PUS1_HUMAN
ID PUS1_HUMAN Reviewed; 427 AA.
AC Q9Y606; A8K877; B3KQC1; Q8WYT2; Q9BU44;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Pseudouridylate synthase 1 homolog {ECO:0000305};
DE EC=5.4.99.- {ECO:0000269|PubMed:31477916, ECO:0000269|PubMed:35051350, ECO:0000305|PubMed:24722331};
DE AltName: Full=tRNA pseudouridine synthase 1 {ECO:0000305};
DE EC=5.4.99.12 {ECO:0000305|PubMed:24722331};
DE AltName: Full=tRNA pseudouridine(38-40) synthase;
DE AltName: Full=tRNA pseudouridylate synthase I;
DE AltName: Full=tRNA-uridine isomerase I;
DE Flags: Precursor;
GN Name=PUS1 {ECO:0000303|PubMed:17056637, ECO:0000312|HGNC:HGNC:15508};
GN ORFNames=PP8985 {ECO:0000303|PubMed:15498874};
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).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Mammary gland, 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 MRNA] (ISOFORMS 1 AND 2).
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 NUCLEOTIDE SEQUENCE [MRNA] OF 63-427.
RC TISSUE=Cervix carcinoma;
RX PubMed=10094309; DOI=10.1017/s1355838299981591;
RA Chen J., Patton J.R.;
RT "Cloning and characterization of a mammalian pseudouridine synthase.";
RL RNA 5:409-419(1999).
RN [5]
RP VARIANT MLASA1 TRP-144, AND TISSUE SPECIFICITY.
RX PubMed=15108122; DOI=10.1086/421530;
RA Bykhovskaya Y., Casas K., Mengesha E., Inbal A., Fischel-Ghodsian N.;
RT "Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial
RT myopathy and sideroblastic anemia (MLASA).";
RL Am. J. Hum. Genet. 74:1303-1308(2004).
RN [6]
RP INVOLVEMENT IN MLASA1, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15772074; DOI=10.1074/jbc.m500216200;
RA Patton J.R., Bykhovskaya Y., Mengesha E., Bertolotto C.,
RA Fischel-Ghodsian N.;
RT "Mitochondrial myopathy and sideroblastic anemia (MLASA): missense mutation
RT in the pseudouridine synthase 1 (PUS1) gene is associated with the loss of
RT tRNA pseudouridylation.";
RL J. Biol. Chem. 280:19823-19828(2005).
RN [7]
RP INVOLVEMENT IN MLASA1.
RX PubMed=15971356; DOI=10.1177/08830738050200051301;
RA Zeharia A., Fischel-Ghodsian N., Casas K., Bykhocskaya Y., Tamari H.,
RA Lev D., Mimouni M., Lerman-Sagie T.;
RT "Mitochondrial myopathy, sideroblastic anemia, and lactic acidosis: an
RT autosomal recessive syndrome in Persian Jews caused by a mutation in the
RT PUS1 gene.";
RL J. Child Neurol. 20:449-452(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-420 AND THR-426, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-133.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [10]
RP VARIANT MLASA1 220-GLU--ASP-427 DEL, AND SUBCELLULAR LOCATION (ISOFORMS 1
RP AND 2).
RX PubMed=17056637; DOI=10.1136/jmg.2006.045252;
RA Fernandez-Vizarra E., Berardinelli A., Valente L., Tiranti V., Zeviani M.;
RT "Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers
RT affected by myopathy, lactic acidosis and sideroblastic anaemia (MLASA).";
RL J. Med. Genet. 44:173-180(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-420 AND THR-426, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
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 [13]
RP VARIANT MLASA1 220-GLU--ASP-427 DEL.
RX PubMed=21686963; DOI=10.1136/bcr.05.2009.1889;
RA Fernandez-Vizarra E., Berardinelli A., Valente L., Tiranti V., Zeviani M.;
RT "Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers
RT affected by myopathy, lactic acidosis and sideroblastic anaemia (MLASA).";
RL BMJ Case Rep. 2009:0-0(2009).
RN [14]
RP VARIANT MLASA1 TRP-144.
RX PubMed=19731322; DOI=10.1002/pbc.22244;
RA Bergmann A.K., Campagna D.R., McLoughlin E.M., Agarwal S., Fleming M.D.,
RA Bottomley S.S., Neufeld E.J.;
RT "Systematic molecular genetic analysis of congenital sideroblastic anemia:
RT evidence for genetic heterogeneity and identification of novel mutations.";
RL Pediatr. Blood Cancer 54:273-278(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415; SER-420 AND THR-426, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-420 AND THR-426, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-420 AND THR-426, AND
RP IDENTIFICATION BY 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-420 AND THR-426, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP VARIANT MLASA1 TRP-295.
RX PubMed=25227147; DOI=10.1038/ejhg.2014.192;
RA Metodiev M.D., Assouline Z., Landrieu P., Chretien D., Bader-Meunier B.,
RA Guitton C., Munnich A., Roetig A.;
RT "Unusual clinical expression and long survival of a pseudouridylate
RT synthase (PUS1) mutation into adulthood.";
RL Eur. J. Hum. Genet. 23:880-882(2015).
RN [22]
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 [23]
RP VARIANT MLASA1 GLN-295.
RX PubMed=26556812; DOI=10.1007/s10048-015-0465-x;
RA Cao M., Dona M., Valentino M.L., Valentino L., Semplicini C., Maresca A.,
RA Cassina M., Torraco A., Galletta E., Manfioli V., Soraru G., Carelli V.,
RA Stramare R., Bertini E., Carrozzo R., Salviati L., Pegoraro E.;
RT "Clinical and molecular study in a long-surviving patient with MLASA
RT syndrome due to novel PUS1 mutations.";
RL Neurogenetics 17:65-70(2016).
RN [24]
RP VARIANT MLASA1 ARG-101.
RX PubMed=28832011; DOI=10.4274/tjh.2017.0231;
RA Kasapkara C.S., Tuemer L., Zanetti N., Ezgue F., Lamantea E., Zeviani M.;
RT "A myopathy, lactic acidosis, sideroblastic anemia (MLASA) case due to a
RT novel PUS1 mutation.";
RL Turk. J. Haematol. 34:376-377(2017).
RN [25]
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 [26]
RP VARIANT MLASA1 311-GLU--ASP-427 DEL.
RX PubMed=32287105; DOI=10.1097/mph.0000000000001806;
RA Oncul U., Unal-Ince E., Kuloglu Z., Teber-Tiras S., Kaygusuz G.,
RA Eminoglu F.T.;
RT "A novel PUS1 mutation in 2 siblings with MLASA syndrome: a review of the
RT literature.";
RL J. Pediatr. Hematol. Oncol. 43:e592-e595(2021).
RN [27]
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 [28] {ECO:0007744|PDB:4IQM, ECO:0007744|PDB:4ITS, ECO:0007744|PDB:4J37}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 79-408, AND SUBUNIT.
RX PubMed=23707380; DOI=10.1016/j.jmb.2013.05.014;
RA Czudnochowski N., Wang A.L., Finer-Moore J., Stroud R.M.;
RT "In human pseudouridine synthase 1 (hPus1), a C-terminal helical insert
RT blocks tRNA from binding in the same orientation as in the Pus1 bacterial
RT homologue TruA, consistent with their different target selectivities.";
RL J. Mol. Biol. 425:3875-3887(2013).
RN [29] {ECO:0007744|PDB:4NZ6, ECO:0007744|PDB:4NZ7}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 83-394 OF WILD-TYPE AND MUTANT
RP ALA-146, FUNCTION, ACTIVE SITE, MUTAGENESIS OF ASP-146, AND SUBUNIT.
RX PubMed=24722331; DOI=10.1371/journal.pone.0094610;
RA Huet T., Miannay F.A., Patton J.R., Thore S.;
RT "Steroid receptor RNA activator (SRA) modification by the human
RT pseudouridine synthase 1 (hPus1p): RNA binding, activity, and atomic
RT model.";
RL PLoS ONE 9:e94610-e94610(2014).
CC -!- FUNCTION: Pseudouridylate synthase that catalyzes pseudouridylation of
CC tRNAs and mRNAs (PubMed:15772074, PubMed:24722331). Acts on positions
CC 27/28 in the anticodon stem and also positions 34 and 36 in the
CC anticodon of an intron containing tRNA (PubMed:24722331). Also
CC catalyzes pseudouridylation of mRNAs: mediates pseudouridylation of
CC mRNAs with the consensus sequence 5'-UGUAG-3' (PubMed:31477916,
CC PubMed:35051350). Acts as a regulator of pre-mRNA splicing by mediating
CC pseudouridylation of pre-mRNAs at locations associated with
CC alternatively spliced regions (PubMed:35051350). Pseudouridylation of
CC pre-mRNAs near splice sites directly regulates mRNA splicing and mRNA
CC 3'-end processing (PubMed:35051350). Involved in regulation of nuclear
CC receptor activity through pseudouridylation of SRA1 mRNA
CC (PubMed:24722331). {ECO:0000269|PubMed:15772074,
CC ECO:0000269|PubMed:24722331, ECO:0000269|PubMed:31477916,
CC ECO:0000269|PubMed:35051350}.
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:24722331};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=uridine(38/39/40) in tRNA = pseudouridine(38/39/40) in tRNA;
CC Xref=Rhea:RHEA:22376, Rhea:RHEA-COMP:10085, Rhea:RHEA-COMP:10087,
CC ChEBI:CHEBI:65314, ChEBI:CHEBI:65315; EC=5.4.99.12;
CC Evidence={ECO:0000305|PubMed:24722331};
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: Monomer (PubMed:23707380, PubMed:24722331). Forms a complex
CC with RARG and the SRA1 RNA in the nucleus (By similarity).
CC {ECO:0000250|UniProtKB:Q9WU56, ECO:0000269|PubMed:23707380,
CC ECO:0000269|PubMed:24722331}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion
CC {ECO:0000269|PubMed:17056637, ECO:0000305|PubMed:15772074}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:17056637, ECO:0000305|PubMed:15772074}. Cytoplasm
CC {ECO:0000305|PubMed:15772074}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y606-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y606-2; Sequence=VSP_020116;
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:15108122). High levels of
CC expression found in brain and skeletal muscle (PubMed:15108122).
CC {ECO:0000269|PubMed:15108122}.
CC -!- DISEASE: Myopathy with lactic acidosis and sideroblastic anemia 1
CC (MLASA1) [MIM:600462]: A rare oxidative phosphorylation disorder
CC specific to skeletal muscle and bone marrow. Affected individuals
CC manifest progressive muscle weakness, exercise intolerance, lactic
CC acidosis, sideroblastic anemia and delayed growth.
CC {ECO:0000269|PubMed:15108122, ECO:0000269|PubMed:15772074,
CC ECO:0000269|PubMed:15971356, ECO:0000269|PubMed:16959974,
CC ECO:0000269|PubMed:17056637, ECO:0000269|PubMed:19731322,
CC ECO:0000269|PubMed:21686963, ECO:0000269|PubMed:25227147,
CC ECO:0000269|PubMed:26556812, ECO:0000269|PubMed:28832011,
CC ECO:0000269|PubMed:32287105}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tRNA pseudouridine synthase TruA family.
CC {ECO:0000305}.
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DR EMBL; AF318369; AAL55876.1; -; mRNA.
DR EMBL; AK074659; BAG51983.1; -; mRNA.
DR EMBL; AK292242; BAF84931.1; -; mRNA.
DR EMBL; BC002901; AAH02901.1; -; mRNA.
DR EMBL; BC009505; AAH09505.2; -; mRNA.
DR EMBL; BC019320; AAH19320.2; -; mRNA.
DR EMBL; AF116238; AAD21042.1; -; mRNA.
DR CCDS; CCDS31928.1; -. [Q9Y606-2]
DR CCDS; CCDS9275.2; -. [Q9Y606-1]
DR RefSeq; NP_001002019.1; NM_001002019.2. [Q9Y606-2]
DR RefSeq; NP_001002020.1; NM_001002020.2. [Q9Y606-2]
DR RefSeq; NP_079491.2; NM_025215.5. [Q9Y606-1]
DR PDB; 4IQM; X-ray; 1.80 A; A=79-408.
DR PDB; 4ITS; X-ray; 1.85 A; A=79-408.
DR PDB; 4J37; X-ray; 1.75 A; A=79-408.
DR PDB; 4NZ6; X-ray; 2.00 A; A/B=83-394.
DR PDB; 4NZ7; X-ray; 2.70 A; A=83-394.
DR PDBsum; 4IQM; -.
DR PDBsum; 4ITS; -.
DR PDBsum; 4J37; -.
DR PDBsum; 4NZ6; -.
DR PDBsum; 4NZ7; -.
DR AlphaFoldDB; Q9Y606; -.
DR SMR; Q9Y606; -.
DR BioGRID; 123236; 127.
DR IntAct; Q9Y606; 21.
DR MINT; Q9Y606; -.
DR STRING; 9606.ENSP00000365837; -.
DR iPTMnet; Q9Y606; -.
DR PhosphoSitePlus; Q9Y606; -.
DR SwissPalm; Q9Y606; -.
DR BioMuta; PUS1; -.
DR DMDM; 114152895; -.
DR EPD; Q9Y606; -.
DR jPOST; Q9Y606; -.
DR MassIVE; Q9Y606; -.
DR MaxQB; Q9Y606; -.
DR PaxDb; Q9Y606; -.
DR PeptideAtlas; Q9Y606; -.
DR PRIDE; Q9Y606; -.
DR ProteomicsDB; 86569; -. [Q9Y606-1]
DR ProteomicsDB; 86570; -. [Q9Y606-2]
DR Antibodypedia; 32008; 166 antibodies from 28 providers.
DR DNASU; 80324; -.
DR Ensembl; ENST00000376649.8; ENSP00000365837.3; ENSG00000177192.14. [Q9Y606-1]
DR Ensembl; ENST00000443358.6; ENSP00000392451.2; ENSG00000177192.14. [Q9Y606-2]
DR GeneID; 80324; -.
DR KEGG; hsa:80324; -.
DR MANE-Select; ENST00000376649.8; ENSP00000365837.3; NM_025215.6; NP_079491.2.
DR UCSC; uc001ujf.4; human. [Q9Y606-1]
DR CTD; 80324; -.
DR DisGeNET; 80324; -.
DR GeneCards; PUS1; -.
DR HGNC; HGNC:15508; PUS1.
DR HPA; ENSG00000177192; Low tissue specificity.
DR MalaCards; PUS1; -.
DR MIM; 600462; phenotype.
DR MIM; 608109; gene.
DR neXtProt; NX_Q9Y606; -.
DR OpenTargets; ENSG00000177192; -.
DR Orphanet; 2598; Mitochondrial myopathy and sideroblastic anemia.
DR PharmGKB; PA34047; -.
DR VEuPathDB; HostDB:ENSG00000177192; -.
DR eggNOG; KOG2553; Eukaryota.
DR GeneTree; ENSGT00950000183160; -.
DR InParanoid; Q9Y606; -.
DR OMA; AVMIGYC; -.
DR PhylomeDB; Q9Y606; -.
DR TreeFam; TF314367; -.
DR BRENDA; 5.4.99.B22; 2681.
DR PathwayCommons; Q9Y606; -.
DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol. [Q9Y606-2]
DR Reactome; R-HSA-6787450; tRNA modification in the mitochondrion. [Q9Y606-1]
DR SignaLink; Q9Y606; -.
DR BioGRID-ORCS; 80324; 38 hits in 1089 CRISPR screens.
DR ChiTaRS; PUS1; human.
DR GeneWiki; PUS1; -.
DR GenomeRNAi; 80324; -.
DR Pharos; Q9Y606; Tbio.
DR PRO; PR:Q9Y606; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9Y606; protein.
DR Bgee; ENSG00000177192; Expressed in granulocyte and 152 other tissues.
DR ExpressionAtlas; Q9Y606; baseline and differential.
DR Genevisible; Q9Y606; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0009982; F:pseudouridine synthase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0002153; F:steroid receptor RNA activator RNA binding; IDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB.
DR GO; GO:0106029; F:tRNA pseudouridine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0070902; P:mitochondrial tRNA pseudouridine synthesis; TAS:Reactome.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:1990481; P:mRNA pseudouridine synthesis; IDA:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0031119; P:tRNA pseudouridine synthesis; IMP:UniProtKB.
DR CDD; cd02568; PseudoU_synth_PUS1_PUS2; 1.
DR Gene3D; 3.30.70.580; -; 1.
DR Gene3D; 3.30.70.660; -; 1.
DR InterPro; IPR020103; PsdUridine_synth_cat_dom_sf.
DR InterPro; IPR001406; PsdUridine_synth_TruA.
DR InterPro; IPR020097; PsdUridine_synth_TruA_a/b_dom.
DR InterPro; IPR020095; PsdUridine_synth_TruA_C.
DR InterPro; IPR041708; PUS1/PUS2-like.
DR InterPro; IPR020094; TruA/RsuA/RluB/E/F_N.
DR PANTHER; PTHR11142; PTHR11142; 1.
DR Pfam; PF01416; PseudoU_synth_1; 1.
DR SUPFAM; SSF55120; SSF55120; 1.
DR TIGRFAMs; TIGR00071; hisT_truA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; Isomerase;
KW Mitochondrion; mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Primary mitochondrial disease; Reference proteome; Transit peptide;
KW tRNA processing.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..427
FT /note="Pseudouridylate synthase 1 homolog"
FT /id="PRO_0000057517"
FT REGION 20..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 407..427
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..83
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 146
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:24722331,
FT ECO:0007744|PDB:4ITS, ECO:0007744|PDB:4NZ6"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 420
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 426
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_020116"
FT VARIANT 101
FT /note="Q -> R (in MLASA1; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28832011"
FT /id="VAR_086155"
FT VARIANT 133
FT /note="D -> N (in dbSNP:rs76655496)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036447"
FT VARIANT 144
FT /note="R -> W (in MLASA1; dbSNP:rs104894371)"
FT /evidence="ECO:0000269|PubMed:15108122,
FT ECO:0000269|PubMed:19731322"
FT /id="VAR_021788"
FT VARIANT 220..427
FT /note="Missing (in MLASA1)"
FT /evidence="ECO:0000269|PubMed:17056637,
FT ECO:0000269|PubMed:21686963"
FT /id="VAR_086156"
FT VARIANT 295
FT /note="R -> Q (in MLASA1; unknown pathological
FT significance; mild phenotype)"
FT /evidence="ECO:0000269|PubMed:26556812"
FT /id="VAR_086157"
FT VARIANT 295
FT /note="R -> W (in MLASA1; unknown pathological
FT significance; mild phenotype)"
FT /evidence="ECO:0000269|PubMed:25227147"
FT /id="VAR_086158"
FT VARIANT 311..427
FT /note="Missing (in MLASA1)"
FT /evidence="ECO:0000269|PubMed:32287105"
FT /id="VAR_086159"
FT MUTAGEN 146
FT /note="D->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:24722331"
FT CONFLICT 70
FT /note="K -> R (in Ref. 4; AAD21042)"
FT /evidence="ECO:0000305"
FT STRAND 83..92
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:4IQM"
FT HELIX 112..122
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 128..132
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 134..137
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 150..161
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 166..172
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 178..186
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 192..195
FT /evidence="ECO:0007829|PDB:4IQM"
FT STRAND 198..206
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 207..210
FT /evidence="ECO:0007829|PDB:4J37"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 226..238
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:4IQM"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:4IQM"
FT STRAND 260..268
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 277..288
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 293..305
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 313..317
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:4J37"
FT STRAND 333..338
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 341..344
FT /evidence="ECO:0007829|PDB:4IQM"
FT HELIX 359..361
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 362..371
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 373..384
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 386..391
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 392..396
FT /evidence="ECO:0007829|PDB:4J37"
FT HELIX 401..404
FT /evidence="ECO:0007829|PDB:4IQM"
SQ SEQUENCE 427 AA; 47470 MW; ACE9FA6AE0F178BA CRC64;
MGLQLRALLG AFGRWTLRLG PRPSCSPRMA GNAEPPPAGA ACPQDRRSCS GRAGGDRVWE
DGEHPAKKLK SGGDEERREK PPKRKIVLLM AYSGKGYHGM QRNVGSSQFK TIEDDLVSAL
VRSGCIPENH GEDMRKMSFQ RCARTDKGVS AAGQVVSLKV WLIDDILEKI NSHLPSHIRI
LGLKRVTGGF NSKNRCDART YCYLLPTFAF AHKDRDVQDE TYRLSAETLQ QVNRLLACYK
GTHNFHNFTS QKGPQDPSAC RYILEMYCEE PFVREGLEFA VIRVKGQSFM MHQIRKMVGL
VVAIVKGYAP ESVLERSWGT EKVDVPKAPG LGLVLERVHF EKYNQRFGND GLHEPLDWAQ
EEGKVAAFKE EHIYPTIIGT ERDERSMAQW LSTLPIHNFS ATALTAGGTG AKVPSPLEGS
EGDGDTD
