TISIDB

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus
Domain	PF05179 RNA pol II accessory factor PF16050 Paf1 complex subunit CDC73 N-terminal
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 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.

> Gene Ontology [ TOP ]
Biological Process	GO:0000082 G1/S transition of mitotic cell cycle GO:0001704 formation of primary germ layer GO:0001706 endoderm formation GO:0001711 endodermal cell fate commitment GO:0002237 response to molecule of bacterial origin GO:0002683 negative regulation of immune system process GO:0006354 DNA-templated transcription, elongation GO:0006368 transcription elongation from RNA polymerase II promoter GO:0006378 mRNA polyadenylation GO:0006397 mRNA processing GO:0006513 protein monoubiquitination GO:0007346 regulation of mitotic cell cycle GO:0007369 gastrulation GO:0007492 endoderm development GO:0010390 histone monoubiquitination GO:0010948 negative regulation of cell cycle process GO:0016055 Wnt signaling pathway GO:0016570 histone modification GO:0016574 histone ubiquitination GO:0019827 stem cell population maintenance GO:0030099 myeloid cell differentiation GO:0030111 regulation of Wnt signaling pathway GO:0030177 positive regulation of Wnt signaling pathway GO:0031123 RNA 3'-end processing GO:0031124 mRNA 3'-end processing GO:0031440 regulation of mRNA 3'-end processing GO:0031442 positive regulation of mRNA 3'-end processing GO:0031647 regulation of protein stability GO:0031648 protein destabilization GO:0032496 response to lipopolysaccharide GO:0032784 regulation of DNA-templated transcription, elongation GO:0032786 positive regulation of DNA-templated transcription, elongation GO:0032968 positive regulation of transcription elongation from RNA polymerase II promoter GO:0033523 histone H2B ubiquitination GO:0034243 regulation of transcription elongation from RNA polymerase II promoter GO:0035987 endodermal cell differentiation GO:0043631 RNA polyadenylation GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044843 cell cycle G1/S phase transition GO:0045165 cell fate commitment GO:0045637 regulation of myeloid cell differentiation GO:0045638 negative regulation of myeloid cell differentiation GO:0045786 negative regulation of cell cycle GO:0045930 negative regulation of mitotic cell cycle GO:0048144 fibroblast proliferation GO:0048145 regulation of fibroblast proliferation GO:0048147 negative regulation of fibroblast proliferation GO:0050673 epithelial cell proliferation GO:0050678 regulation of epithelial cell proliferation GO:0050680 negative regulation of epithelial cell proliferation GO:0050684 regulation of mRNA processing GO:0050685 positive regulation of mRNA processing GO:0060795 cell fate commitment involved in formation of primary germ layer GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071396 cellular response to lipid GO:0098727 maintenance of cell number GO:0198738 cell-cell signaling by wnt GO:1901987 regulation of cell cycle phase transition GO:1901988 negative regulation of cell cycle phase transition GO:1901990 regulation of mitotic cell cycle phase transition GO:1901991 negative regulation of mitotic cell cycle phase transition GO:1902806 regulation of cell cycle G1/S phase transition GO:1902807 negative regulation of cell cycle G1/S phase transition GO:1903311 regulation of mRNA metabolic process GO:1903313 positive regulation of mRNA metabolic process GO:1903706 regulation of hemopoiesis GO:1903707 negative regulation of hemopoiesis GO:1904837 beta-catenin-TCF complex assembly GO:2000045 regulation of G1/S transition of mitotic cell cycle GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
Molecular Function	GO:0000993 RNA polymerase II core binding GO:0001098 basal transcription machinery binding GO:0001099 basal RNA polymerase II transcription machinery binding GO:0043175 RNA polymerase core enzyme binding GO:0070063 RNA polymerase binding
Cellular Component	GO:0000428 DNA-directed RNA polymerase complex GO:0000781 chromosome, telomeric region GO:0000784 nuclear chromosome, telomeric region GO:0008023 transcription elongation factor complex GO:0016591 DNA-directed RNA polymerase II, holoenzyme GO:0016593 Cdc73/Paf1 complex GO:0030880 RNA polymerase complex GO:0044454 nuclear chromosome part GO:0055029 nuclear DNA-directed RNA polymerase complex GO:0061695 transferase complex, transferring phosphorus-containing groups GO:0098687 chromosomal region

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-8866654: E3 ubiquitin ligases ubiquitinate target proteins R-HSA-112387: Elongation arrest and recovery R-HSA-112382: Formation of RNA Pol II elongation complex R-HSA-201722: Formation of the beta-catenin R-HSA-74160: Gene Expression R-HSA-5632684: Hedgehog 'on' state R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-8852135: Protein ubiquitination R-HSA-674695: RNA Polymerase II Pre-transcription Events R-HSA-73857: RNA Polymerase II Transcription R-HSA-75955: RNA Polymerase II Transcription Elongation R-HSA-162582: Signal Transduction R-HSA-5358351: Signaling by Hedgehog R-HSA-195721: Signaling by Wnt R-HSA-201681: TCF dependent signaling in response to WNT

> KEGG and Reactome Pathway

[ TOP ]

KEGG

Reactome

R-HSA-8866654: E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-112387: Elongation arrest and recovery
R-HSA-112382: Formation of RNA Pol II elongation complex
R-HSA-201722: Formation of the beta-catenin
R-HSA-74160: Gene Expression
R-HSA-5632684: Hedgehog 'on' state
R-HSA-392499: Metabolism of proteins
R-HSA-597592: Post-translational protein modification
R-HSA-8852135: Protein ubiquitination
R-HSA-674695: RNA Polymerase II Pre-transcription Events
R-HSA-73857: RNA Polymerase II Transcription
R-HSA-75955: RNA Polymerase II Transcription Elongation
R-HSA-162582: Signal Transduction
R-HSA-5358351: Signaling by Hedgehog
R-HSA-195721: Signaling by Wnt
R-HSA-201681: TCF dependent signaling in response to WNT

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CDC73 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

[ TOP ]

Statistical results of CDC73 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: 1.03; FDR: 0.034400	Sensitive to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.57	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the expression difference of CDC73 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.118	0.644
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.011	0.995
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.209	0.857
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.07	0.786
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.175	0.923
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.063	0.978
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.106	0.787
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.083	0.961
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.329	0.862
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.2	0.866
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.614	0.729
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.03	0.555

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of CDC73 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CDC73. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CDC73. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CDC73. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CDC73. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CDC73 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CDC73 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CDC73
Name	cell division cycle 73
Aliases	parafibromin; FIHP; Paf1/RNA polymerase II complex component; C1orf28; HRPT2; HRPT1; chromosome 1 open readi ......
Chromosomal Location	1q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CDC73 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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