Tbio CDC73 Parafibromin

Protein Summary

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. This gene encodes a tumor suppressor that is involved in transcriptional and post-transcriptional control pathways. The protein is a component of the the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex. This protein appears to facilitate the association of 3' mRNA processing factors with actively-transcribed chromatin. Mutations in this gene have been linked to hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and parathyroid carcinoma. [provided by RefSeq, Jul 2009]

Uniprot Accession IDs

• Q6P1J9
• A6NLZ8
• B2RBR2
• Q6PK51
• Q96A07
• Q9H245
• Q9H5L7

Gene Name

• CDC73

Ensembl ID

• ENST00000367435
• ENSP00000356405
• ENSG00000134371
• ENST00000650099
• ENSP00000498073

Symbol

• C1orf28
• HRPT2
• HYX
• FIHP
• HPTJT
• HRPT1
• HRPT2
• C1orf28

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
co-expressed gene	1
biological process	0.98
transcription factor perturbation	0.91
kinase perturbation	0.88
transcription factor binding site profile	0.81

Related Tools

GENEVA

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ARCHS4

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 322.73   (req: < 5)

Gene RIFs: 92   (req: <= 3)

Antibodies: 248   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 322.73   (req: >= 5)

Gene RIFs: 92   (req: > 3)

Antibodies: 248   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 26

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cell division cycle 73	VGNC:1213	745351
Macaque	cell division cycle 73		712256
Mouse	cell division cycle 73, Paf1/RNA polymerase II complex component	MGI:2384876	214498
Rat	cell division cycle 73	RGD:1311766	304832
Dog	cell division cycle 73	VGNC:39011	478955

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cell division cycle 73
Macaque	cell division cycle 73
Mouse	cell division cycle 73, Paf1/RNA polymerase II complex component
Rat	cell division cycle 73
Dog	cell division cycle 73

Protein Data Bank (2)

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (65)

Reactome (15)

WikiPathways (50)

E3 ubiquitin ligases ubiquitinate target proteins (R-HSA-8866654)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	E3 ubiquitin ligases ubiquitinate target proteins	110 targets	R-HSA-8866654
Reactome	Formation of RNA Pol II elongation complex	61 targets	R-HSA-112382
Reactome	Formation of the beta-catenin:TCF transactivating complex	61 targets	R-HSA-201722
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Hedgehog 'on' state	87 targets	R-HSA-5632684

Name	Explore in Pharos	Explore in Source
E3 ubiquitin ligases ubiquitinate target proteins	110 targets	R-HSA-8866654
Formation of RNA Pol II elongation complex	61 targets	R-HSA-112382
Formation of the beta-catenin:TCF transactivating complex	61 targets	R-HSA-201722
Gene expression (Transcription)	1452 targets	R-HSA-74160
Hedgehog 'on' state	87 targets	R-HSA-5632684

Gene Ontology Terms (31)

Functions (1)

Components (5)

Processes (25)

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Items per page:

10

1 – 1 of 1

GO Term	Evidence	Assigned by
RNA polymerase II complex binding	Inferred from Direct Assay (IDA)	UniProtKB

Protein-Protein Interactions (203)

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1 – 10 of 203

• See Interactions on String-DB

LEO1

Tbio

Family: Enzyme

Novelty: 0.00851903

p_int: 1

Score: 0.999

Data Source: BioPlex,Reactome,STRINGDB

CTR9

Tbio

Family: Enzyme

Novelty: 0.04434964

p_int: 0.999999771

p_ni: 2.18e-7

p_wrong: 1.1e-8

Score: 0.999

Data Source: BioPlex,STRINGDB

PAF1

Tbio

Family: Enzyme

Novelty: 0.00200047

p_int: 0.999933011

p_ni: 0.000066989

Score: 0.999

Data Source: BioPlex,STRINGDB

TULP2

Tdark

Family: TF

Novelty: 0.20144336

p_int: 0.974897962

p_ni: 0.025102038

Score: 0.81

Data Source: BioPlex,STRINGDB

ERMAP

Tbio

Novelty: 0.04270359

p_int: 0.893406645

p_ni: 0.106593355

Score: 0.187

Data Source: BioPlex,STRINGDB

WDR61

Tbio

Novelty: 0.01405991

Score: 0.999

Data Source: STRINGDB

RTF1

Tbio

Family: Enzyme

Novelty: 0.02255644

Score: 0.999

Data Source: STRINGDB

SUPT16H

Tbio

Family: Enzyme

Novelty: 0.01026868

Score: 0.993

Data Source: STRINGDB

SUPT5H

Tbio

Novelty: 0.00775042

Score: 0.992

Data Source: STRINGDB

SSRP1

Tbio

Family: TF

Novelty: 0.0143993

Score: 0.992

Data Source: STRINGDB

Publication Statistics

PubMed Score  322.73

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PubTator Score  229.9

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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3D-structure
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Cell cycle
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adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype