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Parafibromin (Cell division cycle protein 73 homolog) (Hyperparathyroidism 2 protein homolog)

 CDC73_RAT               Reviewed;         531 AA.
Q4V8C8;
20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
05-JUL-2005, sequence version 1.
23-MAY-2018, entry version 86.
RecName: Full=Parafibromin;
AltName: Full=Cell division cycle protein 73 homolog;
AltName: Full=Hyperparathyroidism 2 protein homolog;
Name=Cdc73; Synonyms=Hrpt2;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Testis;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
-!- 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
KMT2A/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). {ECO:0000250}.
-!- SUBUNIT: Component of the PAF1 complex, which consists of CDC73,
PAF1, LEO1, CTR9, RTF1 and WDR61 (By similarity). The PAF1 complex
interacts with PHF5A. Within the PAF1 complex interacts directly
with PHF5A (By similarity). Interacts with POLR2A, CPSF1, CPSF4,
CSTF2, KMT2A/MLL1 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. Interacts with PTPN11 (By similarity). Interacts with
SETD5 (By similarity). {ECO:0000250|UniProtKB:Q6P1J9,
ECO:0000250|UniProtKB:Q8JZM7}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
-!- PTM: Phosphorylated. Dephosphorylated by PTPN11.
{ECO:0000250|UniProtKB:Q6P1J9}.
-!- SIMILARITY: Belongs to the CDC73 family. {ECO:0000305}.
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EMBL; BC097445; AAH97445.1; -; mRNA.
RefSeq; NP_001019940.1; NM_001024769.1.
UniGene; Rn.162332; -.
ProteinModelPortal; Q4V8C8; -.
SMR; Q4V8C8; -.
STRING; 10116.ENSRNOP00000004495; -.
iPTMnet; Q4V8C8; -.
PhosphoSitePlus; Q4V8C8; -.
PaxDb; Q4V8C8; -.
PRIDE; Q4V8C8; -.
GeneID; 304832; -.
KEGG; rno:304832; -.
UCSC; RGD:1311766; rat.
CTD; 79577; -.
RGD; 1311766; Cdc73.
eggNOG; KOG3786; Eukaryota.
eggNOG; COG5157; LUCA.
HOGENOM; HOG000007819; -.
HOVERGEN; HBG055033; -.
InParanoid; Q4V8C8; -.
KO; K15175; -.
PhylomeDB; Q4V8C8; -.
PRO; PR:Q4V8C8; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0016593; C:Cdc73/Paf1 complex; ISS:UniProtKB.
GO; GO:0005634; C:nucleus; ISS:UniProtKB.
GO; GO:0000993; F:RNA polymerase II core binding; ISS:UniProtKB.
GO; GO:0001076; F:transcription factor activity, RNA polymerase II transcription factor binding; IBA:GO_Central.
GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
GO; GO:0001711; P:endodermal cell fate commitment; ISS:UniProtKB.
GO; GO:0016570; P:histone modification; IBA:GO_Central.
GO; GO:0006378; P:mRNA polyadenylation; ISS:UniProtKB.
GO; GO:0008285; P:negative regulation of cell proliferation; ISS:UniProtKB.
GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISS:UniProtKB.
GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISS:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; ISS:UniProtKB.
GO; GO:0031442; P:positive regulation of mRNA 3'-end processing; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; ISS:UniProtKB.
GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
GO; GO:0034402; P:recruitment of 3'-end processing factors to RNA polymerase II holoenzyme complex; IBA:GO_Central.
GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB.
GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; IEA:InterPro.
GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
Gene3D; 3.40.50.11990; -; 1.
InterPro; IPR007852; Cdc73/Parafibromin.
InterPro; IPR031336; CDC73_C.
InterPro; IPR038103; CDC73_C_sf.
InterPro; IPR032041; Cdc73_N.
PANTHER; PTHR12466; PTHR12466; 1.
Pfam; PF05179; CDC73_C; 1.
Pfam; PF16050; CDC73_N; 1.
2: Evidence at transcript level;
Acetylation; Cell cycle; Complete proteome; Isopeptide bond; Nucleus;
Phosphoprotein; Reference proteome; Transcription; Tumor suppressor;
Ubl conjugation; Wnt signaling pathway.
INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:Q6P1J9}.
CHAIN 2 531 Parafibromin.
/FTId=PRO_0000191805.
REGION 200 531 Interaction with POLR2A and PAF1.
{ECO:0000250}.
REGION 200 250 Interaction with CTNNB1. {ECO:0000250}.
MOTIF 125 139 Nuclear localization signal.
{ECO:0000250}.
COMPBIAS 361 364 Poly-Ile.
MOD_RES 2 2 N-acetylalanine.
{ECO:0000250|UniProtKB:Q6P1J9}.
MOD_RES 212 212 Phosphoserine.
{ECO:0000250|UniProtKB:Q6P1J9}.
CROSSLNK 198 198 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q6P1J9}.
CROSSLNK 301 301 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q6P1J9}.
CROSSLNK 308 308 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q6P1J9}.
CROSSLNK 321 321 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q6P1J9}.
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


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