Full text data of AHCY
AHCY
(SAHH)
[Confidence: high (present in two of the MS resources)]
Adenosylhomocysteinase; AdoHcyase; 3.3.1.1 (S-adenosyl-L-homocysteine hydrolase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Adenosylhomocysteinase; AdoHcyase; 3.3.1.1 (S-adenosyl-L-homocysteine hydrolase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00012007
IPI00012007 Similar to Adenosylhomocysteinase regulation of the intracellular concentration of adenosylhomocysteine, competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00012007 Similar to Adenosylhomocysteinase regulation of the intracellular concentration of adenosylhomocysteine, competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P23526
ID SAHH_HUMAN Reviewed; 432 AA.
AC P23526; A8K307; B3KUN3; E1P5P2; F5H737; Q96A36;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Adenosylhomocysteinase;
DE Short=AdoHcyase;
DE EC=3.3.1.1;
DE AltName: Full=S-adenosyl-L-homocysteine hydrolase;
GN Name=AHCY; Synonyms=SAHH;
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 1), AND VARIANT ASN-86.
RC TISSUE=Placenta;
RX PubMed=2596825; DOI=10.1111/j.1469-1809.1989.tb01781.x;
RA Coulter-Karis D.E., Hershfield M.S.;
RT "Sequence of full length cDNA for human S-adenosylhomocysteine
RT hydrolase.";
RL Ann. Hum. Genet. 53:169-175(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis, and Umbilical cord blood;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, and Skin;
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 [7]
RP PROTEIN SEQUENCE OF 2-6; 104-108 AND 198-202.
RX PubMed=7786017; DOI=10.1006/abbi.1995.1306;
RA Gupta R.A., Yuan C.-S., Ault-Riche D.B., Borchardt R.T.;
RT "Limited proteolysis of S-adenosylhomocysteine hydrolase: implications
RT for the three-dimensional structure.";
RL Arch. Biochem. Biophys. 319:365-371(1995).
RN [8]
RP PROTEIN SEQUENCE OF 2-34; 95-103; 143-186; 215-226; 336-343 AND
RP 389-405, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Gottlieb E.;
RL Submitted (MAR-2008) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 122-432 (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=2574561; DOI=10.1111/j.1469-1809.1989.tb01780.x;
RA Arredondo-Vega F.X., Charlton J.A., Edwards Y.H., Hopkinson D.A.,
RA Whitehouse D.B.;
RT "Isozyme and DNA analysis of human S-adenosyl-L-homocysteine hydrolase
RT (AHCY).";
RL Ann. Hum. Genet. 53:157-167(1989).
RN [10]
RP PROTEIN SEQUENCE OF 175-186 AND 319-327.
RX PubMed=7608178; DOI=10.1074/jbc.270.27.16140;
RA Yuan C.S., Borchardt R.T.;
RT "Photoaffinity labeling of human placental S-adenosylhomocysteine
RT hydrolase with [2-3H]8-azido-adenosine.";
RL J. Biol. Chem. 270:16140-16146(1995).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH NAD AND
RP ADENOSINE ANALOG, SUBUNIT, AND COFACTOR.
RC TISSUE=Placenta;
RX PubMed=9586999; DOI=10.1038/nsb0598-369;
RA Turner M.A., Yuan C.S., Borchardt R.T., Hershfield M.S., Smith G.D.,
RA Howell P.L.;
RT "Structure determination of selenomethionyl S-adenosylhomocysteine
RT hydrolase using data at a single wavelength.";
RL Nat. Struct. Biol. 5:369-376(1998).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) IN COMPLEX WITH NAD AND
RP NEPLANOCIN A, FUNCTION, AND COFACTOR.
RX PubMed=12590576; DOI=10.1021/bi0262350;
RA Yang X., Hu Y., Yin D.H., Turner M.A., Wang M., Borchardt R.T.,
RA Howell P.L., Kuczera K., Schowen R.L.;
RT "Catalytic strategy of S-adenosyl-L-homocysteine hydrolase:
RT transition-state stabilization and the avoidance of abortive
RT reactions.";
RL Biochemistry 42:1900-1909(2003).
RN [15]
RP VARIANT TRP-38.
RX PubMed=15241484; DOI=10.1038/sj.ejhg.5201237;
RA Gellekink H., den Heijer M., Kluijtmans L.A., Blom H.J.;
RT "Effect of genetic variation in the human S-adenosylhomocysteine
RT hydrolase gene on total homocysteine concentrations and risk of
RT recurrent venous thrombosis.";
RL Eur. J. Hum. Genet. 12:942-948(2004).
RN [16]
RP VARIANT HMAHCHD CYS-143.
RX PubMed=15024124; DOI=10.1073/pnas.0400658101;
RA Baric I., Fumic K., Glenn B., Cuk M., Schulze A., Finkelstein J.D.,
RA James S.J., Mejaski-Bosnjak V., Pazanin L., Pogribny I.P., Rados M.,
RA Sarnavka V., Scukanec-Spoljar M., Allen R.H., Stabler S., Uzelac L.,
RA Vugrek O., Wagner C., Zeisel S., Mudd S.H.;
RT "S-adenosylhomocysteine hydrolase deficiency in a human: a genetic
RT disorder of methionine metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4234-4239(2004).
RN [17]
RP VARIANTS HMAHCHD VAL-89 AND CYS-143.
RX PubMed=16736098; DOI=10.1007/s10545-006-0240-0;
RA Buist N.R., Glenn B., Vugrek O., Wagner C., Stabler S., Allen R.H.,
RA Pogribny I., Schulze A., Zeisel S.H., Baric I., Mudd S.H.;
RT "S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man.";
RL J. Inherit. Metab. Dis. 29:538-545(2006).
RN [18]
RP VARIANTS HMAHCHD CYS-49 AND GLY-86.
RX PubMed=19177456; DOI=10.1002/humu.20985;
RA Vugrek O., Beluzic R., Nakic N., Mudd S.H.;
RT "S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel
RT mutations with lethal outcome.";
RL Hum. Mutat. 30:E555-E565(2009).
RN [19]
RP VARIANTS HMAHCHD CYS-49 AND GLY-86.
RX PubMed=20852937; DOI=10.1007/s10545-010-9171-x;
RA Grubbs R., Vugrek O., Deisch J., Wagner C., Stabler S., Allen R.,
RA Baric I., Rados M., Mudd S.H.;
RT "S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal
RT hydrops and fatal outcomes.";
RL J. Inherit. Metab. Dis. 33:705-713(2010).
CC -!- FUNCTION: Adenosylhomocysteine is a competitive inhibitor of S-
CC adenosyl-L-methionine-dependent methyl transferase reactions;
CC therefore adenosylhomocysteinase may play a key role in the
CC control of methylations via regulation of the intracellular
CC concentration of adenosylhomocysteine.
CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-homocysteine + H(2)O = L-
CC homocysteine + adenosine.
CC -!- COFACTOR: Binds 1 NAD per subunit.
CC -!- PATHWAY: Amino-acid biosynthesis; L-homocysteine biosynthesis; L-
CC homocysteine from S-adenosyl-L-homocysteine: step 1/1.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Identified by
CC mass spectrometry in melanosome fractions from stage I to stage
CC IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P23526-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P23526-2; Sequence=VSP_045404;
CC Note=No experimental confirmation available;
CC -!- DISEASE: Hypermethioninemia with S-adenosylhomocysteine hydrolase
CC deficiency (HMAHCHD) [MIM:613752]: A metabolic disorder
CC characterized by hypermethioninemia associated with failure to
CC thrive, mental and motor retardation, facial dysmorphism with
CC abnormal hair and teeth, and myocardiopathy. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
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DR EMBL; M61831; AAA51681.1; -; mRNA.
DR EMBL; M61832; AAA51682.1; -; mRNA.
DR EMBL; BT006697; AAP35343.1; -; mRNA.
DR EMBL; AK097610; BAG53495.1; -; mRNA.
DR EMBL; AK290422; BAF83111.1; -; mRNA.
DR EMBL; AL356299; CAC09528.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76279.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76280.1; -; Genomic_DNA.
DR EMBL; BC010018; AAH10018.1; -; mRNA.
DR EMBL; BC011606; AAH11606.1; -; mRNA.
DR PIR; A43629; A43629.
DR RefSeq; NP_000678.1; NM_000687.2.
DR RefSeq; NP_001155238.1; NM_001161766.1.
DR RefSeq; XP_005260372.1; XM_005260315.1.
DR RefSeq; XP_005260373.1; XM_005260316.1.
DR RefSeq; XP_005260374.1; XM_005260317.1.
DR UniGene; Hs.388004; -.
DR PDB; 1A7A; X-ray; 2.80 A; A/B=1-432.
DR PDB; 1LI4; X-ray; 2.01 A; A=1-432.
DR PDB; 3NJ4; X-ray; 2.50 A; A/B/C/D=1-432.
DR PDBsum; 1A7A; -.
DR PDBsum; 1LI4; -.
DR PDBsum; 3NJ4; -.
DR ProteinModelPortal; P23526; -.
DR SMR; P23526; 3-432.
DR IntAct; P23526; 13.
DR MINT; MINT-5000523; -.
DR STRING; 9606.ENSP00000217426; -.
DR BindingDB; P23526; -.
DR ChEMBL; CHEMBL2664; -.
DR GuidetoPHARMACOLOGY; 1233; -.
DR PhosphoSite; P23526; -.
DR DMDM; 20141702; -.
DR REPRODUCTION-2DPAGE; IPI00012007; -.
DR PaxDb; P23526; -.
DR PeptideAtlas; P23526; -.
DR PRIDE; P23526; -.
DR DNASU; 191; -.
DR Ensembl; ENST00000217426; ENSP00000217426; ENSG00000101444.
DR Ensembl; ENST00000538132; ENSP00000442820; ENSG00000101444.
DR GeneID; 191; -.
DR KEGG; hsa:191; -.
DR UCSC; uc002xai.3; human.
DR CTD; 191; -.
DR GeneCards; GC20M032868; -.
DR HGNC; HGNC:343; AHCY.
DR HPA; HPA041225; -.
DR HPA; HPA044675; -.
DR MIM; 180960; gene.
DR MIM; 613752; phenotype.
DR neXtProt; NX_P23526; -.
DR Orphanet; 88618; Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency.
DR PharmGKB; PA24636; -.
DR eggNOG; COG0499; -.
DR HOGENOM; HOG000227987; -.
DR HOVERGEN; HBG005041; -.
DR InParanoid; P23526; -.
DR KO; K01251; -.
DR OMA; EVNPIRA; -.
DR OrthoDB; EOG76739S; -.
DR PhylomeDB; P23526; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P23526; -.
DR UniPathway; UPA00314; UER00076.
DR ChiTaRS; AHCY; human.
DR EvolutionaryTrace; P23526; -.
DR GenomeRNAi; 191; -.
DR NextBio; 780; -.
DR PRO; PR:P23526; -.
DR ArrayExpress; P23526; -.
DR Bgee; P23526; -.
DR CleanEx; HS_AHCY; -.
DR Genevestigator; P23526; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0004013; F:adenosylhomocysteinase activity; TAS:UniProtKB.
DR GO; GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome.
DR GO; GO:0032259; P:methylation; TAS:Reactome.
DR GO; GO:0006730; P:one-carbon metabolic process; NAS:UniProtKB.
DR GO; GO:0000096; P:sulfur amino acid metabolic process; TAS:Reactome.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR000043; Adenosylhomocysteinase.
DR InterPro; IPR015878; Ado_hCys_hydrolase_NAD-bd.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR020082; S-Ado-L-homoCys_hydrolase_CS.
DR PANTHER; PTHR23420; PTHR23420; 1.
DR Pfam; PF05221; AdoHcyase; 1.
DR Pfam; PF00670; AdoHcyase_NAD; 1.
DR PIRSF; PIRSF001109; Ad_hcy_hydrolase; 1.
DR SMART; SM00996; AdoHcyase; 1.
DR SMART; SM00997; AdoHcyase_NAD; 1.
DR TIGRFAMs; TIGR00936; ahcY; 1.
DR PROSITE; PS00738; ADOHCYASE_1; 1.
DR PROSITE; PS00739; ADOHCYASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation; Hydrolase;
KW NAD; One-carbon metabolism; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 432 Adenosylhomocysteinase.
FT /FTId=PRO_0000116902.
FT NP_BIND 157 159 NAD.
FT NP_BIND 222 227 NAD.
FT NP_BIND 299 301 NAD.
FT BINDING 57 57 Substrate (By similarity).
FT BINDING 131 131 Substrate (By similarity).
FT BINDING 156 156 Substrate (By similarity).
FT BINDING 186 186 Substrate (By similarity).
FT BINDING 190 190 Substrate (By similarity).
FT BINDING 243 243 NAD.
FT BINDING 248 248 NAD.
FT BINDING 346 346 NAD.
FT BINDING 353 353 NAD.
FT MOD_RES 2 2 N-acetylserine.
FT VAR_SEQ 1 28 Missing (in isoform 2).
FT /FTId=VSP_045404.
FT VARIANT 38 38 R -> W (in dbSNP:rs13043752).
FT /FTId=VAR_052286.
FT VARIANT 49 49 R -> C (in HMAHCHD).
FT /FTId=VAR_058588.
FT VARIANT 86 86 D -> G (in HMAHCHD).
FT /FTId=VAR_058589.
FT VARIANT 86 86 D -> N.
FT /FTId=VAR_006934.
FT VARIANT 89 89 A -> V (in HMAHCHD).
FT /FTId=VAR_058590.
FT VARIANT 143 143 Y -> C (in HMAHCHD).
FT /FTId=VAR_058591.
FT CONFLICT 249 249 A -> V (in Ref. 3; BAG53495).
FT STRAND 8 10
FT HELIX 12 14
FT HELIX 15 26
FT HELIX 30 39
FT TURN 40 42
FT TURN 44 47
FT STRAND 49 54
FT HELIX 58 69
FT STRAND 73 77
FT STRAND 79 82
FT HELIX 86 94
FT STRAND 99 101
FT HELIX 107 115
FT STRAND 118 120
FT STRAND 126 133
FT HELIX 134 142
FT HELIX 144 149
FT STRAND 152 155
FT HELIX 158 169
FT STRAND 175 179
FT HELIX 184 187
FT HELIX 190 207
FT STRAND 215 219
FT HELIX 223 234
FT STRAND 238 242
FT HELIX 246 254
FT HELIX 262 265
FT TURN 266 268
FT STRAND 270 274
FT STRAND 277 279
FT HELIX 284 287
FT STRAND 294 298
FT STRAND 300 302
FT HELIX 308 314
FT STRAND 316 322
FT STRAND 325 329
FT STRAND 335 339
FT HELIX 340 342
FT HELIX 345 348
FT HELIX 355 374
FT HELIX 376 378
FT STRAND 381 384
FT HELIX 388 399
FT TURN 400 403
FT HELIX 411 417
FT STRAND 421 423
SQ SEQUENCE 432 AA; 47716 MW; 2833C025F969553E CRC64;
MSDKLPYKVA DIGLAAWGRK ALDIAENEMP GLMRMRERYS ASKPLKGARI AGCLHMTVET
AVLIETLVTL GAEVQWSSCN IFSTQDHAAA AIAKAGIPVY AWKGETDEEY LWCIEQTLYF
KDGPLNMILD DGGDLTNLIH TKYPQLLPGI RGISEETTTG VHNLYKMMAN GILKVPAINV
NDSVTKSKFD NLYGCRESLI DGIKRATDVM IAGKVAVVAG YGDVGKGCAQ ALRGFGARVI
ITEIDPINAL QAAMEGYEVT TMDEACQEGN IFVTTTGCID IILGRHFEQM KDDAIVCNIG
HFDVEIDVKW LNENAVEKVN IKPQVDRYRL KNGRRIILLA EGRLVNLGCA MGHPSFVMSN
SFTNQVMAQI ELWTHPDKYP VGVHFLPKKL DEAVAEAHLG KLNVKLTKLT EKQAQYLGMS
CDGPFKPDHY RY
//
ID SAHH_HUMAN Reviewed; 432 AA.
AC P23526; A8K307; B3KUN3; E1P5P2; F5H737; Q96A36;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Adenosylhomocysteinase;
DE Short=AdoHcyase;
DE EC=3.3.1.1;
DE AltName: Full=S-adenosyl-L-homocysteine hydrolase;
GN Name=AHCY; Synonyms=SAHH;
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 1), AND VARIANT ASN-86.
RC TISSUE=Placenta;
RX PubMed=2596825; DOI=10.1111/j.1469-1809.1989.tb01781.x;
RA Coulter-Karis D.E., Hershfield M.S.;
RT "Sequence of full length cDNA for human S-adenosylhomocysteine
RT hydrolase.";
RL Ann. Hum. Genet. 53:169-175(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis, and Umbilical cord blood;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, and Skin;
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 [7]
RP PROTEIN SEQUENCE OF 2-6; 104-108 AND 198-202.
RX PubMed=7786017; DOI=10.1006/abbi.1995.1306;
RA Gupta R.A., Yuan C.-S., Ault-Riche D.B., Borchardt R.T.;
RT "Limited proteolysis of S-adenosylhomocysteine hydrolase: implications
RT for the three-dimensional structure.";
RL Arch. Biochem. Biophys. 319:365-371(1995).
RN [8]
RP PROTEIN SEQUENCE OF 2-34; 95-103; 143-186; 215-226; 336-343 AND
RP 389-405, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Gottlieb E.;
RL Submitted (MAR-2008) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 122-432 (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=2574561; DOI=10.1111/j.1469-1809.1989.tb01780.x;
RA Arredondo-Vega F.X., Charlton J.A., Edwards Y.H., Hopkinson D.A.,
RA Whitehouse D.B.;
RT "Isozyme and DNA analysis of human S-adenosyl-L-homocysteine hydrolase
RT (AHCY).";
RL Ann. Hum. Genet. 53:157-167(1989).
RN [10]
RP PROTEIN SEQUENCE OF 175-186 AND 319-327.
RX PubMed=7608178; DOI=10.1074/jbc.270.27.16140;
RA Yuan C.S., Borchardt R.T.;
RT "Photoaffinity labeling of human placental S-adenosylhomocysteine
RT hydrolase with [2-3H]8-azido-adenosine.";
RL J. Biol. Chem. 270:16140-16146(1995).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH NAD AND
RP ADENOSINE ANALOG, SUBUNIT, AND COFACTOR.
RC TISSUE=Placenta;
RX PubMed=9586999; DOI=10.1038/nsb0598-369;
RA Turner M.A., Yuan C.S., Borchardt R.T., Hershfield M.S., Smith G.D.,
RA Howell P.L.;
RT "Structure determination of selenomethionyl S-adenosylhomocysteine
RT hydrolase using data at a single wavelength.";
RL Nat. Struct. Biol. 5:369-376(1998).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) IN COMPLEX WITH NAD AND
RP NEPLANOCIN A, FUNCTION, AND COFACTOR.
RX PubMed=12590576; DOI=10.1021/bi0262350;
RA Yang X., Hu Y., Yin D.H., Turner M.A., Wang M., Borchardt R.T.,
RA Howell P.L., Kuczera K., Schowen R.L.;
RT "Catalytic strategy of S-adenosyl-L-homocysteine hydrolase:
RT transition-state stabilization and the avoidance of abortive
RT reactions.";
RL Biochemistry 42:1900-1909(2003).
RN [15]
RP VARIANT TRP-38.
RX PubMed=15241484; DOI=10.1038/sj.ejhg.5201237;
RA Gellekink H., den Heijer M., Kluijtmans L.A., Blom H.J.;
RT "Effect of genetic variation in the human S-adenosylhomocysteine
RT hydrolase gene on total homocysteine concentrations and risk of
RT recurrent venous thrombosis.";
RL Eur. J. Hum. Genet. 12:942-948(2004).
RN [16]
RP VARIANT HMAHCHD CYS-143.
RX PubMed=15024124; DOI=10.1073/pnas.0400658101;
RA Baric I., Fumic K., Glenn B., Cuk M., Schulze A., Finkelstein J.D.,
RA James S.J., Mejaski-Bosnjak V., Pazanin L., Pogribny I.P., Rados M.,
RA Sarnavka V., Scukanec-Spoljar M., Allen R.H., Stabler S., Uzelac L.,
RA Vugrek O., Wagner C., Zeisel S., Mudd S.H.;
RT "S-adenosylhomocysteine hydrolase deficiency in a human: a genetic
RT disorder of methionine metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4234-4239(2004).
RN [17]
RP VARIANTS HMAHCHD VAL-89 AND CYS-143.
RX PubMed=16736098; DOI=10.1007/s10545-006-0240-0;
RA Buist N.R., Glenn B., Vugrek O., Wagner C., Stabler S., Allen R.H.,
RA Pogribny I., Schulze A., Zeisel S.H., Baric I., Mudd S.H.;
RT "S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man.";
RL J. Inherit. Metab. Dis. 29:538-545(2006).
RN [18]
RP VARIANTS HMAHCHD CYS-49 AND GLY-86.
RX PubMed=19177456; DOI=10.1002/humu.20985;
RA Vugrek O., Beluzic R., Nakic N., Mudd S.H.;
RT "S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel
RT mutations with lethal outcome.";
RL Hum. Mutat. 30:E555-E565(2009).
RN [19]
RP VARIANTS HMAHCHD CYS-49 AND GLY-86.
RX PubMed=20852937; DOI=10.1007/s10545-010-9171-x;
RA Grubbs R., Vugrek O., Deisch J., Wagner C., Stabler S., Allen R.,
RA Baric I., Rados M., Mudd S.H.;
RT "S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal
RT hydrops and fatal outcomes.";
RL J. Inherit. Metab. Dis. 33:705-713(2010).
CC -!- FUNCTION: Adenosylhomocysteine is a competitive inhibitor of S-
CC adenosyl-L-methionine-dependent methyl transferase reactions;
CC therefore adenosylhomocysteinase may play a key role in the
CC control of methylations via regulation of the intracellular
CC concentration of adenosylhomocysteine.
CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-homocysteine + H(2)O = L-
CC homocysteine + adenosine.
CC -!- COFACTOR: Binds 1 NAD per subunit.
CC -!- PATHWAY: Amino-acid biosynthesis; L-homocysteine biosynthesis; L-
CC homocysteine from S-adenosyl-L-homocysteine: step 1/1.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Identified by
CC mass spectrometry in melanosome fractions from stage I to stage
CC IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P23526-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P23526-2; Sequence=VSP_045404;
CC Note=No experimental confirmation available;
CC -!- DISEASE: Hypermethioninemia with S-adenosylhomocysteine hydrolase
CC deficiency (HMAHCHD) [MIM:613752]: A metabolic disorder
CC characterized by hypermethioninemia associated with failure to
CC thrive, mental and motor retardation, facial dysmorphism with
CC abnormal hair and teeth, and myocardiopathy. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC -----------------------------------------------------------------------
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DR EMBL; M61831; AAA51681.1; -; mRNA.
DR EMBL; M61832; AAA51682.1; -; mRNA.
DR EMBL; BT006697; AAP35343.1; -; mRNA.
DR EMBL; AK097610; BAG53495.1; -; mRNA.
DR EMBL; AK290422; BAF83111.1; -; mRNA.
DR EMBL; AL356299; CAC09528.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76279.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76280.1; -; Genomic_DNA.
DR EMBL; BC010018; AAH10018.1; -; mRNA.
DR EMBL; BC011606; AAH11606.1; -; mRNA.
DR PIR; A43629; A43629.
DR RefSeq; NP_000678.1; NM_000687.2.
DR RefSeq; NP_001155238.1; NM_001161766.1.
DR RefSeq; XP_005260372.1; XM_005260315.1.
DR RefSeq; XP_005260373.1; XM_005260316.1.
DR RefSeq; XP_005260374.1; XM_005260317.1.
DR UniGene; Hs.388004; -.
DR PDB; 1A7A; X-ray; 2.80 A; A/B=1-432.
DR PDB; 1LI4; X-ray; 2.01 A; A=1-432.
DR PDB; 3NJ4; X-ray; 2.50 A; A/B/C/D=1-432.
DR PDBsum; 1A7A; -.
DR PDBsum; 1LI4; -.
DR PDBsum; 3NJ4; -.
DR ProteinModelPortal; P23526; -.
DR SMR; P23526; 3-432.
DR IntAct; P23526; 13.
DR MINT; MINT-5000523; -.
DR STRING; 9606.ENSP00000217426; -.
DR BindingDB; P23526; -.
DR ChEMBL; CHEMBL2664; -.
DR GuidetoPHARMACOLOGY; 1233; -.
DR PhosphoSite; P23526; -.
DR DMDM; 20141702; -.
DR REPRODUCTION-2DPAGE; IPI00012007; -.
DR PaxDb; P23526; -.
DR PeptideAtlas; P23526; -.
DR PRIDE; P23526; -.
DR DNASU; 191; -.
DR Ensembl; ENST00000217426; ENSP00000217426; ENSG00000101444.
DR Ensembl; ENST00000538132; ENSP00000442820; ENSG00000101444.
DR GeneID; 191; -.
DR KEGG; hsa:191; -.
DR UCSC; uc002xai.3; human.
DR CTD; 191; -.
DR GeneCards; GC20M032868; -.
DR HGNC; HGNC:343; AHCY.
DR HPA; HPA041225; -.
DR HPA; HPA044675; -.
DR MIM; 180960; gene.
DR MIM; 613752; phenotype.
DR neXtProt; NX_P23526; -.
DR Orphanet; 88618; Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency.
DR PharmGKB; PA24636; -.
DR eggNOG; COG0499; -.
DR HOGENOM; HOG000227987; -.
DR HOVERGEN; HBG005041; -.
DR InParanoid; P23526; -.
DR KO; K01251; -.
DR OMA; EVNPIRA; -.
DR OrthoDB; EOG76739S; -.
DR PhylomeDB; P23526; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P23526; -.
DR UniPathway; UPA00314; UER00076.
DR ChiTaRS; AHCY; human.
DR EvolutionaryTrace; P23526; -.
DR GenomeRNAi; 191; -.
DR NextBio; 780; -.
DR PRO; PR:P23526; -.
DR ArrayExpress; P23526; -.
DR Bgee; P23526; -.
DR CleanEx; HS_AHCY; -.
DR Genevestigator; P23526; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0004013; F:adenosylhomocysteinase activity; TAS:UniProtKB.
DR GO; GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome.
DR GO; GO:0032259; P:methylation; TAS:Reactome.
DR GO; GO:0006730; P:one-carbon metabolic process; NAS:UniProtKB.
DR GO; GO:0000096; P:sulfur amino acid metabolic process; TAS:Reactome.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR000043; Adenosylhomocysteinase.
DR InterPro; IPR015878; Ado_hCys_hydrolase_NAD-bd.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR020082; S-Ado-L-homoCys_hydrolase_CS.
DR PANTHER; PTHR23420; PTHR23420; 1.
DR Pfam; PF05221; AdoHcyase; 1.
DR Pfam; PF00670; AdoHcyase_NAD; 1.
DR PIRSF; PIRSF001109; Ad_hcy_hydrolase; 1.
DR SMART; SM00996; AdoHcyase; 1.
DR SMART; SM00997; AdoHcyase_NAD; 1.
DR TIGRFAMs; TIGR00936; ahcY; 1.
DR PROSITE; PS00738; ADOHCYASE_1; 1.
DR PROSITE; PS00739; ADOHCYASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation; Hydrolase;
KW NAD; One-carbon metabolism; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 432 Adenosylhomocysteinase.
FT /FTId=PRO_0000116902.
FT NP_BIND 157 159 NAD.
FT NP_BIND 222 227 NAD.
FT NP_BIND 299 301 NAD.
FT BINDING 57 57 Substrate (By similarity).
FT BINDING 131 131 Substrate (By similarity).
FT BINDING 156 156 Substrate (By similarity).
FT BINDING 186 186 Substrate (By similarity).
FT BINDING 190 190 Substrate (By similarity).
FT BINDING 243 243 NAD.
FT BINDING 248 248 NAD.
FT BINDING 346 346 NAD.
FT BINDING 353 353 NAD.
FT MOD_RES 2 2 N-acetylserine.
FT VAR_SEQ 1 28 Missing (in isoform 2).
FT /FTId=VSP_045404.
FT VARIANT 38 38 R -> W (in dbSNP:rs13043752).
FT /FTId=VAR_052286.
FT VARIANT 49 49 R -> C (in HMAHCHD).
FT /FTId=VAR_058588.
FT VARIANT 86 86 D -> G (in HMAHCHD).
FT /FTId=VAR_058589.
FT VARIANT 86 86 D -> N.
FT /FTId=VAR_006934.
FT VARIANT 89 89 A -> V (in HMAHCHD).
FT /FTId=VAR_058590.
FT VARIANT 143 143 Y -> C (in HMAHCHD).
FT /FTId=VAR_058591.
FT CONFLICT 249 249 A -> V (in Ref. 3; BAG53495).
FT STRAND 8 10
FT HELIX 12 14
FT HELIX 15 26
FT HELIX 30 39
FT TURN 40 42
FT TURN 44 47
FT STRAND 49 54
FT HELIX 58 69
FT STRAND 73 77
FT STRAND 79 82
FT HELIX 86 94
FT STRAND 99 101
FT HELIX 107 115
FT STRAND 118 120
FT STRAND 126 133
FT HELIX 134 142
FT HELIX 144 149
FT STRAND 152 155
FT HELIX 158 169
FT STRAND 175 179
FT HELIX 184 187
FT HELIX 190 207
FT STRAND 215 219
FT HELIX 223 234
FT STRAND 238 242
FT HELIX 246 254
FT HELIX 262 265
FT TURN 266 268
FT STRAND 270 274
FT STRAND 277 279
FT HELIX 284 287
FT STRAND 294 298
FT STRAND 300 302
FT HELIX 308 314
FT STRAND 316 322
FT STRAND 325 329
FT STRAND 335 339
FT HELIX 340 342
FT HELIX 345 348
FT HELIX 355 374
FT HELIX 376 378
FT STRAND 381 384
FT HELIX 388 399
FT TURN 400 403
FT HELIX 411 417
FT STRAND 421 423
SQ SEQUENCE 432 AA; 47716 MW; 2833C025F969553E CRC64;
MSDKLPYKVA DIGLAAWGRK ALDIAENEMP GLMRMRERYS ASKPLKGARI AGCLHMTVET
AVLIETLVTL GAEVQWSSCN IFSTQDHAAA AIAKAGIPVY AWKGETDEEY LWCIEQTLYF
KDGPLNMILD DGGDLTNLIH TKYPQLLPGI RGISEETTTG VHNLYKMMAN GILKVPAINV
NDSVTKSKFD NLYGCRESLI DGIKRATDVM IAGKVAVVAG YGDVGKGCAQ ALRGFGARVI
ITEIDPINAL QAAMEGYEVT TMDEACQEGN IFVTTTGCID IILGRHFEQM KDDAIVCNIG
HFDVEIDVKW LNENAVEKVN IKPQVDRYRL KNGRRIILLA EGRLVNLGCA MGHPSFVMSN
SFTNQVMAQI ELWTHPDKYP VGVHFLPKKL DEAVAEAHLG KLNVKLTKLT EKQAQYLGMS
CDGPFKPDHY RY
//
MIM
180960
*RECORD*
*FIELD* NO
180960
*FIELD* TI
*180960 S-ADENOSYLHOMOCYSTEINE HYDROLASE; AHCY
;;SAHH
*FIELD* TX
DESCRIPTION
The AHCY gene encodes S-adenosylhomocysteine hydrolase (EC 3.3.1.1),
read morewhich catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine
and homocysteine (summary by Baric et al., 2004).
CLONING
Coulter-Karis and Hershfield (1989) isolated cDNA clones for human AHCY
from a placental cDNA library. The deduced 432-amino acid protein has a
molecular mass of 47.6 kD with 97% identity to the rat protein.
GENE FUNCTION
Baric et al. (2004) noted that S-adenosylhomocysteine hydrolase
catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and
homocysteine. In eukaryotes, this is the major route for disposal of the
S-adenosylhomocysteine formed as a common product of each of many
S-adenosylmethionine-dependent methyltransferases. The reaction is
reversible, but under normal conditions the removal of both adenosine
and homocysteine is sufficiently rapid to maintain the flux in the
direction of hydrolysis. Physiologically, S-adenosylhomocysteine
hydrolysis serves not only to sustain the flux of methionine sulfur
toward cysteine, but is believed also to play a critical role in the
regulation of biologic methylations.
EVOLUTION
Hershfield and Francke (1982) noted that in ADA deficiency (see 102700),
adenosine and deoxyadenosine accumulate and, respectively, inhibit and
inactivate S-adenosylhomocysteine hydrolase. The fact that both SAHH and
ADA are on chromosome 20 suggests an evolutionary relationship. SAHH,
which is a eukaryotic enzyme, probably arose after ADA, which occurs
also in prokaryotes. Evolution of SAHH may have required the
simultaneous occurrence of ADA to avoid the adverse effects of adenosine
and deoxyadenosine. Alternatively, tandem reduplication of a portion of
the ADA gene encoding a binding domain for adenosine may have occurred
and further changes may have led to the SAHH gene. SAHH is a major high
affinity cytoplasmic adenosine-binding protein.
MAPPING
By analysis of human-Chinese hamster hybrids, Hershfield and Francke
(1982) assigned the AHCY gene to chromosome 20.
By study of rearranged human chromosomes in human-rodent cell hybrids,
Mohandas et al. (1984) assigned the SAHH locus to 20cen-q13.1 and the
ADA gene (608958) to 20q13.1-qter. Eiberg and Mohr (1985) looked at
linkage of ADA and SAHH in their Danish family data; 8 families were
informative for polymorphism of these enzymes. The data gave a maximum
lod score of 1.59 at theta = 0.15 for males and females combined. In an
informative South African family, Bissbort et al. (1987) found a
recombination fraction of about 0.18 between SAHH and ADA. Combined with
the published findings in Danish families, the recombination fraction
for the pooled data was calculated to be 0.4 in men, 0.08 in women, and
0.13 in the sexes taken together.
MOLECULAR GENETICS
Bissbort et al. (1983) found that the SAHH gene is polymorphic in
southwest Germany with 2 common alleles: SAHH*1 and SAHH*2, with
frequencies of 0.96 and 0.04, respectively. In the Japanese population,
Akiyama et al. (1984) estimated the gene frequencies of SAHH*1 and
SAHH*2 to be 0.953 and 0.047, respectively, similar to the results
reported by Bissbort et al. (1983).
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
By starch gel electrophoresis, Arredondo-Vega et al. (1989) identified 2
variant alleles in erythrocyte AHCY. In a British population, the gene
frequencies were 0.024 for AHCY*2 and 0.006 for AHCY*3. Variant isozyme
patterns could not be distinguished by isoelectric focusing.
Among 237 red blood cell samples from unrelated individuals in Croatia,
Kloor et al. (2006) identified 4 different electromorphic SAHH variants.
SAHH*4 was a new variant, present at a frequency of 0.015. Gene
frequencies for SAHH*1, SAHH*2, and SAHH*3 were 0.941, 0.032, and 0.006,
respectively. The authors identified a 'silent' allele with
significantly decreased enzyme activity, which they designated SAHH*0.
The frequency of SAHH*0 was 0.006, yielding an expected incidence for
homozygous individuals with SAHH deficiency of 1 in 30,000 in this
population.
- Hypermethioninemia with S-Adenosylhomocysteine Hydrolase
Deficiency
In a Croatian boy with S-adenosylhomocysteine hydrolase deficiency,
Baric et al. (2004) identified compound heterozygosity for 2 mutations
in the AHCY gene (180960.0001 and 180960.0002). In discussing the basis
of the pathologic effects of S-adenosylhomocysteine hydrolase
deficiency, Baric et al. (2004) pointed to the numerous
S-adenosylmethionine-dependent methyltransferases, which are inhibited
to a greater or lesser extent by S-adenosylhomocysteine. They pointed
out that changes in DNA methylation patterns are heritable and could
negatively affect tissue-specific gene expression during embryogenesis
and after birth. Because the silencing of genes by inappropriate
methylation is the functional equivalent of somatic mutations, the
heritability of DNA methylation patterns suggests that restoration of
'normal' genomic methylation patterns may not occur.
*FIELD* AV
.0001
HYPERMETHIONINEMIA WITH S-ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY
AHCY, TRP112TER
In a Croatian boy with hypermethioninemia and S-adenosylhomocysteine
hydrolase deficiency (613752), Baric et al. (2004) identified compound
heterozygosity for mutations in exon 2 of the AHCY gene: a change of
codon codon 112 from TGG (trp) to TGA (stop) (W112X) and a change of
codon 143 from TAC (tyr) to TGC (cys) (Y143C; 180960.0002), which were
maternally and paternally derived, respectively.
.0002
HYPERMETHIONINEMIA WITH S-ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY
AHCY, TYR143CYS
See 180960.0001 and Baric et al. (2004).
*FIELD* RF
1. Akiyama, K.; Nakamura, S.; Abe, K.: Gene frequencies of S-adenosylhomocysteine
hydrolase (SAHH) in a Japanese population. Hum. Genet. 68: 191-192,
1984.
2. Arredondo-Vega, F. X.; Charlton, J. A.; Edwards, Y. H.; Hopkinson,
D. A.; Whitehouse, D. B.: Isozyme and DNA analysis of human S-adenosyl-L-homocysteine
hydrolase (AHCY). Ann. Hum. Genet. 53: 157-167, 1989.
3. Baric, I.; Fumic, K.; Glenn, B.; Cuk, M.; Schulze, A.; Finkelstein,
J. D.; James, S. J.; Mejaski-Bosnjak, V.; Pazanin, L.; Pogribny, I.
P.; Rados, M.; Sarnavka, V.; Scukanec-Spoljar, M.; Allen, R. H.; Stabler,
S.; Uzelac, L.; Vugrek, O.; Wagner, C.; Zeisel, S.; Mudd, S. H.:
S-adenosylhomocysteine hydrolase deficiency in a human: a genetic
disorder of methionine metabolism. Proc. Nat. Acad. Sci. 101: 4234-4239,
2004.
4. Bissbort, S.; Bender, K.; Wienker, T. F.; Grzeschik, K. H.: Genetics
of human S-adenosylhomocysteine hydrolase: a new polymorphism in man. Hum.
Genet. 65: 68-71, 1983.
5. Bissbort, S.; Hitzeroth, H. W.; van den Berg, C. T.; Wienker, T.
F.: Linkage relationship between the genes for adenosine deaminase
and S-adenosyl-homocysteine hydrolase on human chromosome 20. Hum.
Genet. 77: 277-279, 1987.
6. Coulter-Karis, D. E.; Hershfield, M. S.: Sequence of full length
cDNA for human S-adenosylhomocysteine hydrolase. Ann. Hum. Genet. 53:
169-175, 1989.
7. Eiberg, H.; Mohr, J.: Linkage data concerning the ADA-AHCY relationship.
(Abstract) Cytogenet. Cell Genet. 40: 622 only, 1985.
8. Hershfield, M. S.; Francke, U.: The human gene for S-adenosylhomocysteine
hydrolase and adenosine deaminase are syntenic on chromosome 20. Science 216:
739-742, 1982.
9. Kloor, D.; Fumic, K.; Attig, S.; Tete, M.; Osswald, H.; Baric,
I.; Tomiuk, J.; Kompf, J.: Studies of S-adenosylhomocysteine-hydrolase
polymorphism in a Croatian population. J. Hum. Genet. 51: 21-24,
2006.
10. Mohandas, T.; Sparkes, R. S.; Suh, E. J.; Hershfield, M. S.:
Regional localization of the human genes for S-adenosylhomocysteine
hydrolase (cen-q131) and adenosine deaminase (q131-qter) on chromosome
20. Hum. Genet. 66: 292-295, 1984.
11. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
*FIELD* CN
Cassandra L. Kniffin - updated: 3/2/2006
Victor A. McKusick - updated: 4/28/2004
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 02/21/2011
carol: 2/21/2011
wwang: 3/3/2006
ckniffin: 3/2/2006
ckniffin: 10/28/2004
tkritzer: 5/6/2004
terry: 4/28/2004
mgross: 3/17/2004
joanna: 6/23/1997
mimadm: 3/25/1995
warfield: 3/7/1994
supermim: 3/16/1992
carol: 2/24/1992
carol: 12/20/1990
supermim: 3/20/1990
*RECORD*
*FIELD* NO
180960
*FIELD* TI
*180960 S-ADENOSYLHOMOCYSTEINE HYDROLASE; AHCY
;;SAHH
*FIELD* TX
DESCRIPTION
The AHCY gene encodes S-adenosylhomocysteine hydrolase (EC 3.3.1.1),
read morewhich catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine
and homocysteine (summary by Baric et al., 2004).
CLONING
Coulter-Karis and Hershfield (1989) isolated cDNA clones for human AHCY
from a placental cDNA library. The deduced 432-amino acid protein has a
molecular mass of 47.6 kD with 97% identity to the rat protein.
GENE FUNCTION
Baric et al. (2004) noted that S-adenosylhomocysteine hydrolase
catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and
homocysteine. In eukaryotes, this is the major route for disposal of the
S-adenosylhomocysteine formed as a common product of each of many
S-adenosylmethionine-dependent methyltransferases. The reaction is
reversible, but under normal conditions the removal of both adenosine
and homocysteine is sufficiently rapid to maintain the flux in the
direction of hydrolysis. Physiologically, S-adenosylhomocysteine
hydrolysis serves not only to sustain the flux of methionine sulfur
toward cysteine, but is believed also to play a critical role in the
regulation of biologic methylations.
EVOLUTION
Hershfield and Francke (1982) noted that in ADA deficiency (see 102700),
adenosine and deoxyadenosine accumulate and, respectively, inhibit and
inactivate S-adenosylhomocysteine hydrolase. The fact that both SAHH and
ADA are on chromosome 20 suggests an evolutionary relationship. SAHH,
which is a eukaryotic enzyme, probably arose after ADA, which occurs
also in prokaryotes. Evolution of SAHH may have required the
simultaneous occurrence of ADA to avoid the adverse effects of adenosine
and deoxyadenosine. Alternatively, tandem reduplication of a portion of
the ADA gene encoding a binding domain for adenosine may have occurred
and further changes may have led to the SAHH gene. SAHH is a major high
affinity cytoplasmic adenosine-binding protein.
MAPPING
By analysis of human-Chinese hamster hybrids, Hershfield and Francke
(1982) assigned the AHCY gene to chromosome 20.
By study of rearranged human chromosomes in human-rodent cell hybrids,
Mohandas et al. (1984) assigned the SAHH locus to 20cen-q13.1 and the
ADA gene (608958) to 20q13.1-qter. Eiberg and Mohr (1985) looked at
linkage of ADA and SAHH in their Danish family data; 8 families were
informative for polymorphism of these enzymes. The data gave a maximum
lod score of 1.59 at theta = 0.15 for males and females combined. In an
informative South African family, Bissbort et al. (1987) found a
recombination fraction of about 0.18 between SAHH and ADA. Combined with
the published findings in Danish families, the recombination fraction
for the pooled data was calculated to be 0.4 in men, 0.08 in women, and
0.13 in the sexes taken together.
MOLECULAR GENETICS
Bissbort et al. (1983) found that the SAHH gene is polymorphic in
southwest Germany with 2 common alleles: SAHH*1 and SAHH*2, with
frequencies of 0.96 and 0.04, respectively. In the Japanese population,
Akiyama et al. (1984) estimated the gene frequencies of SAHH*1 and
SAHH*2 to be 0.953 and 0.047, respectively, similar to the results
reported by Bissbort et al. (1983).
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
By starch gel electrophoresis, Arredondo-Vega et al. (1989) identified 2
variant alleles in erythrocyte AHCY. In a British population, the gene
frequencies were 0.024 for AHCY*2 and 0.006 for AHCY*3. Variant isozyme
patterns could not be distinguished by isoelectric focusing.
Among 237 red blood cell samples from unrelated individuals in Croatia,
Kloor et al. (2006) identified 4 different electromorphic SAHH variants.
SAHH*4 was a new variant, present at a frequency of 0.015. Gene
frequencies for SAHH*1, SAHH*2, and SAHH*3 were 0.941, 0.032, and 0.006,
respectively. The authors identified a 'silent' allele with
significantly decreased enzyme activity, which they designated SAHH*0.
The frequency of SAHH*0 was 0.006, yielding an expected incidence for
homozygous individuals with SAHH deficiency of 1 in 30,000 in this
population.
- Hypermethioninemia with S-Adenosylhomocysteine Hydrolase
Deficiency
In a Croatian boy with S-adenosylhomocysteine hydrolase deficiency,
Baric et al. (2004) identified compound heterozygosity for 2 mutations
in the AHCY gene (180960.0001 and 180960.0002). In discussing the basis
of the pathologic effects of S-adenosylhomocysteine hydrolase
deficiency, Baric et al. (2004) pointed to the numerous
S-adenosylmethionine-dependent methyltransferases, which are inhibited
to a greater or lesser extent by S-adenosylhomocysteine. They pointed
out that changes in DNA methylation patterns are heritable and could
negatively affect tissue-specific gene expression during embryogenesis
and after birth. Because the silencing of genes by inappropriate
methylation is the functional equivalent of somatic mutations, the
heritability of DNA methylation patterns suggests that restoration of
'normal' genomic methylation patterns may not occur.
*FIELD* AV
.0001
HYPERMETHIONINEMIA WITH S-ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY
AHCY, TRP112TER
In a Croatian boy with hypermethioninemia and S-adenosylhomocysteine
hydrolase deficiency (613752), Baric et al. (2004) identified compound
heterozygosity for mutations in exon 2 of the AHCY gene: a change of
codon codon 112 from TGG (trp) to TGA (stop) (W112X) and a change of
codon 143 from TAC (tyr) to TGC (cys) (Y143C; 180960.0002), which were
maternally and paternally derived, respectively.
.0002
HYPERMETHIONINEMIA WITH S-ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY
AHCY, TYR143CYS
See 180960.0001 and Baric et al. (2004).
*FIELD* RF
1. Akiyama, K.; Nakamura, S.; Abe, K.: Gene frequencies of S-adenosylhomocysteine
hydrolase (SAHH) in a Japanese population. Hum. Genet. 68: 191-192,
1984.
2. Arredondo-Vega, F. X.; Charlton, J. A.; Edwards, Y. H.; Hopkinson,
D. A.; Whitehouse, D. B.: Isozyme and DNA analysis of human S-adenosyl-L-homocysteine
hydrolase (AHCY). Ann. Hum. Genet. 53: 157-167, 1989.
3. Baric, I.; Fumic, K.; Glenn, B.; Cuk, M.; Schulze, A.; Finkelstein,
J. D.; James, S. J.; Mejaski-Bosnjak, V.; Pazanin, L.; Pogribny, I.
P.; Rados, M.; Sarnavka, V.; Scukanec-Spoljar, M.; Allen, R. H.; Stabler,
S.; Uzelac, L.; Vugrek, O.; Wagner, C.; Zeisel, S.; Mudd, S. H.:
S-adenosylhomocysteine hydrolase deficiency in a human: a genetic
disorder of methionine metabolism. Proc. Nat. Acad. Sci. 101: 4234-4239,
2004.
4. Bissbort, S.; Bender, K.; Wienker, T. F.; Grzeschik, K. H.: Genetics
of human S-adenosylhomocysteine hydrolase: a new polymorphism in man. Hum.
Genet. 65: 68-71, 1983.
5. Bissbort, S.; Hitzeroth, H. W.; van den Berg, C. T.; Wienker, T.
F.: Linkage relationship between the genes for adenosine deaminase
and S-adenosyl-homocysteine hydrolase on human chromosome 20. Hum.
Genet. 77: 277-279, 1987.
6. Coulter-Karis, D. E.; Hershfield, M. S.: Sequence of full length
cDNA for human S-adenosylhomocysteine hydrolase. Ann. Hum. Genet. 53:
169-175, 1989.
7. Eiberg, H.; Mohr, J.: Linkage data concerning the ADA-AHCY relationship.
(Abstract) Cytogenet. Cell Genet. 40: 622 only, 1985.
8. Hershfield, M. S.; Francke, U.: The human gene for S-adenosylhomocysteine
hydrolase and adenosine deaminase are syntenic on chromosome 20. Science 216:
739-742, 1982.
9. Kloor, D.; Fumic, K.; Attig, S.; Tete, M.; Osswald, H.; Baric,
I.; Tomiuk, J.; Kompf, J.: Studies of S-adenosylhomocysteine-hydrolase
polymorphism in a Croatian population. J. Hum. Genet. 51: 21-24,
2006.
10. Mohandas, T.; Sparkes, R. S.; Suh, E. J.; Hershfield, M. S.:
Regional localization of the human genes for S-adenosylhomocysteine
hydrolase (cen-q131) and adenosine deaminase (q131-qter) on chromosome
20. Hum. Genet. 66: 292-295, 1984.
11. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
*FIELD* CN
Cassandra L. Kniffin - updated: 3/2/2006
Victor A. McKusick - updated: 4/28/2004
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 02/21/2011
carol: 2/21/2011
wwang: 3/3/2006
ckniffin: 3/2/2006
ckniffin: 10/28/2004
tkritzer: 5/6/2004
terry: 4/28/2004
mgross: 3/17/2004
joanna: 6/23/1997
mimadm: 3/25/1995
warfield: 3/7/1994
supermim: 3/16/1992
carol: 2/24/1992
carol: 12/20/1990
supermim: 3/20/1990
MIM
613752
*RECORD*
*FIELD* NO
613752
*FIELD* TI
#613752 HYPERMETHIONINEMIA WITH S-ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY
*FIELD* TX
read moreA number sign (#) is used with this entry because hypermethioninemia
with deficiency of S-adenosylhomocysteine hydrolase can be caused by
compound heterozygous mutation in the AHCY gene (180960) on chromosome
20q11.
CLINICAL FEATURES
In 3 daughters of Tunisian parents who were not known to be related but
came from the same village in Tunisia, Labrune et al. (1990) described
hypermethioninemia associated with failure to thrive, mental and motor
retardation, facial dysmorphism with abnormal hair and teeth, and
myocardiopathy. Hepatic S-adenosylhomocysteine hydrolase activity was
decreased by 80% in the 3 children. Neonatal cholestasis was also a
feature. A fourth daughter, who died of hepatic failure at the age of 9
months, was probably also affected. The disorder was presumably
autosomal recessive.
Baric et al. (2004) reported a Croatian boy with hypermethioninemia and
deficiency of S-adenosylhomocysteine hydrolase. The patient's
psychomotor development was slow until his fifth month when stagnation
and regression were noted. The main problems were hypotonia,
sluggishness, lack of interest, and very poor head control. Electron
microscopy of muscle showed numerous abnormal myelin figures; liver
biopsy showed mild hepatitis with sparse rough endoplasmic reticulum. At
age 12 months, brain MRI showed white matter atrophy and abnormally slow
myelination. Hypermethioninemia was present in the initial metabolic
study at age 8 months, and persisted without tyrosine elevation. Plasma
total homocysteine was slightly elevated; in plasma,
S-adenosylmethionine was 30-fold and S-adenosylhomocysteine 150-fold
elevated. Activity of S-adenosylhomocysteine hydrolase was approximately
3% of control values in liver and was 5 to 10% of control values in red
blood cells and cultured fibroblasts. Leukocyte DNA was hypermethylated.
Other causes of hypermethioninemia include hereditary tyrosinemia
(276700), cystathionine beta-synthase deficiency (236200), and
methionine adenosyltransferase deficiency (250850).
INHERITANCE
Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency is
an autosomal recessive disorder (Baric et al., 2004).
PATHOGENESIS
In discussing the basis of the pathologic effects of
S-adenosylhomocysteine hydrolase deficiency, Baric et al. (2004) pointed
to the numerous S-adenosylmethionine-dependent methyltransferases, which
are inhibited to a greater or lesser extent by S-adenosylhomocysteine.
They pointed out that changes in DNA methylation patterns are heritable
and could negatively affect tissue-specific gene expression during
embryogenesis and after birth. Because the silencing of genes by
inappropriate methylation is the functional equivalent of somatic
mutations, the heritability of DNA methylation patterns suggests that
restoration of 'normal' genomic methylation patterns may not occur.
MOLECULAR GENETICS
In a Croatian boy with S-adenosylhomocysteine hydrolase deficiency,
Baric et al. (2004) identified compound heterozygosity for 2 mutations
in the AHCY gene (180960.0001 and 180960.0002).
*FIELD* RF
1. Baric, I.; Fumic, K.; Glenn, B.; Cuk, M.; Schulze, A.; Finkelstein,
J. D.; James, S. J.; Mejaski-Bosnjak, V.; Pazanin, L.; Pogribny, I.
P.; Rados, M.; Sarnavka, V.; Scukanec-Spoljar, M.; Allen, R. H.; Stabler,
S.; Uzelac, L.; Vugrek, O.; Wagner, C.; Zeisel, S.; Mudd, S. H.:
S-adenosylhomocysteine hydrolase deficiency in a human: a genetic
disorder of methionine metabolism. Proc. Nat. Acad. Sci. 101: 4234-4239,
2004.
2. Labrune, P.; Perignon, J. L.; Rault, M.; Brunet, C.; Lutun, H.;
Charpentier, C.; Saudubray, J. M.; Odievre, M.: Familial hypermethioninemia
partially responsive to dietary restriction. J. Pediat. 117: 220-226,
1990.
*FIELD* CS
Growth:
Failure to thrive
Neuro:
Mental and motor retardation
Facies:
Facial dysmorphism
Hair:
Abnormal hair
Teeth:
Abnormal teeth
Cardiac:
Myocardiopathy
Lab:
Placental S-adenosylhomocysteine hydrolase deficiency;
Hypermethioninemia
Inheritance:
Autosomal recessive
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 02/21/2011
*FIELD* CD
Carol A. Bocchini: 2/21/2011
*FIELD* ED
carol: 10/14/2011
carol: 2/21/2011
*RECORD*
*FIELD* NO
613752
*FIELD* TI
#613752 HYPERMETHIONINEMIA WITH S-ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY
*FIELD* TX
read moreA number sign (#) is used with this entry because hypermethioninemia
with deficiency of S-adenosylhomocysteine hydrolase can be caused by
compound heterozygous mutation in the AHCY gene (180960) on chromosome
20q11.
CLINICAL FEATURES
In 3 daughters of Tunisian parents who were not known to be related but
came from the same village in Tunisia, Labrune et al. (1990) described
hypermethioninemia associated with failure to thrive, mental and motor
retardation, facial dysmorphism with abnormal hair and teeth, and
myocardiopathy. Hepatic S-adenosylhomocysteine hydrolase activity was
decreased by 80% in the 3 children. Neonatal cholestasis was also a
feature. A fourth daughter, who died of hepatic failure at the age of 9
months, was probably also affected. The disorder was presumably
autosomal recessive.
Baric et al. (2004) reported a Croatian boy with hypermethioninemia and
deficiency of S-adenosylhomocysteine hydrolase. The patient's
psychomotor development was slow until his fifth month when stagnation
and regression were noted. The main problems were hypotonia,
sluggishness, lack of interest, and very poor head control. Electron
microscopy of muscle showed numerous abnormal myelin figures; liver
biopsy showed mild hepatitis with sparse rough endoplasmic reticulum. At
age 12 months, brain MRI showed white matter atrophy and abnormally slow
myelination. Hypermethioninemia was present in the initial metabolic
study at age 8 months, and persisted without tyrosine elevation. Plasma
total homocysteine was slightly elevated; in plasma,
S-adenosylmethionine was 30-fold and S-adenosylhomocysteine 150-fold
elevated. Activity of S-adenosylhomocysteine hydrolase was approximately
3% of control values in liver and was 5 to 10% of control values in red
blood cells and cultured fibroblasts. Leukocyte DNA was hypermethylated.
Other causes of hypermethioninemia include hereditary tyrosinemia
(276700), cystathionine beta-synthase deficiency (236200), and
methionine adenosyltransferase deficiency (250850).
INHERITANCE
Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency is
an autosomal recessive disorder (Baric et al., 2004).
PATHOGENESIS
In discussing the basis of the pathologic effects of
S-adenosylhomocysteine hydrolase deficiency, Baric et al. (2004) pointed
to the numerous S-adenosylmethionine-dependent methyltransferases, which
are inhibited to a greater or lesser extent by S-adenosylhomocysteine.
They pointed out that changes in DNA methylation patterns are heritable
and could negatively affect tissue-specific gene expression during
embryogenesis and after birth. Because the silencing of genes by
inappropriate methylation is the functional equivalent of somatic
mutations, the heritability of DNA methylation patterns suggests that
restoration of 'normal' genomic methylation patterns may not occur.
MOLECULAR GENETICS
In a Croatian boy with S-adenosylhomocysteine hydrolase deficiency,
Baric et al. (2004) identified compound heterozygosity for 2 mutations
in the AHCY gene (180960.0001 and 180960.0002).
*FIELD* RF
1. Baric, I.; Fumic, K.; Glenn, B.; Cuk, M.; Schulze, A.; Finkelstein,
J. D.; James, S. J.; Mejaski-Bosnjak, V.; Pazanin, L.; Pogribny, I.
P.; Rados, M.; Sarnavka, V.; Scukanec-Spoljar, M.; Allen, R. H.; Stabler,
S.; Uzelac, L.; Vugrek, O.; Wagner, C.; Zeisel, S.; Mudd, S. H.:
S-adenosylhomocysteine hydrolase deficiency in a human: a genetic
disorder of methionine metabolism. Proc. Nat. Acad. Sci. 101: 4234-4239,
2004.
2. Labrune, P.; Perignon, J. L.; Rault, M.; Brunet, C.; Lutun, H.;
Charpentier, C.; Saudubray, J. M.; Odievre, M.: Familial hypermethioninemia
partially responsive to dietary restriction. J. Pediat. 117: 220-226,
1990.
*FIELD* CS
Growth:
Failure to thrive
Neuro:
Mental and motor retardation
Facies:
Facial dysmorphism
Hair:
Abnormal hair
Teeth:
Abnormal teeth
Cardiac:
Myocardiopathy
Lab:
Placental S-adenosylhomocysteine hydrolase deficiency;
Hypermethioninemia
Inheritance:
Autosomal recessive
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 02/21/2011
*FIELD* CD
Carol A. Bocchini: 2/21/2011
*FIELD* ED
carol: 10/14/2011
carol: 2/21/2011