UTP25_DANRE
ID UTP25_DANRE Reviewed; 753 AA.
AC Q6PEH4; Q8JHI5;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=U3 small nucleolar RNA-associated protein 25 homolog;
DE AltName: Full=Digestive organ expansion factor;
DE AltName: Full=UTP25 small subunit processor component;
GN Name=utp25;
GN Synonyms=def {ECO:0000303|PubMed:16322560, ECO:0000303|PubMed:23357851,
GN ECO:0000303|PubMed:27657329}, diexf;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND FUNCTION.
RC TISSUE=Embryo;
RX PubMed=12006978; DOI=10.1038/ng896;
RA Golling G., Amsterdam A., Sun Z., Antonelli M., Maldonado E., Chen W.,
RA Burgess S., Haldi M., Artzt K., Farrington S., Lin S.-Y., Nissen R.M.,
RA Hopkins N.;
RT "Insertional mutagenesis in zebrafish rapidly identifies genes essential
RT for early vertebrate development.";
RL Nat. Genet. 31:135-140(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=16322560; DOI=10.1101/gad.1366405;
RA Chen J., Ruan H., Ng S.M., Gao C., Soo H.M., Wu W., Zhang Z., Wen Z.,
RA Lane D.P., Peng J.;
RT "Loss of function of def selectively up-regulates Delta113p53 expression to
RT arrest expansion growth of digestive organs in zebrafish.";
RL Genes Dev. 19:2900-2911(2005).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=23357851; DOI=10.1038/cr.2013.16;
RA Tao T., Shi H., Guan Y., Huang D., Chen Y., Lane D.P., Chen J., Peng J.;
RT "Def defines a conserved nucleolar pathway that leads p53 to proteasome-
RT independent degradation.";
RL Cell Res. 23:620-634(2013).
RN [5]
RP FUNCTION, INTERACTION WITH CAPN3, PHOSPHORYLATION AT SER-50; SER-58;
RP SER-62; SER-87 AND SER-92, AND MUTAGENESIS OF SER-58; SER-62; SER-87 AND
RP SER-92.
RX PubMed=27657329; DOI=10.1371/journal.pbio.1002555;
RA Guan Y., Huang D., Chen F., Gao C., Tao T., Shi H., Zhao S., Liao Z.,
RA Lo L.J., Wang Y., Chen J., Peng J.;
RT "Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle
RT Progression through Def Recruitment of Calpain3.";
RL PLoS Biol. 14:e1002555-e1002555(2016).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28263972; DOI=10.1038/onc.2016.527;
RA Tao T., Sondalle S.B., Shi H., Zhu S., Perez-Atayde A.R., Peng J.,
RA Baserga S.J., Look A.T.;
RT "The pre-rRNA processing factor DEF is rate limiting for the pathogenesis
RT of MYCN-driven neuroblastoma.";
RL Oncogene 36:3852-3867(2017).
CC -!- FUNCTION: Component of the ribosomal small subunit processome for the
CC biogenesis of ribosomes, functions in pre-ribosomal RNA (pre-rRNA)
CC processing (PubMed:28263972). Essential for embryonic development in
CC part through the regulation of p53 pathway. Required for the expansion
CC growth of intestine, liver and exocrine pancreas, but not endocrine
CC pancreas. May not play a major role during the early stage of
CC endodermal organogenesis. Also involved in the sympathetic neuronal
CC development (PubMed:28263972). Triggers the degradation of p53/TP53 and
CC Delta113p53 isoform in a ubiquitination pathway independent way
CC (PubMed:23357851). Mediates, with CAPN3, the proteasome-independent
CC degradation of p53/TP53 (PubMed:23357851, PubMed:27657329).
CC {ECO:0000269|PubMed:12006978, ECO:0000269|PubMed:16322560,
CC ECO:0000269|PubMed:23357851, ECO:0000269|PubMed:27657329,
CC ECO:0000269|PubMed:28263972}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:16322560,
CC ECO:0000269|PubMed:23357851}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in digestive organs at the later
CC stage of organogenesis. Expressed in liver, gut and exocrine pancreas,
CC but not in the islets. {ECO:0000269|PubMed:16322560,
CC ECO:0000269|PubMed:23357851}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in the embryos at 12 hpf and 1
CC dpf and expressed at high level at 3 dpf and 4 dpf, but at a lower
CC level at 5 dpf. At 2 dpf, ubiquitously expressed, but enriched in the
CC mid and hindbrain boundary. Through 3-5 dpf, expressed mainly in the
CC gut, liver, pancreas and pharynx. {ECO:0000269|PubMed:16322560}.
CC -!- PTM: Phosphorylated. Phosphorylation is required to facilitate the
CC nucleolar localzsation of CAPN3 and promote p53/TP53 degradation in the
CC nucleolus which promotes cell cycle progression and liver development.
CC {ECO:0000269|PubMed:27657329}.
CC -!- DISRUPTION PHENOTYPE: Confers hypoplastic digestive organs and
CC selectively up-regulates the expression of the Delta113p53 isoform but
CC not p53, resulting in compromised organ growth in def mutant fish. Loss
CC of function affects sympathetic neuronal development (PubMed:27657329).
CC {ECO:0000269|PubMed:16322560, ECO:0000269|PubMed:23357851,
CC ECO:0000269|PubMed:27657329}.
CC -!- SIMILARITY: Belongs to the UTP25 family. {ECO:0000305}.
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DR EMBL; AF506211; AAM34655.1; -; mRNA.
DR EMBL; BC058062; AAH58062.1; -; mRNA.
DR RefSeq; NP_775380.1; NM_173273.1.
DR AlphaFoldDB; Q6PEH4; -.
DR STRING; 7955.ENSDARP00000011386; -.
DR PaxDb; Q6PEH4; -.
DR Ensembl; ENSDART00000026726; ENSDARP00000011386; ENSDARG00000017696.
DR GeneID; 286787; -.
DR KEGG; dre:286787; -.
DR CTD; 27042; -.
DR ZFIN; ZDB-GENE-021217-2; utp25.
DR eggNOG; KOG2340; Eukaryota.
DR GeneTree; ENSGT00390000000709; -.
DR HOGENOM; CLU_018705_1_1_1; -.
DR InParanoid; Q6PEH4; -.
DR OMA; KYFRQTI; -.
DR OrthoDB; 257318at2759; -.
DR PhylomeDB; Q6PEH4; -.
DR TreeFam; TF105930; -.
DR Reactome; R-DRE-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR PRO; PR:Q6PEH4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 13.
DR Bgee; ENSDARG00000017696; Expressed in gastrula and 30 other tissues.
DR ExpressionAtlas; Q6PEH4; baseline.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:ZFIN.
DR GO; GO:0032040; C:small-subunit processome; IBA:GO_Central.
DR GO; GO:0019843; F:rRNA binding; IBA:GO_Central.
DR GO; GO:0034511; F:U3 snoRNA binding; IBA:GO_Central.
DR GO; GO:0048546; P:digestive tract morphogenesis; IMP:ZFIN.
DR GO; GO:0048568; P:embryonic organ development; IMP:UniProtKB.
DR GO; GO:0031017; P:exocrine pancreas development; IMP:ZFIN.
DR GO; GO:0090594; P:inflammatory response to wounding; IMP:ZFIN.
DR GO; GO:0000462; P:maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IMP:ZFIN.
DR GO; GO:0035265; P:organ growth; IMP:ZFIN.
DR GO; GO:0030163; P:protein catabolic process; IGI:ZFIN.
DR GO; GO:0031648; P:protein destabilization; IMP:ZFIN.
DR GO; GO:1902570; P:protein localization to nucleolus; IDA:UniProtKB.
DR GO; GO:0042254; P:ribosome biogenesis; IMP:ZFIN.
DR GO; GO:0048485; P:sympathetic nervous system development; IMP:ZFIN.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR010678; UTP25.
DR PANTHER; PTHR12933; PTHR12933; 1.
DR Pfam; PF06862; UTP25; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..753
FT /note="U3 small nucleolar RNA-associated protein 25
FT homolog"
FT /id="PRO_0000254153"
FT REGION 1..189
FT /note="Promotes p53/TP53 degradation"
FT /evidence="ECO:0000269|PubMed:23357851"
FT REGION 1..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 377..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 566..627
FT /note="Promotes p53/TP53 degradation"
FT /evidence="ECO:0000269|PubMed:23357851"
FT REGION 628..689
FT /note="Represses p53/TP53 degradation"
FT /evidence="ECO:0000269|PubMed:23357851"
FT COMPBIAS 1..44
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..128
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..148
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27657329"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27657329"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27657329"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27657329"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27657329"
FT MUTAGEN 58
FT /note="S->A: Decreases p53/TP53 degradation, cell cycle
FT progression and liver development; when associated with A-
FT 62."
FT /evidence="ECO:0000269|PubMed:27657329"
FT MUTAGEN 62
FT /note="S->A: Decreases p53/TP53 degradation, cell cycle
FT progression and liver development; when associated with A-
FT 58."
FT /evidence="ECO:0000269|PubMed:27657329"
FT MUTAGEN 87
FT /note="S->A: Decreases nucleolar localzsation of CAPN3,
FT p53/TP53 degradation, cell cycle progression and liver
FT development; when associated with A-92."
FT /evidence="ECO:0000269|PubMed:27657329"
FT MUTAGEN 92
FT /note="S->A: Decreases nucleolar localzsation of CAPN3,
FT p53/TP53 degradation, cell cycle progression and liver
FT development; when associated with A-87."
FT /evidence="ECO:0000269|PubMed:27657329"
FT CONFLICT 7
FT /note="G -> C (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 49
FT /note="D -> E (in Ref. 2; AAH58062)"
FT /evidence="ECO:0000305"
FT CONFLICT 79
FT /note="Q -> R (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 116..118
FT /note="EED -> VEE (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="C -> S (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="S -> N (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 415
FT /note="D -> Y (in Ref. 2; AAH58062)"
FT /evidence="ECO:0000305"
FT CONFLICT 447
FT /note="G -> S (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 587
FT /note="F -> S (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 605
FT /note="H -> D (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 611
FT /note="P -> R (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 616
FT /note="F -> L (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 623
FT /note="L -> M (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="A -> V (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 669
FT /note="Y -> H (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
FT CONFLICT 752
FT /note="S -> N (in Ref. 1; AAM34655)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 753 AA; 86802 MW; 9B71909685860B10 CRC64;
MGKRRRGKQE IDNLTKKQKK HLKEFGEQHP FHDKVVERPE KTQILRLPDS PQRPEPDSED
DSDAEQPSAY QKLLSTMIQG DEDDVESEDE ESEEEDNEEE AEVEGDSEEE VEDTDEEDGN
DAEEVLEDKV EETSDKLQKK HPEKTNGDVE ENEEAEMEGE FTDKKNEAAF CLETNMPAEG
EENTAQQEQD EDMFVKHQEI ELSEEEVGRI SQGSKVKTQV KWAKLGVLQC MCPLERFPAI
GQASSAPLPP IHKTLEANWH LLNLPFGAAT DVTELQKEML GLMGTYRDLY LANLSPLKEA
KEVRSAYCLH ALNHVLKANS RVLRNNAKLK ESKNGDEDFR DQGLTRPKVL ILVPFRDGAL
RVVQTFMTLL EPKGKKTDAS NKKRFKEEYG EETDEKPPNL QRPDDYHAVF SGNIDDHFRI
GMSILRHSMR LYAPFYSSDI IIASPLGLRT VLGAEGEKKR DHDFLSSIEL LIVDQADVFL
MQNWEHLLHV LEHLNLQPLD SHGVDFSRVR MWNLNNWAAY YRQTLVFSAI QEPQITNILT
KHCHNYRGQV CSKTIPKIGS ICQVLVQLPH VFQMFHSDSF MDQDARFQFF VDKILPQYRD
SVMSHTFIYV PSYFDFVRLR NYLKKEDVSF ANISEYSQRS EVSRARHYFQ KGEKQFLLFS
ERFHFYKRYT IKGIHNLIFY GLPTYPHFYS EVCNMLQAGV REGGASVSFT CTALYSRYDV
HRLAAITGAD RAAQMLQSKK TTHLFITGEE KST
