TBL1Y_HUMAN
ID TBL1Y_HUMAN Reviewed; 522 AA.
AC Q9BQ87; A1L4B3;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=F-box-like/WD repeat-containing protein TBL1Y;
DE AltName: Full=Transducin beta-like protein 1Y;
DE AltName: Full=Transducin-beta-like protein 1, Y-linked;
GN Name=TBL1Y; Synonyms=TBL1;
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], AND TISSUE SPECIFICITY.
RX PubMed=12815422; DOI=10.1038/nature01722;
RA Skaletsky H., Kuroda-Kawaguchi T., Minx P.J., Cordum H.S., Hillier L.W.,
RA Brown L.G., Repping S., Pyntikova T., Ali J., Bieri T., Chinwalla A.,
RA Delehaunty A., Delehaunty K., Du H., Fewell G., Fulton L., Fulton R.,
RA Graves T.A., Hou S.-F., Latrielle P., Leonard S., Mardis E., Maupin R.,
RA McPherson J., Miner T., Nash W., Nguyen C., Ozersky P., Pepin K., Rock S.,
RA Rohlfing T., Scott K., Schultz B., Strong C., Tin-Wollam A., Yang S.-P.,
RA Waterston R.H., Wilson R.K., Rozen S., Page D.C.;
RT "The male-specific region of the human Y chromosome is a mosaic of discrete
RT sequence classes.";
RL Nature 423:825-837(2003).
RN [2]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 INTERACTION WITH NCOR2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP INVOLVEMENT IN DFNY2, VARIANT DFNY2 VAL-69, AND CHARACTERIZATION OF VARIANT
RP DFNY2 VAL-69.
RX PubMed=30341416; DOI=10.1038/s41431-018-0282-4;
RA Di Stazio M., Collesi C., Vozzi D., Liu W., Myers M., Morgan A.,
RA D Adamo P.A., Girotto G., Rubinato E., Giacca M., Gasparini P.;
RT "TBL1Y: a new gene involved in syndromic hearing loss.";
RL Eur. J. Hum. Genet. 27:466-474(2019).
CC -!- FUNCTION: F-box-like protein involved in the recruitment of the
CC ubiquitin/19S proteasome complex to nuclear receptor-regulated
CC transcription units. Plays an essential role in transcription
CC activation mediated by nuclear receptors. Probably acts as integral
CC component of corepressor complexes that mediates the recruitment of the
CC 19S proteasome complex, leading to the subsequent proteasomal
CC degradation of transcription repressor complexes, thereby allowing
CC cofactor exchange (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Probable component of the N-Cor repressor complex and some E3
CC ubiquitin ligase complex. Interacts with NCOR2 (PubMed:30341416).
CC {ECO:0000269|PubMed:30341416}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:30341416}.
CC -!- TISSUE SPECIFICITY: Fetal brain and prostate. Expressed in the cochlear
CC spiral ganglion neurons, and in outer and inner hair cells
CC (PubMed:30341416). {ECO:0000269|PubMed:12815422,
CC ECO:0000269|PubMed:30341416}.
CC -!- DOMAIN: The F-box-like domain is related to the F-box domain, and
CC apparently displays the same function as component of ubiquitin E3
CC ligase complexes. {ECO:0000250}.
CC -!- DISEASE: Deafness, Y-linked 2 (DFNY2) [MIM:400047]: A form of non-
CC syndromic sensorineural hearing loss. Sensorineural deafness results
CC from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. DFNY2 patients show bilateral symmetric hearing loss
CC ranging from mild to severe, with onset in the third to fifth decades
CC of life. {ECO:0000269|PubMed:30341416}. Note=The disease may be caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the WD repeat EBI family. {ECO:0000305}.
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DR EMBL; AF332220; AAK13472.1; -; mRNA.
DR EMBL; AF332221; AAK13473.1; -; mRNA.
DR EMBL; AF332222; AAK13474.1; -; mRNA.
DR EMBL; CH471163; EAW59126.1; -; Genomic_DNA.
DR EMBL; BC130471; AAI30472.1; -; mRNA.
DR EMBL; BC130473; AAI30474.1; -; mRNA.
DR CCDS; CCDS14779.1; -.
DR RefSeq; NP_150600.1; NM_033284.1.
DR RefSeq; NP_599020.1; NM_134258.1.
DR RefSeq; NP_599021.1; NM_134259.1.
DR AlphaFoldDB; Q9BQ87; -.
DR SMR; Q9BQ87; -.
DR BioGRID; 124751; 44.
DR CORUM; Q9BQ87; -.
DR IntAct; Q9BQ87; 31.
DR MINT; Q9BQ87; -.
DR iPTMnet; Q9BQ87; -.
DR PhosphoSitePlus; Q9BQ87; -.
DR BioMuta; TBL1Y; -.
DR DMDM; 23396873; -.
DR EPD; Q9BQ87; -.
DR jPOST; Q9BQ87; -.
DR MassIVE; Q9BQ87; -.
DR MaxQB; Q9BQ87; -.
DR PaxDb; Q9BQ87; -.
DR PeptideAtlas; Q9BQ87; -.
DR PRIDE; Q9BQ87; -.
DR ProteomicsDB; 78642; -.
DR Antibodypedia; 41670; 87 antibodies from 17 providers.
DR DNASU; 90665; -.
DR Ensembl; ENST00000346432.3; ENSP00000328879.4; ENSG00000092377.15.
DR Ensembl; ENST00000355162.6; ENSP00000347289.2; ENSG00000092377.15.
DR Ensembl; ENST00000383032.6; ENSP00000372499.1; ENSG00000092377.15.
DR GeneID; 90665; -.
DR KEGG; hsa:90665; -.
DR MANE-Select; ENST00000383032.6; ENSP00000372499.1; NM_033284.2; NP_150600.1.
DR UCSC; uc004frb.3; human.
DR CTD; 90665; -.
DR DisGeNET; 90665; -.
DR GeneCards; TBL1Y; -.
DR HGNC; HGNC:18502; TBL1Y.
DR HPA; ENSG00000092377; Tissue enhanced (prostate, thyroid gland).
DR MalaCards; TBL1Y; -.
DR MIM; 400033; gene.
DR MIM; 400047; phenotype.
DR neXtProt; NX_Q9BQ87; -.
DR OpenTargets; ENSG00000092377; -.
DR PharmGKB; PA38564; -.
DR VEuPathDB; HostDB:ENSG00000092377; -.
DR GeneTree; ENSGT00940000153421; -.
DR HOGENOM; CLU_007609_2_0_1; -.
DR InParanoid; Q9BQ87; -.
DR OMA; TERWYWE; -.
DR PhylomeDB; Q9BQ87; -.
DR TreeFam; TF323190; -.
DR PathwayCommons; Q9BQ87; -.
DR SignaLink; Q9BQ87; -.
DR SIGNOR; Q9BQ87; -.
DR BioGRID-ORCS; 90665; 15 hits in 696 CRISPR screens.
DR ChiTaRS; TBL1Y; human.
DR GenomeRNAi; 90665; -.
DR Pharos; Q9BQ87; Tbio.
DR PRO; PR:Q9BQ87; -.
DR Proteomes; UP000005640; Chromosome Y.
DR RNAct; Q9BQ87; protein.
DR Bgee; ENSG00000092377; Expressed in adrenal tissue and 71 other tissues.
DR ExpressionAtlas; Q9BQ87; baseline and differential.
DR Genevisible; Q9BQ87; HS.
DR GO; GO:0000118; C:histone deacetylase complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0016575; P:histone deacetylation; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR045183; Ebi-like.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR006594; LisH.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR22846; PTHR22846; 1.
DR Pfam; PF08513; LisH; 1.
DR Pfam; PF00400; WD40; 6.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00667; LisH; 1.
DR SMART; SM00320; WD40; 8.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50896; LISH; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 4.
DR PROSITE; PS50082; WD_REPEATS_2; 6.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Deafness; Disease variant; Isopeptide bond;
KW Non-syndromic deafness; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Ubl conjugation;
KW Ubl conjugation pathway; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9BZK7"
FT CHAIN 2..522
FT /note="F-box-like/WD repeat-containing protein TBL1Y"
FT /id="PRO_0000051264"
FT DOMAIN 4..36
FT /note="LisH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126"
FT DOMAIN 41..86
FT /note="F-box-like"
FT REPEAT 177..216
FT /note="WD 1"
FT REPEAT 233..272
FT /note="WD 2"
FT REPEAT 274..313
FT /note="WD 3"
FT REPEAT 316..354
FT /note="WD 4"
FT REPEAT 357..396
FT /note="WD 5"
FT REPEAT 399..447
FT /note="WD 6"
FT REPEAT 450..489
FT /note="WD 7"
FT REPEAT 491..521
FT /note="WD 8"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZK7"
FT MOD_RES 102
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BHJ5"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZK7"
FT CROSSLNK 287
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BZK7"
FT VARIANT 69
FT /note="D -> V (in DFNY2; unknown pathological significance;
FT increased protein degradation; dbSNP:rs199659121)"
FT /evidence="ECO:0000269|PubMed:30341416"
FT /id="VAR_082113"
SQ SEQUENCE 522 AA; 56688 MW; 4E020216422442D8 CRC64;
MSITSDEVNF LVYRYLQESG FSHSAFTFGI ESHISQSNIN GTLVPPSALI SILQKGLQYV
EAEISINKDG TVFDSRPIES LSLIVAVIPD VVQMRQQAFG EKLTQQQASA AATEASAMAK
AATMTPAAIS QQNPPKNREA TVNGEENGAH EINNHSKPME IDGDVEIPPN KATVLRGHES
EVFICAWNPV SDLLASGSGD STARIWNLNE NSNGGSTQLV LRHCIREGGH DVPSNKDVTS
LDWNSDGTLL AMGSYDGFAR IWTENGNLAS TLGQHKGPIF ALKWNKKGNY VLSAGVDKTT
IIWDAHTGEA KQQFPFHSAP ALDVDWQNNM TFASCSTDMC IHVCRLGCDH PVKTFQGHTN
EVNAIKWDPS GMLLASCSDD MTLKIWSMKQ DACVHDLQAH SKEIYTIKWS PTGPATSNPN
SSIMLASASF DSTVRLWDVE QGVCTHTLMK HQEPVYSVAF SPDGKYLASG SFDKYVHIWN
TQSGSLVHSY QGTGGIFEVC WNARGDKVGA SASDGSVCVL DL
