PUS3_HUMAN
ID PUS3_HUMAN Reviewed; 481 AA.
AC Q9BZE2; B2RAM0; Q96D17; Q96J23; Q96NB4;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=tRNA pseudouridine(38/39) synthase;
DE EC=5.4.99.45 {ECO:0000269|PubMed:27055666};
DE AltName: Full=tRNA pseudouridine synthase 3;
DE AltName: Full=tRNA pseudouridylate synthase 3;
DE AltName: Full=tRNA-uridine isomerase 3;
GN Name=PUS3; ORFNames=FKSG32;
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 [MRNA].
RA Wang Y.-G., Gong L.;
RT "Identification and characterization of FKSG32, a novel gene expressed in
RT lung carcinoid.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ASP-3 AND SER-46.
RC TISSUE=Lung;
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], AND VARIANTS ASP-3; SER-46 AND
RP ASP-460.
RC TISSUE=Pancreas, and 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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-456 AND THR-468, 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 [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-466, 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 INVOLVEMENT IN NEDMIGS, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27055666; DOI=10.1007/s00439-016-1665-7;
RA Shaheen R., Han L., Faqeih E., Ewida N., Alobeid E., Phizicky E.M.,
RA Alkuraya F.S.;
RT "A homozygous truncating mutation in PUS3 expands the role of tRNA
RT modification in normal cognition.";
RL Hum. Genet. 135:707-713(2016).
CC -!- FUNCTION: Formation of pseudouridine at position 39 in the anticodon
CC stem and loop of transfer RNAs. {ECO:0000269|PubMed:27055666}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=uridine(38/39) in tRNA = pseudouridine(38/39) in tRNA;
CC Xref=Rhea:RHEA:42564, Rhea:RHEA-COMP:10117, Rhea:RHEA-COMP:10118,
CC ChEBI:CHEBI:65314, ChEBI:CHEBI:65315; EC=5.4.99.45;
CC Evidence={ECO:0000269|PubMed:27055666};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- DISEASE: Neurodevelopmental disorder with microcephaly and gray sclerae
CC (NEDMIGS) [MIM:617051]: An autosomal recessive disorder characterized
CC by global developmental delay, hypotonia, profoundly impaired
CC intellectual development with poor or absent language, mild
CC microcephaly, abnormal visual fixation, and seizures in most patients.
CC Affected individuals also have gray sclerae.
CC {ECO:0000269|PubMed:27055666}. 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; AF325689; AAG50280.1; -; mRNA.
DR EMBL; AK055702; BAB70990.1; -; mRNA.
DR EMBL; AK314251; BAG36917.1; -; mRNA.
DR EMBL; BC004822; AAH04822.1; -; mRNA.
DR EMBL; BC013427; AAH13427.2; -; mRNA.
DR CCDS; CCDS8466.1; -.
DR RefSeq; NP_001258914.1; NM_001271985.1.
DR RefSeq; NP_112597.3; NM_031307.3.
DR AlphaFoldDB; Q9BZE2; -.
DR SMR; Q9BZE2; -.
DR BioGRID; 123665; 3.
DR IntAct; Q9BZE2; 4.
DR STRING; 9606.ENSP00000227474; -.
DR iPTMnet; Q9BZE2; -.
DR PhosphoSitePlus; Q9BZE2; -.
DR BioMuta; PUS3; -.
DR DMDM; 126302589; -.
DR EPD; Q9BZE2; -.
DR jPOST; Q9BZE2; -.
DR MassIVE; Q9BZE2; -.
DR MaxQB; Q9BZE2; -.
DR PaxDb; Q9BZE2; -.
DR PeptideAtlas; Q9BZE2; -.
DR PRIDE; Q9BZE2; -.
DR ProteomicsDB; 79820; -.
DR Antibodypedia; 46038; 95 antibodies from 22 providers.
DR DNASU; 83480; -.
DR Ensembl; ENST00000227474.8; ENSP00000227474.3; ENSG00000110060.9.
DR Ensembl; ENST00000530811.5; ENSP00000432386.1; ENSG00000110060.9.
DR GeneID; 83480; -.
DR KEGG; hsa:83480; -.
DR MANE-Select; ENST00000227474.8; ENSP00000227474.3; NM_031307.4; NP_112597.4.
DR UCSC; uc001qcy.3; human.
DR CTD; 83480; -.
DR DisGeNET; 83480; -.
DR GeneCards; PUS3; -.
DR HGNC; HGNC:25461; PUS3.
DR HPA; ENSG00000110060; Low tissue specificity.
DR MalaCards; PUS3; -.
DR MIM; 616283; gene.
DR MIM; 617051; phenotype.
DR neXtProt; NX_Q9BZE2; -.
DR OpenTargets; ENSG00000110060; -.
DR Orphanet; 488627; Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome.
DR PharmGKB; PA134874048; -.
DR VEuPathDB; HostDB:ENSG00000110060; -.
DR eggNOG; KOG2554; Eukaryota.
DR GeneTree; ENSGT00950000183160; -.
DR HOGENOM; CLU_014673_2_0_1; -.
DR InParanoid; Q9BZE2; -.
DR OMA; NLFRCDF; -.
DR OrthoDB; 1093493at2759; -.
DR PhylomeDB; Q9BZE2; -.
DR TreeFam; TF314428; -.
DR PathwayCommons; Q9BZE2; -.
DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol.
DR SignaLink; Q9BZE2; -.
DR BioGRID-ORCS; 83480; 29 hits in 1092 CRISPR screens.
DR GenomeRNAi; 83480; -.
DR Pharos; Q9BZE2; Tbio.
DR PRO; PR:Q9BZE2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BZE2; protein.
DR Bgee; ENSG00000110060; Expressed in buccal mucosa cell and 207 other tissues.
DR ExpressionAtlas; Q9BZE2; baseline and differential.
DR Genevisible; Q9BZE2; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0009982; F:pseudouridine synthase activity; IMP:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR GO; GO:0106029; F:tRNA pseudouridine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:1990481; P:mRNA pseudouridine synthesis; IBA:GO_Central.
DR GO; GO:0006400; P:tRNA modification; TAS:Reactome.
DR GO; GO:0031119; P:tRNA pseudouridine synthesis; IMP:UniProtKB.
DR CDD; cd02569; PseudoU_synth_ScPus3; 1.
DR Gene3D; 3.30.70.580; -; 1.
DR Gene3D; 3.30.70.660; -; 1.
DR HAMAP; MF_00171; TruA; 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; IPR041707; Pus3-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 Acetylation; Intellectual disability; Isomerase; Nucleus; Phosphoprotein;
KW Reference proteome; tRNA processing.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..481
FT /note="tRNA pseudouridine(38/39) synthase"
FT /id="PRO_0000057520"
FT REGION 29..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..43
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 118
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 195
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 456
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 466
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 468
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VARIANT 3
FT /note="Y -> D (in dbSNP:rs622756)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_030836"
FT VARIANT 46
FT /note="A -> S (in dbSNP:rs549990)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_030837"
FT VARIANT 460
FT /note="E -> D (in dbSNP:rs3088241)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030838"
FT CONFLICT 145
FT /note="F -> L (in Ref. 2; BAB70990)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 481 AA; 55647 MW; 54B93653DB333535 CRC64;
MAYNDTDRNQ TEKLLKRVRE LEQEVQRLKK EQAKNKEDSN IRENSAGAGK TKRAFDFSAH
GRRHVALRIA YMGWGYQGFA SQENTNNTIE EKLFEALTKT RLVESRQTSN YHRCGRTDKG
VSAFGQVISL DLRSQFPRGR DSEDFNVKEE ANAAAEEIRY THILNRVLPP DIRILAWAPV
EPSFSARFSC LERTYRYFFP RADLDIVTMD YAAQKYVGTH DFRNLCKMDV ANGVINFQRT
ILSAQVQLVG QSPGEGRWQE PFQLCQFEVT GQAFLYHQVR CMMAILFLIG QGMEKPEIID
ELLNIEKNPQ KPQYSMAVEF PLVLYDCKFE NVKWIYDQEA QEFNITHLQQ LWANHAVKTH
MLYSMLQGLD TVPVPCGIGP KMDGMTEWGN VKPSVIKQTS AFVEGVKMRT YKPLMDRPKC
QGLESRIQHF VRRGRIEHPH LFHEEETKAK RDCNDTLEEE NTNLETPTKR VCVDTEIKSI
I
