RUSD3_HUMAN
ID RUSD3_HUMAN Reviewed; 351 AA.
AC Q6P087; B4DS39; Q6P6A9; Q8N1B2; Q8NAV3;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 3.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Mitochondrial mRNA pseudouridine synthase RPUSD3;
DE EC=5.4.99.- {ECO:0000269|PubMed:27974379};
DE AltName: Full=RNA pseudouridylate synthase domain-containing protein 3;
DE Flags: Precursor;
GN Name=RPUSD3 {ECO:0000303|PubMed:27667664, ECO:0000312|HGNC:HGNC:28437};
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] (ISOFORM 3).
RC TISSUE=Brain;
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=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 8-351 (ISOFORM 2), AND VARIANT HIS-34.
RC TISSUE=Bone marrow, Brain, and Eye;
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 [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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [7]
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 [8]
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 [9]
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 [10]
RP SUBCELLULAR LOCATION.
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).
CC -!- FUNCTION: Catalyzes uridine to pseudouridine isomerization
CC (pseudouridylation) of specific mitochondrial mRNAs (mt-mRNAs), a post-
CC transcriptional modification necessary for their translation. Acts at
CC position 390 in COXI mt-mRNA and at position 697-699 in mitochondrial
CC COXIII mt-mRNA (PubMed:27974379). As a component of a functional
CC protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2,
CC FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S
CC mt-rRNA abundance and may play a role in mitochondrial ribosome
CC biogenesis (PubMed:27667664). {ECO:0000269|PubMed:27667664,
CC ECO:0000269|PubMed:27974379}.
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:0000305|PubMed:27974379};
CC -!- SUBUNIT: Forms a regulatory protein-RNA complex, consisting of RCC1L,
CC NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA.
CC {ECO:0000269|PubMed:27667664}.
CC -!- INTERACTION:
CC Q6P087; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-5458784, EBI-3867333;
CC Q6P087; Q15323: KRT31; NbExp=3; IntAct=EBI-5458784, EBI-948001;
CC Q6P087; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-5458784, EBI-11959885;
CC Q6P087; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-5458784, EBI-10172290;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:27974379}. Note=Localizes to mitochondrial RNA
CC granules, platforms for post-transcriptional RNA modification and
CC ribosome assembly. {ECO:0000269|PubMed:27974379,
CC ECO:0000269|PubMed:28082677}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6P087-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P087-2; Sequence=VSP_027870;
CC Name=3;
CC IsoId=Q6P087-3; Sequence=VSP_027869;
CC -!- SIMILARITY: Belongs to the pseudouridine synthase RluA family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-9 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH62362.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH65741.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK092026; BAC03794.1; -; mRNA.
DR EMBL; AK299556; BAG61501.1; -; mRNA.
DR EMBL; AC018809; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64008.1; -; Genomic_DNA.
DR EMBL; BC032135; AAH32135.1; -; mRNA.
DR EMBL; BC062362; AAH62362.1; ALT_INIT; mRNA.
DR EMBL; BC065741; AAH65741.1; ALT_INIT; mRNA.
DR RefSeq; NP_001136019.1; NM_001142547.1. [Q6P087-2]
DR RefSeq; NP_775930.2; NM_173659.3. [Q6P087-1]
DR AlphaFoldDB; Q6P087; -.
DR SMR; Q6P087; -.
DR BioGRID; 130092; 209.
DR IntAct; Q6P087; 24.
DR MINT; Q6P087; -.
DR STRING; 9606.ENSP00000373331; -.
DR iPTMnet; Q6P087; -.
DR PhosphoSitePlus; Q6P087; -.
DR BioMuta; RPUSD3; -.
DR DMDM; 294862493; -.
DR EPD; Q6P087; -.
DR jPOST; Q6P087; -.
DR MassIVE; Q6P087; -.
DR MaxQB; Q6P087; -.
DR PaxDb; Q6P087; -.
DR PeptideAtlas; Q6P087; -.
DR PRIDE; Q6P087; -.
DR ProteomicsDB; 66804; -. [Q6P087-1]
DR ProteomicsDB; 66805; -. [Q6P087-2]
DR ProteomicsDB; 66806; -. [Q6P087-3]
DR Antibodypedia; 25685; 57 antibodies from 15 providers.
DR DNASU; 285367; -.
DR Ensembl; ENST00000383820.9; ENSP00000373331.5; ENSG00000156990.14. [Q6P087-1]
DR Ensembl; ENST00000433535.6; ENSP00000398921.2; ENSG00000156990.14. [Q6P087-2]
DR GeneID; 285367; -.
DR KEGG; hsa:285367; -.
DR MANE-Select; ENST00000383820.10; ENSP00000373331.6; NM_173659.5; NP_775930.3.
DR UCSC; uc011atk.3; human. [Q6P087-1]
DR CTD; 285367; -.
DR DisGeNET; 285367; -.
DR GeneCards; RPUSD3; -.
DR HGNC; HGNC:28437; RPUSD3.
DR HPA; ENSG00000156990; Low tissue specificity.
DR MIM; 617759; gene.
DR neXtProt; NX_Q6P087; -.
DR OpenTargets; ENSG00000156990; -.
DR PharmGKB; PA134924883; -.
DR VEuPathDB; HostDB:ENSG00000156990; -.
DR eggNOG; KOG1919; Eukaryota.
DR GeneTree; ENSGT00940000161059; -.
DR HOGENOM; CLU_016902_2_0_1; -.
DR InParanoid; Q6P087; -.
DR OMA; PTVTYWA; -.
DR OrthoDB; 1378690at2759; -.
DR PhylomeDB; Q6P087; -.
DR TreeFam; TF337899; -.
DR PathwayCommons; Q6P087; -.
DR SignaLink; Q6P087; -.
DR BioGRID-ORCS; 285367; 136 hits in 1080 CRISPR screens.
DR ChiTaRS; RPUSD3; human.
DR GenomeRNAi; 285367; -.
DR Pharos; Q6P087; Tdark.
DR PRO; PR:Q6P087; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q6P087; protein.
DR Bgee; ENSG00000156990; Expressed in endothelial cell and 185 other tissues.
DR ExpressionAtlas; Q6P087; baseline and differential.
DR Genevisible; Q6P087; HS.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
DR GO; GO:0035770; C:ribonucleoprotein granule; IDA:FlyBase.
DR GO; GO:0009982; F:pseudouridine synthase activity; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000455; P:enzyme-directed rRNA pseudouridine synthesis; IBA:GO_Central.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0070131; P:positive regulation of mitochondrial translation; IMP:UniProtKB.
DR CDD; cd02869; PseudoU_synth_RluA_like; 1.
DR InterPro; IPR020103; PsdUridine_synth_cat_dom_sf.
DR InterPro; IPR006145; PsdUridine_synth_RsuA/RluA.
DR Pfam; PF00849; PseudoU_synth_2; 1.
DR SUPFAM; SSF55120; SSF55120; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Isomerase; Mitochondrion; mRNA processing;
KW Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..25
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 26..351
FT /note="Mitochondrial mRNA pseudouridine synthase RPUSD3"
FT /id="PRO_0000300822"
FT REGION 33..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 89..103
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027870"
FT VAR_SEQ 137..351
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_027869"
FT VARIANT 34
FT /note="D -> H (in dbSNP:rs17855991)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_034885"
FT VARIANT 173
FT /note="A -> P (in dbSNP:rs34244989)"
FT /id="VAR_059763"
FT VARIANT 181
FT /note="A -> P (in dbSNP:rs34244989)"
FT /id="VAR_034886"
SQ SEQUENCE 351 AA; 38461 MW; 7C308C9C56AC5C4F CRC64;
MRAVLAREMD GRRVLGRFWS GWRRGLGVRP VPEDAGFGTE ARHQRQPRGS CQRSGPLGDQ
PFAGLLPKNL SREELVDALR AAVVDRKGPL VTLNKPQGLP VTGKPGELTL FSVLPELSQS
LGLREQELQV VRASGKESSG LVLLSSCPQT ASRLQKYFTH ARRAQRPTAT YCAVTDGIPA
ASEGKIQAAL KLEHIDGVNL TVPVKAPSRK DILEGVKKTL SHFRVVATGS GCALVQLQPL
TVFSSQLQVH MVLQLCPVLG DHMYSARVGT VLGQRFLLPA ENNKPQRQVL DEALLRRLHL
TPSQAAQLPL HLHLHRLLLP GTRARDTPVE LLAPLPPYFS RTLQCLGLRL Q
