CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011933
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Dihydropyrimidine dehydrogenase [NADP(+)] 
Protein Synonyms/Alias
 DHPDHase; DPD; Dihydrothymine dehydrogenase; Dihydrouracil dehydrogenase 
Gene Name
 DPYD 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
63ENNFDDIKHTTLGERubiquitination[1]
81REAMRCLKCADAPCQubiquitination[1]
89CADAPCQKSCPTNLDubiquitination[1, 2]
98CPTNLDIKSFITSIAubiquitination[1]
107FITSIANKNYYGAAKubiquitination[1]
181PSLPPPEKMSEAYSAubiquitination[1]
259GVKIICGKSLSVNEMubiquitination[1]
272EMTLSTLKEKGYKAAubiquitination[1]
274TLSTLKEKGYKAAFIubiquitination[1]
315DFLPLVAKGSKAGMCubiquitination[1]
318PLVAKGSKAGMCACHubiquitination[1, 3]
365RVFIVFRKGFVNIRAubiquitination[1]
381PEEMELAKEEKCEFLacetylation[3]
381PEEMELAKEEKCEFLubiquitination[1, 3]
384MELAKEEKCEFLPFLacetylation[3, 4, 5]
384MELAKEEKCEFLPFLubiquitination[1]
418TEQDETGKWNEDEDQubiquitination[1]
448VLSDPKVKEALSPIKubiquitination[1]
455KEALSPIKFNRWGLPubiquitination[1]
580TKTFSLDKDIVTNVSubiquitination[1]
656DWTELAKKSEDSGADubiquitination[1]
709VQIPFFAKLTPNVTDubiquitination[1, 6]
725VSIARAAKEGGANGVubiquitination[1]
758WPAVGIAKRTTYGGVubiquitination[1]
841LKALLYLKSIEELQDubiquitination[1]
874RIAELMDKKLPSFGPubiquitination[1]
875IAELMDKKLPSFGPYubiquitination[1]
894KKIIAENKIRLKEQNubiquitination[1]
898AENKIRLKEQNVAFSubiquitination[1, 3]
908NVAFSPLKRNCFIPKubiquitination[1, 2]
915KRNCFIPKRPIPTIKubiquitination[3]
922KRPIPTIKDVIGKALubiquitination[1]
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] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [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] 
Functional Description
 Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil. 
Sequence Annotation
 DOMAIN 69 100 4Fe-4S ferredoxin-type 1.
 DOMAIN 944 976 4Fe-4S ferredoxin-type 2.
 DOMAIN 978 1007 4Fe-4S ferredoxin-type 3.
 NP_BIND 194 198 FAD (By similarity).
 NP_BIND 218 226 FAD (By similarity).
 NP_BIND 340 343 NADP (By similarity).
 NP_BIND 364 365 NADP (By similarity).
 NP_BIND 437 439 NADP (By similarity).
 NP_BIND 480 489 FAD (By similarity).
 NP_BIND 481 487 NADP (By similarity).
 NP_BIND 574 575 FMN (By similarity).
 NP_BIND 793 795 FMN (By similarity).
 NP_BIND 816 817 FMN (By similarity).
 REGION 668 670 Substrate binding (By similarity).
 REGION 736 737 Substrate binding (By similarity).
 ACT_SITE 671 671 Proton acceptor (By similarity).
 METAL 79 79 Iron-sulfur 1 (4Fe-4S) (By similarity).
 METAL 82 82 Iron-sulfur 1 (4Fe-4S) (By similarity).
 METAL 87 87 Iron-sulfur 1 (4Fe-4S) (By similarity).
 METAL 91 91 Iron-sulfur 2 (4Fe-4S) (By similarity).
 METAL 130 130 Iron-sulfur 2 (4Fe-4S) (By similarity).
 METAL 136 136 Iron-sulfur 2 (4Fe-4S) (By similarity).
 METAL 140 140 Iron-sulfur 1 (4Fe-4S) (By similarity).
 METAL 156 156 Iron-sulfur 2 (4Fe-4S) (By similarity).
 METAL 953 953 Iron-sulfur 3 (4Fe-4S) (By similarity).
 METAL 956 956 Iron-sulfur 3 (4Fe-4S) (By similarity).
 METAL 959 959 Iron-sulfur 3 (4Fe-4S) (By similarity).
 METAL 963 963 Iron-sulfur 3 (4Fe-4S) (By similarity).
 METAL 986 986 Iron-sulfur 4 (4Fe-4S) (By similarity).
 METAL 989 989 Iron-sulfur 4 (4Fe-4S) (By similarity).
 METAL 992 992 Iron-sulfur 4 (4Fe-4S) (By similarity).
 METAL 996 996 Iron-sulfur 4 (4Fe-4S) (By similarity).
 BINDING 129 129 FAD; via carbonyl oxygen (By similarity).
 BINDING 235 235 FAD (By similarity).
 BINDING 261 261 FAD; via amide nitrogen and carbonyl
 BINDING 371 371 NADP (By similarity).
 BINDING 550 550 FMN (By similarity).
 BINDING 609 609 Substrate (By similarity).
 BINDING 709 709 FMN (By similarity).
 BINDING 767 767 FMN; via amide nitrogen (By similarity).
 MOD_RES 384 384 N6-acetyllysine.  
Keyword
 4Fe-4S; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; FAD; Flavoprotein; FMN; Iron; Iron-sulfur; Metal-binding; NADP; Nucleotide-binding; Oxidoreductase; Polymorphism; Reference proteome; Repeat. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1025 AA 
Protein Sequence
MAPVLSKDSA DIESILALNP RTQTHATLCS TSAKKLDKKH WKRNPDKNCF NCEKLENNFD 60
DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF ITSIANKNYY GAAKMIFSDN 120
PLGLTCGMVC PTSDLCVGGC NLYATEEGPI NIGGLQQFAT EVFKAMSIPQ IRNPSLPPPE 180
KMSEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV 240
VNFEIELMKD LGVKIICGKS LSVNEMTLST LKEKGYKAAF IGIGLPEPNK DAIFQGLTQD 300
QGFYTSKDFL PLVAKGSKAG MCACHSPLPS IRGVVIVLGA GDTAFDCATS ALRCGARRVF 360
IVFRKGFVNI RAVPEEMELA KEEKCEFLPF LSPRKVIVKG GRIVAMQFVR TEQDETGKWN 420
EDEDQMVHLK ADVVISAFGS VLSDPKVKEA LSPIKFNRWG LPEVDPETMQ TSEAWVFAGG 480
DVVGLANTTV ESVNDGKQAS WYIHKYVQSQ YGASVSAKPE LPLFYTPIDL VDISVEMAGL 540
KFINPFGLAS ATPATSTSMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPMY 600
GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNKNDW TELAKKSEDS 660
GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVQIPFFAKL TPNVTDIVSI 720
ARAAKEGGAN GVTATNTVSG LMGLKSDGTP WPAVGIAKRT TYGGVSGTAI RPIALRAVTS 780
IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL 840
KSIEELQDWD GQSPATVSHQ KGKPVPRIAE LMDKKLPSFG PYLEQRKKII AENKIRLKEQ 900
NVAFSPLKRN CFIPKRPIPT IKDVIGKALQ YLGTFGELSN VEQVVAMIDE EMCINCGKCY 960
MTCNDSGYQA IQFDPETHLP TITDTCTGCT LCLSVCPIVD CIKMVSRTTP YEPKRGVPLS 1020
VNPVC 1025 
Gene Ontology
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
 GO:0004158; F:dihydroorotate oxidase activity; IEA:InterPro.
 GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; IDA:UniProtKB.
 GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0050661; F:NADP binding; ISS:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0019483; P:beta-alanine biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0006145; P:purine nucleobase catabolic process; IMP:UniProtKB.
 GO:0006214; P:thymidine catabolic process; IDA:UniProtKB.
 GO:0006210; P:thymine catabolic process; IDA:UniProtKB.
 GO:0006222; P:UMP biosynthetic process; IEA:InterPro.
 GO:0006212; P:uracil catabolic process; IDA:UniProtKB. 
Interpro
 IPR017896; 4Fe4S_Fe-S-bd.
 IPR017900; 4Fe4S_Fe_S_CS.
 IPR013785; Aldolase_TIM.
 IPR005720; Dihydroorotate_DH.
 IPR012135; Dihydroorotate_DH_1_2.
 IPR012285; Fum_reductase_C.
 IPR009051; Helical_ferredxn. 
Pfam
 PF01180; DHO_dh 
SMART
  
PROSITE
 PS00198; 4FE4S_FER_1
 PS51379; 4FE4S_FER_2 
PRINTS