CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004012
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Inosine-5'-monophosphate dehydrogenase 2 
Protein Synonyms/Alias
 IMP dehydrogenase 2; IMPD 2; IMPDH 2; IMPDH-II 
Gene Name
 IMPDH2 
Gene Synonyms/Alias
 IMPD2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
108ANEVRKVKKYEQGFIubiquitination[1]
109NEVRKVKKYEQGFITubiquitination[1, 2]
124DPVVLSPKDRVRDVFubiquitination[1, 2, 3, 4]
134VRDVFEAKARHGFCGubiquitination[1, 3, 4, 5, 6]
181FLEEIMTKREDLVVAubiquitination[1]
195APAGITLKEANEILQubiquitination[1, 3, 4, 5, 6, 7]
206EILQRSKKGKLPIVNubiquitination[1, 4, 8]
208LQRSKKGKLPIVNEDubiquitination[1, 2, 3, 4, 5, 6, 8, 9, 10]
238RDYPLASKDAKKQLLubiquitination[1, 3]
242LASKDAKKQLLCGAAubiquitination[1, 2]
291INMIKYIKDKYPNLQubiquitination[1, 8]
293MIKYIKDKYPNLQVIacetylation[11]
293MIKYIKDKYPNLQVIubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 9]
311VVTAAQAKNLIDAGVubiquitination[3, 4]
349PQATAVYKVSEYARRubiquitination[5, 6, 12]
422GSLDAMDKHLSSQNRubiquitination[1, 2, 3, 4, 5, 6]
436RYFSEADKIKVAQGVacetylation[13]
436RYFSEADKIKVAQGVubiquitination[1, 3]
438FSEADKIKVAQGVSGubiquitination[1, 3]
450VSGAVQDKGSIHKFVubiquitination[1, 3, 4, 5, 6]
455QDKGSIHKFVPYLIAubiquitination[1, 2, 5, 6]
474SCQDIGAKSLTQVRAubiquitination[1, 2, 5, 6]
489MMYSGELKFEKRTSSubiquitination[1, 5, 6]
511HSLHSYEKRLF****acetylation[13]
511HSLHSYEKRLF****ubiquitination[1, 3]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [8] 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]
 [9] 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]
 [10] 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]
 [11] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [12] 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]
 [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] 
Functional Description
 Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate- limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors. 
Sequence Annotation
 DOMAIN 114 173 CBS 1.
 DOMAIN 179 237 CBS 2.
 NP_BIND 274 276 NAD.
 NP_BIND 324 326 NAD (By similarity).
 REGION 364 366 IMP binding.
 REGION 387 388 IMP binding.
 REGION 411 415 IMP binding (By similarity).
 ACT_SITE 331 331 Thioimidate intermediate.
 METAL 326 326 Potassium; via carbonyl oxygen.
 METAL 328 328 Potassium; via carbonyl oxygen.
 METAL 331 331 Potassium; via carbonyl oxygen.
 METAL 500 500 Potassium; via carbonyl oxygen; shared
 METAL 501 501 Potassium; via carbonyl oxygen; shared
 METAL 502 502 Potassium; via carbonyl oxygen; shared
 BINDING 329 329 IMP (By similarity).
 BINDING 441 441 IMP (By similarity).
 MOD_RES 122 122 Phosphoserine.
 MOD_RES 400 400 Phosphotyrosine.
 MOD_RES 416 416 Phosphoserine.
 MOD_RES 511 511 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; CBS domain; Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding; GMP biosynthesis; Metal-binding; NAD; Nucleus; Oxidoreductase; Phosphoprotein; Potassium; Purine biosynthesis; Reference proteome; Repeat; RNA-binding. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 514 AA 
Protein Sequence
MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD LTSALTKKIT 60
LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ ANEVRKVKKY EQGFITDPVV 120
LSPKDRVRDV FEAKARHGFC GIPITDTGRM GSRLVGIISS RDIDFLKEEE HDCFLEEIMT 180
KREDLVVAPA GITLKEANEI LQRSKKGKLP IVNEDDELVA IIARTDLKKN RDYPLASKDA 240
KKQLLCGAAI GTHEDDKYRL DLLAQAGVDV VVLDSSQGNS IFQINMIKYI KDKYPNLQVI 300
GGNVVTAAQA KNLIDAGVDA LRVGMGSGSI CITQEVLACG RPQATAVYKV SEYARRFGVP 360
VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY FFSDGIRLKK YRGMGSLDAM 420
DKHLSSQNRY FSEADKIKVA QGVSGAVQDK GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR 480
AMMYSGELKF EKRTSSAQVE GGVHSLHSYE KRLF 514 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0003938; F:IMP dehydrogenase activity; TAS:ProtInc.
 GO:0046872; F:metal ion binding; IEA:HAMAP.
 GO:0000166; F:nucleotide binding; IDA:UniProtKB.
 GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
 GO:0006177; P:GMP biosynthetic process; IEA:HAMAP.
 GO:0046651; P:lymphocyte proliferation; IEA:Compara.
 GO:0051289; P:protein homotetramerization; IEA:Compara.
 GO:0006144; P:purine nucleobase metabolic process; TAS:Reactome.
 GO:0009168; P:purine ribonucleoside monophosphate biosynthetic process; TAS:Reactome.
 GO:0060041; P:retina development in camera-type eye; IEA:Compara. 
Interpro
 IPR013785; Aldolase_TIM.
 IPR000644; Cysta_beta_synth_core.
 IPR005990; IMP_DH.
 IPR015875; IMP_DH/GMP_Rdtase_CS.
 IPR001093; IMP_DH_GMPRt. 
Pfam
 PF00571; CBS
 PF00478; IMPDH 
SMART
 SM00116; CBS 
PROSITE
 PS51371; CBS
 PS00487; IMP_DH_GMP_RED 
PRINTS