Biol. Chem. 282:
25597-25603, 2007.

16. Shapira, M.; Tur-Kaspa, I.; Bosgraaf, L.; Livni, N.; Grant, A.
D.; Grisaru, D.; Korner, M.; Ebstein, R. P.; Soreq, H.: A transcription-activating
polymorphism in the ACHE promoter associated with acute sensitivity
to anti-acetylcholinesterases. Hum. Molec. Genet. 9: 1273-1281,
2000.

17. Soreq, H.; Ben-Aziz, R.; Prody, C. A.; Seidman, S.; Gnatt, A.;
Neville, L.; Lieman-Hurwitz, J.; Lev-Lehman, E.; Ginzberg, D.; Lapidot-Lifson,
Y.; Zakut, H.: Molecular cloning and construction of the coding region
for human acetylcholinesterase reveals a G+C-rich attenuating structure. Proc.
Nat. Acad. Sci. 87: 9688-9692, 1990.

18. Telen, M. J.; Whitsett, C. F.: Erythrocyte acetylcholinesterase
bears the Cartwright blood group antigens. (Abstract) Clin. Res. 40:
170A only, 1992.

19. Volpicelli-Daley, L. A.; Duysen, E. G.; Lockridge, O.; Levey,
A. I.: Altered hippocampal muscarinic receptors in acetylcholinesterase-deficient
mice. Ann. Neurol. 53: 788-796, 2003.

20. Xie, H. Q.; Choi, R. C. Y.; Leung, K. W.; Chen, V. P.; Chu, G.
K. Y.; Tsim, K. W. K.: Transcriptional regulation of proline-rich
membrane anchor (PRiMA) of globular form acetylcholinesterase in neuron:
an inductive effect of neuron differentiation. Brain Res. 1265:
13-23, 2009.

21. Xie, H. Q.; Liang, D.; Leung, K. W.; Chen, V. P.; Zhu, K. Y.;
Chan, W. K. B.; Choi, R. C. Y.; Massoulie, J.; Tsim, K. W. K.: Targeting
acetylcholinesterase to membrane rafts: a function mediated by the
proline-rich membrane anchor (PRiMA) in neurons. J. Biol. Chem. 285:
11537-11546, 2010.

*FIELD* CN
Matthew B. Gross - updated: 3/31/2011
Patricia A. Hartz - updated: 3/24/2011
Cassandra L. Kniffin - updated: 8/14/2003
Ada Hamosh - updated: 1/22/2002
George E. Tiller - updated: 6/29/2000
Wilson H. Y. Lo - updated: 8/6/1999
Victor A. McKusick - updated: 5/13/1997

*FIELD* CD
Victor A. McKusick: 12/15/1988

*FIELD* ED
mgross: 03/31/2011
mgross: 3/31/2011
terry: 3/24/2011
carol: 9/3/2010
alopez: 8/4/2010
mgross: 3/17/2004
cwells: 8/19/2003
ckniffin: 8/14/2003
alopez: 1/24/2002
terry: 1/22/2002
alopez: 6/29/2000
carol: 8/6/1999
alopez: 5/13/1997
terry: 5/6/1997
mark: 11/27/1996
carol: 4/6/1994
carol: 5/21/1993
carol: 4/14/1993
carol: 11/2/1992
carol: 10/15/1992
carol: 8/13/1992

MIM 112100
*RECORD*
*FIELD* NO
112100
*FIELD* TI
#112100 YT BLOOD GROUP ANTIGEN
;;CARTWRIGHT ANTIGEN
*FIELD* TX
A number sign (#) is used with this entry because of the finding that
read morethis blood group system is an antigenic expression of the
acetylcholinesterase molecule (ACHE; 100740).

DESCRIPTION

The antibody defining the very common antigen Yt(a) was the cause of a
cross-matching difficulty investigated by Eaton et al. (1956). It was
presumed to be the result of previous transfusions. Among 1,051 English
people, 4 negatives were found. Positives showed 2 grades of strength of
reaction; on the assumption that the weaker reactors represented
heterozygotes, an estimate of gene frequency simply by counting was
possible.

Telen et al. (1990) found that the Yt (Cartwright) red cell antigen
resided on an unidentified phosphatidylinositol (PI)-linked protein.
Telen and Whitsett (1992) identified a patient with the hitherto
unreported Yt(a-b-) phenotype in whom studies allowed localization of
the Yt antigens to the acetylcholinesterase molecule. Telen and Whitsett
(1992) found that binding of antibodies to several membrane proteins
including CD55 (125240), CD58 (153420), and CD59 (107271) were normal,
whereas 4 monoclonal antibodies to different acetylcholinesterase
epitopes reacted only weakly with Yt(a-b-) erythrocytes. In addition,
enzymatic assay of acetylcholinesterase activity of Yt(a-b-)
erythrocytes demonstrated only 15% of the normal amount of enzyme
activity. The use of anti-Yt(a) in radioimmunoprecipitation experiments
demonstrated the expected 160 kD of the acetylcholinesterase molecule
from normal erythrocyte membrane proteins, but not from Yt(a-b-)
erythrocytes. Spring et al. (1992) obtained similar results. Thus,
acetylcholinesterase is the PI-linked protein that represents the Yt
antigen.

MAPPING

Coghlan et al. (1989) found loose linkage of Yt and the Kell blood group
locus (110900); the maximum lod score was 3.48 at theta = 0.28. The
mapping of the Kell blood group locus to chromosome 7 means that the YT
locus is also on 7q. This was directly demonstrated by Zelinski et al.
(1991) who found close linkage to COL1A2 (120160); peak lod = 3.61 at
theta = 0.00. It was also tightly linked to DNA marker D7S13; peak lod =
3.31 at theta = 0.00.

MOLECULAR GENETICS

Bartels et al. (1993) demonstrated that the wildtype sequence of the
ACHE gene, which corresponds to the YT1 blood group antigen, has
histidine at codon 322 (CAC) and that the rare variant, the YT2 blood
group antigen, has asparagine (AAC) at that position (100740.0001).

*FIELD* SA
Giles et al. (1967); Race and Sanger (1975); Roychoudhury and Nei
(1988)
*FIELD* RF
1. Bartels, C. F.; Zelinski, T.; Lockridge, O.: Mutation at codon
322 in the human acetylcholinesterase (ACHE) gene accounts for YT
blood group polymorphism. Am. J. Hum. Genet. 52: 928-936, 1993.

2. Coghlan, G.; Kaita, H.; Belcher, E.; Philipps, S.; Wong, P.; McAlpine,
P. J.; Zelinski, T.; Lewis, M.: Genetic linkage between the Kell
and Yt blood group loci. (Abstract) Cytogenet. Cell Genet. 51: 978
only, 1989.

3. Eaton, B. R.; Morton, J. A.; Pickles, M. M.; White, K. E.: A new
antibody anti-Yt(a), characterizing a blood group antigen of high
incidence. Brit. J. Haemat. 2: 333-341, 1956.

4. Giles, C. M.; Metaxas-Buhler, M.; Romanski, Y.; Metaxas, M. N.
: Studies on the Yt blood group system. Vox Sang. 13: 171-180, 1967.

5. Race, R. R.; Sanger, R.: Blood Groups in Man. Oxford: Blackwell
Sci. Publ. (pub.) (6th ed.): 1975. Pp. 379-382.

6. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World Distribution.
New York: Oxford Univ. Press (pub.) 1988.

7. Spring, F. A.; Gardner, B.; Anstee, D. J.: Evidence that the antigens
of the Yt blood group system are located on human erythrocyte acetylcholinesterase. Blood 80:
2136-2141, 1992.

8. Telen, M. J.; Rosse, W. F.; Parker, C. J.; Moulds, M. K.; Moulds,
J. J.: Evidence that several high-frequency human blood group antigens
reside on phosphatidylinositol-linked erythrocyte membrane proteins. Blood 75:
1404-1407, 1990.

9. Telen, M. J.; Whitsett, C. F.: Erythrocyte acetylcholinesterase
bears the Cartwright blood group antigens. (Abstract) Clin. Res. 40:
170A only, 1992.

10. Zelinski, T.; White, L.; Coghlan, G.; Philipps, S.: Assignment
of the YT blood group locus to chromosome 7q. Genomics 11: 165-167,
1991.

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
alopez: 04/18/2011
carol: 9/3/2010
davew: 8/18/1994
mimadm: 2/11/1994
carol: 10/19/1993
carol: 7/13/1993
carol: 12/1/1992
carol: 10/13/1992

RBCC Red Blood Cell Collection

Full text data of ACHE