CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006356
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA replication licensing factor MCM4 
Protein Synonyms/Alias
 CDC21 homolog; P1-CDC21 
Gene Name
 MCM4 
Gene Synonyms/Alias
 CDC21 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
123PDLGSAQKGLQVDLQubiquitination[1, 2]
163DVNVAACKENFQRFLubiquitination[2]
179RFIDPLAKEEENVGIubiquitination[1, 3]
216NVNCEHIKSFDKNLYubiquitination[2, 4]
220EHIKSFDKNLYRQLIacetylation[5]
220EHIKSFDKNLYRQLIubiquitination[1, 2, 3, 4]
349NRSLFSDKQMIKLQEubiquitination[2]
381AHNDLVDKVQPGDRVubiquitination[2]
409NPRVSNVKSVYKTHIubiquitination[2]
439LDEEAEQKLFSEKRVubiquitination[2, 4]
450EKRVELLKELSRKPDacetylation[5]
450EKRVELLKELSRKPDubiquitination[1, 2, 4]
455LLKELSRKPDIYERLubiquitination[1, 2]
477IYEHEDIKKGILLQLubiquitination[1]
478YEHEDIKKGILLQLFubiquitination[2]
536RGQYTSGKGSSAVGLubiquitination[1, 2, 3, 4, 6]
549GLTAYVMKDPETRQLubiquitination[1, 2]
578CCIDEFDKMNESTRSubiquitination[1, 7]
600QQTLSIAKAGIICQLubiquitination[2, 6, 7, 8, 9, 10]
627IESQWNPKKTTIENIubiquitination[1, 3, 4, 9]
628ESQWNPKKTTIENIQubiquitination[1, 2, 3, 6, 10]
746RLAEAHAKVRLSNKVubiquitination[1, 9]
752AKVRLSNKVEAIDVEubiquitination[1, 2, 3, 4, 7, 10]
762AIDVEEAKRLHREALubiquitination[1, 2, 3, 7, 9, 10]
770RLHREALKQSATDPRubiquitination[1, 2, 10]
814KLILSKGKTPALKYQubiquitination[2, 4]
819KGKTPALKYQQLFEDacetylation[11]
819KGKTPALKYQQLFEDubiquitination[1, 2, 3, 4, 7, 10]
837QSDIAITKDMFEEALubiquitination[1, 2, 10]
858DFLTVTGKTVRLL**acetylation[10, 11, 12]
858DFLTVTGKTVRLL**ubiquitination[1, 2, 4, 9, 10]
Reference
 [1] 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]
 [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] 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] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [9] 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]
 [10] 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]
 [11] 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]
 [12] 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
 Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. 
Sequence Annotation
 DOMAIN 458 667 MCM.
 NP_BIND 510 517 ATP (Potential).
 MOTIF 642 645 Arginine finger.
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 26 26 Phosphoserine.
 MOD_RES 31 31 Phosphoserine.
 MOD_RES 32 32 Phosphoserine.
 MOD_RES 34 34 Phosphoserine.
 MOD_RES 120 120 Phosphoserine.
 MOD_RES 131 131 Phosphoserine.
 MOD_RES 142 142 Phosphoserine.
 MOD_RES 145 145 Phosphoserine.
 MOD_RES 220 220 N6-acetyllysine.
 MOD_RES 450 450 N6-acetyllysine.  
Keyword
 Acetylation; ATP-binding; Cell cycle; Complete proteome; DNA replication; DNA-binding; Helicase; Hydrolase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 863 AA 
Protein Sequence
MSSPASTPSR RGSRRGRATP AQTPRSEDAR SSPSQRRRGE DSTSTGELQP MPTSPGVDLQ 60
SPAAQDVLFS SPPQMHSSAI PLDFDVSSPL TYGTPSSRVE GTPRSGVRGT PVRQRPDLGS 120
AQKGLQVDLQ SDGAAAEDIV ASEQSLGQKL VIWGTDVNVA ACKENFQRFL QRFIDPLAKE 180
EENVGIDITE PLYMQRLGEI NVIGEPFLNV NCEHIKSFDK NLYRQLISYP QEVIPTFDMA 240
VNEIFFDRYP DSILEHQIQV RPFNALKTKN MRNLNPEDID QLITISGMVI RTSQLIPEMQ 300
EAFFQCQVCA HTTRVEMDRG RIAEPSVCGR CHTTHSMALI HNRSLFSDKQ MIKLQESPED 360
MPAGQTPHTV ILFAHNDLVD KVQPGDRVNV TGIYRAVPIR VNPRVSNVKS VYKTHIDVIH 420
YRKTDAKRLH GLDEEAEQKL FSEKRVELLK ELSRKPDIYE RLASALAPSI YEHEDIKKGI 480
LLQLFGGTRK DFSHTGRGKF RAEINILLCG DPGTSKSQLL QYVYNLVPRG QYTSGKGSSA 540
VGLTAYVMKD PETRQLVLQT GALVLSDNGI CCIDEFDKMN ESTRSVLHEV MEQQTLSIAK 600
AGIICQLNAR TSVLAAANPI ESQWNPKKTT IENIQLPHTL LSRFDLIFLL LDPQDEAYDR 660
RLAHHLVALY YQSEEQAEEE LLDMAVLKDY IAYAHSTIMP RLSEEASQAL IEAYVDMRKI 720
GSSRGMVSAY PRQLESLIRL AEAHAKVRLS NKVEAIDVEE AKRLHREALK QSATDPRTGI 780
VDISILTTGM SATSRKRKEE LAEALKKLIL SKGKTPALKY QQLFEDIRGQ SDIAITKDMF 840
EEALRALADD DFLTVTGKTV RLL 863 
Gene Ontology
 GO:0042555; C:MCM complex; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005524; F:ATP binding; NAS:UniProtKB.
 GO:0003678; F:DNA helicase activity; IEA:Compara.
 GO:0003697; F:single-stranded DNA binding; IEA:Compara.
 GO:0006270; P:DNA replication initiation; IEA:InterPro.
 GO:0006271; P:DNA strand elongation involved in DNA replication; TAS:Reactome.
 GO:0006268; P:DNA unwinding involved in replication; IEA:Compara.
 GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome. 
Interpro
 IPR003593; AAA+_ATPase.
 IPR008047; MCM_4.
 IPR018525; MCM_CS.
 IPR001208; MCM_DNA-dep_ATPase.
 IPR012340; NA-bd_OB-fold.
 IPR027417; P-loop_NTPase.
 IPR004039; Rubredoxin-type_fold. 
Pfam
 PF00493; MCM 
SMART
 SM00382; AAA
 SM00350; MCM 
PROSITE
 PS00847; MCM_1
 PS50051; MCM_2 
PRINTS
 PR01657; MCMFAMILY.
 PR01660; MCMPROTEIN4.