Q6P1J9 · CDC73_HUMAN
- ProteinParafibromin
- GeneCDC73
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids531 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameParafibromin
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6P1J9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Hyperparathyroidism 1 (HRPT1)
- Note
- DescriptionAn autosomal dominant disorder characterized by hypercalcemia, elevated parathyroid hormone (PTH) levels, and uniglandular or multiglandular parathyroid hyperplasia, adenomas, and carcinomas.
- See alsoMIM:145000
Natural variants in HRPT1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_064931 | 63 | L>P | in HRPT1; uncertain significance; dbSNP:rs1060500015 | |
VAR_024082 | 64 | L>P | in HRPT1; does not affect interaction with the Pfa1 complex; dbSNP:rs121434264 | |
VAR_064933 | 95 | L>P | in HRPT1; uncertain significance; found as somatic mutation in a parathyroid adenoma sample from a patient who also carries a germline frameshift mutation; dbSNP:rs2103117916 |
Hyperparathyroidism 2 with jaw tumors (HRPT2)
- Note
- DescriptionAn autosomal dominant neoplasia syndrome characterized by primary hyperparathyroidism, ossifying fibroma of the maxilla and/or mandible, renal tumor, and uterine tumors. It is associated with increased risk of parathyroid cancer.
- See alsoMIM:145001
Natural variants in HRPT2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_064928 | 5-10 | missing | in HRPT2; uncertain significance; found as somatic mutation in a parathyroid carcinoma sample from a patient who also carries a germline mutation causing a splicing defect | |
VAR_064936 | 379 | D>N | in HRPT2; dbSNP:rs971586985 |
Parathyroid carcinoma (PRTC)
- Note
- DescriptionThese 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.
- See alsoMIM:608266
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_064927 | 2 | found in parathyroid adenoma samples; somatic mutation; parathyroid adenoma samples are from a patient with isolated hyperparathyroidism who also carries germline mutation P-91 | |||
Sequence: A → S | ||||||
Natural variant | VAR_064928 | 5-10 | in HRPT2; uncertain significance; found as somatic mutation in a parathyroid carcinoma sample from a patient who also carries a germline mutation causing a splicing defect | |||
Sequence: Missing | ||||||
Natural variant | VAR_064929 | 34 | found in a clear cell renal carcinoma sample; somatic mutation; unlike wild-type protein the mutant is defective in suppressing CCND1 expression in vivo | |||
Sequence: K → Q | ||||||
Natural variant | VAR_064930 | 59 | found in a parathyroid carcinoma sample; somatic mutation; dbSNP:rs2103113963 | |||
Sequence: S → F | ||||||
Natural variant | VAR_064931 | 63 | in HRPT1; uncertain significance; dbSNP:rs1060500015 | |||
Sequence: L → P | ||||||
Natural variant | VAR_024082 | 64 | in HRPT1; does not affect interaction with the Pfa1 complex; dbSNP:rs121434264 | |||
Sequence: L → P | ||||||
Natural variant | VAR_064932 | 91 | found in a patient with isolated hyperparathyroidism and parathyroid adenomas; dbSNP:rs2103117887 | |||
Sequence: R → P | ||||||
Natural variant | VAR_064933 | 95 | in HRPT1; uncertain significance; found as somatic mutation in a parathyroid adenoma sample from a patient who also carries a germline frameshift mutation; dbSNP:rs2103117916 | |||
Sequence: L → P | ||||||
Natural variant | VAR_064934 | 272 | found in a parathyroid adenoma sample; dbSNP:rs752383339 | |||
Sequence: N → S | ||||||
Natural variant | VAR_064935 | 292 | found in a Wilms tumor sample; somatic mutation | |||
Sequence: R → K | ||||||
Natural variant | VAR_064936 | 379 | in HRPT2; dbSNP:rs971586985 | |||
Sequence: D → N | ||||||
Natural variant | VAR_031825 | 384 | in dbSNP:rs35590728 | |||
Sequence: L → P |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 975 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000191803 | 2-531 | UniProt | Parafibromin | |||
Sequence: ADVLSVLRQYNIQKKEIVVKGDEVIFGEFSWPKNVKTNYVVWGTGKEGQPREYYTLDSILFLLNNVHLSHPVYVRRAATENIPVVRRPDRKDLLGYLNGEASTSASIDRSAPLEIGLQRSTQVKRAADEVLAEAKKPRIEDEECVRLDKERLAARLEGHKEGIVQTEQIRSLSEAMSVEKIAAIKAKIMAKKRSTIKTDLDDDITALKQRSFVDAEVDVTRDIVSRERVWRTRTTILQSTGKNFSKNIFAILQSVKAREEGRAPEQRPAPNAAPVDPTLRTKQPIPAAYNRYDQERFKGKEETEGFKIDTMGTYHGMTLKSVTEGASARKTQTPAAQPVPRPVSQARPPPNQKKGSRTPIIIIPAATTSLITMLNAKDLLQDLKFVPSDEKKKQGCQRENETLIQRRKDQMQPGGTAISVTVPYRVVDQPLKLMPQDWDRVVAVFVQGPAWQFKGWPWLLPDGSPVDIFAKIKAFHLKYDEVRLDPNVQKWDVTVLELSYHKRHLDRPVFLRFWETLDRYMVKHKSHLRF | |||||||
Modified residue (large scale data) | 178 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 198 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue | 212 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 212 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 301 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Cross-link | 308 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 315 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Cross-link | 321 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 345 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated. Dephosphorylated by PTPN11.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Found in adrenal and parathyroid glands, kidney and heart.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8 (PubMed:19952111, PubMed:20178742).
The PAF1 complex interacts with PHF5A. Within the PAF1 complex interacts directly with PHF5A (By similarity).
Interacts with POLR2A, CPSF1, CPSF4, CSTF2, KMT2A/MLL1 and CTNNB1 (PubMed:15632063, PubMed:15923622, PubMed:16630820, PubMed:19136632, PubMed:20541477).
Interacts with a Set1-like complex that has histone methyltransferase activity and methylates histone H3 (PubMed:15632063).
Found in a complex with BCL9L or BCL9, CDC73, CTNNB1 and PYGO1 indicative for the participation in a nuclear Wnt signaling complex (PubMed:17113272).
Interacts with PTPN11 (PubMed:26742426).
Interacts with SETD5 (By similarity).
The PAF1 complex interacts with PHF5A. Within the PAF1 complex interacts directly with PHF5A (By similarity).
Interacts with POLR2A, CPSF1, CPSF4, CSTF2, KMT2A/MLL1 and CTNNB1 (PubMed:15632063, PubMed:15923622, PubMed:16630820, PubMed:19136632, PubMed:20541477).
Interacts with a Set1-like complex that has histone methyltransferase activity and methylates histone H3 (PubMed:15632063).
Found in a complex with BCL9L or BCL9, CDC73, CTNNB1 and PYGO1 indicative for the participation in a nuclear Wnt signaling complex (PubMed:17113272).
Interacts with PTPN11 (PubMed:26742426).
Interacts with SETD5 (By similarity).
(Microbial infection) The PAF1 complex interacts with Zika virus French Polynesia 10087PF/2013 non-structural protein 5/NS5 (PubMed:30550790).
The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription (PubMed:30550790).
The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription (PubMed:30550790).
(Microbial infection) The PAF1 complex interacts with Dengue virus DENV2 16681 non-structural protein 5/NS5 (PubMed:30550790).
The PAF1 complex interacts with Dengue virus DENV4 Dominica/814669/1981 non-structural protein 5/NS5 (PubMed:30550790).
The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription (PubMed:30550790).
The PAF1 complex interacts with Dengue virus DENV4 Dominica/814669/1981 non-structural protein 5/NS5 (PubMed:30550790).
The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription (PubMed:30550790).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 125-139 | Nuclear localization signal | ||||
Sequence: KRAADEVLAEAKKPR | ||||||
Region | 200-250 | Interaction with CTNNB1 | ||||
Sequence: DLDDDITALKQRSFVDAEVDVTRDIVSRERVWRTRTTILQSTGKNFSKNIF | ||||||
Region | 200-531 | Interaction with POLR2A and PAF1 | ||||
Sequence: DLDDDITALKQRSFVDAEVDVTRDIVSRERVWRTRTTILQSTGKNFSKNIFAILQSVKAREEGRAPEQRPAPNAAPVDPTLRTKQPIPAAYNRYDQERFKGKEETEGFKIDTMGTYHGMTLKSVTEGASARKTQTPAAQPVPRPVSQARPPPNQKKGSRTPIIIIPAATTSLITMLNAKDLLQDLKFVPSDEKKKQGCQRENETLIQRRKDQMQPGGTAISVTVPYRVVDQPLKLMPQDWDRVVAVFVQGPAWQFKGWPWLLPDGSPVDIFAKIKAFHLKYDEVRLDPNVQKWDVTVLELSYHKRHLDRPVFLRFWETLDRYMVKHKSHLRF | ||||||
Region | 260-292 | Disordered | ||||
Sequence: EEGRAPEQRPAPNAAPVDPTLRTKQPIPAAYNR | ||||||
Compositional bias | 325-340 | Polar residues | ||||
Sequence: EGASARKTQTPAAQPV | ||||||
Region | 325-358 | Disordered | ||||
Sequence: EGASARKTQTPAAQPVPRPVSQARPPPNQKKGSR |
Sequence similarities
Belongs to the CDC73 family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length531
- Mass (Da)60,577
- Last updated2004-07-05 v1
- Checksum894A7448DBC0E793
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8Y640 | A0A2R8Y640_HUMAN | CDC73 | 197 | ||
A0AAQ5BGL0 | A0AAQ5BGL0_HUMAN | CDC73 | 432 | ||
A0AAQ5BGL4 | A0AAQ5BGL4_HUMAN | CDC73 | 97 | ||
A0A2R8YHB3 | A0A2R8YHB3_HUMAN | CDC73 | 385 | ||
A0A1B0GUB2 | A0A1B0GUB2_HUMAN | CDC73 | 450 | ||
A0A3B3IRP5 | A0A3B3IRP5_HUMAN | CDC73 | 482 | ||
A0A3B3ISN2 | A0A3B3ISN2_HUMAN | CDC73 | 104 |
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 123 | in Ref. 5; AAH14351 | ||||
Sequence: Q → G | ||||||
Sequence conflict | 184-187 | in Ref. 2; BAB15608 | ||||
Sequence: AIKA → CNQT | ||||||
Compositional bias | 325-340 | Polar residues | ||||
Sequence: EGASARKTQTPAAQPV | ||||||
Sequence conflict | 372 | in Ref. 2; BAB15608 | ||||
Sequence: I → K |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF312865 EMBL· GenBank· DDBJ | AAG45339.1 EMBL· GenBank· DDBJ | mRNA | ||
AK026969 EMBL· GenBank· DDBJ | BAB15608.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK314772 EMBL· GenBank· DDBJ | BAG37309.1 EMBL· GenBank· DDBJ | mRNA | ||
AL139133 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL390863 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471067 EMBL· GenBank· DDBJ | EAW91250.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC007325 EMBL· GenBank· DDBJ | AAH07325.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
BC014351 EMBL· GenBank· DDBJ | AAH14351.2 EMBL· GenBank· DDBJ | mRNA | ||
BC065037 EMBL· GenBank· DDBJ | AAH65037.1 EMBL· GenBank· DDBJ | mRNA |