ID:CDC73_HUMAN DESCRIPTION: RecName: Full=Parafibromin; AltName: Full=Cell division cycle protein 73 homolog; AltName: Full=Hyperparathyroidism 2 protein; 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 MLL1; it promotes leukemogenesis though association with MLL-rearranged oncoproteins, such as MLL-MLLT3/AF9 and MLL-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. SUBUNIT: Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and WDR61. Interacts with POLR2A, CPSF1, CPSF4, CSTF2, MLL and CTNNB1. Interacts with a Set1-like complex that has histone methyltransferase activity and methylates histone H3. Found in a complex with BCL9L or BCL9, CDC73, CTNNB1 and PYGO1 indicative for the participation in a nuclear Wnt signaling complex. INTERACTION: O00512:BCL9; NbExp=2; IntAct=EBI-930143, EBI-533127; P35222:CTNNB1; NbExp=9; IntAct=EBI-930143, EBI-491549; Q6PD62:CTR9; NbExp=15; IntAct=EBI-930143, EBI-1019583; Q8WVC0:LEO1; NbExp=11; IntAct=EBI-930143, EBI-932432; Q03164:MLL; NbExp=4; IntAct=EBI-930143, EBI-591370; Q8N7H5:PAF1; NbExp=25; IntAct=EBI-930143, EBI-2607770; P24928:POLR2A; NbExp=5; IntAct=EBI-930143, EBI-295301; Q92541:RTF1; NbExp=12; IntAct=EBI-930143, EBI-1055239; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Found in adrenal and parathyroid glands, kidney and heart. DISEASE: Defects in CDC73 are a cause of familial isolated hyperparathyroidism (FIHP) [MIM:145000]; also known as hyperparathyroidism type 1 (HRPT1). FIHP is an autosomal dominant disorder characterized by hypercalcemia, elevated parathyroid hormone (PTH) levels, and uniglandular or multiglandular parathyroid tumors. DISEASE: Defects in CDC73 are the cause of hyperparathyroidism-jaw tumor syndrome (HPT-JT) [MIM:145001]; also known as hyperparathyroidism type 2 (HRPT2) or familial primary hyperparathyroidism with multiple ossifying jaw fibromas. HPT-JT is an autosomal dominant, multiple neoplasia syndrome primarily characterized by hyperparathyroidism due to parathyroid tumors. Thirty percent of individuals with HPT-JT may also develop ossifying fibromas, primarily of the mandible and maxilla, which are distinc from the brown tumors associated with severe hyperparathyroidism. Kidney lesions may also occur in HPT-JT as bilateral cysts, renal hamartomas or Wilms tumors. DISEASE: Defects in CDC73 are a cause of parathyroid carcinoma (PRTC) [MIM:608266]. These cancers characteristically result in more profound clinical manifestations of hyperparathyroidism than do parathyroid adenomas, the most frequent cause of primary hyperparathyroidism. Early en bloc resection of the primary tumor is the only curative treatment. SIMILARITY: Belongs to the CDC73 family. SEQUENCE CAUTION: Sequence=AAH07325.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 300; Sequence=BAB15608.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CDC73D181ch1q31.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CDC73";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF05179 - RNA pol II accessory factor, Cdc73 family, C-terminal PF16050 - Paf1 complex subunit CDC73 N-terminal
ModBase Predicted Comparative 3D Structure on Q6P1J9
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK226038 - Homo sapiens mRNA for parafibromin variant, clone: FCC102E01. AK026969 - Homo sapiens cDNA: FLJ23316 fis, clone HEP12031. AK300929 - Homo sapiens cDNA FLJ57893 complete cds, highly similar to Parafibromin. BC065037 - Homo sapiens cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae), mRNA (cDNA clone MGC:74779 IMAGE:6170851), complete cds. AF312865 - Homo sapiens C1orf28 mRNA, complete cds. KJ894687 - Synthetic construct Homo sapiens clone ccsbBroadEn_04081 CDC73 gene, encodes complete protein. KR711138 - Synthetic construct Homo sapiens clone CCSBHm_00020642 CDC73 (CDC73) mRNA, encodes complete protein. KR711139 - Synthetic construct Homo sapiens clone CCSBHm_00020643 CDC73 (CDC73) mRNA, encodes complete protein. AK314772 - Homo sapiens cDNA, FLJ95641. AB590625 - Synthetic construct DNA, clone: pFN21AE2190, Homo sapiens CDC73 gene for cell division cycle 73, Paf1/RNA polymerase II complex component, homolog, without stop codon, in Flexi system. EU831865 - Synthetic construct Homo sapiens clone HAIB:100066894; DKFZo004D0722 cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae) protein (CDC73) gene, encodes complete protein. EU831787 - Synthetic construct Homo sapiens clone HAIB:100066816; DKFZo008D0721 cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae) protein (CDC73) gene, encodes complete protein. BC014351 - Homo sapiens cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:3681328), partial cds. CU676969 - Synthetic construct Homo sapiens gateway clone IMAGE:100019065 5' read CDC73 mRNA. KU178771 - Homo sapiens cell division cycle 73 Paf1/RNA polymerase II complex component-like protein isoform 1 (CDC73) mRNA, partial cds. KU178772 - Homo sapiens cell division cycle 73 Paf1/RNA polymerase II complex component-like protein isoform 2 (CDC73) mRNA, partial cds, alternatively spliced. KJ903175 - Synthetic construct Homo sapiens clone ccsbBroadEn_12569 CDC73 gene, encodes complete protein. BC007325 - Homo sapiens cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:3830169), partial cds. CU688012 - Synthetic construct Homo sapiens gateway clone IMAGE:100021733 5' read CDC73 mRNA. BC056410 - Homo sapiens cDNA clone IMAGE:6197638, **** WARNING: chimeric clone ****. BC013075 - Homo sapiens cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:3453851). JD566284 - Sequence 547308 from Patent EP1572962. JD245094 - Sequence 226118 from Patent EP1572962. JD507418 - Sequence 488442 from Patent EP1572962. JD418849 - Sequence 399873 from Patent EP1572962. DQ579152 - Homo sapiens piRNA piR-47264, complete sequence.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q6P1J9 (Reactome details) participates in the following event(s):
R-HSA-3322424 Beta-catenin recruits CDC73 and LEO1 R-HSA-5635845 GLI proteins bind CDC73 R-HSA-112379 Recruitment of elongation factors to form elongation complex R-HSA-8942099 RNF20:RNF40 binds PAF complex, Ubiquitin:UBE2A,B (Ubiquitin:RAD6), WAC and Histone H2B R-HSA-113429 Elongating transcript encounters a lesion in the template R-HSA-112385 Addition of nucleotides leads to transcript elongation R-HSA-113411 2-4 nt.backtracking of Pol II complex on the template leading to elongation pausing R-HSA-113412 Pol II elongation complex moves on the template as transcript elongates R-HSA-113414 7-14 nt. Backtracking of Pol II complex on the template leading to elongation arrest R-HSA-112392 Resumption of elongation after recovery from pausing R-HSA-113413 TFIIS-mediated recovery of elongation from arrest R-HSA-112395 Abortive termination of elongation after arrest R-HSA-112396 Separation of elongating transcript from template R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex R-HSA-5632684 Hedgehog 'on' state R-HSA-112382 Formation of RNA Pol II elongation complex R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins R-HSA-674695 RNA Polymerase II Pre-transcription Events R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-5358351 Signaling by Hedgehog R-HSA-75955 RNA Polymerase II Transcription Elongation R-HSA-8852135 Protein ubiquitination R-HSA-73857 RNA Polymerase II Transcription R-HSA-195721 Signaling by WNT R-HSA-162582 Signal Transduction R-HSA-597592 Post-translational protein modification R-HSA-74160 Gene expression (Transcription) R-HSA-392499 Metabolism of proteins
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
