OSGL1_HUMAN
ID OSGL1_HUMAN Reviewed; 414 AA.
AC Q9H4B0; Q96EV9; Q96NH5;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03179};
DE EC=2.3.1.234 {ECO:0000255|HAMAP-Rule:MF_03179, ECO:0000305|PubMed:29760464, ECO:0000305|PubMed:32047918};
DE AltName: Full=N6-L-threonylcarbamoyladenine synthase {ECO:0000255|HAMAP-Rule:MF_03179};
DE Short=t(6)A synthase {ECO:0000255|HAMAP-Rule:MF_03179};
DE AltName: Full=O-sialoglycoprotein endopeptidase-like protein 1 {ECO:0000255|HAMAP-Rule:MF_03179};
DE Short=OSGEP-like protein 1;
DE AltName: Full=t(6)A37 threonylcarbamoyladenosine biosynthesis protein OSGEPL1 {ECO:0000255|HAMAP-Rule:MF_03179};
DE AltName: Full=tRNA threonylcarbamoyladenosine biosynthesis protein OSGEPL1 {ECO:0000255|HAMAP-Rule:MF_03179};
DE Flags: Precursor;
GN Name=OSGEPL1 {ECO:0000255|HAMAP-Rule:MF_03179}; Synonyms=GCP1;
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] (ISOFORM 3).
RC TISSUE=Uterus;
RA Chen J.M., Fortunato M., Barrett A.J.;
RT "Cloning and sequencing of a second human putative sialoglycoprotease
RT homologue.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19694617; DOI=10.1042/bj20091023;
RA Haussuehl K., Huesgen P.F., Meier M., Dessi P., Glaser E., Adamski J.,
RA Adamska I.;
RT "Eukaryotic GCP1 is a conserved mitochondrial protein required for
RT progression of embryo development beyond the globular stage in Arabidopsis
RT thaliana.";
RL Biochem. J. 423:333-341(2009).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=29760464; DOI=10.1038/s41467-018-04250-4;
RA Lin H., Miyauchi K., Harada T., Okita R., Takeshita E., Komaki H.,
RA Fujioka K., Yagasaki H., Goto Y.I., Yanaka K., Nakagawa S., Sakaguchi Y.,
RA Suzuki T.;
RT "CO2-sensitive tRNA modification associated with human mitochondrial
RT disease.";
RL Nat. Commun. 9:1875-1875(2018).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, ACETYLATION AT LYS-74; LYS-140;
RP LYS-203; LYS-230; LYS-240 AND LYS-299, AND MUTAGENESIS OF LYS-203 AND
RP LYS-299.
RX PubMed=32047918; DOI=10.1093/nar/gkaa093;
RA Zhou J.B., Wang Y., Zeng Q.Y., Meng S.X., Wang E.D., Zhou X.L.;
RT "Molecular basis for t6A modification in human mitochondria.";
RL Nucleic Acids Res. 48:3181-3194(2020).
CC -!- FUNCTION: Required for the formation of a threonylcarbamoyl group on
CC adenosine at position 37 (t(6)A37) in mitochondrial tRNAs that read
CC codons beginning with adenine. Probably involved in the transfer of the
CC threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6
CC group of A37. Involved in mitochondrial genome maintenance.
CC {ECO:0000255|HAMAP-Rule:MF_03179, ECO:0000269|PubMed:29760464,
CC ECO:0000269|PubMed:32047918}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine(37) in tRNA + L-threonylcarbamoyladenylate = AMP +
CC H(+) + N(6)-L-threonylcarbamoyladenosine(37) in tRNA;
CC Xref=Rhea:RHEA:37059, Rhea:RHEA-COMP:10162, Rhea:RHEA-COMP:10163,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:73682, ChEBI:CHEBI:74411,
CC ChEBI:CHEBI:74418, ChEBI:CHEBI:456215; EC=2.3.1.234;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03179,
CC ECO:0000305|PubMed:29760464, ECO:0000305|PubMed:32047918};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03179};
CC Note=Binds 1 divalent metal cation per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_03179};
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_03179,
CC ECO:0000269|PubMed:32047918}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03179,
CC ECO:0000269|PubMed:19694617, ECO:0000269|PubMed:29760464}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9H4B0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H4B0-2; Sequence=VSP_028830;
CC Name=3;
CC IsoId=Q9H4B0-3; Sequence=VSP_028828, VSP_028829;
CC -!- TISSUE SPECIFICITY: Widely expressed, with maximum expression in
CC pituitary gland, prostate, rectum and uterus.
CC {ECO:0000269|PubMed:19694617}.
CC -!- SIMILARITY: Belongs to the KAE1 / TsaD family. {ECO:0000255|HAMAP-
CC Rule:MF_03179}.
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DR EMBL; AJ295148; CAC14666.1; ALT_TERM; mRNA.
DR EMBL; AK055441; BAB70923.1; -; mRNA.
DR EMBL; AC013468; AAY14771.1; -; Genomic_DNA.
DR EMBL; BC011904; AAH11904.1; -; mRNA.
DR CCDS; CCDS46472.1; -. [Q9H4B0-1]
DR RefSeq; NP_071748.2; NM_022353.2. [Q9H4B0-1]
DR RefSeq; XP_005246823.1; XM_005246766.3.
DR RefSeq; XP_006712748.1; XM_006712685.1.
DR RefSeq; XP_011509933.1; XM_011511631.1.
DR RefSeq; XP_016860165.1; XM_017004676.1. [Q9H4B0-1]
DR RefSeq; XP_016860166.1; XM_017004677.1.
DR RefSeq; XP_016860167.1; XM_017004678.1.
DR RefSeq; XP_016860168.1; XM_017004679.1.
DR RefSeq; XP_016860169.1; XM_017004680.1.
DR AlphaFoldDB; Q9H4B0; -.
DR SMR; Q9H4B0; -.
DR BioGRID; 122095; 6.
DR IntAct; Q9H4B0; 1.
DR STRING; 9606.ENSP00000264151; -.
DR GlyGen; Q9H4B0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H4B0; -.
DR PhosphoSitePlus; Q9H4B0; -.
DR BioMuta; OSGEPL1; -.
DR DMDM; 160013222; -.
DR EPD; Q9H4B0; -.
DR jPOST; Q9H4B0; -.
DR MassIVE; Q9H4B0; -.
DR MaxQB; Q9H4B0; -.
DR PaxDb; Q9H4B0; -.
DR PeptideAtlas; Q9H4B0; -.
DR PRIDE; Q9H4B0; -.
DR ProteomicsDB; 80814; -. [Q9H4B0-1]
DR ProteomicsDB; 80815; -. [Q9H4B0-2]
DR ProteomicsDB; 80816; -. [Q9H4B0-3]
DR Antibodypedia; 34028; 76 antibodies from 21 providers.
DR DNASU; 64172; -.
DR Ensembl; ENST00000264151.10; ENSP00000264151.5; ENSG00000128694.12. [Q9H4B0-1]
DR Ensembl; ENST00000519810.5; ENSP00000428859.1; ENSG00000128694.12. [Q9H4B0-2]
DR Ensembl; ENST00000522700.5; ENSP00000429697.1; ENSG00000128694.12. [Q9H4B0-1]
DR GeneID; 64172; -.
DR KEGG; hsa:64172; -.
DR MANE-Select; ENST00000264151.10; ENSP00000264151.5; NM_022353.3; NP_071748.2.
DR UCSC; uc002uqz.2; human. [Q9H4B0-1]
DR CTD; 64172; -.
DR GeneCards; OSGEPL1; -.
DR HGNC; HGNC:23075; OSGEPL1.
DR HPA; ENSG00000128694; Low tissue specificity.
DR MIM; 619634; gene.
DR neXtProt; NX_Q9H4B0; -.
DR OpenTargets; ENSG00000128694; -.
DR PharmGKB; PA134959704; -.
DR VEuPathDB; HostDB:ENSG00000128694; -.
DR eggNOG; KOG2707; Eukaryota.
DR GeneTree; ENSGT00940000153744; -.
DR HOGENOM; CLU_023208_1_2_1; -.
DR InParanoid; Q9H4B0; -.
DR OMA; HLEGHIY; -.
DR OrthoDB; 656684at2759; -.
DR PhylomeDB; Q9H4B0; -.
DR TreeFam; TF314600; -.
DR PathwayCommons; Q9H4B0; -.
DR SignaLink; Q9H4B0; -.
DR BioGRID-ORCS; 64172; 8 hits in 1077 CRISPR screens.
DR ChiTaRS; OSGEPL1; human.
DR GenomeRNAi; 64172; -.
DR Pharos; Q9H4B0; Tbio.
DR PRO; PR:Q9H4B0; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9H4B0; protein.
DR Bgee; ENSG00000128694; Expressed in biceps brachii and 183 other tissues.
DR ExpressionAtlas; Q9H4B0; baseline and differential.
DR Genevisible; Q9H4B0; HS.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061711; F:N(6)-L-threonylcarbamoyladenine synthase activity; IDA:UniProtKB.
DR GO; GO:0002949; P:tRNA threonylcarbamoyladenosine modification; IDA:UniProtKB.
DR HAMAP; MF_01445; TsaD; 1.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR000905; Gcp-like_dom.
DR InterPro; IPR017861; KAE1/TsaD.
DR InterPro; IPR022450; TsaD.
DR PANTHER; PTHR11735; PTHR11735; 1.
DR PANTHER; PTHR11735:SF6; PTHR11735:SF6; 1.
DR Pfam; PF00814; TsaD; 1.
DR PRINTS; PR00789; OSIALOPTASE.
DR SUPFAM; SSF53067; SSF53067; 1.
DR TIGRFAMs; TIGR00329; gcp_kae1; 1.
PE 1: Evidence at protein level;
KW Acetylation; Acyltransferase; Alternative splicing; Metal-binding;
KW Mitochondrion; Reference proteome; Transferase; Transit peptide;
KW tRNA processing.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT CHAIN 30..414
FT /note="tRNA N6-adenosine threonylcarbamoyltransferase,
FT mitochondrial"
FT /id="PRO_0000307778"
FT BINDING 147
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT BINDING 151
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT BINDING 169..173
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT BINDING 202
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT BINDING 222
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT BINDING 329..330
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT BINDING 357
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT BINDING 358
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03179"
FT MOD_RES 74
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:32047918"
FT MOD_RES 140
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:32047918"
FT MOD_RES 203
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:32047918"
FT MOD_RES 230
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:32047918"
FT MOD_RES 240
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:32047918"
FT MOD_RES 299
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:32047918"
FT VAR_SEQ 274..298
FT /note="EKGQILSSAADIAATVQHTMACHLV -> FLISKVEQINIPGLCLKIAAHFC
FT RY (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_028828"
FT VAR_SEQ 299..414
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_028829"
FT VAR_SEQ 365..414
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_028830"
FT VARIANT 229
FT /note="A -> P (in dbSNP:rs3749014)"
FT /id="VAR_036651"
FT MUTAGEN 203
FT /note="K->Q: Mimics acetylation; decreased formation of
FT tRNA threonylcarbamoyladenosine modification."
FT /evidence="ECO:0000269|PubMed:32047918"
FT MUTAGEN 299
FT /note="K->Q: Mimics acetylation; increased formation of
FT tRNA threonylcarbamoyladenosine modification."
FT /evidence="ECO:0000269|PubMed:32047918"
FT CONFLICT 31
FT /note="G -> E (in Ref. 1; CAC14666)"
FT /evidence="ECO:0000305"
FT CONFLICT 209
FT /note="S -> P (in Ref. 2; BAB70923)"
FT /evidence="ECO:0000305"
FT CONFLICT 252
FT /note="S -> P (in Ref. 2; BAB70923)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="Y -> C (in Ref. 2; BAB70923)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 414 AA; 45123 MW; A536B333F5C6B8DD CRC64;
MLILTKTAGV FFKPSKRKVY EFLRSFNFHP GTLFLHKIVL GIETSCDDTA AAVVDETGNV
LGEAIHSQTE VHLKTGGIVP PAAQQLHREN IQRIVQEALS ASGVSPSDLS AIATTIKPGL
ALSLGVGLSF SLQLVGQLKK PFIPIHHMEA HALTIRLTNK VEFPFLVLLI SGGHCLLALV
QGVSDFLLLG KSLDIAPGDM LDKVARRLSL IKHPECSTMS GGKAIEHLAK QGNRFHFDIK
PPLHHAKNCD FSFTGLQHVT DKIIMKKEKE EGIEKGQILS SAADIAATVQ HTMACHLVKR
THRAILFCKQ RDLLPQNNAV LVASGGVASN FYIRRALEIL TNATQCTLLC PPPRLCTDNG
IMIAWNGIER LRAGLGILHD IEGIRYEPKC PLGVDISKEV GEASIKVPQL KMEI
