SAHH_HUMAN
ID SAHH_HUMAN Reviewed; 432 AA.
AC P23526; A8K307; B3KUN3; E1P5P2; F5H737; Q96A36;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Adenosylhomocysteinase;
DE Short=AdoHcyase;
DE EC=3.3.1.1 {ECO:0000269|PubMed:10933798};
DE AltName: Full=S-adenosyl-L-homocysteine hydrolase;
GN Name=AHCY; Synonyms=SAHH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [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 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 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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 for
RT 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 389-405,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION
RP BY 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 hydrolase
RT with [2-3H]8-azido-adenosine.";
RL J. Biol. Chem. 270:16140-16146(1995).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10933798; DOI=10.1021/bi000595a;
RA Yin D., Yang X., Hu Y., Kuczera K., Schowen R.L., Borchardt R.T.,
RA Squier T.C.;
RT "Substrate binding stabilizes S-adenosylhomocysteine hydrolase in a closed
RT conformation.";
RL Biochemistry 39:9811-9818(2000).
RN [12]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., 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 [13]
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., Buerckstuemmer T.,
RA 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP HYDROXYBUTYRYLATION AT LYS-186.
RX PubMed=29192674; DOI=10.1038/cr.2017.149;
RA Huang H., Luo Z., Qi S., Huang J., Xu P., Wang X., Gao L., Li F., Wang J.,
RA Zhao W., Gu W., Chen Z., Dai L., Dai J., Zhao Y.;
RT "Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation
RT pathway.";
RL Cell Res. 28:111-125(2018).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH NAD AND ADENOSINE
RP 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 [18]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) IN COMPLEX WITH NAD AND NEPLANOCIN
RP A, 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: transition-
RT state stabilization and the avoidance of abortive reactions.";
RL Biochemistry 42:1900-1909(2003).
RN [19]
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 hydrolase
RT gene on total homocysteine concentrations and risk of recurrent venous
RT thrombosis.";
RL Eur. J. Hum. Genet. 12:942-948(2004).
RN [20]
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 disorder
RT of methionine metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4234-4239(2004).
RN [21]
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 [22]
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 mutations
RT with lethal outcome.";
RL Hum. Mutat. 30:E555-E565(2009).
RN [23]
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., Baric I.,
RA 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: Catalyzes the hydrolysis of S-adenosyl-L-homocysteine to form
CC adenosine and homocysteine (PubMed:10933798). Binds copper ions (By
CC similarity). {ECO:0000250|UniProtKB:P50247,
CC ECO:0000269|PubMed:10933798}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + S-adenosyl-L-homocysteine = adenosine + L-homocysteine;
CC Xref=Rhea:RHEA:21708, ChEBI:CHEBI:15377, ChEBI:CHEBI:16335,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:58199; EC=3.3.1.1;
CC Evidence={ECO:0000269|PubMed:10933798};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21709;
CC Evidence={ECO:0000305|PubMed:10933798};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000269|PubMed:12590576, ECO:0000269|PubMed:9586999};
CC Note=Binds 1 NAD(+) per subunit. {ECO:0000269|PubMed:12590576,
CC ECO:0000269|PubMed:9586999};
CC -!- PATHWAY: Amino-acid biosynthesis; L-homocysteine biosynthesis; L-
CC homocysteine from S-adenosyl-L-homocysteine: step 1/1.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:12590576,
CC ECO:0000269|PubMed:9586999}.
CC -!- INTERACTION:
CC P23526; Q6AI12: ANKRD40; NbExp=8; IntAct=EBI-1053240, EBI-2838246;
CC P23526; Q92624: APPBP2; NbExp=3; IntAct=EBI-1053240, EBI-743771;
CC P23526; Q9BV19: C1orf50; NbExp=12; IntAct=EBI-1053240, EBI-2874661;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17081065}.
CC Melanosome {ECO:0000269|PubMed:17081065}. Note=Identified by mass
CC spectrometry in melanosome fractions from stage I to stage 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 -!- DISEASE: Hypermethioninemia with S-adenosylhomocysteine hydrolase
CC deficiency (HMAHCHD) [MIM:613752]: A metabolic disorder characterized
CC by hypermethioninemia associated with failure to thrive, mental and
CC motor retardation, facial dysmorphism with abnormal hair and teeth, and
CC myocardiopathy. {ECO:0000269|PubMed:15024124,
CC ECO:0000269|PubMed:16736098, ECO:0000269|PubMed:19177456,
CC ECO:0000269|PubMed:20852937}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000305}.
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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; -; NOT_ANNOTATED_CDS; 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 CCDS; CCDS13233.1; -. [P23526-1]
DR CCDS; CCDS54457.1; -. [P23526-2]
DR PIR; A43629; A43629.
DR RefSeq; NP_000678.1; NM_000687.3. [P23526-1]
DR RefSeq; NP_001155238.1; NM_001161766.1. [P23526-2]
DR RefSeq; NP_001309013.1; NM_001322084.1. [P23526-2]
DR RefSeq; NP_001309014.1; NM_001322085.1. [P23526-2]
DR RefSeq; XP_005260374.1; XM_005260317.2. [P23526-2]
DR RefSeq; XP_011526961.1; XM_011528659.1. [P23526-2]
DR RefSeq; XP_016883197.1; XM_017027708.1.
DR RefSeq; XP_016883198.1; XM_017027709.1. [P23526-1]
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 PDB; 4PFJ; X-ray; 2.30 A; A/B=1-432.
DR PDB; 4PGF; X-ray; 2.59 A; A/B=1-432.
DR PDB; 4YVF; X-ray; 2.70 A; A/B=1-432.
DR PDB; 5W49; X-ray; 2.40 A; A/B=4-432.
DR PDB; 5W4B; X-ray; 2.65 A; A/B/C/D/E/F=4-432.
DR PDBsum; 1A7A; -.
DR PDBsum; 1LI4; -.
DR PDBsum; 3NJ4; -.
DR PDBsum; 4PFJ; -.
DR PDBsum; 4PGF; -.
DR PDBsum; 4YVF; -.
DR PDBsum; 5W49; -.
DR PDBsum; 5W4B; -.
DR AlphaFoldDB; P23526; -.
DR SMR; P23526; -.
DR BioGRID; 106696; 143.
DR DIP; DIP-50557N; -.
DR IntAct; P23526; 52.
DR MINT; P23526; -.
DR STRING; 9606.ENSP00000217426; -.
DR BindingDB; P23526; -.
DR ChEMBL; CHEMBL2664; -.
DR DrugBank; DB03216; (1'R,2'S)-9-(2-Hydroxy-3'-Keto-Cyclopenten-1-yl)Adenine.
DR DrugBank; DB03273; 3'-Oxo-Adenosine.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB03769; D-Eritadenine.
DR DrugCentral; P23526; -.
DR GuidetoPHARMACOLOGY; 1233; -.
DR GlyGen; P23526; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P23526; -.
DR MetOSite; P23526; -.
DR PhosphoSitePlus; P23526; -.
DR SwissPalm; P23526; -.
DR BioMuta; AHCY; -.
DR DMDM; 20141702; -.
DR REPRODUCTION-2DPAGE; IPI00012007; -.
DR EPD; P23526; -.
DR jPOST; P23526; -.
DR MassIVE; P23526; -.
DR MaxQB; P23526; -.
DR PaxDb; P23526; -.
DR PeptideAtlas; P23526; -.
DR PRIDE; P23526; -.
DR ProteomicsDB; 27374; -.
DR ProteomicsDB; 54126; -. [P23526-1]
DR Antibodypedia; 35085; 405 antibodies from 32 providers.
DR DNASU; 191; -.
DR Ensembl; ENST00000217426.7; ENSP00000217426.2; ENSG00000101444.13. [P23526-1]
DR Ensembl; ENST00000538132.1; ENSP00000442820.1; ENSG00000101444.13. [P23526-2]
DR GeneID; 191; -.
DR KEGG; hsa:191; -.
DR MANE-Select; ENST00000217426.7; ENSP00000217426.2; NM_000687.4; NP_000678.1.
DR UCSC; uc002xai.4; human. [P23526-1]
DR CTD; 191; -.
DR DisGeNET; 191; -.
DR GeneCards; AHCY; -.
DR HGNC; HGNC:343; AHCY.
DR HPA; ENSG00000101444; Low tissue specificity.
DR MalaCards; AHCY; -.
DR MIM; 180960; gene.
DR MIM; 613752; phenotype.
DR neXtProt; NX_P23526; -.
DR OpenTargets; ENSG00000101444; -.
DR Orphanet; 88618; S-adenosylhomocysteine hydrolase deficiency.
DR PharmGKB; PA24636; -.
DR VEuPathDB; HostDB:ENSG00000101444; -.
DR eggNOG; KOG1370; Eukaryota.
DR GeneTree; ENSGT00950000182981; -.
DR HOGENOM; CLU_025194_2_1_1; -.
DR InParanoid; P23526; -.
DR OMA; NKYGCRE; -.
DR PhylomeDB; P23526; -.
DR TreeFam; TF300415; -.
DR BioCyc; MetaCyc:HS02273-MON; -.
DR BRENDA; 3.3.1.1; 2681.
DR PathwayCommons; P23526; -.
DR Reactome; R-HSA-156581; Methylation.
DR Reactome; R-HSA-1614635; Sulfur amino acid metabolism.
DR Reactome; R-HSA-2408508; Metabolism of ingested SeMet, Sec, MeSec into H2Se.
DR Reactome; R-HSA-5578997; Defective AHCY causes HMAHCHD.
DR SABIO-RK; P23526; -.
DR SignaLink; P23526; -.
DR UniPathway; UPA00314; UER00076.
DR BioGRID-ORCS; 191; 494 hits in 1095 CRISPR screens.
DR ChiTaRS; AHCY; human.
DR EvolutionaryTrace; P23526; -.
DR GenomeRNAi; 191; -.
DR Pharos; P23526; Tchem.
DR PRO; PR:P23526; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P23526; protein.
DR Bgee; ENSG00000101444; Expressed in lower esophagus mucosa and 98 other tissues.
DR ExpressionAtlas; P23526; baseline and differential.
DR Genevisible; P23526; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0004013; F:adenosylhomocysteinase activity; IDA:UniProtKB.
DR GO; GO:0030554; F:adenyl nucleotide binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0051287; F:NAD binding; IEA:Ensembl.
DR GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0042745; P:circadian sleep/wake cycle; IEA:Ensembl.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0019510; P:S-adenosylhomocysteine catabolic process; IEA:Ensembl.
DR GO; GO:0033353; P:S-adenosylmethionine cycle; IBA:GO_Central.
DR CDD; cd00401; SAHH; 1.
DR Gene3D; 3.40.50.1480; -; 2.
DR HAMAP; MF_00563; AdoHcyase; 1.
DR InterPro; IPR042172; Adenosylhomocyst_ase-like_sf.
DR InterPro; IPR000043; Adenosylhomocysteinase-like.
DR InterPro; IPR015878; Ado_hCys_hydrolase_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
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 SUPFAM; SSF51735; SSF51735; 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; Copper; Cytoplasm;
KW Direct protein sequencing; Disease variant; Hydrolase; Hydroxylation; NAD;
KW One-carbon metabolism; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7786017, ECO:0000269|Ref.8"
FT CHAIN 2..432
FT /note="Adenosylhomocysteinase"
FT /id="PRO_0000116902"
FT BINDING 57
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 131
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 156
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 157..159
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12590576,
FT ECO:0000269|PubMed:9586999"
FT BINDING 186
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 190
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 222..227
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12590576,
FT ECO:0000269|PubMed:9586999"
FT BINDING 243
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12590576,
FT ECO:0000269|PubMed:9586999"
FT BINDING 248
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12590576,
FT ECO:0000269|PubMed:9586999"
FT BINDING 299..301
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12590576,
FT ECO:0000269|PubMed:9586999"
FT BINDING 346
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12590576,
FT ECO:0000269|PubMed:9586999"
FT BINDING 353
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12590576,
FT ECO:0000269|PubMed:9586999"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 186
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000269|PubMed:29192674"
FT MOD_RES 193
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P50247"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045404"
FT VARIANT 38
FT /note="R -> W (in dbSNP:rs13043752)"
FT /evidence="ECO:0000269|PubMed:15241484"
FT /id="VAR_052286"
FT VARIANT 49
FT /note="R -> C (in HMAHCHD; dbSNP:rs369428934)"
FT /evidence="ECO:0000269|PubMed:19177456,
FT ECO:0000269|PubMed:20852937"
FT /id="VAR_058588"
FT VARIANT 86
FT /note="D -> G (in HMAHCHD; dbSNP:rs773162208)"
FT /evidence="ECO:0000269|PubMed:19177456,
FT ECO:0000269|PubMed:20852937"
FT /id="VAR_058589"
FT VARIANT 86
FT /note="D -> N"
FT /evidence="ECO:0000269|PubMed:2596825"
FT /id="VAR_006934"
FT VARIANT 89
FT /note="A -> V (in HMAHCHD; dbSNP:rs755222515)"
FT /evidence="ECO:0000269|PubMed:16736098"
FT /id="VAR_058590"
FT VARIANT 143
FT /note="Y -> C (in HMAHCHD; dbSNP:rs121918608)"
FT /evidence="ECO:0000269|PubMed:15024124,
FT ECO:0000269|PubMed:16736098"
FT /id="VAR_058591"
FT CONFLICT 249
FT /note="A -> V (in Ref. 3; BAG53495)"
FT /evidence="ECO:0000305"
FT STRAND 8..10
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 15..26
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 30..39
FT /evidence="ECO:0007829|PDB:1LI4"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:1LI4"
FT TURN 44..47
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 49..54
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 58..69
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:5W49"
FT HELIX 86..94
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 107..115
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 121..124
FT /evidence="ECO:0007829|PDB:5W49"
FT STRAND 126..133
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 134..142
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 144..149
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 158..169
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 190..207
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 223..234
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 238..242
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 246..254
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:1LI4"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 270..274
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:3NJ4"
FT HELIX 284..287
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 294..298
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 308..314
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 316..322
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 335..339
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 345..348
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 355..374
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 376..378
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 381..384
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 388..399
FT /evidence="ECO:0007829|PDB:1LI4"
FT TURN 400..403
FT /evidence="ECO:0007829|PDB:1LI4"
FT HELIX 411..417
FT /evidence="ECO:0007829|PDB:1LI4"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:3NJ4"
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
