ID LAGE3_HUMAN Reviewed; 143 AA. AC Q14657; Q5HY39; Q8IZ78; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2004, sequence version 2. DT 27-MAR-2024, entry version 169. DE RecName: Full=EKC/KEOPS complex subunit LAGE3 {ECO:0000305}; DE AltName: Full=L antigen family member 3 {ECO:0000303|PubMed:12384295}; DE AltName: Full=Protein ESO-3 {ECO:0000303|PubMed:12384295}; DE AltName: Full=Protein ITBA2 {ECO:0000303|PubMed:8786131}; GN Name=LAGE3 {ECO:0000312|HGNC:HGNC:26058}; GN Synonyms=DXS9879E, ESO3 {ECO:0000303|PubMed:12384295}, GN ITBA2 {ECO:0000303|PubMed:8786131}; 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 GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Blood, and Pancreas; 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-143, AND TISSUE SPECIFICITY. RC TISSUE=Liver; RX PubMed=8786131; DOI=10.1006/geno.1996.0293; RA Faranda S., Frattini A., Zucchi I., Patrosso C., Milanesi L., Montagna C., RA Vezzoni P.; RT "Characterization and fine localization of two new genes in Xq28 using the RT genomic sequence/EST database screening approach."; RL Genomics 34:323-327(1996). RN [4] RP IDENTIFICATION, AND TISSUE SPECIFICITY. RX PubMed=12384295; DOI=10.1016/s0378-1119(02)00879-x; RA Alpen B., Guere A.O., Scanlan M.J., Old L.J., Chen Y.-T.; RT "A new member of the NY-ESO-1 gene family is ubiquitously expressed in RT somatic tissues and evolutionarily conserved."; RL Gene 297:141-149(2002). 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 IDENTIFICATION IN THE EKC/KEOPS COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=22912744; DOI=10.1371/journal.pone.0042822; RA Costessi A., Mahrour N., Sharma V., Stunnenberg R., Stoel M.A., Tijchon E., RA Conaway J.W., Conaway R.C., Stunnenberg H.G.; RT "The human EKC/KEOPS complex is recruited to Cullin2 ubiquitin ligases by RT the human tumour antigen PRAME."; RL PLoS ONE 7:E42822-E42822(2012). RN [7] 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 [8] RP IDENTIFICATION IN THE EKC/KEOPS COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=27903914; DOI=10.1093/nar/gkw1181; RA Wan L.C., Maisonneuve P., Szilard R.K., Lambert J.P., Ng T.F., Manczyk N., RA Huang H., Laister R., Caudy A.A., Gingras A.C., Durocher D., Sicheri F.; RT "Proteomic analysis of the human KEOPS complex identifies C14ORF142 as a RT core subunit homologous to yeast Gon7."; RL Nucleic Acids Res. 45:805-817(2017). RN [9] {ECO:0007744|PDB:6GWJ} RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH GON7 AND OSGEP, AND RP IDENTIFICATION IN THE EKC/KEOPS COMPLEX. RX PubMed=31481669; DOI=10.1038/s41467-019-11951-x; RA Arrondel C., Missoury S., Snoek R., Patat J., Menara G., Collinet B., RA Liger D., Durand D., Gribouval O., Boyer O., Buscara L., Martin G., RA Machuca E., Nevo F., Lescop E., Braun D.A., Boschat A.C., Sanquer S., RA Guerrera I.C., Revy P., Parisot M., Masson C., Boddaert N., Charbit M., RA Decramer S., Novo R., Macher M.A., Ranchin B., Bacchetta J., Laurent A., RA Collardeau-Frachon S., van Eerde A.M., Hildebrandt F., Magen D., RA Antignac C., van Tilbeurgh H., Mollet G.; RT "Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to RT Galloway-Mowat syndrome."; RL Nat. Commun. 10:3967-3967(2019). RN [10] RP INVOLVEMENT IN GAMOS2, VARIANTS GAMOS2 PHE-106 AND SER-137, IDENTIFICATION RP IN THE EKC/KEOPS COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=28805828; DOI=10.1038/ng.3933; RA Braun D.A., Rao J., Mollet G., Schapiro D., Daugeron M.C., Tan W., RA Gribouval O., Boyer O., Revy P., Jobst-Schwan T., Schmidt J.M., RA Lawson J.A., Schanze D., Ashraf S., Ullmann J.F.P., Hoogstraten C.A., RA Boddaert N., Collinet B., Martin G., Liger D., Lovric S., Furlano M., RA Guerrera I.C., Sanchez-Ferras O., Hu J.F., Boschat A.C., Sanquer S., RA Menten B., Vergult S., De Rocker N., Airik M., Hermle T., Shril S., RA Widmeier E., Gee H.Y., Choi W.I., Sadowski C.E., Pabst W.L., Warejko J.K., RA Daga A., Basta T., Matejas V., Scharmann K., Kienast S.D., Behnam B., RA Beeson B., Begtrup A., Bruce M., Ch'ng G.S., Lin S.P., Chang J.H., RA Chen C.H., Cho M.T., Gaffney P.M., Gipson P.E., Hsu C.H., Kari J.A., RA Ke Y.Y., Kiraly-Borri C., Lai W.M., Lemyre E., Littlejohn R.O., Masri A., RA Moghtaderi M., Nakamura K., Ozaltin F., Praet M., Prasad C., Prytula A., RA Roeder E.R., Rump P., Schnur R.E., Shiihara T., Sinha M.D., Soliman N.A., RA Soulami K., Sweetser D.A., Tsai W.H., Tsai J.D., Topaloglu R., Vester U., RA Viskochil D.H., Vatanavicharn N., Waxler J.L., Wierenga K.J., Wolf M.T.F., RA Wong S.N., Leidel S.A., Truglio G., Dedon P.C., Poduri A., Mane S., RA Lifton R.P., Bouchard M., Kannu P., Chitayat D., Magen D., Callewaert B., RA van Tilbeurgh H., Zenker M., Antignac C., Hildebrandt F.; RT "Mutations in KEOPS-complex genes cause nephrotic syndrome with primary RT microcephaly."; RL Nat. Genet. 49:1529-1538(2017). CC -!- FUNCTION: Component of the EKC/KEOPS complex that is required for the CC formation of a threonylcarbamoyl group on adenosine at position 37 CC (t(6)A37) in tRNAs that read codons beginning with adenine CC (PubMed:22912744, PubMed:27903914). The complex is probably involved in CC the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP CC (TC-AMP) to the N6 group of A37 (PubMed:22912744, PubMed:27903914). CC LAGE3 functions as a dimerization module for the complex CC (PubMed:22912744, PubMed:27903914). {ECO:0000305|PubMed:22912744, CC ECO:0000305|PubMed:27903914}. CC -!- SUBUNIT: Component of the EKC/KEOPS complex composed of at least GON7, CC TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes. CC {ECO:0000269|PubMed:22912744, ECO:0000269|PubMed:27903914, CC ECO:0000269|PubMed:28805828, ECO:0000269|PubMed:31481669}. CC -!- INTERACTION: CC Q14657; Q9ULX6: AKAP8L; NbExp=3; IntAct=EBI-1052105, EBI-357530; CC Q14657; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1052105, EBI-3867333; CC Q14657; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-1052105, EBI-5916454; CC Q14657; Q9BXV9: GON7; NbExp=15; IntAct=EBI-1052105, EBI-6256593; CC Q14657; O75031: HSF2BP; NbExp=3; IntAct=EBI-1052105, EBI-7116203; CC Q14657; A0A0C4DGM4: HYKK; NbExp=3; IntAct=EBI-1052105, EBI-10236738; CC Q14657; Q6A162: KRT40; NbExp=6; IntAct=EBI-1052105, EBI-10171697; CC Q14657; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-1052105, EBI-10171774; CC Q14657; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-1052105, EBI-10172526; CC Q14657; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-1052105, EBI-2548751; CC Q14657; Q13064: MKRN3; NbExp=3; IntAct=EBI-1052105, EBI-2340269; CC Q14657; Q9NPF4: OSGEP; NbExp=4; IntAct=EBI-1052105, EBI-1056510; CC Q14657; O76083: PDE9A; NbExp=3; IntAct=EBI-1052105, EBI-742764; CC Q14657; O76083-2: PDE9A; NbExp=3; IntAct=EBI-1052105, EBI-11524542; CC Q14657; Q9NW61: PLEKHJ1; NbExp=3; IntAct=EBI-1052105, EBI-1057560; CC Q14657; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-1052105, EBI-302345; CC Q14657; O75817: POP7; NbExp=3; IntAct=EBI-1052105, EBI-366574; CC Q14657; P28065: PSMB9; NbExp=4; IntAct=EBI-1052105, EBI-603300; CC Q14657; P36406: TRIM23; NbExp=3; IntAct=EBI-1052105, EBI-740098; CC Q14657; P14373: TRIM27; NbExp=3; IntAct=EBI-1052105, EBI-719493; CC Q14657; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-1052105, EBI-2559305; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28805828}. Nucleus CC {ECO:0000269|PubMed:22912744, ECO:0000269|PubMed:27903914, CC ECO:0000269|PubMed:28805828}. CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:12384295, CC ECO:0000269|PubMed:8786131}. CC -!- DISEASE: Galloway-Mowat syndrome 2, X-linked (GAMOS2) [MIM:301006]: A CC form of Galloway-Mowat syndrome, a severe renal-neurological disease CC characterized by early-onset nephrotic syndrome associated with CC microcephaly, central nervous system abnormalities, developmental CC delays, and a propensity for seizures. Brain anomalies include gyration CC defects ranging from lissencephaly to pachygyria and polymicrogyria, CC and cerebellar hypoplasia. Most patients show facial dysmorphism CC characterized by a small, narrow forehead, large/floppy ears, deep-set CC eyes, hypertelorism and micrognathia. Additional variable features are CC visual impairment and arachnodactyly. Most patients die in early CC childhood. {ECO:0000269|PubMed:28805828}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the CTAG/PCC1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA63489.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BX936365; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015744; AAH15744.2; -; mRNA. DR EMBL; BC062330; AAH62330.1; -; mRNA. DR EMBL; X92896; CAA63489.1; ALT_FRAME; mRNA. DR CCDS; CCDS14753.1; -. DR RefSeq; NP_006005.2; NM_006014.4. DR PDB; 6GWJ; X-ray; 1.95 A; B=1-143. DR PDBsum; 6GWJ; -. DR AlphaFoldDB; Q14657; -. DR SASBDB; Q14657; -. DR SMR; Q14657; -. DR BioGRID; 113888; 112. DR ComplexPortal; CPX-2252; KEOPS tRNA N6-adenosine threonylcarbamoyltransferase complex. DR CORUM; Q14657; -. DR IntAct; Q14657; 32. DR MINT; Q14657; -. DR STRING; 9606.ENSP00000349923; -. DR GlyCosmos; Q14657; 1 site, 2 glycans. DR GlyGen; Q14657; 1 site, 2 O-linked glycans (1 site). DR iPTMnet; Q14657; -. DR PhosphoSitePlus; Q14657; -. DR BioMuta; LAGE3; -. DR DMDM; 54041570; -. DR EPD; Q14657; -. DR jPOST; Q14657; -. DR MassIVE; Q14657; -. DR MaxQB; Q14657; -. DR PaxDb; 9606-ENSP00000349923; -. DR PeptideAtlas; Q14657; -. DR ProteomicsDB; 60095; -. DR Pumba; Q14657; -. DR Antibodypedia; 31283; 34 antibodies from 17 providers. DR DNASU; 8270; -. DR Ensembl; ENST00000357360.5; ENSP00000349923.4; ENSG00000196976.8. DR GeneID; 8270; -. DR KEGG; hsa:8270; -. DR MANE-Select; ENST00000357360.5; ENSP00000349923.4; NM_006014.5; NP_006005.2. DR UCSC; uc033fbs.1; human. DR AGR; HGNC:26058; -. DR CTD; 8270; -. DR DisGeNET; 8270; -. DR GeneCards; LAGE3; -. DR HGNC; HGNC:26058; LAGE3. DR HPA; ENSG00000196976; Low tissue specificity. DR MalaCards; LAGE3; -. DR MIM; 300060; gene. DR MIM; 301006; phenotype. DR neXtProt; NX_Q14657; -. DR OpenTargets; ENSG00000196976; -. DR Orphanet; 2065; Galloway-Mowat syndrome. DR PharmGKB; PA128394540; -. DR VEuPathDB; HostDB:ENSG00000196976; -. DR eggNOG; ENOG502SBSA; Eukaryota. DR GeneTree; ENSGT00410000025802; -. DR HOGENOM; CLU_113770_2_2_1; -. DR InParanoid; Q14657; -. DR OMA; HQRVIGK; -. DR OrthoDB; 2947415at2759; -. DR PhylomeDB; Q14657; -. DR TreeFam; TF337064; -. DR PathwayCommons; Q14657; -. DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol. DR SignaLink; Q14657; -. DR BioGRID-ORCS; 8270; 216 hits in 770 CRISPR screens. DR ChiTaRS; LAGE3; human. DR GenomeRNAi; 8270; -. DR Pharos; Q14657; Tdark. DR PRO; PR:Q14657; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q14657; Protein. DR Bgee; ENSG00000196976; Expressed in oocyte and 186 other cell types or tissues. DR Genevisible; Q14657; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0000408; C:EKC/KEOPS complex; IDA:UniProtKB. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0008033; P:tRNA processing; IEA:UniProtKB-KW. DR GO; GO:0070525; P:tRNA threonylcarbamoyladenosine metabolic process; IBA:GO_Central. DR Gene3D; 3.30.310.50; Alpha-D-phosphohexomutase, C-terminal domain; 1. DR InterPro; IPR015419; CTAG/Pcc1. DR PANTHER; PTHR31283; EKC/KEOPS COMPLEX SUBUNIT PCC1 FAMILY MEMBER; 1. DR PANTHER; PTHR31283:SF19; EKC_KEOPS COMPLEX SUBUNIT LAGE3; 1. DR Pfam; PF09341; Pcc1; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Disease variant; Epilepsy; KW Intellectual disability; Nucleus; Reference proteome; tRNA processing. FT CHAIN 1..143 FT /note="EKC/KEOPS complex subunit LAGE3" FT /id="PRO_0000218924" FT REGION 1..57 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VARIANT 106 FT /note="V -> F (in GAMOS2; dbSNP:rs1557211306)" FT /evidence="ECO:0000269|PubMed:28805828" FT /id="VAR_080374" FT VARIANT 137 FT /note="F -> S (in GAMOS2; dbSNP:rs1557211209)" FT /evidence="ECO:0000269|PubMed:28805828" FT /id="VAR_080375" FT STRAND 61..68 FT /evidence="ECO:0007829|PDB:6GWJ" FT HELIX 72..82 FT /evidence="ECO:0007829|PDB:6GWJ" FT TURN 88..92 FT /evidence="ECO:0007829|PDB:6GWJ" FT STRAND 93..100 FT /evidence="ECO:0007829|PDB:6GWJ" FT STRAND 103..111 FT /evidence="ECO:0007829|PDB:6GWJ" FT HELIX 113..137 FT /evidence="ECO:0007829|PDB:6GWJ" SQ SEQUENCE 143 AA; 14804 MW; AD164559371449F8 CRC64; MRDADADAGG GADGGDGRGG HSCRGGVDTA AAPAGGAPPA HAPGPGRDAA SAARGSRMRP HIFTLSVPFP TPLEAEIAHG SLAPDAEPHQ RVVGKDLTVS GRILVVRWKA EDCRLLRISV INFLDQLSLV VRTMQRFGPP VSR //