Reviewed, UniProtKB/Swiss-Prot Q6P1J9 (CDC73_HUMAN)

Names and origin

Protein names

Recommended name:
    Parafibromin
Alternative name(s):
    Cell division cycle protein 73 homolog
    Hyperparathyroidism 2 protein

Gene names

Name:	CDC73
Synonyms:	C1orf28, HRPT2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	531 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

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.
Subunit structure	Part of the PAF1 complex. Interacts with the RNA polymerase II large subunit (RPB1) and LEO1. Interacts with a Set1-like complex that has histone methyltransferase activity and methylates histone H3. Found in a complex with BCL9L, CDC73, CTNNB1 and PYGO1.
Subcellular location	Nucleus.
Tissue specificity	Found in adrenal and parathyroid glands, kidney and heart.
Involvement in 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. 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. Defects in CDC73 are a cause of parathyroid carcinoma [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.
Sequence similarities	Belongs to the CDC73 family.
Sequence caution	The sequence AAH07325.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence starting in position 300.

Ontologies

Keywords
Biological process	Cell cycle Transcription
Cellular component	Nucleus
Disease	Disease mutation
Molecular function	Anti-oncogene
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Ref.12 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL9	O00512	1	EBI-930143,EBI-533127
CTNNB1	P35222	4	EBI-930143,EBI-491549
TCF4	P15884	1	EBI-930143,EBI-533224

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 531	531	Parafibromin		PRO_0000191803
Regions
	Motif	125 – 139	15	Nuclear localization signal
	Compositional bias	361 – 364	4	Poly-Ile
Amino acid modifications
	Modified residue	212	1	Phosphoserine
Natural variations
	Natural variant	64	1	L → P in FIHP; does not affect interaction with the Pfa1 complex.		VAR_024082
	Natural variant	384	1	L → P: dbSNP rs35590728.		VAR_031825
Experimental info
	Sequence conflict	123	1	Q → G in AAH14351. Ref.4
	Sequence conflict	184 – 187	4	AIKA → CNQT in BAB15608. Ref.5
	Sequence conflict	372	1	I → K in BAB15608. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q6P1J9-1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 894A7448DBC0E793	FASTA	531	60,577
	10 20 30 40 50 60 MADVLSVLRQ YNIQKKEIVV KGDEVIFGEF SWPKNVKTNY VVWGTGKEGQ PREYYTLDSI 70 80 90 100 110 120 LFLLNNVHLS HPVYVRRAAT ENIPVVRRPD RKDLLGYLNG EASTSASIDR SAPLEIGLQR 130 140 150 160 170 180 STQVKRAADE VLAEAKKPRI EDEECVRLDK ERLAARLEGH KEGIVQTEQI RSLSEAMSVE 190 200 210 220 230 240 KIAAIKAKIM AKKRSTIKTD LDDDITALKQ RSFVDAEVDV TRDIVSRERV WRTRTTILQS 250 260 270 280 290 300 TGKNFSKNIF AILQSVKARE EGRAPEQRPA PNAAPVDPTL RTKQPIPAAY NRYDQERFKG 310 320 330 340 350 360 KEETEGFKID TMGTYHGMTL KSVTEGASAR KTQTPAAQPV PRPVSQARPP PNQKKGSRTP 370 380 390 400 410 420 IIIIPAATTS LITMLNAKDL LQDLKFVPSD EKKKQGCQRE NETLIQRRKD QMQPGGTAIS 430 440 450 460 470 480 VTVPYRVVDQ PLKLMPQDWD RVVAVFVQGP AWQFKGWPWL LPDGSPVDIF AKIKAFHLKY 490 500 510 520 530 DEVRLDPNVQ KWDVTVLELS YHKRHLDRPV FLRFWETLDR YMVKHKSHLR F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus." Sood R., Bonner T.I., Malakowska I., Stephan D.A., Robbins C.M., Connors T.D., Morgenbesser S.D., Su K., Faruque M.U., Pinkett H., Graham C., Baxevanis A.D., Klinger K.W., Landes G.M., Trent J.M., Carpten J.D. Genomics 73:211-222(2001) [PubMed: 11318611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye and Urinary bladder.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 156-531.
[6]	"The parafibromin tumor suppressor protein is part of a human Paf1 complex." Rozenblatt-Rosen O., Hughes C.M., Nannepaga S.J., Shanmugam K.S., Copeland T.D., Guszczynski T., Resau J.H., Meyerson M. Mol. Cell. Biol. 25:612-620(2005) [PubMed: 15632063] [Abstract] Cited for: FUNCTION, INTERACTION WITH PAF1 AND LEO1, INTERACTION WITH RNA POLYMERASE II, INTERACTION WITH SET1-LIKE COMPLEX, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT FIHP PRO-64.
[7]	"The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II." Yart A., Gstaiger M., Wirbelauer C., Pecnik M., Anastasiou D., Hess D., Krek W. Mol. Cell. Biol. 25:5052-5060(2005) [PubMed: 15923622] [Abstract] Cited for: FUNCTION, INTERACTION WITH PAF1, INTERACTION WITH RNA POLYMERASE II.
[8]	"Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression." Woodard G.E., Lin L., Zhang J.-H., Agarwal S.K., Marx S.J., Simonds W.F. Oncogene 24:1272-1276(2005) [PubMed: 15580289] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[9]	"Identification of a functional bipartite nuclear localization signal in the tumor suppressor parafibromin." Hahn M.A., Marsh D.J. Oncogene 24:6241-6248(2005) [PubMed: 16116486] [Abstract] Cited for: CHARACTERIZATION OF NUCLEAR LOCALIZATION SIGNAL.
[10]	"HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome." Carpten J.D., Robbins C.M., Villablanca A., Forsberg L., Presciuttini S., Bailey-Wilson J., Simonds W.F., Gillanders E.M., Kennedy A.M., Chen J.D., Agarwal S.K., Sood R., Jones M.P., Moses T.Y., Haven C., Petillo D., Leotlela P.D., Harding B. , Cameron D., Pannett A.A., Hoeoeg A., Heath H. III, James-Newton L.A., Robinson B., Zarbo R.J., Cavaco B.M., Wassif W., Perrier N.D., Rosen I.B., Kristoffersson U., Turnpenny P.D., Farnebo L.-O., Besser G.M., Jackson C.E., Morreau H., Trent J.M., Thakker R.V., Marx S.J., Teh B.T., Larsson C., Hobbs M.R. Nat. Genet. 32:676-680(2002) [PubMed: 12434154] [Abstract] Cited for: INVOLVEMENT IN HYPERPARATHYROIDISM-JAW TUMOR SYNDROME, VARIANT FIHP PRO-64.
[11]	"Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma." Shattuck T.M., Vaelimaeki S., Obara T., Gaz R.D., Clark O.H., Shoback D., Wierman M.E., Tojo K., Robbins C.M., Carpten J.D., Farnebo L.-O., Larsson C., Arnold A. N. Engl. J. Med. 349:1722-1729(2003) [PubMed: 14585940] [Abstract] Cited for: INVOLVEMENT IN PARATHYROID CARCINOMA.
[12]	"BCL9-2 binds Arm/beta-catenin in a Tyr142-independent manner and requires Pygopus for its function in Wg/Wnt signaling." Hoffmans R., Basler K. Mech. Dev. 124:59-67(2007) [PubMed: 17113272] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH BCL9L; CTNNB1 AND PYGO1.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF312865 mRNA. Translation: AAG45339.1. AL139133, AL390863 Genomic DNA. Translation: CAH71049.1. AL390863, AL139133 Genomic DNA. Translation: CAH71589.1. CH471067 Genomic DNA. Translation: EAW91250.1. BC007325 mRNA. Translation: AAH07325.1. Sequence problems. BC014351 mRNA. Translation: AAH14351.2. BC065037 mRNA. Translation: AAH65037.1. AK026969 mRNA. Translation: BAB15608.1. Different initiation.
RefSeq	NP_078805.3.
UniGene	Hs.576497
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6P1J9.
PTM databases
PhosphoSite	Q6P1J9.
Genome annotation databases
Ensembl	ENSG00000134371. Homo sapiens. [Contig view]
GeneID	79577.
KEGG	hsa:79577.
Organism-specific databases
H-InvDB	HIX0021545.
HGNC	HGNC:16783. CDC73.
HPA	CAB016359.
MIM	145000. phenotype. 145001. phenotype. 607393. gene. 608266. phenotype.
Orphanet	99879. Hyperparathyroidism, familial, isolated (FIHPT). 2207. Hyperparathyroidism, primary, familial. 99877. Parathyroid adenoma.
PharmGKB	PA29464.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q6P1J9.
HOVERGEN	Q6P1J9.
Gene expression databases
ArrayExpress	Q6P1J9.
CleanEx	HS_CDC73.
GermOnline	ENSG00000134371. Homo sapiens.
Family and domain databases
InterPro	IPR007852. RNA_pol_access_fac_Cdc73. [Graphical view]
PANTHER	PTHR12466. Cdc73. 1 hit.
Pfam	PF05179. CDC73. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	68562.
SOURCE	Search...

Entry information

Entry name

CDC73_HUMAN

Accession

Primary (citable) accession number: Q6P1J9
Secondary accession number(s): A6NLZ8 , Q6PK51, Q96A07, Q9H245, Q9H5L7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	July 5, 2004
Last modified:	November 25, 2008
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)