CDC73_HUMAN
ID CDC73_HUMAN Reviewed; 531 AA.
AC Q6P1J9; A6NLZ8; B2RBR2; Q6PK51; Q96A07; Q9H245; Q9H5L7;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Parafibromin;
DE AltName: Full=Cell division cycle protein 73 homolog;
DE AltName: Full=Hyperparathyroidism 2 protein;
GN Name=CDC73; Synonyms=C1orf28, HRPT2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11318611; DOI=10.1006/geno.2001.6500;
RA Sood R., Bonner T.I., Malakowska I., Stephan D.A., Robbins C.M.,
RA Connors T.D., Morgenbesser S.D., Su K., Faruque M.U., Pinkett H.,
RA Graham C., Baxevanis A.D., Klinger K.W., Landes G.M., Trent J.M.,
RA Carpten J.D.;
RT "Cloning and characterization of 13 novel transcripts and the human RGS8
RT gene from the 1q25 region encompassing the hereditary prostate cancer
RT (HPC1) locus.";
RL Genomics 73:211-222(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Urinary bladder;
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 [6]
RP PROTEIN SEQUENCE OF 2-9; 38-47; 78-87; 111-120; 127-136; 172-181; 212-222;
RP 235-243; 248-257; 332-342; 379-385 AND 400-407, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney, and Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.,
RA Ramsay A., Leung H.Y.;
RL Submitted (FEB-2008) to UniProtKB.
RN [7]
RP FUNCTION, INTERACTION WITH PAF1; LEO1 AND POLR2A, INTERACTION WITH
RP SET1-LIKE COMPLEX, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT
RP HRPT1 PRO-64.
RX PubMed=15632063; DOI=10.1128/mcb.25.2.612-620.2005;
RA Rozenblatt-Rosen O., Hughes C.M., Nannepaga S.J., Shanmugam K.S.,
RA Copeland T.D., Guszczynski T., Resau J.H., Meyerson M.;
RT "The parafibromin tumor suppressor protein is part of a human Paf1
RT complex.";
RL Mol. Cell. Biol. 25:612-620(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PAF1 AND POLR2A.
RX PubMed=15923622; DOI=10.1128/mcb.25.12.5052-5060.2005;
RA Yart A., Gstaiger M., Wirbelauer C., Pecnik M., Anastasiou D., Hess D.,
RA Krek W.;
RT "The HRPT2 tumor suppressor gene product parafibromin associates with human
RT PAF1 and RNA polymerase II.";
RL Mol. Cell. Biol. 25:5052-5060(2005).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
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 [10]
RP CHARACTERIZATION OF NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=16116486; DOI=10.1038/sj.onc.1208778;
RA Hahn M.A., Marsh D.J.;
RT "Identification of a functional bipartite nuclear localization signal in
RT the tumor suppressor parafibromin.";
RL Oncogene 24:6241-6248(2005).
RN [11]
RP INVOLVEMENT IN HRPT2, INVOLVEMENT IN HRPT1, AND VARIANT HRPT1 PRO-64.
RX PubMed=12434154; DOI=10.1038/ng1048;
RA Carpten J.D., Robbins C.M., Villablanca A., Forsberg L., Presciuttini S.,
RA Bailey-Wilson J., Simonds W.F., Gillanders E.M., Kennedy A.M., Chen J.D.,
RA Agarwal S.K., Sood R., Jones M.P., Moses T.Y., Haven C., Petillo D.,
RA Leotlela P.D., Harding B., Cameron D., Pannett A.A., Hoeoeg A.,
RA Heath H. III, James-Newton L.A., Robinson B., Zarbo R.J., Cavaco B.M.,
RA Wassif W., Perrier N.D., Rosen I.B., Kristoffersson U., Turnpenny P.D.,
RA Farnebo L.-O., Besser G.M., Jackson C.E., Morreau H., Trent J.M.,
RA Thakker R.V., Marx S.J., Teh B.T., Larsson C., Hobbs M.R.;
RT "HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor
RT syndrome.";
RL Nat. Genet. 32:676-680(2002).
RN [12]
RP INVOLVEMENT IN PRTC.
RX PubMed=14585940; DOI=10.1056/nejmoa031237;
RA Shattuck T.M., Vaelimaeki S., Obara T., Gaz R.D., Clark O.H., Shoback D.,
RA Wierman M.E., Tojo K., Robbins C.M., Carpten J.D., Farnebo L.-O.,
RA Larsson C., Arnold A.;
RT "Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid
RT carcinoma.";
RL N. Engl. J. Med. 349:1722-1729(2003).
RN [13]
RP FUNCTION.
RX PubMed=16989776; DOI=10.1016/j.bbrc.2006.08.169;
RA Zhang C., Kong D., Tan M.H., Pappas D.L. Jr., Wang P.F., Chen J.,
RA Farber L., Zhang N., Koo H.M., Weinreich M., Williams B.O., Teh B.T.;
RT "Parafibromin inhibits cancer cell growth and causes G1 phase arrest.";
RL Biochem. Biophys. Res. Commun. 350:17-24(2006).
RN [14]
RP FUNCTION, AND INTERACTION WITH CTNNB1.
RX PubMed=16630820; DOI=10.1016/j.cell.2006.01.053;
RA Mosimann C., Hausmann G., Basler K.;
RT "Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct
RT association with beta-catenin/Armadillo.";
RL Cell 125:327-341(2006).
RN [15]
RP IDENTIFICATION IN A COMPLEX WITH BCL9L; CTNNB1 AND PYGO1.
RX PubMed=17113272; DOI=10.1016/j.mod.2006.09.006;
RA Hoffmans R., Basler K.;
RT "BCL9-2 binds Arm/beta-catenin in a Tyr142-independent manner and requires
RT Pygopus for its function in Wg/Wnt signaling.";
RL Mech. Dev. 124:59-67(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP IDENTIFICATION IN THE PAF1 COMPLEX, AND FUNCTION OF THE PAF1 COMPLEX.
RX PubMed=19952111; DOI=10.1101/gad.1834709;
RA Chen Y., Yamaguchi Y., Tsugeno Y., Yamamoto J., Yamada T., Nakamura M.,
RA Hisatake K., Handa H.;
RT "DSIF, the Paf1 complex, and Tat-SF1 have nonredundant, cooperative roles
RT in RNA polymerase II elongation.";
RL Genes Dev. 23:2765-2777(2009).
RN [18]
RP FUNCTION, AND INTERACTION WITH CPSF1; CPSF4 AND CSTF2.
RX PubMed=19136632; DOI=10.1073/pnas.0812023106;
RA Rozenblatt-Rosen O., Nagaike T., Francis J.M., Kaneko S., Glatt K.A.,
RA Hughes C.M., LaFramboise T., Manley J.L., Meyerson M.;
RT "The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3'
RT mRNA processing factors.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:755-760(2009).
RN [19]
RP FUNCTION OF THE PAF1 COMPLEX, AND INTERACTION WITH KMT2A.
RX PubMed=20541477; DOI=10.1016/j.ccr.2010.04.012;
RA Muntean A.G., Tan J., Sitwala K., Huang Y., Bronstein J., Connelly J.A.,
RA Basrur V., Elenitoba-Johnson K.S., Hess J.L.;
RT "The PAF complex synergizes with MLL fusion proteins at HOX loci to promote
RT leukemogenesis.";
RL Cancer Cell 17:609-621(2010).
RN [20]
RP IDENTIFICATION IN THE PAF1 COMPLEX, COMPOSITION OF THE PAF1 COMPLEX, AND
RP FUNCTION OF THE PAF1 COMPLEX.
RX PubMed=20178742; DOI=10.1016/j.cell.2009.12.050;
RA Kim J., Guermah M., Roeder R.G.;
RT "The human PAF1 complex acts in chromatin transcription elongation both
RT independently and cooperatively with SII/TFIIS.";
RL Cell 140:491-503(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP FUNCTION, AND FUNCTION OF THE PAF1 COMPLEX.
RX PubMed=21329879; DOI=10.1016/j.molcel.2011.01.022;
RA Nagaike T., Logan C., Hotta I., Rozenblatt-Rosen O., Meyerson M.,
RA Manley J.L.;
RT "Transcriptional activators enhance polyadenylation of mRNA precursors.";
RL Mol. Cell 41:409-418(2011).
RN [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-301, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [28]
RP INTERACTION WITH PTPN11, DEPHOSPHORYLATION BY PTPN11, AND PHOSPHORYLATION.
RX PubMed=26742426; DOI=10.1016/j.bbrc.2015.12.117;
RA Noda S., Takahashi A., Hayashi T., Tanuma S., Hatakeyama M.;
RT "Determination of the catalytic activity of LEOPARD syndrome-associated
RT SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in
RT Wnt signaling.";
RL Biochem. Biophys. Res. Commun. 469:1133-1139(2016).
RN [29]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-198; LYS-301; LYS-308 AND
RP LYS-321, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [30]
RP INTERACTION WITH ZIKA VIRUS FRENCH POLYNESIA 10087PF/2013 NS5; DENGUE VIRUS
RP DENV2 16681 NS5 AND DENGUE VIRUS DENV4 DOMINICA/814669/1981 NS5.
RX PubMed=30550790; DOI=10.1016/j.cell.2018.11.028;
RA Shah P.S., Link N., Jang G.M., Sharp P.P., Zhu T., Swaney D.L.,
RA Johnson J.R., Von Dollen J., Ramage H.R., Satkamp L., Newton B.,
RA Huettenhain R., Petit M.J., Baum T., Everitt A., Laufman O., Tassetto M.,
RA Shales M., Stevenson E., Iglesias G.N., Shokat L., Tripathi S.,
RA Balasubramaniam V., Webb L.G., Aguirre S., Willsey A.J., Garcia-Sastre A.,
RA Pollard K.S., Cherry S., Gamarnik A.V., Marazzi I., Taunton J.,
RA Fernandez-Sesma A., Bellen H.J., Andino R., Krogan N.J.;
RT "Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms
RT of Dengue and Zika Virus Pathogenesis.";
RL Cell 175:1931-1945(2018).
RN [31]
RP VARIANT HRPT1 PRO-64.
RX PubMed=12960210; DOI=10.1136/jmg.40.9.657;
RA Howell V.M., Haven C.J., Kahnoski K., Khoo S.K., Petillo D., Chen J.,
RA Fleuren G.J., Robinson B.G., Delbridge L.W., Philips J., Nelson A.E.,
RA Krause U., Hammje K., Dralle H., Hoang-Vu C., Gimm O., Marsh D.J.,
RA Morreau H., Teh B.T.;
RT "HRPT2 mutations are associated with malignancy in sporadic parathyroid
RT tumours.";
RL J. Med. Genet. 40:657-663(2003).
RN [32]
RP VARIANT HRPT2 5-LEU--GLN-10 DEL, AND INVOLVEMENT IN HRPT2.
RX PubMed=15613436; DOI=10.1210/jc.2004-0991;
RA Moon S.D., Park J.H., Kim E.M., Kim J.H., Han J.H., Yoo S.J., Yoon K.H.,
RA Kang M.I., Lee K.W., Son H.Y., Kang S.K., Oh S.J., Kim K.M., Yoon S.J.,
RA Park J.G., Kim I.J., Kang H.C., Hong S.W., Kim K.R., Cha B.Y.;
RT "A Novel IVS2-1G>A mutation causes aberrant splicing of the HRPT2 gene in a
RT family with hyperparathyroidism-jaw tumor syndrome.";
RL J. Clin. Endocrinol. Metab. 90:878-883(2005).
RN [33]
RP VARIANT HRPT2 ASN-379, VARIANT HRPT1 PRO-95, AND INVOLVEMENT IN HRPT1.
RX PubMed=16487440; DOI=10.1111/j.1365-2265.2006.02460.x;
RA Bradley K.J., Cavaco B.M., Bowl M.R., Harding B., Cranston T., Fratter C.,
RA Besser G.M., Conceicao Pereira M., Davie M.W., Dudley N., Leite V.,
RA Sadler G.P., Seller A., Thakker R.V.;
RT "Parafibromin mutations in hereditary hyperparathyroidism syndromes and
RT parathyroid tumours.";
RL Clin. Endocrinol. (Oxf.) 64:299-306(2006).
RN [34]
RP VARIANT SER-272, AND ASSOCIATION WITH PARATHYROID ADENOMA.
RX PubMed=16728578; DOI=10.1677/erc.1.01058;
RA Juhlin C., Larsson C., Yakoleva T., Leibiger I., Leibiger B., Alimov A.,
RA Weber G., Hoog A., Villablanca A.;
RT "Loss of parafibromin expression in a subset of parathyroid adenomas.";
RL Endocr. Relat. Cancer 13:509-523(2006).
RN [35]
RP VARIANT PHE-59, AND ASSOCIATION WITH PARATHYROID CARCINOMA.
RX PubMed=17555500; DOI=10.1111/j.1365-2265.2007.02894.x;
RA Haven C.J., van Puijenbroek M., Tan M.H., Teh B.T., Fleuren G.J.,
RA van Wezel T., Morreau H.;
RT "Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded
RT (sporadic) parathyroid carcinomas.";
RL Clin. Endocrinol. (Oxf.) 67:370-376(2007).
RN [36]
RP VARIANTS SER-2 AND PRO-91, AND ASSOCIATION WITH PARATHYROID ADENOMA.
RX PubMed=17639062; DOI=10.1677/erc-06-0092;
RA Cetani F., Pardi E., Ambrogini E., Viacava P., Borsari S., Lemmi M.,
RA Cianferotti L., Miccoli P., Pinchera A., Arnold A., Marcocci C.;
RT "Different somatic alterations of the HRPT2 gene in a patient with
RT recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline
RT mutation.";
RL Endocr. Relat. Cancer 14:493-499(2007).
RN [37]
RP VARIANTS GLN-34 AND LYS-292, CHARACTERIZATION OF VARIANT GLN-34, AND
RP ASSOCIATION WITH RENAL TUMORS.
RX PubMed=17130827; DOI=10.1038/sj.onc.1210131;
RA Zhao J., Yart A., Frigerio S., Perren A., Schraml P., Weisstanner C.,
RA Stallmach T., Krek W., Moch H.;
RT "Sporadic human renal tumors display frequent allelic imbalances and novel
RT mutations of the HRPT2 gene.";
RL Oncogene 26:3440-3449(2007).
RN [38]
RP VARIANT HRPT1 PRO-63, AND INVOLVEMENT IN HRPT1.
RX PubMed=18755853; DOI=10.1677/erc-08-0066;
RA Masi G., Barzon L., Iacobone M., Viel G., Porzionato A., Macchi V.,
RA De Caro R., Favia G., Palu G.;
RT "Clinical, genetic, and histopathologic investigation of CDC73-related
RT familial hyperparathyroidism.";
RL Endocr. Relat. Cancer 15:1115-1126(2008).
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; it
CC promotes leukemogenesis through association with KMT2A/MLL1-rearranged
CC oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL.
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. In case of infection by influenza A
CC strain H3N2, PAF1C associates with viral NS1 protein, thereby
CC regulating gene transcription. 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. {ECO:0000269|PubMed:15580289,
CC ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15923622,
CC ECO:0000269|PubMed:16630820, ECO:0000269|PubMed:16989776,
CC ECO:0000269|PubMed:19136632, ECO:0000269|PubMed:19952111,
CC ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477,
CC ECO:0000269|PubMed:21329879}.
CC -!- SUBUNIT: Component of the PAF1 complex, which consists of CDC73, PAF1,
CC LEO1, CTR9, RTF1 and WDR61 (PubMed:19952111, PubMed:20178742). The PAF1
CC complex interacts with PHF5A. Within the PAF1 complex interacts
CC directly with PHF5A (By similarity). Interacts with POLR2A, CPSF1,
CC CPSF4, CSTF2, KMT2A/MLL1 and CTNNB1 (PubMed:15632063, PubMed:15923622,
CC PubMed:16630820, PubMed:19136632, PubMed:20541477). Interacts with a
CC Set1-like complex that has histone methyltransferase activity and
CC methylates histone H3 (PubMed:15632063). Found in a complex with BCL9L
CC or BCL9, CDC73, CTNNB1 and PYGO1 indicative for the participation in a
CC nuclear Wnt signaling complex (PubMed:17113272). Interacts with PTPN11
CC (PubMed:26742426). Interacts with SETD5 (By similarity).
CC {ECO:0000250|UniProtKB:Q8JZM7, ECO:0000269|PubMed:15632063,
CC ECO:0000269|PubMed:15923622, ECO:0000269|PubMed:16630820,
CC ECO:0000269|PubMed:17113272, ECO:0000269|PubMed:19136632,
CC ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742,
CC ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:26742426}.
CC -!- SUBUNIT: (Microbial infection) The PAF1 complex interacts with Zika
CC virus French Polynesia 10087PF/2013 non-structural protein 5/NS5
CC (PubMed:30550790). The interaction with viral NS5 proteins may reduce
CC the antiviral immune response by inhibiting the recruitment of the PAF1
CC complex to interferon-stimulated genes, thus preventing their
CC transcription (PubMed:30550790). {ECO:0000269|PubMed:30550790}.
CC -!- SUBUNIT: (Microbial infection) The PAF1 complex interacts with Dengue
CC virus DENV2 16681 non-structural protein 5/NS5 (PubMed:30550790). The
CC PAF1 complex interacts with Dengue virus DENV4 Dominica/814669/1981
CC non-structural protein 5/NS5 (PubMed:30550790). The interaction with
CC viral NS5 proteins may reduce the antiviral immune response by
CC inhibiting the recruitment of the PAF1 complex to interferon-stimulated
CC genes, thus preventing their transcription (PubMed:30550790).
CC {ECO:0000269|PubMed:30550790}.
CC -!- INTERACTION:
CC Q6P1J9; P13196: ALAS1; NbExp=9; IntAct=EBI-930143, EBI-3905054;
CC Q6P1J9; O00512: BCL9; NbExp=2; IntAct=EBI-930143, EBI-533127;
CC Q6P1J9; Q8NHQ1: CEP70; NbExp=10; IntAct=EBI-930143, EBI-739624;
CC Q6P1J9; O95639: CPSF4; NbExp=3; IntAct=EBI-930143, EBI-725860;
CC Q6P1J9; P33240: CSTF2; NbExp=5; IntAct=EBI-930143, EBI-711360;
CC Q6P1J9; P35222: CTNNB1; NbExp=10; IntAct=EBI-930143, EBI-491549;
CC Q6P1J9; Q6PD62: CTR9; NbExp=23; IntAct=EBI-930143, EBI-1019583;
CC Q6P1J9; Q96KQ7: EHMT2; NbExp=3; IntAct=EBI-930143, EBI-744366;
CC Q6P1J9; A1L4K1: FSD2; NbExp=9; IntAct=EBI-930143, EBI-5661036;
CC Q6P1J9; Q08379: GOLGA2; NbExp=12; IntAct=EBI-930143, EBI-618309;
CC Q6P1J9; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-930143, EBI-5916454;
CC Q6P1J9; O75031: HSF2BP; NbExp=4; IntAct=EBI-930143, EBI-7116203;
CC Q6P1J9; Q8N6L0: KASH5; NbExp=6; IntAct=EBI-930143, EBI-749265;
CC Q6P1J9; Q03164: KMT2A; NbExp=4; IntAct=EBI-930143, EBI-591370;
CC Q6P1J9; Q8WVC0: LEO1; NbExp=17; IntAct=EBI-930143, EBI-932432;
CC Q6P1J9; Q5JR59: MTUS2; NbExp=5; IntAct=EBI-930143, EBI-742948;
CC Q6P1J9; Q5JR59-3: MTUS2; NbExp=6; IntAct=EBI-930143, EBI-11522433;
CC Q6P1J9; Q8N7H5: PAF1; NbExp=31; IntAct=EBI-930143, EBI-2607770;
CC Q6P1J9; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-930143, EBI-79165;
CC Q6P1J9; P24928: POLR2A; NbExp=6; IntAct=EBI-930143, EBI-295301;
CC Q6P1J9; Q06124-2: PTPN11; NbExp=2; IntAct=EBI-930143, EBI-17635971;
CC Q6P1J9; Q15276: RABEP1; NbExp=3; IntAct=EBI-930143, EBI-447043;
CC Q6P1J9; Q5VTR2: RNF20; NbExp=3; IntAct=EBI-930143, EBI-2372238;
CC Q6P1J9; Q92541: RTF1; NbExp=12; IntAct=EBI-930143, EBI-1055239;
CC Q6P1J9; Q15047: SETDB1; NbExp=3; IntAct=EBI-930143, EBI-79691;
CC Q6P1J9; Q12800: TFCP2; NbExp=8; IntAct=EBI-930143, EBI-717422;
CC Q6P1J9; P36406: TRIM23; NbExp=3; IntAct=EBI-930143, EBI-740098;
CC Q6P1J9; Q9BZW7: TSGA10; NbExp=8; IntAct=EBI-930143, EBI-744794;
CC Q6P1J9; Q9H9H4: VPS37B; NbExp=3; IntAct=EBI-930143, EBI-4400866;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15580289,
CC ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15923622}.
CC -!- TISSUE SPECIFICITY: Found in adrenal and parathyroid glands, kidney and
CC heart. {ECO:0000269|PubMed:15580289}.
CC -!- PTM: Phosphorylated. Dephosphorylated by PTPN11.
CC {ECO:0000269|PubMed:26742426}.
CC -!- DISEASE: Hyperparathyroidism 1 (HRPT1) [MIM:145000]: An autosomal
CC dominant disorder characterized by hypercalcemia, elevated parathyroid
CC hormone (PTH) levels, and uniglandular or multiglandular parathyroid
CC hyperplasia, adenomas, and carcinomas. {ECO:0000269|PubMed:12434154,
CC ECO:0000269|PubMed:12960210, ECO:0000269|PubMed:15632063,
CC ECO:0000269|PubMed:16487440, ECO:0000269|PubMed:18755853}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hyperparathyroidism 2 with jaw tumors (HRPT2) [MIM:145001]: An
CC autosomal dominant neoplasia syndrome characterized by primary
CC hyperparathyroidism, ossifying fibroma of the maxilla and/or mandible,
CC renal tumor, and uterine tumors. It is associated with increased risk
CC of parathyroid cancer. {ECO:0000269|PubMed:12434154,
CC ECO:0000269|PubMed:15613436, ECO:0000269|PubMed:16487440}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Parathyroid carcinoma (PRTC) [MIM:608266]: These cancers
CC characteristically result in more profound clinical manifestations of
CC hyperparathyroidism than do parathyroid adenomas, the most frequent
CC cause of primary hyperparathyroidism. Early en bloc resection of the
CC primary tumor is the only curative treatment.
CC {ECO:0000269|PubMed:14585940}. Note=The gene represented in this entry
CC is involved in disease pathogenesis.
CC -!- SIMILARITY: Belongs to the CDC73 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH07325.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 300.; Evidence={ECO:0000305};
CC Sequence=BAB15608.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDC73ID181ch1q31.html";
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DR EMBL; AF312865; AAG45339.1; -; mRNA.
DR EMBL; AK026969; BAB15608.1; ALT_INIT; mRNA.
DR EMBL; AK314772; BAG37309.1; -; mRNA.
DR EMBL; AL139133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL390863; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91250.1; -; Genomic_DNA.
DR EMBL; BC007325; AAH07325.1; ALT_SEQ; mRNA.
DR EMBL; BC014351; AAH14351.2; -; mRNA.
DR EMBL; BC065037; AAH65037.1; -; mRNA.
DR CCDS; CCDS1382.1; -.
DR RefSeq; NP_078805.3; NM_024529.4.
DR PDB; 5YDE; X-ray; 1.02 A; A=1-111.
DR PDB; 5YDF; X-ray; 1.40 A; A/B=1-100.
DR PDB; 6TED; EM; 3.10 A; X=1-531.
DR PDB; 7OOP; EM; 2.90 A; Z=1-531.
DR PDB; 7OPC; EM; 3.00 A; Z=1-531.
DR PDB; 7OPD; EM; 3.00 A; Z=1-531.
DR PDBsum; 5YDE; -.
DR PDBsum; 5YDF; -.
DR PDBsum; 6TED; -.
DR PDBsum; 7OOP; -.
DR PDBsum; 7OPC; -.
DR PDBsum; 7OPD; -.
DR AlphaFoldDB; Q6P1J9; -.
DR SMR; Q6P1J9; -.
DR BioGRID; 122724; 359.
DR CORUM; Q6P1J9; -.
DR DIP; DIP-37884N; -.
DR IntAct; Q6P1J9; 247.
DR MINT; Q6P1J9; -.
DR STRING; 9606.ENSP00000356405; -.
DR GlyGen; Q6P1J9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6P1J9; -.
DR PhosphoSitePlus; Q6P1J9; -.
DR BioMuta; CDC73; -.
DR DMDM; 74749063; -.
DR EPD; Q6P1J9; -.
DR jPOST; Q6P1J9; -.
DR MassIVE; Q6P1J9; -.
DR MaxQB; Q6P1J9; -.
DR PaxDb; Q6P1J9; -.
DR PeptideAtlas; Q6P1J9; -.
DR PRIDE; Q6P1J9; -.
DR ProteomicsDB; 66834; -.
DR ABCD; Q6P1J9; 3 sequenced antibodies.
DR Antibodypedia; 4286; 271 antibodies from 36 providers.
DR DNASU; 79577; -.
DR Ensembl; ENST00000367435.5; ENSP00000356405.4; ENSG00000134371.14.
DR GeneID; 79577; -.
DR KEGG; hsa:79577; -.
DR MANE-Select; ENST00000367435.5; ENSP00000356405.4; NM_024529.5; NP_078805.3.
DR UCSC; uc001gtb.4; human.
DR CTD; 79577; -.
DR DisGeNET; 79577; -.
DR GeneCards; CDC73; -.
DR GeneReviews; CDC73; -.
DR HGNC; HGNC:16783; CDC73.
DR HPA; ENSG00000134371; Low tissue specificity.
DR MalaCards; CDC73; -.
DR MIM; 145000; phenotype.
DR MIM; 145001; phenotype.
DR MIM; 607393; gene.
DR MIM; 608266; phenotype.
DR neXtProt; NX_Q6P1J9; -.
DR OpenTargets; ENSG00000134371; -.
DR Orphanet; 99879; Familial isolated hyperparathyroidism.
DR Orphanet; 99880; Hyperparathyroidism-jaw tumor syndrome.
DR Orphanet; 143; Parathyroid carcinoma.
DR PharmGKB; PA29464; -.
DR VEuPathDB; HostDB:ENSG00000134371; -.
DR eggNOG; KOG3786; Eukaryota.
DR GeneTree; ENSGT00390000001114; -.
DR HOGENOM; CLU_025849_0_1_1; -.
DR InParanoid; Q6P1J9; -.
DR OMA; CAFHLKY; -.
DR OrthoDB; 720340at2759; -.
DR PhylomeDB; Q6P1J9; -.
DR TreeFam; TF313016; -.
DR PathwayCommons; Q6P1J9; -.
DR Reactome; R-HSA-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-HSA-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-HSA-75955; RNA Polymerase II Transcription Elongation.
DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR SignaLink; Q6P1J9; -.
DR SIGNOR; Q6P1J9; -.
DR BioGRID-ORCS; 79577; 771 hits in 1097 CRISPR screens.
DR ChiTaRS; CDC73; human.
DR GeneWiki; CDC73; -.
DR GenomeRNAi; 79577; -.
DR Pharos; Q6P1J9; Tbio.
DR PRO; PR:Q6P1J9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6P1J9; protein.
DR Bgee; ENSG00000134371; Expressed in calcaneal tendon and 187 other tissues.
DR ExpressionAtlas; Q6P1J9; baseline and differential.
DR Genevisible; Q6P1J9; HS.
DR GO; GO:0016593; C:Cdc73/Paf1 complex; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000993; F:RNA polymerase II complex binding; IDA: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:0033523; P:histone H2B ubiquitination; IDA:UniProtKB.
DR GO; GO:0010390; P:histone monoubiquitination; IDA:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:UniProtKB.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IDA: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; IMP:UniProtKB.
DR GO; GO:0031442; P:positive regulation of mRNA 3'-end processing; IMP: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; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; IDA:GO_Central.
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 3D-structure; Acetylation; Cell cycle; Direct protein sequencing;
KW Disease variant; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Tumor suppressor; Ubl conjugation; Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..531
FT /note="Parafibromin"
FT /id="PRO_0000191803"
FT REGION 200..531
FT /note="Interaction with POLR2A and PAF1"
FT REGION 200..250
FT /note="Interaction with CTNNB1"
FT /evidence="ECO:0000269|PubMed:16630820"
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 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:0000269|Ref.6, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT CROSSLNK 198
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 301
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 308
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 321
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 2
FT /note="A -> S (found in parathyroid adenoma samples;
FT somatic mutation; parathyroid adenoma samples are from a
FT patient with isolated hyperparathyroidism who also carries
FT germline mutation P-91)"
FT /evidence="ECO:0000269|PubMed:17639062"
FT /id="VAR_064927"
FT VARIANT 5..10
FT /note="Missing (in HRPT2; unknown pathological
FT significance; found as somatic mutation in a parathyroid
FT carcinoma sample from a patient who also carries a germline
FT mutation causing a splicing defect)"
FT /evidence="ECO:0000269|PubMed:15613436"
FT /id="VAR_064928"
FT VARIANT 34
FT /note="K -> Q (found in a clear cell renal carcinoma
FT sample; somatic mutation; unlike wild-type protein the
FT mutant is defective in suppressing CCND1 expression in
FT vivo)"
FT /evidence="ECO:0000269|PubMed:17130827"
FT /id="VAR_064929"
FT VARIANT 59
FT /note="S -> F (found in a parathyroid carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17555500"
FT /id="VAR_064930"
FT VARIANT 63
FT /note="L -> P (in HRPT1; unknown pathological significance;
FT dbSNP:rs1060500015)"
FT /evidence="ECO:0000269|PubMed:18755853"
FT /id="VAR_064931"
FT VARIANT 64
FT /note="L -> P (in HRPT1; does not affect interaction with
FT the Pfa1 complex; dbSNP:rs121434264)"
FT /evidence="ECO:0000269|PubMed:12434154,
FT ECO:0000269|PubMed:12960210, ECO:0000269|PubMed:15632063"
FT /id="VAR_024082"
FT VARIANT 91
FT /note="R -> P (found in a patient with isolated
FT hyperparathyroidism and parathyroid adenomas)"
FT /evidence="ECO:0000269|PubMed:17639062"
FT /id="VAR_064932"
FT VARIANT 95
FT /note="L -> P (in HRPT1; unknown pathological significance;
FT found as somatic mutation in a parathyroid adenoma sample
FT from a patient who also carries a germline frameshift
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16487440"
FT /id="VAR_064933"
FT VARIANT 272
FT /note="N -> S (found in a parathyroid adenoma sample;
FT dbSNP:rs752383339)"
FT /evidence="ECO:0000269|PubMed:16728578"
FT /id="VAR_064934"
FT VARIANT 292
FT /note="R -> K (found in a Wilms tumor sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17130827"
FT /id="VAR_064935"
FT VARIANT 379
FT /note="D -> N (in HRPT2; dbSNP:rs971586985)"
FT /evidence="ECO:0000269|PubMed:16487440"
FT /id="VAR_064936"
FT VARIANT 384
FT /note="L -> P (in dbSNP:rs35590728)"
FT /id="VAR_031825"
FT CONFLICT 123
FT /note="Q -> G (in Ref. 5; AAH14351)"
FT /evidence="ECO:0000305"
FT CONFLICT 184..187
FT /note="AIKA -> CNQT (in Ref. 2; BAB15608)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="I -> K (in Ref. 2; BAB15608)"
FT /evidence="ECO:0000305"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:5YDE"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:5YDE"
FT STRAND 24..27
FT /evidence="ECO:0007829|PDB:5YDE"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:5YDE"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:5YDE"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:5YDE"
FT HELIX 57..65
FT /evidence="ECO:0007829|PDB:5YDE"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:5YDE"
FT HELIX 71..81
FT /evidence="ECO:0007829|PDB:5YDE"
FT HELIX 88..98
FT /evidence="ECO:0007829|PDB:5YDE"
FT HELIX 219..227
FT /evidence="ECO:0007829|PDB:7OOP"
FT HELIX 235..238
FT /evidence="ECO:0007829|PDB:7OOP"
FT HELIX 247..259
FT /evidence="ECO:0007829|PDB:7OOP"
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
