CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005188
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Adenosylhomocysteinase 
Protein Synonyms/Alias
 AdoHcyase; S-adenosyl-L-homocysteine hydrolase 
Gene Name
 AHCY 
Gene Synonyms/Alias
 SAHH 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
4****MSDKLPYKVADacetylation[1]
4****MSDKLPYKVADubiquitination[2]
8MSDKLPYKVADIGLAubiquitination[2, 3, 4]
20GLAAWGRKALDIAENubiquitination[2, 5]
43RERYSASKPLKGARIubiquitination[1, 2, 6]
46YSASKPLKGARIAGCubiquitination[1, 2]
166TGVHNLYKMMANGILacetylation[7]
166TGVHNLYKMMANGILubiquitination[1, 2, 3, 4, 8, 9, 10, 11]
174MMANGILKVPAINVNubiquitination[2, 9, 10]
186NVNDSVTKSKFDNLYubiquitination[1, 2, 5, 9, 10, 11, 12]
188NDSVTKSKFDNLYGCubiquitination[1, 2, 3, 4, 5, 9, 10, 12]
204ESLIDGIKRATDVMIubiquitination[1, 2, 12]
226AGYGDVGKGCAQALRubiquitination[1, 2, 3, 4, 5, 10]
318LNENAVEKVNIKPQVubiquitination[2]
322AVEKVNIKPQVDRYRubiquitination[1, 2, 10]
389GVHFLPKKLDEAVAEubiquitination[2]
401VAEAHLGKLNVKLTKacetylation[1, 7, 13, 14]
401VAEAHLGKLNVKLTKubiquitination[2]
405HLGKLNVKLTKLTEKubiquitination[1, 2, 9]
408KLNVKLTKLTEKQAQacetylation[1, 13, 14]
412KLTKLTEKQAQYLGMubiquitination[3, 4]
Reference
 [1] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [7] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [8] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [9] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [10] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [11] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [12] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [13] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [14] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773] 
Functional Description
 Adenosylhomocysteine is a competitive inhibitor of S- adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine. 
Sequence Annotation
 NP_BIND 157 159 NAD.
 NP_BIND 222 227 NAD.
 NP_BIND 299 301 NAD.
 BINDING 57 57 Substrate (By similarity).
 BINDING 131 131 Substrate (By similarity).
 BINDING 156 156 Substrate (By similarity).
 BINDING 186 186 Substrate (By similarity).
 BINDING 190 190 Substrate (By similarity).
 BINDING 243 243 NAD.
 BINDING 248 248 NAD.
 BINDING 346 346 NAD.
 BINDING 353 353 NAD.
 MOD_RES 2 2 N-acetylserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Hydrolase; NAD; One-carbon metabolism; Polymorphism; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 432 AA 
Protein Sequence
MSDKLPYKVA DIGLAAWGRK ALDIAENEMP GLMRMRERYS ASKPLKGARI AGCLHMTVET 60
AVLIETLVTL GAEVQWSSCN IFSTQDHAAA AIAKAGIPVY AWKGETDEEY LWCIEQTLYF 120
KDGPLNMILD DGGDLTNLIH TKYPQLLPGI RGISEETTTG VHNLYKMMAN GILKVPAINV 180
NDSVTKSKFD NLYGCRESLI DGIKRATDVM IAGKVAVVAG YGDVGKGCAQ ALRGFGARVI 240
ITEIDPINAL QAAMEGYEVT TMDEACQEGN IFVTTTGCID IILGRHFEQM KDDAIVCNIG 300
HFDVEIDVKW LNENAVEKVN IKPQVDRYRL KNGRRIILLA EGRLVNLGCA MGHPSFVMSN 360
SFTNQVMAQI ELWTHPDKYP VGVHFLPKKL DEAVAEAHLG KLNVKLTKLT EKQAQYLGMS 420
CDGPFKPDHY RY 432 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
 GO:0043005; C:neuron projection; IEA:Compara.
 GO:0005634; C:nucleus; IEA:Compara.
 GO:0004013; F:adenosylhomocysteinase activity; TAS:UniProtKB.
 GO:0030554; F:adenyl nucleotide binding; IEA:Compara.
 GO:0051287; F:NAD binding; IEA:Compara.
 GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome.
 GO:0002439; P:chronic inflammatory response to antigenic stimulus; IEA:Compara.
 GO:0042745; P:circadian sleep/wake cycle; IEA:Compara.
 GO:0032259; P:methylation; TAS:Reactome.
 GO:0006730; P:one-carbon metabolic process; NAS:UniProtKB.
 GO:0001666; P:response to hypoxia; IEA:Compara.
 GO:0007584; P:response to nutrient; IEA:Compara.
 GO:0019510; P:S-adenosylhomocysteine catabolic process; IEA:Compara.
 GO:0000096; P:sulfur amino acid metabolic process; TAS:Reactome.
 GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. 
Interpro
 IPR000043; Adenosylhomocysteinase.
 IPR015878; Ado_hCys_hydrolase_NAD-bd.
 IPR016040; NAD(P)-bd_dom.
 IPR020082; S-Ado-L-homoCys_hydrolase_CS. 
Pfam
 PF05221; AdoHcyase
 PF00670; AdoHcyase_NAD 
SMART
 SM00996; AdoHcyase
 SM00997; AdoHcyase_NAD 
PROSITE
 PS00738; ADOHCYASE_1
 PS00739; ADOHCYASE_2 
PRINTS