RUSD4_HUMAN
ID RUSD4_HUMAN Reviewed; 377 AA.
AC Q96CM3; E9PML2; Q96K56;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Pseudouridylate synthase RPUSD4, mitochondrial {ECO:0000305};
DE EC=5.4.99.- {ECO:0000269|PubMed:27974379};
DE AltName: Full=RNA pseudouridylate synthase domain-containing protein 4 {ECO:0000305};
DE Flags: Precursor;
GN Name=RPUSD4 {ECO:0000303|PubMed:27667664, ECO:0000312|HGNC:HGNC:25898};
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] (ISOFORMS 1 AND 2), AND VARIANT
RP ARG-44.
RC TISSUE=Mammary gland, and Neuroblastoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=23435261; DOI=10.1038/nmeth.2377;
RA Stadler C., Rexhepaj E., Singan V.R., Murphy R.F., Pepperkok R., Uhlen M.,
RA Simpson J.C., Lundberg E.;
RT "Immunofluorescence and fluorescent-protein tagging show high correlation
RT for protein localization in mammalian cells.";
RL Nat. Methods 10:315-323(2013).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [6]
RP SUBUNIT, AND FUNCTION.
RX PubMed=27667664; DOI=10.1016/j.cmet.2016.08.017;
RA Arroyo J.D., Jourdain A.A., Calvo S.E., Ballarano C.A., Doench J.G.,
RA Root D.E., Mootha V.K.;
RT "A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative
RT Phosphorylation.";
RL Cell Metab. 24:875-885(2016).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=27974379; DOI=10.15252/embr.201643391;
RA Antonicka H., Choquet K., Lin Z.Y., Gingras A.C., Kleinman C.L.,
RA Shoubridge E.A.;
RT "A pseudouridine synthase module is essential for mitochondrial protein
RT synthesis and cell viability.";
RL EMBO Rep. 18:28-38(2017).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=28082677; DOI=10.1074/jbc.m116.771105;
RA Zaganelli S., Rebelo-Guiomar P., Maundrell K., Rozanska A., Pierredon S.,
RA Powell C.A., Jourdain A.A., Hulo N., Lightowlers R.N.,
RA Chrzanowska-Lightowlers Z.M., Minczuk M., Martinou J.C.;
RT "The pseudouridine synthase RPUSD4 is an essential component of
RT mitochondrial RNA granules.";
RL J. Biol. Chem. 292:4519-4532(2017).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=35051350; DOI=10.1016/j.molcel.2021.12.023;
RA Martinez N.M., Su A., Burns M.C., Nussbacher J.K., Schaening C., Sathe S.,
RA Yeo G.W., Gilbert W.V.;
RT "Pseudouridine synthases modify human pre-mRNA co-transcriptionally and
RT affect pre-mRNA processing.";
RL Mol. Cell 82:645-659(2022).
RN [10] {ECO:0007744|PDB:5UBA}
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 89-365.
RA Zeng H., Dong A., Tempel W., Bountra C., Arrowsmith C.H., Edwards A.M.,
RA Brown P.J., Wu H.;
RT "The crystal structure of human pseudouridylate synthase domain containing
RT 4.";
RL Submitted (DEC-2016) to the PDB data bank.
CC -!- FUNCTION: Catalyzes uridine to pseudouridine isomerization
CC (pseudouridylation) of different mitochondrial RNA substrates
CC (PubMed:27974379, PubMed:28082677). Acts on position 1397 in 16S
CC mitochondrial ribosomal RNA (16S mt-rRNA) (PubMed:27974379). This
CC modification is required for the assembly of 16S mt-rRNA into a
CC functional mitochondrial ribosome (PubMed:27974379). As a component of
CC a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3,
CC RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA, controls 16S mt-rRNA abundance
CC and is required for intra-mitochondrial translation (PubMed:27667664).
CC Acts on position 39 in mitochondrial tRNA(Phe) (PubMed:28082677). Also
CC catalyzes pseudouridylation of mRNAs in nucleus: acts as a regulator of
CC pre-mRNA splicing by mediating pseudouridylation of pre-mRNAs at
CC locations associated with alternatively spliced regions
CC (PubMed:35051350). Pseudouridylation of pre-mRNAs near splice sites
CC directly regulates mRNA splicing and mRNA 3'-end processing
CC (PubMed:35051350). {ECO:0000269|PubMed:27667664,
CC ECO:0000269|PubMed:27974379, ECO:0000269|PubMed:28082677,
CC ECO:0000269|PubMed:35051350}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=uridine in 5S rRNA = pseudouridine in 5S rRNA;
CC Xref=Rhea:RHEA:47036, Rhea:RHEA-COMP:11730, Rhea:RHEA-COMP:11731,
CC ChEBI:CHEBI:65314, ChEBI:CHEBI:65315;
CC Evidence={ECO:0000305|PubMed:27974379};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a uridine in tRNA = a pseudouridine in tRNA;
CC Xref=Rhea:RHEA:54572, Rhea:RHEA-COMP:13339, Rhea:RHEA-COMP:13934,
CC ChEBI:CHEBI:65314, ChEBI:CHEBI:65315;
CC Evidence={ECO:0000305|PubMed:28082677};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a uridine in mRNA = a pseudouridine in mRNA;
CC Xref=Rhea:RHEA:56644, Rhea:RHEA-COMP:14658, Rhea:RHEA-COMP:14659,
CC ChEBI:CHEBI:65314, ChEBI:CHEBI:65315;
CC Evidence={ECO:0000269|PubMed:35051350};
CC -!- SUBUNIT: Interacts with 16S mt-rRNA, mt-tRNA(Phe) and mt-tRNA(Met)
CC (PubMed:28082677). Forms a regulatory protein-RNA complex, consisting
CC of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA
CC (PubMed:27667664). {ECO:0000269|PubMed:27667664,
CC ECO:0000269|PubMed:28082677}.
CC -!- INTERACTION:
CC Q96CM3; P01100: FOS; NbExp=4; IntAct=EBI-7825200, EBI-852851;
CC Q96CM3; P50440: GATM; NbExp=3; IntAct=EBI-7825200, EBI-2552594;
CC Q96CM3; Q00613: HSF1; NbExp=3; IntAct=EBI-7825200, EBI-719620;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:23435261, ECO:0000269|PubMed:27974379,
CC ECO:0000269|PubMed:28082677}. Nucleus {ECO:0000269|PubMed:23435261}.
CC Cytoplasm {ECO:0000269|PubMed:23435261}. Note=Mainly localizes to
CC mitochondrion (PubMed:23435261, PubMed:27974379, PubMed:28082677).
CC Localizes to mitochondrial RNA granules, platforms for post-
CC transcriptional RNA modification and ribosome assembly
CC (PubMed:27974379, PubMed:28082677). Also found in nucleus and cytoplasm
CC (PubMed:23435261). {ECO:0000269|PubMed:23435261,
CC ECO:0000269|PubMed:27974379, ECO:0000269|PubMed:28082677}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96CM3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96CM3-2; Sequence=VSP_047375;
CC -!- SIMILARITY: Belongs to the pseudouridine synthase RluA family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AK308059; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK027400; BAB55086.1; -; mRNA.
DR EMBL; AK308059; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC014131; AAH14131.1; -; mRNA.
DR CCDS; CCDS53721.1; -. [Q96CM3-2]
DR CCDS; CCDS8469.1; -. [Q96CM3-1]
DR RefSeq; NP_001138299.1; NM_001144827.1. [Q96CM3-2]
DR RefSeq; NP_116184.2; NM_032795.2. [Q96CM3-1]
DR PDB; 5UBA; X-ray; 1.54 A; A=89-365.
DR PDBsum; 5UBA; -.
DR AlphaFoldDB; Q96CM3; -.
DR SMR; Q96CM3; -.
DR BioGRID; 124324; 255.
DR IntAct; Q96CM3; 26.
DR MINT; Q96CM3; -.
DR STRING; 9606.ENSP00000298317; -.
DR iPTMnet; Q96CM3; -.
DR PhosphoSitePlus; Q96CM3; -.
DR BioMuta; RPUSD4; -.
DR DMDM; 74731354; -.
DR EPD; Q96CM3; -.
DR jPOST; Q96CM3; -.
DR MassIVE; Q96CM3; -.
DR MaxQB; Q96CM3; -.
DR PaxDb; Q96CM3; -.
DR PeptideAtlas; Q96CM3; -.
DR PRIDE; Q96CM3; -.
DR ProteomicsDB; 22146; -.
DR ProteomicsDB; 76192; -. [Q96CM3-1]
DR Antibodypedia; 50828; 49 antibodies from 13 providers.
DR DNASU; 84881; -.
DR Ensembl; ENST00000298317.9; ENSP00000298317.4; ENSG00000165526.9. [Q96CM3-1]
DR Ensembl; ENST00000533628.5; ENSP00000433065.1; ENSG00000165526.9. [Q96CM3-2]
DR GeneID; 84881; -.
DR KEGG; hsa:84881; -.
DR MANE-Select; ENST00000298317.9; ENSP00000298317.4; NM_032795.3; NP_116184.2.
DR UCSC; uc001qde.3; human. [Q96CM3-1]
DR CTD; 84881; -.
DR GeneCards; RPUSD4; -.
DR HGNC; HGNC:25898; RPUSD4.
DR HPA; ENSG00000165526; Tissue enhanced (skeletal muscle, tongue).
DR neXtProt; NX_Q96CM3; -.
DR OpenTargets; ENSG00000165526; -.
DR PharmGKB; PA134875000; -.
DR VEuPathDB; HostDB:ENSG00000165526; -.
DR eggNOG; KOG1919; Eukaryota.
DR GeneTree; ENSGT00940000158436; -.
DR HOGENOM; CLU_016902_2_1_1; -.
DR InParanoid; Q96CM3; -.
DR OMA; RMRIAKH; -.
DR OrthoDB; 1378690at2759; -.
DR PhylomeDB; Q96CM3; -.
DR TreeFam; TF337899; -.
DR BRENDA; 5.4.99.B22; 2681.
DR PathwayCommons; Q96CM3; -.
DR SignaLink; Q96CM3; -.
DR BioGRID-ORCS; 84881; 318 hits in 1086 CRISPR screens.
DR ChiTaRS; RPUSD4; human.
DR GenomeRNAi; 84881; -.
DR Pharos; Q96CM3; Tdark.
DR PRO; PR:Q96CM3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96CM3; protein.
DR Bgee; ENSG00000165526; Expressed in skeletal muscle tissue of rectus abdominis and 184 other tissues.
DR ExpressionAtlas; Q96CM3; baseline and differential.
DR Genevisible; Q96CM3; HS.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0035770; C:ribonucleoprotein granule; IDA:FlyBase.
DR GO; GO:1990400; F:mitochondrial ribosomal large subunit rRNA binding; IDA:FlyBase.
DR GO; GO:0009982; F:pseudouridine synthase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IDA:FlyBase.
DR GO; GO:0000455; P:enzyme-directed rRNA pseudouridine synthesis; IBA:GO_Central.
DR GO; GO:0070902; P:mitochondrial tRNA pseudouridine synthesis; IMP:FlyBase.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:1990481; P:mRNA pseudouridine synthesis; IDA:UniProtKB.
DR GO; GO:0070131; P:positive regulation of mitochondrial translation; IMP:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR CDD; cd02869; PseudoU_synth_RluA_like; 1.
DR InterPro; IPR020103; PsdUridine_synth_cat_dom_sf.
DR InterPro; IPR006224; PsdUridine_synth_RluC/D_CS.
DR InterPro; IPR006145; PsdUridine_synth_RsuA/RluA.
DR Pfam; PF00849; PseudoU_synth_2; 1.
DR SUPFAM; SSF55120; SSF55120; 1.
DR PROSITE; PS01129; PSI_RLU; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Isomerase;
KW Mitochondrion; mRNA processing; mRNA splicing; Nucleus; Reference proteome;
KW rRNA processing; Transit peptide; tRNA processing.
FT TRANSIT 1..15
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 16..377
FT /note="Pseudouridylate synthase RPUSD4, mitochondrial"
FT /id="PRO_0000300825"
FT COILED 36..62
FT /evidence="ECO:0000255"
FT ACT_SITE 153
FT /evidence="ECO:0000250|UniProtKB:P0AA39"
FT VAR_SEQ 209..239
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047375"
FT VARIANT 44
FT /note="Q -> R (in dbSNP:rs2282580)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_034887"
FT VARIANT 58
FT /note="D -> G (in dbSNP:rs35468281)"
FT /id="VAR_034888"
FT VARIANT 155
FT /note="E -> D (in dbSNP:rs34809853)"
FT /id="VAR_034889"
FT VARIANT 209
FT /note="A -> V (in dbSNP:rs35157957)"
FT /id="VAR_034890"
FT CONFLICT 29
FT /note="K -> E (in Ref. 1; BAB55086)"
FT /evidence="ECO:0000305"
FT HELIX 89..97
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:5UBA"
FT HELIX 127..139
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 156..165
FT /evidence="ECO:0007829|PDB:5UBA"
FT HELIX 166..177
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 181..191
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 245..252
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 254..265
FT /evidence="ECO:0007829|PDB:5UBA"
FT HELIX 270..279
FT /evidence="ECO:0007829|PDB:5UBA"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:5UBA"
FT HELIX 302..308
FT /evidence="ECO:0007829|PDB:5UBA"
FT HELIX 312..317
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 322..329
FT /evidence="ECO:0007829|PDB:5UBA"
FT STRAND 339..342
FT /evidence="ECO:0007829|PDB:5UBA"
FT HELIX 347..355
FT /evidence="ECO:0007829|PDB:5UBA"
SQ SEQUENCE 377 AA; 42205 MW; 6B5E7DA71212D404 CRC64;
MAAPRWSASG PWIRGNGQGC GSLFTLVSKP FCAAAAASTA INAQRLAEKL RAQKREQDTK
KEPVSTNAVQ RRVQEIVRFT RQLQRVHPNV LAKALTRGIL HQDKNLVVIN KPYGLPVHGG
PGVQLCITDV LPILAKMLHG HKAEPLHLCH RLDKETTGVM VLAWDKDMAH QVQELFRTRQ
VVKKYWAITV HVPMPSAGVV DIPIVEKEAQ GQQQHHKMTL SPSYRMDDGK MVKVRRSRNA
QVAVTQYQVL SSTLSSALVE LQPITGIKHQ LRVHLSFGLD CPILGDHKYS DWNRLAPQKL
SVGTLKKLGL EQSKARYIPL HLHARQLILP ALGSGKEELN LVCKLPRFFV HSLHRLRLEM
PNEDQNENNE AKCLGAQ
