TRUB2_HUMAN
ID TRUB2_HUMAN Reviewed; 331 AA.
AC O95900; B7Z7G5;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Pseudouridylate synthase TRUB2, mitochondrial {ECO:0000305};
DE EC=5.4.99.- {ECO:0000269|PubMed:27974379, ECO:0000269|PubMed:31477916};
DE AltName: Full=TruB pseudouridine synthase homolog 2 {ECO:0000303|PubMed:12736709};
DE AltName: Full=tRNA pseudouridine 55 synthase TRUB2 {ECO:0000305};
DE Short=Psi55 synthase TRUB2 {ECO:0000305};
DE EC=5.4.99.25 {ECO:0000269|PubMed:33023933};
DE Flags: Precursor;
GN Name=TRUB2 {ECO:0000303|PubMed:12736709, ECO:0000312|HGNC:HGNC:17170};
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 1).
RC TISSUE=Brain;
RA Mei G., Yu W., Gibbs R.A.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta, and Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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, AND NOMENCLATURE.
RX PubMed=12736709;
RA Zucchini C., Strippoli P., Biolchi A., Solmi R., Lenzi L., D'Addabbo P.,
RA Carinci P., Valvassori L.;
RT "The human TruB family of pseudouridine synthase genes, including the
RT Dyskeratosis Congenita 1 gene and the novel member TRUB1.";
RL Int. J. Mol. Med. 11:697-704(2003).
RN [6]
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 [7]
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 [8]
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 [9]
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).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31477916; DOI=10.1038/s41589-019-0353-z;
RA Carlile T.M., Martinez N.M., Schaening C., Su A., Bell T.A., Zinshteyn B.,
RA Gilbert W.V.;
RT "mRNA structure determines modification by pseudouridine synthase 1.";
RL Nat. Chem. Biol. 15:966-974(2019).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=33023933; DOI=10.1261/rna.076810.120;
RA Mukhopadhyay S., Deogharia M., Gupta R.;
RT "Mammalian nuclear TRUB1, mitochondrial TRUB2, and cytoplasmic PUS10
RT produce conserved pseudouridine 55 in different sets of tRNA.";
RL RNA 27:66-79(2021).
CC -!- FUNCTION: Minor enzyme contributing to the isomerization of uridine to
CC pseudouridine (pseudouridylation) of specific mitochondrial mRNAs (mt-
CC mRNAs) such as COXI and COXIII mt-mRNAs (PubMed:27974379,
CC PubMed:31477916). As a component of a functional protein-RNA module,
CC consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S
CC mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA
CC abundance and is required for intra-mitochondrial translation
CC (PubMed:27667664). Also catalyzes pseudouridylation of some tRNAs,
CC including synthesis of pseudouridine(55) from uracil-55, in the psi GC
CC loop of a subset of tRNAs (PubMed:33023933).
CC {ECO:0000269|PubMed:27667664, ECO:0000269|PubMed:27974379,
CC ECO:0000269|PubMed:31477916, ECO:0000269|PubMed:33023933}.
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:31477916, ECO:0000305|PubMed:27974379};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=uridine(55) in tRNA = pseudouridine(55) in tRNA;
CC Xref=Rhea:RHEA:42532, Rhea:RHEA-COMP:10101, Rhea:RHEA-COMP:10102,
CC ChEBI:CHEBI:65314, ChEBI:CHEBI:65315; EC=5.4.99.25;
CC Evidence={ECO:0000269|PubMed:33023933};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42533;
CC Evidence={ECO:0000269|PubMed:33023933};
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 -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:27974379, ECO:0000269|PubMed:33023933}.
CC Note=Localizes to mitochondrial RNA granules, platforms for post-
CC transcriptional RNA modification and ribosome assembly.
CC {ECO:0000269|PubMed:27974379, ECO:0000269|PubMed:28082677}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95900-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95900-2; Sequence=VSP_056094;
CC -!- SIMILARITY: Belongs to the pseudouridine synthase TruB family.
CC {ECO:0000305}.
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DR EMBL; AF131848; AAD20059.1; -; mRNA.
DR EMBL; AK001956; BAA92001.1; -; mRNA.
DR EMBL; AK301986; BAH13601.1; -; mRNA.
DR EMBL; AL359091; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001457; AAH01457.1; -; mRNA.
DR CCDS; CCDS6897.1; -. [O95900-1]
DR RefSeq; NP_001316790.1; NM_001329861.1.
DR RefSeq; NP_001316791.1; NM_001329862.1. [O95900-2]
DR RefSeq; NP_001316792.1; NM_001329863.1.
DR RefSeq; NP_056494.1; NM_015679.2. [O95900-1]
DR AlphaFoldDB; O95900; -.
DR SMR; O95900; -.
DR BioGRID; 117942; 355.
DR IntAct; O95900; 46.
DR MINT; O95900; -.
DR STRING; 9606.ENSP00000361982; -.
DR iPTMnet; O95900; -.
DR PhosphoSitePlus; O95900; -.
DR BioMuta; TRUB2; -.
DR EPD; O95900; -.
DR jPOST; O95900; -.
DR MassIVE; O95900; -.
DR MaxQB; O95900; -.
DR PaxDb; O95900; -.
DR PeptideAtlas; O95900; -.
DR PRIDE; O95900; -.
DR ProteomicsDB; 51120; -. [O95900-1]
DR ProteomicsDB; 6868; -.
DR Antibodypedia; 17439; 149 antibodies from 23 providers.
DR DNASU; 26995; -.
DR Ensembl; ENST00000372890.6; ENSP00000361982.4; ENSG00000167112.10. [O95900-1]
DR GeneID; 26995; -.
DR KEGG; hsa:26995; -.
DR MANE-Select; ENST00000372890.6; ENSP00000361982.4; NM_015679.3; NP_056494.1.
DR UCSC; uc004buq.2; human. [O95900-1]
DR CTD; 26995; -.
DR DisGeNET; 26995; -.
DR GeneCards; TRUB2; -.
DR HGNC; HGNC:17170; TRUB2.
DR HPA; ENSG00000167112; Low tissue specificity.
DR MIM; 610727; gene.
DR neXtProt; NX_O95900; -.
DR OpenTargets; ENSG00000167112; -.
DR PharmGKB; PA38209; -.
DR VEuPathDB; HostDB:ENSG00000167112; -.
DR eggNOG; KOG2559; Eukaryota.
DR GeneTree; ENSGT00940000156773; -.
DR HOGENOM; CLU_032087_1_1_1; -.
DR InParanoid; O95900; -.
DR OMA; CIHFQPP; -.
DR PhylomeDB; O95900; -.
DR TreeFam; TF320759; -.
DR PathwayCommons; O95900; -.
DR SignaLink; O95900; -.
DR BioGRID-ORCS; 26995; 182 hits in 1080 CRISPR screens.
DR ChiTaRS; TRUB2; human.
DR GenomeRNAi; 26995; -.
DR Pharos; O95900; Tdark.
DR PRO; PR:O95900; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O95900; protein.
DR Bgee; ENSG00000167112; Expressed in kidney epithelium and 176 other tissues.
DR ExpressionAtlas; O95900; baseline and differential.
DR Genevisible; O95900; 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; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:1990481; P:mRNA pseudouridine synthesis; IDA:FlyBase.
DR GO; GO:0070131; P:positive regulation of mitochondrial translation; IMP:UniProtKB.
DR GO; GO:0008033; P:tRNA processing; IEA:UniProtKB-KW.
DR InterPro; IPR020103; PsdUridine_synth_cat_dom_sf.
DR InterPro; IPR002501; PsdUridine_synth_N.
DR InterPro; IPR039048; Trub2.
DR PANTHER; PTHR13195; PTHR13195; 1.
DR Pfam; PF01509; TruB_N; 1.
DR SUPFAM; SSF55120; SSF55120; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Isomerase; Mitochondrion; mRNA processing;
KW Reference proteome; Transit peptide; tRNA processing.
FT TRANSIT 1..10
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 11..331
FT /note="Pseudouridylate synthase TRUB2, mitochondrial"
FT /id="PRO_0000252090"
FT REGION 296..331
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 302..324
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 98
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y606"
FT VAR_SEQ 1..56
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056094"
FT VARIANT 79
FT /note="P -> L (in dbSNP:rs2231630)"
FT /id="VAR_051608"
FT VARIANT 93
FT /note="V -> L (in dbSNP:rs2072394)"
FT /id="VAR_027749"
FT VARIANT 209
FT /note="T -> S (in dbSNP:rs2231637)"
FT /id="VAR_051609"
SQ SEQUENCE 331 AA; 36694 MW; 60DD5F9FEA998684 CRC64;
MGSAGLSRLH GLFAVYKPPG LKWKHLRDTV ELQLLKGLNA RKPPAPKQRV RFLLGPMEGS
EEKELTLTAT SVPSFINHPL VCGPAFAHLK VGVGHRLDAQ ASGVLVLGVG HGCRLLTDMY
NAHLTKDYTV RGLLGKATDD FREDGRLVEK TTYDHVTREK LDRILAVIQG SHQKALVMYS
NLDLKTQEAY EMAVRGLIRP MNKSPMLITG IRCLYFAPPE FLLEVQCMHE TQKELRKLVH
EIGLELKTTA VCTQVRRTRD GFFTLDSALL RTQWDLTNIQ DAIRAATPQV AAELEKSLSP
GLDTKQLPSP GWSWDSQGPS STLGLERGAG Q
