TPRKB_HUMAN
ID TPRKB_HUMAN Reviewed; 175 AA.
AC Q9Y3C4; D6W5H6; Q8IWR6; Q8IWR7; Q9H3K4;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=EKC/KEOPS complex subunit TPRKB {ECO:0000305};
DE AltName: Full=PRPK-binding protein {ECO:0000303|PubMed:12659830};
DE AltName: Full=TP53RK-binding protein {ECO:0000303|PubMed:12659830};
GN Name=TPRKB {ECO:0000312|HGNC:HGNC:24259};
GN ORFNames=CGI-121 {ECO:0000303|PubMed:10810093,
GN ECO:0000303|PubMed:12659830}, My019;
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] (ISOFORMS 1; 2 AND 3), SUBCELLULAR LOCATION,
RP INTERACTION WITH TP53RK, AND TISSUE SPECIFICITY.
RX PubMed=12659830; DOI=10.1016/s0006-291x(03)00333-4;
RA Miyoshi A., Kito K., Aramoto T., Abe Y., Kobayashi N., Ueda N.;
RT "Identification of CGI-121, a novel PRPK (p53-related protein kinase)-
RT binding protein.";
RL Biochem. Biophys. Res. Commun. 303:399-405(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RA Mao Y.M., Xie Y., Mu Z.M., Li Y., Huang Y.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [7]
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 [8]
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 [9]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE EKC/KEOPS COMPLEX,
RP INVOLVEMENT IN GAMOS5, AND VARIANTS GAMOS5 PRO-136 AND CYS-149.
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).
RN [10]
RP IDENTIFICATION IN THE EKC/KEOPS COMPLEX.
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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS).
RX PubMed=18951093; DOI=10.1016/j.molcel.2008.10.002;
RA Mao D.Y., Neculai D., Downey M., Orlicky S., Haffani Y.Z., Ceccarelli D.F.,
RA Ho J.S., Szilard R.K., Zhang W., Ho C.S., Wan L., Fares C., Rumpel S.,
RA Kurinov I., Arrowsmith C.H., Durocher D., Sicheri F.;
RT "Atomic structure of the KEOPS complex: an ancient protein kinase-
RT containing molecular machine.";
RL Mol. Cell 32:259-275(2008).
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:28805828). 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:28805828).
CC TPRKB acts as an allosteric effector that regulates the t(6)A activity
CC of the complex. TPRKB is not required for tRNA modification
CC (PubMed:22912744, PubMed:28805828). {ECO:0000269|PubMed:28805828,
CC ECO:0000305|PubMed:22912744}.
CC -!- SUBUNIT: Component of the EKC/KEOPS complex composed of at least GON7,
CC TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes
CC (PubMed:22912744, PubMed:28805828). Interacts with TP53RK/PRPK
CC (PubMed:12659830). {ECO:0000269|PubMed:12659830,
CC ECO:0000269|PubMed:22912744, ECO:0000269|PubMed:28805828}.
CC -!- INTERACTION:
CC Q9Y3C4; Q96S44: TP53RK; NbExp=5; IntAct=EBI-750123, EBI-739588;
CC Q9Y3C4; P14373: TRIM27; NbExp=3; IntAct=EBI-750123, EBI-719493;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12659830,
CC ECO:0000269|PubMed:28805828}. Nucleus {ECO:0000269|PubMed:12659830,
CC ECO:0000269|PubMed:22912744, ECO:0000269|PubMed:28805828}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y3C4-1; Sequence=Displayed;
CC Name=2; Synonyms=S1;
CC IsoId=Q9Y3C4-2; Sequence=VSP_023414;
CC Name=3; Synonyms=L1;
CC IsoId=Q9Y3C4-3; Sequence=VSP_023415;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:12659830}.
CC -!- DISEASE: Galloway-Mowat syndrome 5 (GAMOS5) [MIM:617731]: A form of
CC 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 CGI121/TPRKB family. {ECO:0000305}.
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DR EMBL; AY157986; AAN76356.1; -; mRNA.
DR EMBL; AY157987; AAN76357.1; -; mRNA.
DR EMBL; AF060921; AAG43133.1; -; mRNA.
DR EMBL; AF151879; AAD34116.1; -; mRNA.
DR EMBL; CH471053; EAW99720.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99722.1; -; Genomic_DNA.
DR EMBL; BC029492; AAH29492.1; -; mRNA.
DR CCDS; CCDS1927.1; -. [Q9Y3C4-1]
DR CCDS; CCDS82471.1; -. [Q9Y3C4-3]
DR RefSeq; NP_001317315.1; NM_001330386.1. [Q9Y3C4-3]
DR RefSeq; NP_001317316.1; NM_001330387.1. [Q9Y3C4-3]
DR RefSeq; NP_001317317.1; NM_001330388.1. [Q9Y3C4-1]
DR RefSeq; NP_001317318.1; NM_001330389.1. [Q9Y3C4-1]
DR RefSeq; NP_001317320.1; NM_001330391.1. [Q9Y3C4-2]
DR RefSeq; NP_001317321.1; NM_001330392.1. [Q9Y3C4-2]
DR RefSeq; NP_057142.1; NM_016058.3. [Q9Y3C4-1]
DR RefSeq; XP_006712090.1; XM_006712027.3.
DR RefSeq; XP_011531179.1; XM_011532877.2.
DR RefSeq; XP_011531180.1; XM_011532878.2.
DR RefSeq; XP_016859721.1; XM_017004232.1.
DR RefSeq; XP_016859722.1; XM_017004233.1.
DR RefSeq; XP_016859723.1; XM_017004234.1.
DR PDB; 3ENP; X-ray; 2.48 A; A/B=1-175.
DR PDB; 6WQX; X-ray; 2.53 A; A/B=1-175.
DR PDBsum; 3ENP; -.
DR PDBsum; 6WQX; -.
DR AlphaFoldDB; Q9Y3C4; -.
DR SMR; Q9Y3C4; -.
DR BioGRID; 119210; 50.
DR CORUM; Q9Y3C4; -.
DR IntAct; Q9Y3C4; 14.
DR MINT; Q9Y3C4; -.
DR STRING; 9606.ENSP00000272424; -.
DR GlyGen; Q9Y3C4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y3C4; -.
DR MetOSite; Q9Y3C4; -.
DR PhosphoSitePlus; Q9Y3C4; -.
DR BioMuta; TPRKB; -.
DR DMDM; 74735252; -.
DR EPD; Q9Y3C4; -.
DR jPOST; Q9Y3C4; -.
DR MassIVE; Q9Y3C4; -.
DR MaxQB; Q9Y3C4; -.
DR PaxDb; Q9Y3C4; -.
DR PeptideAtlas; Q9Y3C4; -.
DR PRIDE; Q9Y3C4; -.
DR ProteomicsDB; 86011; -. [Q9Y3C4-1]
DR ProteomicsDB; 86012; -. [Q9Y3C4-2]
DR ProteomicsDB; 86013; -. [Q9Y3C4-3]
DR Antibodypedia; 31361; 233 antibodies from 25 providers.
DR DNASU; 51002; -.
DR Ensembl; ENST00000272424.11; ENSP00000272424.5; ENSG00000144034.16. [Q9Y3C4-1]
DR Ensembl; ENST00000318190.7; ENSP00000325398.7; ENSG00000144034.16. [Q9Y3C4-3]
DR Ensembl; ENST00000409716.6; ENSP00000386936.2; ENSG00000144034.16. [Q9Y3C4-3]
DR GeneID; 51002; -.
DR KEGG; hsa:51002; -.
DR MANE-Select; ENST00000272424.11; ENSP00000272424.5; NM_016058.5; NP_057142.1.
DR UCSC; uc002sjn.3; human. [Q9Y3C4-1]
DR CTD; 51002; -.
DR DisGeNET; 51002; -.
DR GeneCards; TPRKB; -.
DR HGNC; HGNC:24259; TPRKB.
DR HPA; ENSG00000144034; Low tissue specificity.
DR MalaCards; TPRKB; -.
DR MIM; 608680; gene.
DR MIM; 617731; phenotype.
DR neXtProt; NX_Q9Y3C4; -.
DR OpenTargets; ENSG00000144034; -.
DR Orphanet; 2065; Galloway-Mowat syndrome.
DR PharmGKB; PA143485660; -.
DR VEuPathDB; HostDB:ENSG00000144034; -.
DR eggNOG; KOG4066; Eukaryota.
DR GeneTree; ENSGT00390000012942; -.
DR HOGENOM; CLU_065847_2_0_1; -.
DR InParanoid; Q9Y3C4; -.
DR OMA; HNVHSEI; -.
DR OrthoDB; 1360669at2759; -.
DR PhylomeDB; Q9Y3C4; -.
DR TreeFam; TF315098; -.
DR PathwayCommons; Q9Y3C4; -.
DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol.
DR SignaLink; Q9Y3C4; -.
DR BioGRID-ORCS; 51002; 445 hits in 1061 CRISPR screens.
DR ChiTaRS; TPRKB; human.
DR EvolutionaryTrace; Q9Y3C4; -.
DR GenomeRNAi; 51002; -.
DR Pharos; Q9Y3C4; Tbio.
DR PRO; PR:Q9Y3C4; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9Y3C4; protein.
DR Bgee; ENSG00000144034; Expressed in right uterine tube and 199 other tissues.
DR Genevisible; Q9Y3C4; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0000408; C:EKC/KEOPS complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0000722; P:telomere maintenance via recombination; IBA:GO_Central.
DR GO; GO:0002949; P:tRNA threonylcarbamoyladenosine modification; IDA:UniProtKB.
DR Gene3D; 3.30.2380.10; -; 1.
DR InterPro; IPR013926; CGI121/TPRKB.
DR InterPro; IPR036504; CGI121/TPRKB_sf.
DR PANTHER; PTHR15840; PTHR15840; 1.
DR Pfam; PF08617; CGI-121; 1.
DR SUPFAM; SSF143870; SSF143870; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; Epilepsy;
KW Intellectual disability; Nucleus; Reference proteome; tRNA processing.
FT CHAIN 1..175
FT /note="EKC/KEOPS complex subunit TPRKB"
FT /id="PRO_0000279220"
FT VAR_SEQ 15..47
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12659830"
FT /id="VSP_023414"
FT VAR_SEQ 47
FT /note="V -> VFHSCCPGWSAMARSWLTATSASRVQAIVLPQPPELLGLQ (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:12659830"
FT /id="VSP_023415"
FT VARIANT 136
FT /note="L -> P (in GAMOS5; dbSNP:rs1553433412)"
FT /evidence="ECO:0000269|PubMed:28805828"
FT /id="VAR_080355"
FT VARIANT 149
FT /note="Y -> C (in GAMOS5; dbSNP:rs1233885358)"
FT /evidence="ECO:0000269|PubMed:28805828"
FT /id="VAR_080356"
FT CONFLICT 147
FT /note="K -> R (in Ref. 2; AAG43133)"
FT /evidence="ECO:0000305"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:3ENP"
FT STRAND 8..10
FT /evidence="ECO:0007829|PDB:6WQX"
FT STRAND 14..22
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 26..35
FT /evidence="ECO:0007829|PDB:3ENP"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 51..65
FT /evidence="ECO:0007829|PDB:3ENP"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:3ENP"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 75..83
FT /evidence="ECO:0007829|PDB:3ENP"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 89..96
FT /evidence="ECO:0007829|PDB:3ENP"
FT STRAND 103..111
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:3ENP"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:6WQX"
FT HELIX 158..171
FT /evidence="ECO:0007829|PDB:3ENP"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:6WQX"
SQ SEQUENCE 175 AA; 19661 MW; FB13C0923148C157 CRC64;
MQLTHQLDLF PECRVTLLLF KDVKNAGDLR RKAMEGTIDG SLINPTVIVD PFQILVAANK
AVHLYKLGKM KTRTLSTEII FNLSPNNNIS EALKKFGISA NDTSILIVYI EEGEKQINQE
YLISQVEGHQ VSLKNLPEIM NITEVKKIYK LSSQEESIGT LLDAIICRMS TKDVL
