CDC73_MOUSE
ID CDC73_MOUSE Reviewed; 531 AA.
AC Q8JZM7;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Parafibromin;
DE AltName: Full=Cell division cycle protein 73 homolog;
DE AltName: Full=Hyperparathyroidism 2 protein homolog;
GN Name=Cdc73;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Adrenal gland;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II, and FVB/N; TISSUE=Kidney, and Mammary tumor;
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).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=15580289; DOI=10.1038/sj.onc.1208274;
RA Woodard G.E., Lin L., Zhang J.-H., Agarwal S.K., Marx S.J., Simonds W.F.;
RT "Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene
RT HRPT2, regulates cyclin D1/PRAD1 expression.";
RL Oncogene 24:1272-1276(2005).
RN [4]
RP FUNCTION.
RX PubMed=19345177; DOI=10.1016/j.stem.2009.03.009;
RA Ding L., Paszkowski-Rogacz M., Nitzsche A., Slabicki M.M., Heninger A.K.,
RA de Vries I., Kittler R., Junqueira M., Shevchenko A., Schulz H., Hubner N.,
RA Doss M.X., Sachinidis A., Hescheler J., Iacone R., Anastassiadis K.,
RA Stewart A.F., Pisabarro M.T., Caldarelli A., Poser I., Theis M.,
RA Buchholz F.;
RT "A genome-scale RNAi screen for Oct4 modulators defines a role of the Paf1
RT complex for embryonic stem cell identity.";
RL Cell Stem Cell 4:403-415(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH SETD5.
RX PubMed=27864380; DOI=10.1242/dev.141465;
RA Osipovich A.B., Gangula R., Vianna P.G., Magnuson M.A.;
RT "Setd5 is essential for mammalian development and the co-transcriptional
RT regulation of histone acetylation.";
RL Development 143:4595-4607(2016).
RN [7]
RP INTERACTION WITH PHF5A, AND SUBUNIT.
RX PubMed=27749823; DOI=10.1038/ncb3424;
RA Strikoudis A., Lazaris C., Trimarchi T., Galvao Neto A.L., Yang Y.,
RA Ntziachristos P., Rothbart S., Buckley S., Dolgalev I., Stadtfeld M.,
RA Strahl B.D., Dynlacht B.D., Tsirigos A., Aifantis I.;
RT "Regulation of transcriptional elongation in pluripotency and cell
RT differentiation by the PHD-finger protein Phf5a.";
RL Nat. Cell Biol. 18:1127-1138(2016).
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 ECO:0000269|PubMed:19345177}.
CC -!- SUBUNIT: Component of the PAF1 complex, which consists of CDC73, PAF1,
CC LEO1, CTR9, RTF1 and WDR61. The PAF1 complex interacts with PHF5A
CC (PubMed:27749823). Within the PAF1 complex interacts directly with
CC PHF5A (PubMed:27749823). Interacts with POLR2A, CPSF1, CPSF4, CSTF2,
CC KMT2A/MLL1 and CTNNB1. Interacts with a Set1-like complex that has
CC histone methyltransferase activity and methylates histone H3. Found in
CC a complex with BCL9L or BCL9, CDC73, CTNNB1 and PYGO1 indicative for
CC the participation in a nuclear Wnt signaling complex. Interacts with
CC PTPN11 (By similarity). Interacts with SETD5 (PubMed:27864380).
CC {ECO:0000250|UniProtKB:Q6P1J9, ECO:0000269|PubMed:27749823,
CC ECO:0000269|PubMed:27864380}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Found in the adrenal gland, kidney, heart, ovary
CC and liver. {ECO:0000269|PubMed:15580289}.
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; AK080861; BAC38048.1; -; mRNA.
DR EMBL; BC027756; AAH27756.1; -; mRNA.
DR EMBL; BC031127; AAH31127.1; -; mRNA.
DR CCDS; CCDS15341.1; -.
DR RefSeq; NP_666103.1; NM_145991.2.
DR AlphaFoldDB; Q8JZM7; -.
DR SMR; Q8JZM7; -.
DR BioGRID; 229532; 8.
DR IntAct; Q8JZM7; 9.
DR MINT; Q8JZM7; -.
DR STRING; 10090.ENSMUSP00000018337; -.
DR iPTMnet; Q8JZM7; -.
DR PhosphoSitePlus; Q8JZM7; -.
DR EPD; Q8JZM7; -.
DR MaxQB; Q8JZM7; -.
DR PaxDb; Q8JZM7; -.
DR PeptideAtlas; Q8JZM7; -.
DR PRIDE; Q8JZM7; -.
DR ProteomicsDB; 281276; -.
DR Antibodypedia; 4286; 271 antibodies from 36 providers.
DR Ensembl; ENSMUST00000018337; ENSMUSP00000018337; ENSMUSG00000026361.
DR GeneID; 214498; -.
DR KEGG; mmu:214498; -.
DR UCSC; uc007cwx.1; mouse.
DR CTD; 79577; -.
DR MGI; MGI:2384876; Cdc73.
DR VEuPathDB; HostDB:ENSMUSG00000026361; -.
DR eggNOG; KOG3786; Eukaryota.
DR GeneTree; ENSGT00390000001114; -.
DR HOGENOM; CLU_025849_0_1_1; -.
DR InParanoid; Q8JZM7; -.
DR OMA; CAFHLKY; -.
DR OrthoDB; 720340at2759; -.
DR PhylomeDB; Q8JZM7; -.
DR TreeFam; TF313016; -.
DR Reactome; R-MMU-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-MMU-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-MMU-5632684; Hedgehog 'on' state.
DR Reactome; R-MMU-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-MMU-75955; RNA Polymerase II Transcription Elongation.
DR Reactome; R-MMU-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR BioGRID-ORCS; 214498; 29 hits in 77 CRISPR screens.
DR ChiTaRS; Cdc73; mouse.
DR PRO; PR:Q8JZM7; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8JZM7; protein.
DR Bgee; ENSMUSG00000026361; Expressed in embryonic post-anal tail and 248 other tissues.
DR ExpressionAtlas; Q8JZM7; baseline and differential.
DR Genevisible; Q8JZM7; MM.
DR GO; GO:0016593; C:Cdc73/Paf1 complex; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0001711; P:endodermal cell fate commitment; IMP:UniProtKB.
DR GO; GO:0033523; P:histone H2B ubiquitination; ISO:MGI.
DR GO; GO:0010390; P:histone monoubiquitination; ISO:MGI.
DR GO; GO:0006378; P:mRNA polyadenylation; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
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:MGI.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; ISO:MGI.
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; IMP: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:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IBA:GO_Central.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0019827; P:stem cell population maintenance; IMP:UniProtKB.
DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.11990; -; 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; PTHR12466; 1.
DR Pfam; PF05179; CDC73_C; 1.
DR Pfam; PF16050; CDC73_N; 1.
PE 1: Evidence at protein 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_0000191804"
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; 60577 MW; 894A7448DBC0E793 CRC64;
MADVLSVLRQ YNIQKKEIVV KGDEVIFGEF SWPKNVKTNY VVWGTGKEGQ PREYYTLDSI
LFLLNNVHLS HPVYVRRAAT ENIPVVRRPD RKDLLGYLNG EASTSASIDR SAPLEIGLQR
STQVKRAADE VLAEAKKPRI EDEECVRLDK ERLAARLEGH KEGIVQTEQI RSLSEAMSVE
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
