CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-015132
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Parafibromin 
Protein Synonyms/Alias
 Cell division cycle protein 73 homolog; Hyperparathyroidism 2 protein 
Gene Name
 CDC73 
Gene Synonyms/Alias
 C1orf28; HRPT2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
47YVVWGTGKEGQPREYubiquitination[1]
136DEVLAEAKKPRIEDEubiquitination[1, 2]
137EVLAEAKKPRIEDEEubiquitination[1]
150EECVRLDKERLAARLubiquitination[1]
161AARLEGHKEGIVQTEubiquitination[1, 2, 3]
181SEAMSVEKIAAIKAKubiquitination[1, 2, 4]
198AKKRSTIKTDLDDDIubiquitination[1]
209DDDITALKQRSFVDAubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 9]
243TILQSTGKNFSKNIFubiquitination[1]
247STGKNFSKNIFAILQubiquitination[1, 3, 4, 5, 7, 8, 9]
257FAILQSVKAREEGRAubiquitination[1, 2, 3]
283VDPTLRTKQPIPAAYubiquitination[1, 2]
321TYHGMTLKSVTEGASubiquitination[8]
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] 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]
 [3] 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]
 [4] 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]
 [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] 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]
 [7] 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]
 [8] 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]
 [9] 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] 
Functional Description
 Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non- phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both indepentently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the cleavage and polyadenylation specificity factor (CPSF) complex and the cleavage stimulation factor (CSTF) complex, and with Wnt signaling. Involved in polyadenylation of mRNA precursors. 
Sequence Annotation
 REGION 200 531 Interaction with POLR2A and PAF1.
 REGION 200 250 Interaction with CTNNB1.
 MOTIF 125 139 Nuclear localization signal.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 212 212 Phosphoserine.  
Keyword
 Acetylation; Cell cycle; Complete proteome; Direct protein sequencing; Disease mutation; Nucleus; Phosphoprotein; Reference proteome; Transcription; Transcription regulation; Tumor suppressor; Wnt signaling pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 531 AA 
Protein Sequence
MADVLSVLRQ YNIQKKEIVV KGDEVIFGEF SWPKNVKTNY VVWGTGKEGQ PREYYTLDSI 60
LFLLNNVHLS HPVYVRRAAT ENIPVVRRPD RKDLLGYLNG EASTSASIDR SAPLEIGLQR 120
STQVKRAADE VLAEAKKPRI EDEECVRLDK ERLAARLEGH KEGIVQTEQI RSLSEAMSVE 180
KIAAIKAKIM AKKRSTIKTD LDDDITALKQ RSFVDAEVDV TRDIVSRERV WRTRTTILQS 240
TGKNFSKNIF AILQSVKARE EGRAPEQRPA PNAAPVDPTL RTKQPIPAAY NRYDQERFKG 300
KEETEGFKID TMGTYHGMTL KSVTEGASAR KTQTPAAQPV PRPVSQARPP PNQKKGSRTP 360
IIIIPAATTS LITMLNAKDL LQDLKFVPSD EKKKQGCQRE NETLIQRRKD QMQPGGTAIS 420
VTVPYRVVDQ PLKLMPQDWD RVVAVFVQGP AWQFKGWPWL LPDGSPVDIF AKIKAFHLKY 480
DEVRLDPNVQ KWDVTVLELS YHKRHLDRPV FLRFWETLDR YMVKHKSHLR F 531 
Gene Ontology
 GO:0016593; C:Cdc73/Paf1 complex; IDA:UniProtKB.
 GO:0000993; F:RNA polymerase II core binding; IDA:UniProtKB.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
 GO:0001711; P:endodermal cell fate commitment; ISS:UniProtKB.
 GO:0033523; P:histone H2B ubiquitination; IDA:UniProtKB.
 GO:0010390; P:histone monoubiquitination; IDA:UniProtKB.
 GO:0006378; P:mRNA polyadenylation; IMP:UniProtKB.
 GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:UniProtKB.
 GO:0048147; P:negative regulation of fibroblast proliferation; IMP:UniProtKB.
 GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IDA:UniProtKB.
 GO:0045638; P:negative regulation of myeloid cell differentiation; IDA:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0031442; P:positive regulation of mRNA 3'-end processing; IMP:UniProtKB.
 GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0030177; P:positive regulation of Wnt receptor signaling pathway; IDA:UniProtKB.
 GO:0031648; P:protein destabilization; IMP:UniProtKB.
 GO:0019827; P:stem cell maintenance; ISS:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 
Interpro
 IPR007852; RNA_pol_access_fac_Cdc73. 
Pfam
 PF05179; CDC73 
SMART
  
PROSITE
  
PRINTS