Q4V8C8 (CDC73_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Parafibromin

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

Gene names

Name:	Cdc73
Synonyms:	Hrpt2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	531 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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. 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 indepentently 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 MLL1. 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. 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 By similarity.
Subunit structure	Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and WDR61. Interacts with POLR2A, CPSF1, CPSF4, CSTF2, MLL and CTNNB1. Interacts with a Set1-like complex that has histone methyltransferase activity and methylates histone H3. Found in a complex with BCL9L or BCL9, CDC73, CTNNB1 and PYGO1 indicative for the participation in a nuclear Wnt signaling complex By similarity.
Subcellular location	Nucleus By similarity.
Sequence similarities	Belongs to the CDC73 family.

Ontologies

Keywords
Biological process	Cell cycle Transcription Wnt signaling pathway
Cellular component	Nucleus
Disease	Tumor suppressor
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cellular response to lipopolysaccharide Inferred from sequence or structural similarity. Source: UniProtKB endodermal cell fate commitment Inferred from sequence or structural similarity. Source: UniProtKB mRNA polyadenylation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of G1/S transition of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of S phase of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of myeloid cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of Wnt receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mRNA 3'-end processing Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription elongation from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB stem cell maintenance Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Cdc73/Paf1 complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	RNA polymerase II core binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 531	530	Parafibromin		PRO_0000191805
Regions
	Region	200 – 531	332	Interaction with POLR2A and PAF1 By similarity
	Region	200 – 250	51	Interaction with CTNNB1 By similarity
	Motif	125 – 139	15	Nuclear localization signal By similarity
	Compositional bias	361 – 364	4	Poly-Ile
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	212	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q4V8C8 [UniParc]. Last modified July 5, 2005. Version 1. Checksum: C99EFF505A4C48FD	FASTA	531	60,603
	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 RSLSEAMLVE 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

[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC097445 mRNA. Translation: AAH97445.1.
IPI	IPI00372006.
RefSeq	NP_001019940.1. NM_001024769.1.
UniGene	Rn.162332.
3D structure databases
ProteinModelPortal	Q4V8C8.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000004495.
PTM databases
PhosphoSite	Q4V8C8.
Proteomic databases
PaxDb	Q4V8C8.
PRIDE	Q4V8C8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	304832.
KEGG	rno:304832.
UCSC	RGD:1311766. rat.
Organism-specific databases
CTD	79577.
RGD	1311766. Cdc73.
Phylogenomic databases
eggNOG	COG5157.
HOGENOM	HOG000007819.
HOVERGEN	HBG055033.
InParanoid	Q4V8C8.
KO	K15175.
OrthoDB	EOG4PC9RV.
Gene expression databases
Genevestigator	Q4V8C8.
GermOnline	ENSRNOG00000003258. Rattus norvegicus.
Family and domain databases
InterPro	IPR007852. RNA_pol_access_fac_Cdc73. [Graphical view]
PANTHER	PTHR12466. PTHR12466. 1 hit.
Pfam	PF05179. CDC73. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	653711.

Entry information

Entry name

CDC73_RAT

Accession

Primary (citable) accession number: Q4V8C8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	July 5, 2005
Last modified:	April 3, 2013
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program