ID   CDC73_RAT               Reviewed;         531 AA.
AC   Q4V8C8;
DT   20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 1.
DT   27-MAR-2024, entry version 109.
DE   RecName: Full=Parafibromin;
DE   AltName: Full=Cell division cycle protein 73 homolog;
DE   AltName: Full=Hyperparathyroidism 2 protein homolog;
GN   Name=Cdc73; Synonyms=Hrpt2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: Tumor suppressor probably involved in transcriptional and
CC       post-transcriptional control pathways. May be involved in cell cycle
CC       progression through the regulation of cyclin D1/PRAD1 expression.
CC       Component of the PAF1 complex (PAF1C) which has multiple functions
CC       during transcription by RNA polymerase II and is implicated in
CC       regulation of development and maintenance of embryonic stem cell
CC       pluripotency. PAF1C associates with RNA polymerase II through
CC       interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-
CC       5'-phosphorylated forms and is involved in transcriptional elongation,
CC       acting both independently and synergistically with TCEA1 and in
CC       cooperation with the DSIF complex and HTATSF1. PAF1C is required for
CC       transcription of Hox and Wnt target genes. PAF1C is involved in
CC       hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1.
CC       PAF1C is involved in histone modifications such as ubiquitination of
CC       histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C
CC       recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2
CC       enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of
CC       'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B
CC       ubiquitination is proposed to be coupled to transcription. PAF1C is
CC       involved in mRNA 3' end formation probably through association with
CC       cleavage and poly(A) factors. Connects PAF1C with the cleavage and
CC       polyadenylation specificity factor (CPSF) complex and the cleavage
CC       stimulation factor (CSTF) complex, and with Wnt signaling. Involved in
CC       polyadenylation of mRNA precursors (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Component of the PAF1 complex, which consists of CDC73, PAF1,
CC       LEO1, CTR9, RTF1 and SKIC8 (By similarity). The PAF1 complex interacts
CC       with PHF5A. Within the PAF1 complex interacts directly with PHF5A (By
CC       similarity). Interacts with POLR2A, CPSF1, CPSF4, CSTF2, KMT2A/MLL1 and
CC       CTNNB1. Interacts with a Set1-like complex that has histone
CC       methyltransferase activity and methylates histone H3. Found in a
CC       complex with BCL9L or BCL9, CDC73, CTNNB1 and PYGO1 indicative for the
CC       participation in a nuclear Wnt signaling complex. Interacts with PTPN11
CC       (By similarity). Interacts with SETD5 (By similarity).
CC       {ECO:0000250|UniProtKB:Q6P1J9, ECO:0000250|UniProtKB:Q8JZM7}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC   -!- PTM: Phosphorylated. Dephosphorylated by PTPN11.
CC       {ECO:0000250|UniProtKB:Q6P1J9}.
CC   -!- SIMILARITY: Belongs to the CDC73 family. {ECO:0000305}.
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DR   EMBL; BC097445; AAH97445.1; -; mRNA.
DR   RefSeq; NP_001019940.1; NM_001024769.1.
DR   AlphaFoldDB; Q4V8C8; -.
DR   SMR; Q4V8C8; -.
DR   BioGRID; 257997; 1.
DR   IntAct; Q4V8C8; 4.
DR   STRING; 10116.ENSRNOP00000004495; -.
DR   iPTMnet; Q4V8C8; -.
DR   PhosphoSitePlus; Q4V8C8; -.
DR   jPOST; Q4V8C8; -.
DR   PaxDb; 10116-ENSRNOP00000004495; -.
DR   GeneID; 304832; -.
DR   KEGG; rno:304832; -.
DR   UCSC; RGD:1311766; rat.
DR   AGR; RGD:1311766; -.
DR   CTD; 79577; -.
DR   RGD; 1311766; Cdc73.
DR   eggNOG; KOG3786; Eukaryota.
DR   InParanoid; Q4V8C8; -.
DR   OrthoDB; 180759at2759; -.
DR   PhylomeDB; Q4V8C8; -.
DR   Reactome; R-RNO-112382; Formation of RNA Pol II elongation complex.
DR   Reactome; R-RNO-201722; Formation of the beta-catenin:TCF transactivating complex.
DR   Reactome; R-RNO-5632684; Hedgehog 'on' state.
DR   Reactome; R-RNO-674695; RNA Polymerase II Pre-transcription Events.
DR   Reactome; R-RNO-75955; RNA Polymerase II Transcription Elongation.
DR   Reactome; R-RNO-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR   PRO; PR:Q4V8C8; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0016593; C:Cdc73/Paf1 complex; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0000993; F:RNA polymerase II complex binding; ISS:UniProtKB.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR   GO; GO:0001711; P:endodermal cell fate commitment; ISS:UniProtKB.
DR   GO; GO:0031124; P:mRNA 3'-end processing; ISS:UniProtKB.
DR   GO; GO:0006378; P:mRNA polyadenylation; ISO:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR   GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISO:RGD.
DR   GO; GO:0048147; P:negative regulation of fibroblast proliferation; ISO:RGD.
DR   GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR   GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISS:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; ISS:UniProtKB.
DR   GO; GO:0031442; P:positive regulation of mRNA 3'-end processing; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
DR   GO; GO:0031648; P:protein destabilization; ISO:RGD.
DR   GO; GO:0034402; P:recruitment of 3'-end processing factors to RNA polymerase II holoenzyme complex; IBA:GO_Central.
DR   GO; GO:0001558; P:regulation of cell growth; ISO:RGD.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB.
DR   GO; GO:0006368; P:transcription elongation by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.11990; RNA polymerase II accessory factor, Cdc73 C-terminal domain; 1.
DR   InterPro; IPR007852; Cdc73/Parafibromin.
DR   InterPro; IPR031336; CDC73_C.
DR   InterPro; IPR038103; CDC73_C_sf.
DR   InterPro; IPR032041; Cdc73_N.
DR   PANTHER; PTHR12466; CDC73 DOMAIN PROTEIN; 1.
DR   PANTHER; PTHR12466:SF8; PARAFIBROMIN; 1.
DR   Pfam; PF05179; CDC73_C; 1.
DR   Pfam; PF16050; CDC73_N; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Cell cycle; Isopeptide bond; Nucleus; Phosphoprotein;
KW   Reference proteome; Transcription; Tumor suppressor; Ubl conjugation;
KW   Wnt signaling pathway.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P1J9"
FT   CHAIN           2..531
FT                   /note="Parafibromin"
FT                   /id="PRO_0000191805"
FT   REGION          200..531
FT                   /note="Interaction with POLR2A and PAF1"
FT                   /evidence="ECO:0000250"
FT   REGION          200..250
FT                   /note="Interaction with CTNNB1"
FT                   /evidence="ECO:0000250"
FT   REGION          260..292
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          325..358
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           125..139
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        325..340
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P1J9"
FT   MOD_RES         212
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P1J9"
FT   CROSSLNK        198
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P1J9"
FT   CROSSLNK        301
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P1J9"
FT   CROSSLNK        308
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P1J9"
FT   CROSSLNK        321
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P1J9"
SQ   SEQUENCE   531 AA;  60603 MW;  C99EFF505A4C48FD CRC64;
     MADVLSVLRQ YNIQKKEIVV KGDEVIFGEF SWPKNVKTNY VVWGTGKEGQ PREYYTLDSI
     LFLLNNVHLS HPVYVRRAAT ENIPVVRRPD RKDLLGYLNG EASTSASIDR SAPLEIGLQR
     STQVKRAADE VLAEAKKPRI EDEECVRLDK ERLAARLEGH KEGIVQTEQI RSLSEAMLVE
     KIAAIKAKIM AKKRSTIKTD LDDDITALKQ RSFVDAEVDV TRDIVSRERV WRTRTTILQS
     TGKNFSKNIF AILQSVKARE EGRAPEQRPA PNAAPVDPTL RTKQPIPAAY NRYDQERFKG
     KEETEGFKID TMGTYHGMTL KSVTEGASAR KTQTPAAQPV PRPVSQARPP PNQKKGSRTP
     IIIIPAATTS LITMLNAKDL LQDLKFVPSD EKKKQGCQRE NETLIQRRKD QMQPGGTAIS
     VTVPYRVVDQ PLKLMPQDWD RVVAVFVQGP AWQFKGWPWL LPDGSPVDIF AKIKAFHLKY
     DEVRLDPNVQ KWDVTVLELS YHKRHLDRPV FLRFWETLDR YMVKHKSHLR F
//