Human Gene CDC73 (uc001gtb.3) Description and Page Index
  Description: Homo sapiens cell division cycle 73 (CDC73), mRNA.
RefSeq Summary (NM_024529): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1660807.236652.1, SRR1660809.65587.1 [ECO:0000332] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr1:193,091,088-193,223,942 Size: 132,855 Total Exon Count: 17 Strand: +
Coding Region
   Position: hg19 chr1:193,091,331-193,219,842 Size: 128,512 Coding Exon Count: 17 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:193,091,088-193,223,942)mRNA (may differ from genome)Protein (531 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CDC73
CDC HuGE Published Literature: CDC73
Positive Disease Associations: Blood Flow Velocity , Body Weights and Measures , Osteoporosis
Related Studies:
  1. Blood Flow Velocity
    Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics. [PubMed 17903301]
    In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
  2. Body Weights and Measures
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  3. Osteoporosis
    Kathryn L Lunetta et al. BMC medical genetics 2007, Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study., BMC medical genetics. [PubMed 17903295]
    Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: CDC73
Diseases sorted by gene-association score: hyperparathyroidism-jaw tumor syndrome* (1692), parathyroid carcinoma* (1321), hyperparathyroidism, familial primary* (1229), hyperparathyroidism 3* (530), cdc73-related parathyroid carcinoma* (500), parathyroid adenoma* (437), cdc73-related disorders* (100), cdc73-related familial isolated hyperparathyroidism* (100), hyperparathyroidism (57), ossifying fibroma (45), fibroma (37), parathyroid gland disease (14), bone benign neoplasm (12), multiple endocrine neoplasia 1 (12), connective tissue benign neoplasm (10), multiple endocrine neoplasia iia (9), clear cell papillary renal cell carcinoma (7), leopard syndrome (7), familial hypocalciuric hypercalcemia (6), fibrous dysplasia (6), hereditary wilms' tumor (6), adenoma (5), endocrine organ benign neoplasm (4), cell type benign neoplasm (1), wilms tumor susceptibility-5 (1), renal cell carcinoma, papillary (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 11.48 RPKM in Artery - Tibial
Total median expression: 322.54 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -116.51243-0.479 Picture PostScript Text
3' UTR -913.234100-0.223 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007852 - RNA_pol_access_fac_Cdc73

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
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene DetailsGene Details Gene DetailsGene DetailsGene Details
Gene SorterGene Sorter Gene SorterGene SorterGene Sorter
 RGDEnsemblFlyBaseWormBaseSGD
 Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence
 AlignmentAlignmentAlignmentAlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000993 RNA polymerase II core binding
GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding
GO:0005515 protein binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001558 regulation of cell growth
GO:0001711 endodermal cell fate commitment
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0006368 transcription elongation from RNA polymerase II promoter
GO:0006378 mRNA polyadenylation
GO:0007049 cell cycle
GO:0008285 negative regulation of cell proliferation
GO:0010390 histone monoubiquitination
GO:0016055 Wnt signaling pathway
GO:0016567 protein ubiquitination
GO:0016570 histone modification
GO:0019827 stem cell population maintenance
GO:0030177 positive regulation of Wnt signaling pathway
GO:0031442 positive regulation of mRNA 3'-end processing
GO:0031648 protein destabilization
GO:0032968 positive regulation of transcription elongation from RNA polymerase II promoter
GO:0033523 histone H2B ubiquitination
GO:0034402 recruitment of 3'-end processing factors to RNA polymerase II holoenzyme complex
GO:0043066 negative regulation of apoptotic process
GO:0045638 negative regulation of myeloid cell differentiation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048147 negative regulation of fibroblast proliferation
GO:0050680 negative regulation of epithelial cell proliferation
GO:0071222 cellular response to lipopolysaccharide
GO:1902808 positive regulation of cell cycle G1/S phase transition
GO:1904837 beta-catenin-TCF complex assembly
GO:2000134 negative regulation of G1/S transition of mitotic cell cycle

Cellular Component:
GO:0000784 nuclear chromosome, telomeric region
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005829 cytosol
GO:0016593 Cdc73/Paf1 complex


-  Descriptions from all associated GenBank mRNAs
  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

-  Other Names for This Gene
  Alternate Gene Symbols: A6NLZ8, B2RBR2, C1orf28, CDC73_HUMAN, HRPT2, NM_024529, NP_078805, Q6P1J9, Q6PK51, Q96A07, Q9H245, Q9H5L7
UCSC ID: uc001gtb.3
RefSeq Accession: NM_024529
Protein: Q6P1J9 (aka CDC73_HUMAN)
CCDS: CCDS1382.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene CDC73:
hrpt2 (CDC73-Related Disorders)
wilms-ov (Wilms Tumor Predisposition)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_024529.4
exon count: 17CDS single in 3' UTR: no RNA size: 5942
ORF size: 1596CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3392.00frame shift in genome: no % Coverage: 99.95
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.