Search Results

Overview

Uniprot IDQ6P1J9
Protein NameParafibromin
Gene NameCDC73
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
136 DEVLAEAKKPRIEDE
181 SEAMSVEKIAAIKAK
188 KIAAIKAKIMAKKRS
243 TILQSTGKNFSKNIF
331 TEGASARKTQTPAAQ
354 ARPPPNQKKGSRTPI

Function

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 independently 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

Protein Sequence

10 MADVLSVLRQ 20 YNIQKKEIVV 30 KGDEVIFGEF 40 SWPKNVKTNY 50 VVWGTGKEGQ 60 PREYYTLDSI 70 LFLLNNVHLS 80 HPVYVRRAAT 90 ENIPVVRRPD 100 RKDLLGYLNG 110 EASTSASIDR 120 SAPLEIGLQR 130 STQVKRAADE 140 VLAEAKKPRI 150 EDEECVRLDK 160 ERLAARLEGH 170 KEGIVQTEQI 180 RSLSEAMSVE 190 KIAAIKAKIM 200 AKKRSTIKTD 210 LDDDITALKQ 220 RSFVDAEVDV 230 TRDIVSRERV 240 WRTRTTILQS 250 TGKNFSKNIF 260 AILQSVKARE 270 EGRAPEQRPA 280 PNAAPVDPTL 290 RTKQPIPAAY 300 NRYDQERFKG 310 KEETEGFKID 320 TMGTYHGMTL 330 KSVTEGASAR 340 KTQTPAAQPV 350 PRPVSQARPP 360 PNQKKGSRTP 370 IIIIPAATTS 380 LITMLNAKDL 390 LQDLKFVPSD 400 EKKKQGCQRE 410 NETLIQRRKD 420 QMQPGGTAIS 430 VTVPYRVVDQ 440 PLKLMPQDWD 450 RVVAVFVQGP 460 AWQFKGWPWL 470 LPDGSPVDIF 480 AKIKAFHLKY 490 DEVRLDPNVQ 500 KWDVTVLELS 510 YHKRHLDRPV 520 FLRFWETLDR 530 YMVKHKSHLR F

Gene Ontology

Classification GO ID Description
Biological Process GO:0031124 mRNA 3'-end processing
Cellular Component GO:0016593 Cdc73/Paf1 complex
Cellular Component GO:0000781 chromosome, telomeric region
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0000993 RNA polymerase II complex binding
Biological Process GO:0071222 cellular response to lipopolysaccharide
Biological Process GO:0001711 endodermal cell fate commitment
Biological Process GO:0008285 negative regulation of cell population proliferation
Biological Process GO:0050680 negative regulation of epithelial cell proliferation
Biological Process GO:0048147 negative regulation of fibroblast proliferation
Biological Process GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
Biological Process GO:0045638 negative regulation of myeloid cell differentiation
Biological Process GO:0000122 negative regulation of transcription by RNA polymerase II
Biological Process GO:1902808 positive regulation of cell cycle G1/S phase transition
Biological Process GO:0031442 positive regulation of mRNA 3'-end processing
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0032968 positive regulation of transcription elongation by RNA polymerase II
Biological Process GO:0030177 positive regulation of Wnt signaling pathway
Biological Process GO:0031648 protein destabilization
Biological Process GO:0019827 stem cell population maintenance
Biological Process GO:0006368 transcription elongation by RNA polymerase II
Biological Process GO:0016055 Wnt signaling pathway

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.