CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005610
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 CAD protein 
Protein Synonyms/Alias
 Glutamine-dependent carbamoyl-phosphate synthase; Aspartate carbamoyltransferase; Dihydroorotase 
Gene Name
 CAD 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
127DTRELTKKLREQGSLubiquitination[1]
137EQGSLLGKLVQNGTEubiquitination[1, 2]
165LVPEVSIKTPRVFNTubiquitination[1, 2, 3]
186LALDCGLKYNQIRCLubiquitination[1, 4, 5]
424SQAIKALKEENIQTLubiquitination[1, 2, 3]
490NCGVELTKAGVLARYubiquitination[1]
592TSQVLVDKSLKGWKEubiquitination[2]
598DKSLKGWKEIEYEVVubiquitination[1, 2]
696RSSALASKATGYPLAubiquitination[1, 2, 3, 6, 7]
739SVDYCVVKIPRWDLSubiquitination[1, 4, 5]
747IPRWDLSKFLRVSTKacetylation[8]
747IPRWDLSKFLRVSTKubiquitination[1, 2, 3, 5, 6, 7]
754KFLRVSTKIGSCMKSubiquitination[1]
760TKIGSCMKSVGEVMGubiquitination[1]
778SFEEAFQKALRMVDEubiquitination[1, 2, 3, 6, 7, 9]
795VGFDHTVKPVSDMELubiquitination[1]
808ELETPTDKRIFVVAAubiquitination[1]
867PDLLQQAKCLGFSDKubiquitination[1]
874KCLGFSDKQIALAVLubiquitination[1]
889STELAVRKLRQELGIubiquitination[1]
1119SSAAAVSKEHPVVISubiquitination[1, 2, 3, 6, 7]
1127EHPVVISKFIQEAKEubiquitination[1, 2, 3]
1211IAKDDQLKVIECNVRubiquitination[1]
1228RSFPFVSKTLGVDLVubiquitination[1, 2, 3, 4]
1262GSGVVGVKVPQFSFSubiquitination[1, 2, 3]
1309AMLSTGFKIPKKNILubiquitination[1, 2, 3]
1313TGFKIPKKNILLTIGubiquitination[1, 2]
1323LLTIGSYKNKSELLPubiquitination[1, 2, 3]
1325TIGSYKNKSELLPTVubiquitination[1, 2, 3]
1411RLSSFVTKGYRTRRLacetylation[8]
1411RLSSFVTKGYRTRRLubiquitination[1, 2, 3, 5, 6, 7, 9]
1431VPLIIDIKCTKLFVEubiquitination[1, 2]
1460VDCMTSQKLVRLPGLubiquitination[1]
1618HICHVARKEEILLIKubiquitination[1, 2]
1625KEEILLIKAAKARGLubiquitination[1, 2]
1657LERLGPGKGEVRPELubiquitination[1, 2, 3, 6, 7]
1778WTPFEGQKVKGTVRRubiquitination[1, 3]
1869GLPAEEPKEKSSRKVubiquitination[1]
1871PAEEPKEKSSRKVAEubiquitination[1]
1875PKEKSSRKVAEPELMubiquitination[1]
1961ERSLDILKGKVMASMubiquitination[2]
1963SLDILKGKVMASMFYubiquitination[1, 3]
2036GAVELAAKHCRRPVIubiquitination[1]
2125FVASRGTKQEEFESIubiquitination[1, 2, 3]
2178IMTRAKKKMVVMHPMubiquitination[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] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] 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] 
Functional Description
 This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). 
Sequence Annotation
 DOMAIN 177 363 Glutamine amidotransferase type-1.
 DOMAIN 519 711 ATP-grasp 1.
 DOMAIN 1052 1243 ATP-grasp 2.
 REGION 2 365 GATase (Glutamine amidotransferase).
 REGION 366 394 Linker.
 REGION 395 1455 CPSase (Carbamoyl-phosphate synthase).
 REGION 395 933 CPSase A.
 REGION 934 1455 CPSase B.
 REGION 1456 1788 DHOase (dihydroorotase).
 REGION 1789 1917 Linker.
 REGION 1918 2225 ATCase (Aspartate transcarbamylase).
 ACT_SITE 252 252 For GATase activity (By similarity).
 ACT_SITE 336 336 For GATase activity (By similarity).
 ACT_SITE 338 338 For GATase activity (By similarity).
 METAL 1471 1471 Zinc (Potential).
 METAL 1473 1473 Zinc (Potential).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 747 747 N6-acetyllysine.
 MOD_RES 1406 1406 Phosphoserine.
 MOD_RES 1411 1411 N6-acetyllysine.
 MOD_RES 1859 1859 Phosphoserine.
 MOD_RES 1884 1884 Phosphothreonine.
 MOD_RES 1900 1900 Phosphoserine.
 MOD_RES 1906 1906 Phosphothreonine.  
Keyword
 Acetylation; Allosteric enzyme; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase; Ligase; Metal-binding; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; Polymorphism; Pyrimidine biosynthesis; Reference proteome; Repeat; Transferase; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 2225 AA 
Protein Sequence
MAALVLEDGS VLRGQPFGAA VSTAGEVVFQ TGMVGYPEAL TDPSYKAQIL VLTYPLIGNY 60
GIPPDEMDEF GLCKWFESSG IHVAALVVGE CCPTPSHWSA TRTLHEWLQQ HGIPGLQGVD 120
TRELTKKLRE QGSLLGKLVQ NGTEPSSLPF LDPNARPLVP EVSIKTPRVF NTGGAPRILA 180
LDCGLKYNQI RCLCQRGAEV TVVPWDHALD SQEYEGLFLS NGPGDPASYP SVVSTLSRVL 240
SEPNPRPVFG ICLGHQLLAL AIGAKTYKMR YGNRGHNQPC LLVGSGRCFL TSQNHGFAVE 300
TDSLPADWAP LFTNANDGSN EGIVHNSLPF FSVQFHPEHQ AGPSDMELLF DIFLETVKEA 360
TAGNPGGQTV RERLTERLCP PGIPTPGSGL PPPRKVLILG SGGLSIGQAG EFDYSGSQAI 420
KALKEENIQT LLINPNIATV QTSQGLADKV YFLPITPHYV TQVIRNERPD GVLLTFGGQT 480
ALNCGVELTK AGVLARYGVR VLGTPVETIE LTEDRRAFAA RMAEIGEHVA PSEAANSLEQ 540
AQAAAERLGY PVLVRAAFAL GGLGSGFASN REELSALVAP AFAHTSQVLV DKSLKGWKEI 600
EYEVVRDAYG NCVTVCNMEN LDPLGIHTGE SIVVAPSQTL NDREYQLLRQ TAIKVTQHLG 660
IVGECNVQYA LNPESEQYYI IEVNARLSRS SALASKATGY PLAYVAAKLA LGIPLPELRN 720
SVTGGTAAFE PSVDYCVVKI PRWDLSKFLR VSTKIGSCMK SVGEVMGIGR SFEEAFQKAL 780
RMVDENCVGF DHTVKPVSDM ELETPTDKRI FVVAAALWAG YSVDRLYELT RIDRWFLHRM 840
KRIIAHAQLL EQHRGQPLPP DLLQQAKCLG FSDKQIALAV LSTELAVRKL RQELGICPAV 900
KQIDTVAAEW PAQTNYLYLT YWGTTHDLTF RTPHVLVLGS GVYRIGSSVE FDWCAVGCIQ 960
QLRKMGYKTI MVNYNPETVS TDYDMCDRLY FDEISFEVVM DIYELENPEG VILSMGGQLP 1020
NNMAMALHRQ QCRVLGTSPE AIDSAENRFK FSRLLDTIGI SQPQWRELSD LESARQFCQT 1080
VGYPCVVRPS YVLSGAAMNV AYTDGDLERF LSSAAAVSKE HPVVISKFIQ EAKEIDVDAV 1140
ASDGVVAAIA ISEHVENAGV HSGDATLVTP PQDITAKTLE RIKAIVHAVG QELQVTGPFN 1200
LQLIAKDDQL KVIECNVRVS RSFPFVSKTL GVDLVALATR VIMGEEVEPV GLMTGSGVVG 1260
VKVPQFSFSR LAGADVVLGV EMTSTGEVAG FGESRCEAYL KAMLSTGFKI PKKNILLTIG 1320
SYKNKSELLP TVRLLESLGY SLYASLGTAD FYTEHGVKVT AVDWHFEEAV DGECPPQRSI 1380
LEQLAEKNFE LVINLSMRGA GGRRLSSFVT KGYRTRRLAA DFSVPLIIDI KCTKLFVEAL 1440
GQIGPAPPLK VHVDCMTSQK LVRLPGLIDV HVHLREPGGT HKEDFASGTA AALAGGITMV 1500
CAMPNTRPPI IDAPALALAQ KLAEAGARCD FALFLGASSE NAGTLGTVAG SAAGLKLYLN 1560
ETFSELRLDS VVQWMEHFET WPSHLPIVAH AEQQTVAAVL MVAQLTQRSV HICHVARKEE 1620
ILLIKAAKAR GLPVTCEVAP HHLFLSHDDL ERLGPGKGEV RPELGSRQDV EALWENMAVI 1680
DCFASDHAPH TLEEKCGSRP PPGFPGLETM LPLLLTAVSE GRLSLDDLLQ RLHHNPRRIF 1740
HLPPQEDTYV EVDLEHEWTI PSHMPFSKAH WTPFEGQKVK GTVRRVVLRG EVAYIDGQVL 1800
VPPGYGQDVR KWPQGAVPQL PPSAPATSEM TTTPERPRRG IPGLPDGRFH LPPRIHRASD 1860
PGLPAEEPKE KSSRKVAEPE LMGTPDGTCY PPPPVPRQAS PQNLGTPGLL HPQTSPLLHS 1920
LVGQHILSVQ QFTKDQMSHL FNVAHTLRMM VQKERSLDIL KGKVMASMFY EVSTRTSSSF 1980
AAAMARLGGA VLSFSEATSS VQKGESLADS VQTMSCYADV VVLRHPQPGA VELAAKHCRR 2040
PVINAGDGVG EHPTQALLDI FTIREELGTV NGMTITMVGD LKHGRTVHSL ACLLTQYRVS 2100
LRYVAPPSLR MPPTVRAFVA SRGTKQEEFE SIEEALPDTD VLYMTRIQKE RFGSTQEYEA 2160
CFGQFILTPH IMTRAKKKMV VMHPMPRVNE ISVEVDSDPR AAYFRQAENG MYIRMALLAT 2220
VLGRF 2225 
Gene Ontology
 GO:0005829; C:cytosol; IDA:BHF-UCL.
 GO:0043025; C:neuronal cell body; ISS:BHF-UCL.
 GO:0016363; C:nuclear matrix; IDA:BHF-UCL.
 GO:0043234; C:protein complex; IEA:Compara.
 GO:0043195; C:terminal bouton; ISS:BHF-UCL.
 GO:0070335; F:aspartate binding; ISS:BHF-UCL.
 GO:0004070; F:aspartate carbamoyltransferase activity; ISS:BHF-UCL.
 GO:0005524; F:ATP binding; ISS:BHF-UCL.
 GO:0004088; F:carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity; ISS:BHF-UCL.
 GO:0004151; F:dihydroorotase activity; ISS:BHF-UCL.
 GO:0042802; F:identical protein binding; ISS:BHF-UCL.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004672; F:protein kinase activity; ISS:BHF-UCL.
 GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; ISS:BHF-UCL.
 GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0070409; P:carbamoyl phosphate biosynthetic process; IEA:InterPro.
 GO:0035690; P:cellular response to drug; IEA:Compara.
 GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Compara.
 GO:0017144; P:drug metabolic process; ISS:BHF-UCL.
 GO:0009790; P:embryo development; IEA:Compara.
 GO:0007565; P:female pregnancy; IEA:Compara.
 GO:0006543; P:glutamine catabolic process; IEA:InterPro.
 GO:0006541; P:glutamine metabolic process; ISS:BHF-UCL.
 GO:0007595; P:lactation; IEA:Compara.
 GO:0031100; P:organ regeneration; IEA:Compara.
 GO:0018107; P:peptidyl-threonine phosphorylation; ISS:BHF-UCL.
 GO:0046777; P:protein autophosphorylation; ISS:BHF-UCL.
 GO:0046134; P:pyrimidine nucleoside biosynthetic process; TAS:Reactome.
 GO:0014075; P:response to amine stimulus; IEA:Compara.
 GO:0031000; P:response to caffeine; IEA:Compara.
 GO:0051414; P:response to cortisol stimulus; IEA:Compara.
 GO:0033574; P:response to testosterone stimulus; IEA:Compara.
 GO:0006228; P:UTP biosynthetic process; IEA:Compara. 
Interpro
 IPR006132; Asp/Orn_carbamoyltranf_P-bd.
 IPR006130; Asp/Orn_carbamoylTrfase.
 IPR002082; Asp_carbamoyltransf.
 IPR006131; Asp_carbamoyltransf_Asp/Orn-bd.
 IPR011761; ATP-grasp.
 IPR013815; ATP_grasp_subdomain_1.
 IPR013816; ATP_grasp_subdomain_2.
 IPR006275; CarbamoylP_synth_lsu.
 IPR005481; CarbamoylP_synth_lsu_N.
 IPR005480; CarbamoylP_synth_lsu_oligo.
 IPR006274; CarbamoylP_synth_ssu.
 IPR002474; CarbamoylP_synth_ssu_N.
 IPR005479; CbamoylP_synth_lsu-like_ATP-bd.
 IPR005483; CbamoylP_synth_lsu_CPSase_dom.
 IPR002195; Dihydroorotase_CS.
 IPR017926; GATASE.
 IPR011059; Metal-dep_hydrolase_composite.
 IPR011607; MGS-like_dom.
 IPR016185; PreATP-grasp_dom. 
Pfam
 PF00289; CPSase_L_chain
 PF02786; CPSase_L_D2
 PF02787; CPSase_L_D3
 PF00988; CPSase_sm_chain
 PF00117; GATase
 PF02142; MGS
 PF00185; OTCace
 PF02729; OTCace_N 
SMART
 SM01096; CPSase_L_D3
 SM01097; CPSase_sm_chain
 SM00851; MGS 
PROSITE
 PS50975; ATP_GRASP
 PS00097; CARBAMOYLTRANSFERASE
 PS00866; CPSASE_1
 PS00867; CPSASE_2
 PS00482; DIHYDROOROTASE_1
 PS00483; DIHYDROOROTASE_2
 PS51273; GATASE_TYPE_1 
PRINTS
 PR00100; AOTCASE.
 PR00101; ATCASE.
 PR00098; CPSASE.