ID UTP25_HUMAN Reviewed; 756 AA. AC Q68CQ4; O75992; Q4VY00; Q63HL9; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2006, sequence version 2. DT 03-MAY-2023, entry version 137. DE RecName: Full=U3 small nucleolar RNA-associated protein 25 homolog {ECO:0000305}; DE AltName: Full=Digestive organ expansion factor homolog; DE AltName: Full=UTP25 small subunit processor component {ECO:0000312|HGNC:HGNC:28440}; GN Name=UTP25 {ECO:0000312|HGNC:HGNC:28440}; GN Synonyms=C1orf107, DEF {ECO:0000303|PubMed:23357851}, GN DIEXF {ECO:0000303|PubMed:25007945}; 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 [LARGE SCALE MRNA], AND VARIANTS GLU-67 AND ASP-111. RC TISSUE=Endometrial adenocarcinoma, and Fetal kidney; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cervix; 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 [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [5] 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 [6] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=22002106; DOI=10.1074/mcp.m111.013680; RA Ahmad Y., Boisvert F.M., Lundberg E., Uhlen M., Lamond A.I.; RT "Systematic analysis of protein pools, isoforms, and modifications RT affecting turnover and subcellular localization."; RL Mol. Cell. Proteomics 11:M111.013680.01-M111.013680.15(2012). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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 [8] RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY MIR195. RX PubMed=25007945; DOI=10.1186/1471-230x-14-123; RA Lei H., Tang J., Li H., Zhang H., Lu C., Chen H., Li W., Xia Y., Tang W.; RT "MiR-195 affects cell migration and cell proliferation by down-regulating RT DIEXF in Hirschsprung's disease."; RL BMC Gastroenterol. 14:123-123(2014). RN [9] RP FUNCTION, INTERACTION WITH CAPN3, AND PHOSPHORYLATION AT SER-50; SER-58 AND RP SER-62. 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 [10] RP VARIANTS GLU-67 AND ASP-111, CHARACTERIZATION OF VARIANTS GLU-67 AND RP ASP-111, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CAPN3. 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). CC -!- FUNCTION: Component of the ribosomal small subunit processome for the CC biogenesis of ribosomes, functions in pre-ribosomal RNA (pre-rRNA) CC processing (By similarity). Essential for embryonic development in part CC through the regulation of p53 pathway. Controls the expansion growth of CC digestive organs and liver (PubMed:25007945, PubMed:27657329, CC PubMed:23357851). Also involved in the sympathetic neuronal development CC (By similarity). Mediates, with CAPN3, the proteasome-independent CC degradation of p53/TP53 (PubMed:23357851, PubMed:27657329). CC {ECO:0000250|UniProtKB:Q6PEH4, ECO:0000269|PubMed:23357851, CC ECO:0000269|PubMed:25007945, ECO:0000269|PubMed:27657329}. CC -!- SUBUNIT: Interacts with CAPN3; the interaction is required for CAPN3 CC translocation to the nucleolus. {ECO:0000269|PubMed:23357851, CC ECO:0000269|PubMed:27657329}. CC -!- INTERACTION: CC Q68CQ4; Q96CW1: AP2M1; NbExp=5; IntAct=EBI-747711, EBI-297683; CC Q68CQ4; Q8NHQ1: CEP70; NbExp=8; IntAct=EBI-747711, EBI-739624; CC Q68CQ4; P43364-2: MAGEA11; NbExp=3; IntAct=EBI-747711, EBI-10178634; CC Q68CQ4; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-747711, EBI-16439278; CC Q68CQ4; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-747711, EBI-10172526; CC Q68CQ4; Q8TD10: MIPOL1; NbExp=4; IntAct=EBI-747711, EBI-2548751; CC Q68CQ4; Q96T51: RUFY1; NbExp=5; IntAct=EBI-747711, EBI-3941207; CC Q68CQ4; Q96T51-2: RUFY1; NbExp=6; IntAct=EBI-747711, EBI-12192715; CC Q68CQ4; Q9BVG3: TRIM62; NbExp=3; IntAct=EBI-747711, EBI-6929619; CC Q68CQ4; Q9C026: TRIM9; NbExp=3; IntAct=EBI-747711, EBI-720828; CC Q68CQ4; Q96DT7-3: ZBTB10; NbExp=3; IntAct=EBI-747711, EBI-12017160; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:22002106, CC ECO:0000269|PubMed:27657329}. CC -!- TISSUE SPECIFICITY: Expressed in colon. {ECO:0000269|PubMed:25007945}. CC -!- INDUCTION: Down-regulated by the miRNA MIR195. CC {ECO:0000269|PubMed:25007945}. CC -!- PTM: Phosphorylated. Phosphorylation is required to promote p53/TP53 CC degradation in the nucleolus which promotes cell cycle progression and CC liver development. {ECO:0000269|PubMed:27657329}. CC -!- SIMILARITY: Belongs to the UTP25 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CR749825; CAH18684.1; -; mRNA. DR EMBL; BX648514; CAH56170.1; -; mRNA. DR EMBL; AL022398; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC022964; AAH22964.1; -; mRNA. DR CCDS; CCDS1493.1; -. DR RefSeq; NP_055203.4; NM_014388.6. DR AlphaFoldDB; Q68CQ4; -. DR BioGRID; 117972; 101. DR IntAct; Q68CQ4; 21. DR MINT; Q68CQ4; -. DR STRING; 9606.ENSP00000419005; -. DR GlyGen; Q68CQ4; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q68CQ4; -. DR PhosphoSitePlus; Q68CQ4; -. DR SwissPalm; Q68CQ4; -. DR BioMuta; DIEXF; -. DR DMDM; 117949399; -. DR EPD; Q68CQ4; -. DR jPOST; Q68CQ4; -. DR MassIVE; Q68CQ4; -. DR MaxQB; Q68CQ4; -. DR PaxDb; Q68CQ4; -. DR PeptideAtlas; Q68CQ4; -. DR ProteomicsDB; 66020; -. DR Antibodypedia; 20703; 84 antibodies from 21 providers. DR DNASU; 27042; -. DR Ensembl; ENST00000491415.7; ENSP00000419005.1; ENSG00000117597.18. DR GeneID; 27042; -. DR KEGG; hsa:27042; -. DR MANE-Select; ENST00000491415.7; ENSP00000419005.1; NM_014388.7; NP_055203.4. DR UCSC; uc001hhr.3; human. DR AGR; HGNC:28440; -. DR CTD; 27042; -. DR DisGeNET; 27042; -. DR GeneCards; UTP25; -. DR HGNC; HGNC:28440; UTP25. DR HPA; ENSG00000117597; Low tissue specificity. DR MIM; 619663; gene. DR neXtProt; NX_Q68CQ4; -. DR OpenTargets; ENSG00000117597; -. DR PharmGKB; PA142672491; -. DR VEuPathDB; HostDB:ENSG00000117597; -. DR eggNOG; KOG2340; Eukaryota. DR GeneTree; ENSGT00390000000709; -. DR HOGENOM; CLU_018705_1_1_1; -. DR InParanoid; Q68CQ4; -. DR OMA; KYFRQTI; -. DR OrthoDB; 5473087at2759; -. DR PhylomeDB; Q68CQ4; -. DR TreeFam; TF105930; -. DR PathwayCommons; Q68CQ4; -. DR Reactome; R-HSA-6790901; rRNA modification in the nucleus and cytosol. DR Reactome; R-HSA-6791226; Major pathway of rRNA processing in the nucleolus and cytosol. DR SignaLink; Q68CQ4; -. DR BioGRID-ORCS; 27042; 677 hits in 1151 CRISPR screens. DR ChiTaRS; DIEXF; human. DR GenomeRNAi; 27042; -. DR Pharos; Q68CQ4; Tbio. DR PRO; PR:Q68CQ4; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q68CQ4; protein. DR Bgee; ENSG00000117597; Expressed in endothelial cell and 208 other tissues. DR ExpressionAtlas; Q68CQ4; baseline and differential. DR Genevisible; Q68CQ4; HS. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0032040; C:small-subunit processome; IBA:GO_Central. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0019843; F:rRNA binding; IBA:GO_Central. DR GO; GO:0034511; F:U3 snoRNA binding; IBA:GO_Central. DR GO; GO:0048568; P:embryonic organ development; IMP:UniProtKB. DR GO; GO:0000462; P:maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:GO_Central. DR GO; GO:0040019; P:positive regulation of embryonic development; ISS:UniProtKB. DR GO; GO:0030163; P:protein catabolic process; IMP:UniProtKB. DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB. DR GO; GO:1902570; P:protein localization to nucleolus; IDA:UniProtKB. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR010678; UTP25. DR PANTHER; PTHR12933; ORF PROTEIN-RELATED; 1. DR PANTHER; PTHR12933:SF0; U3 SMALL NUCLEOLAR RNA-ASSOCIATED PROTEIN 25 HOMOLOG; 1. DR Pfam; PF06862; UTP25; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. PE 1: Evidence at protein level; KW Developmental protein; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..756 FT /note="U3 small nucleolar RNA-associated protein 25 FT homolog" FT /id="PRO_0000254149" FT REGION 1..185 FT /note="Promotes p53/TP53 degradation" FT /evidence="ECO:0000250|UniProtKB:Q6PEH4" FT REGION 1..159 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 573..635 FT /note="Promotes p53/TP53 degradation" FT /evidence="ECO:0000250|UniProtKB:Q6PEH4" FT REGION 636..697 FT /note="Represses p53/TP53 degradation" FT /evidence="ECO:0000250|UniProtKB:Q6PEH4" FT COMPBIAS 1..17 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 19..42 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 83..124 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 10 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 50 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:27657329" FT MOD_RES 52 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PEH4" FT MOD_RES 58 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:27657329" FT MOD_RES 60 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PEH4" FT MOD_RES 62 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:27657329" FT MOD_RES 64 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PEH4" FT VARIANT 67 FT /note="Q -> E (decreases degradation of p53/TP53; FT dbSNP:rs585627)" FT /evidence="ECO:0000269|PubMed:17974005, FT ECO:0000269|PubMed:23357851" FT /id="VAR_028827" FT VARIANT 111 FT /note="G -> D (decreases degradation of p53/TP53; FT dbSNP:rs61747285)" FT /evidence="ECO:0000269|PubMed:17974005, FT ECO:0000269|PubMed:23357851" FT /id="VAR_084648" FT CONFLICT 258 FT /note="T -> A (in Ref. 1; CAH56170)" FT /evidence="ECO:0000305" SQ SEQUENCE 756 AA; 87055 MW; A8821B0AC4BF4067 CRC64; MGKRGSRSQS QLLNTLTKKQ KKHLRDFGEE HPFYDRVSRK EAKPQICQLS ESSDSSDSES DSESEPQQVS GYHRLLATLK NVSEEEEEDE EEEEEEDSIV DDAEMNDEDG GSDVSVEEEM AAESTESPEN VALSADPEGK EDGEEPPGTS QTSPEEFTDA KHESLFSLET NFLEEESGDN SSLKASQDPF LQHVNKELKE KAIQAVATNP KTTHELKWPI LGQLFFSSKF QKLETFKPPK DIDLKSLHLQ KPLESTWTKT NSQFLSGPQK SSSPFTPLQK ELFLIMNSYR DLFYPERTAL KNGEEIRHVY CLHVINHILK ANAQVLGNNS RRRSQKFGVG DDDDFRDQGL TRPKVLIVVP FREAALRVVQ LFISLLEGDS KKKIIVSNKK RFQGEYGSDP EERPPNLKRP EDYEAVFVGN IDDHFRIGVA ILQRSIRLYA PFYSSDILIA SPLGLRTIIG GEGEKKRDFD FLSSIELLII DQADIYLMQN WEHVLHLMNH MNLLPLDSHG VDFSRVRMWS LNNWSKYYRQ TLLFGALQDA QINSVFNKYC VNMQGQVAVR NVPMTGSISH VLVQLPHVFQ RMEAENLASV IDARFNFFVN KILPQYRDAV MSHTLIYIPS YFDFVRLRNY FKKEELNFTH ICEYTQKSGV SRARHFFLQG EKQFLLFTER FHFYKRYTIK GIRNLIFYEL PTYPHFYSEI CNMLRATNRG EEATWTCTVL YSKYDAQRLA AVVGVERAAQ MLQSNKNVHL FITGEK //