ID ZBT7B_MOUSE Reviewed; 544 AA. AC Q64321; Q80VV5; DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 16-AUG-2004, sequence version 2. DT 27-MAR-2024, entry version 185. DE RecName: Full=Zinc finger and BTB domain-containing protein 7B {ECO:0000305}; DE AltName: Full=Krueppel-related zinc finger protein cKrox; DE Short=c-Krox; DE AltName: Full=T-helper-inducing POZ/Krueppel-like factor; DE AltName: Full=Zinc finger protein 67; DE Short=Zfp-67; DE AltName: Full=Zinc finger protein Th-POK {ECO:0000303|PubMed:24880459}; GN Name=Zbtb7b {ECO:0000312|MGI:MGI:102755}; GN Synonyms=Thpok {ECO:0000303|PubMed:24880459}, Zfp67; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary tumor; 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-544, FUNCTION, TISSUE SPECIFICITY, AND RP DEVELOPMENTAL STAGE. RX PubMed=7937772; DOI=10.1073/pnas.91.20.9372; RA Galera P., Musso M., Ducy P., Karsenty G.; RT "c-Krox, a transcriptional regulator of type I collagen gene expression, is RT preferentially expressed in skin."; RL Proc. Natl. Acad. Sci. U.S.A. 91:9372-9376(1994). RN [3] RP FUNCTION, TISSUE SPECIFICITY, AND VARIANT HD GLY-389. RX PubMed=15729333; DOI=10.1038/nature03338; RA He X., He X., Dave V.P., Zhang Y., Hua X., Nicolas E., Xu W., Roe B.A., RA Kappes D.J.; RT "The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T- RT cell lineage commitment."; RL Nature 433:826-833(2005). RN [4] RP FUNCTION. RX PubMed=18258917; DOI=10.1126/science.1151844; RA Setoguchi R., Tachibana M., Naoe Y., Muroi S., Akiyama K., Tezuka C., RA Okuda T., Taniuchi I.; RT "Repression of the transcription factor Th-POK by Runx complexes in RT cytotoxic T cell development."; RL Science 319:822-825(2008). RN [5] RP ACETYLATION AT LYS-210; LYS-216 AND LYS-339, MUTAGENESIS OF LYS-207; RP LYS-210; LYS-216; LYS-339 AND LYS-343, AND UBIQUITINATION AT LYS-210; RP LYS-216 AND LYS-339. RX PubMed=20810990; DOI=10.4049/jimmunol.1001462; RA Zhang M., Zhang J., Rui J., Liu X.; RT "p300-mediated acetylation stabilizes the Th-inducing POK factor."; RL J. Immunol. 185:3960-3969(2010). RN [6] RP FUNCTION, MUTAGENESIS OF LEU-21 AND 27-GLN-ARG-28, VARIANT HD GLY-389, RP CHARACTERIZATION OF VARIANT HD GLY-389, HOMODIMERIZATION, SUBCELLULAR RP LOCATION, AND INTERACTION WITH HDAC4 AND HDAC5. RX PubMed=22730529; DOI=10.4049/jimmunol.1201077; RA Rui J., Liu H., Zhu X., Cui Y., Liu X.; RT "Epigenetic silencing of CD8 genes by ThPOK-mediated deacetylation during RT CD4 T cell differentiation."; RL J. Immunol. 189:1380-1390(2012). RN [7] RP FUNCTION, VARIANT HELPLESS ARG-102, AND CHARACTERIZATION OF VARIANT RP ARG-102. RX PubMed=23105140; DOI=10.4049/jimmunol.1201486; RA Enders A., Stankovic S., Teh C., Uldrich A.P., Yabas M., Juelich T., RA Altin J.A., Frankenreiter S., Bergmann H., Roots C.M., Kyparissoudis K., RA Goodnow C.C., Godfrey D.I.; RT "ZBTB7B (Th-POK) regulates the development of IL-17-producing CD1d- RT restricted mouse NKT cells."; RL J. Immunol. 189:5240-5249(2012). RN [8] RP FUNCTION. RX PubMed=23481257; DOI=10.1038/emboj.2013.47; RA Tanaka H., Naito T., Muroi S., Seo W., Chihara R., Miyamoto C., RA Kominami R., Taniuchi I.; RT "Epigenetic Thpok silencing limits the time window to choose CD4(+) helper- RT lineage fate in the thymus."; RL EMBO J. 32:1183-1194(2013). RN [9] RP FUNCTION, AND VARIANT HD GLY-389. RX PubMed=24880459; DOI=10.1038/ni.2917; RA Luckey M.A., Kimura M.Y., Waickman A.T., Feigenbaum L., Singer A., RA Park J.H.; RT "The transcription factor ThPOK suppresses Runx3 and imposes CD4(+) lineage RT fate by inducing the SOCS suppressors of cytokine signaling."; RL Nat. Immunol. 15:638-645(2014). RN [10] RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, RP AND INTERACTION WITH HNRNPU; NCL; NEDD4 AND YBX1. RX PubMed=28784777; DOI=10.1073/pnas.1703494114; RA Li S., Mi L., Yu L., Yu Q., Liu T., Wang G.X., Zhao X.Y., Wu J., Lin J.D.; RT "Zbtb7b engages the long noncoding RNA Blnc1 to drive brown and beige fat RT development and thermogenesis."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E7111-E7120(2017). RN [11] RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, INDUCTION BY INSULIN, RP AND SUBCELLULAR LOCATION. RX PubMed=29420538; DOI=10.1371/journal.pgen.1007211; RA Zhang R., Ma H., Gao Y., Wu Y., Qiao Y., Geng A., Cai C., Han Y., RA Zeng Y.A., Liu X., Ge G.; RT "Th-POK regulates mammary gland lactation through mTOR-SREBP pathway."; RL PLoS Genet. 14:E1007211-E1007211(2018). CC -!- FUNCTION: Transcription regulator that acts as a key regulator of CC lineage commitment of immature T-cell precursors. Exerts distinct CC biological functions in the mammary epithelial cells and T cells in a CC tissue-specific manner (PubMed:15729333, PubMed:29420538). Necessary CC and sufficient for commitment of CD4 lineage, while its absence causes CC CD8 commitment. Development of immature T-cell precursors (thymocytes) CC to either the CD4 helper or CD8 killer T-cell lineages correlates CC precisely with their T-cell receptor specificity for major CC histocompatibility complex class II or class I molecules, respectively. CC Cross-antagonism between ZBTB7B and CBF complexes are determinative to CC CD4 versus CD8 cell fate decision (PubMed:15729333, PubMed:24880459, CC PubMed:18258917, PubMed:23481257). Suppresses RUNX3 expression and CC imposes CD4+ lineage fate by inducing the SOCS suppressors of cytokine CC signaling. induces, as a transcriptional activator, SOCS genes CC expression which represses RUNX3 expression and promotes the CD4+ CC lineage fate (PubMed:24880459). During CD4 lineage commitment, CC associates with multiple sites at the CD8 locus, acting as a negative CC regulator of the CD8 promoter and enhancers by epigenetic silencing CC through the recruitment of class II histone deacetylases, such as HDAC4 CC and HDAC5, to these loci (PubMed:22730529). Regulates the development CC of IL17-producing CD1d-restricted naural killer (NK) T cells CC (PubMed:23105140). Also functions as an important metabolic regulator CC in the lactating mammary glands. Critical feed-forward regulator of CC insulin signaling in mammary gland lactation, directly regulates CC expression of insulin receptor substrate-1 (IRS-1) and insulin-induced CC Akt-mTOR-SREBP signaling (PubMed:29420538). Transcriptional repressor CC of the collagen COL1A1 and COL1A2 genes. May also function as a CC repressor of fibronectin and possibly other extracellular matrix genes CC (PubMed:7937772). Potent driver of brown fat development, thermogenesis CC and cold-induced beige fat formation (PubMed:28784777). Recruits the CC brown fat lncRNA 1 (Blnc1):HNRNPU ribonucleoprotein complex to activate CC thermogenic gene expression in brown and beige adipocytes CC (PubMed:28784777). {ECO:0000269|PubMed:15729333, CC ECO:0000269|PubMed:18258917, ECO:0000269|PubMed:22730529, CC ECO:0000269|PubMed:23105140, ECO:0000269|PubMed:23481257, CC ECO:0000269|PubMed:24880459, ECO:0000269|PubMed:28784777, CC ECO:0000269|PubMed:29420538, ECO:0000269|PubMed:7937772}. CC -!- SUBUNIT: Homodimerizes (PubMed:22730529). Interacts with NCL, NEDD4 and CC YBX1 (PubMed:28784777). Interacts with HNRNPU (via RNA-binding RGG-box CC region); the interaction facilitates the recruitment of long non-coding CC RNA Blnc1 by ZBTB7B (PubMed:28784777). Interacts with HDAC4 and HDAC5; CC the interaction allows the recruitment of HDAC4 and HDAC5 on CD8 loci CC for deacetylation and possible inhibition of CD8 genes expression CC (PubMed:22730529). {ECO:0000269|PubMed:22730529, CC ECO:0000269|PubMed:28784777}. CC -!- INTERACTION: CC Q64321; Q8CIH5: Plcg2; NbExp=3; IntAct=EBI-642868, EBI-617954; CC Q64321; Q61029: Tmpo; NbExp=2; IntAct=EBI-642868, EBI-6172136; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22730529, CC ECO:0000269|PubMed:29420538}. CC -!- TISSUE SPECIFICITY: Widely expressed, with a higher level in skin. CC Expressed in thymus. Restricted to CD4 cells (mature single positive CC CD4(+) and intermediate CD4(+)CD8(+) cells). Expressed in the luminal CC epithelial cells in the mammary glands where is up-regulated at late CC pregnancy and lactation (PubMed:29420538). Expression is enriched in CC brown fat (PubMed:28784777). {ECO:0000269|PubMed:15729333, CC ECO:0000269|PubMed:28784777, ECO:0000269|PubMed:29420538, CC ECO:0000269|PubMed:7937772}. CC -!- DEVELOPMENTAL STAGE: Expressed, beginning at 9.5 days of gestation and CC at 10.5 days in regions destined to become skin. In adult animals, CC expression is predominantly in skin (PubMed:7937772). Expression is CC significantly increased during brown adipocyte differentiation CC (PubMed:28784777). {ECO:0000269|PubMed:28784777, CC ECO:0000269|PubMed:7937772}. CC -!- INDUCTION: Expression in mammary glands is induced by insulin. CC {ECO:0000269|PubMed:29420538}. CC -!- PTM: Acetylated directly and specifically by EP300. EP300-mediated CC acetylation of Lys-210, Lys-216 and Lys-339 stabilizes the protein by CC antagonizing ubiquitin conjugation. {ECO:0000269|PubMed:20810990}. CC -!- PTM: Ubiquitinated, leading to proteasomal degradation. Competes with CC acetylation on Lys-210, Lys-216 and Lys-339. CC {ECO:0000269|PubMed:20810990}. CC -!- DISEASE: Note=Defects in Zbtb7b are the cause of helper deficient CC disease (HD) or helpless disease. HD and helpless mice are CC distinguished by the virtual absence of peripheral T-cells of the CC CD4(+)CD8(-) major histocompatibility complex (MHC) class II-restricted CC T-helper subset due to a specific block in thymic development. The CC developmental defect is selective for CD4(+)CD8(-) cells; the CC maturation of CD4(-)CD8(+) and gamma delta T-cells is normal indicating CC that lineage commitment is specifically perturbed without affecting CC positive selection. In helpless disease, NKT cells are CC hyperproliferative, most lack CD4 and instead express CD8. The majority CC of NKT cells in the thymus produce IL17 with high frequency while very CC few produce IFNG or other cytokines (PubMed:23105140). CC {ECO:0000269|PubMed:15729333, ECO:0000269|PubMed:22730529, CC ECO:0000269|PubMed:23105140, ECO:0000269|PubMed:24880459}. CC -!- DISRUPTION PHENOTYPE: Mutant females are unable to efficiently secrete CC milk lipid and to nurse the offspring. They show normal mammary gland CC morphogenesis in puberty and alveologenesis in pregnancy, but are CC defective in triggering the onset of lactation upon parturition with CC large cellular lipid droplets retained within alveolar epithelial cells CC (PubMed:29420538). Mice are more sensitive to cold temperature, with CC impaired cold-induced transcriptional remodeling in brown fat and CC diminished browning of inguinal white fat (PubMed:28784777). CC {ECO:0000269|PubMed:28784777, ECO:0000269|PubMed:29420538}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA61956.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAA61956.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305}; CC Sequence=CAA85307.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAA85307.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; 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; BC046533; AAH46533.1; -; mRNA. DR EMBL; L35307; AAA61956.1; ALT_SEQ; mRNA. DR EMBL; Z36549; CAA85307.1; ALT_SEQ; mRNA. DR CCDS; CCDS17504.1; -. DR PIR; I49603; I49603. DR RefSeq; NP_033591.2; NM_009565.4. DR RefSeq; XP_006501376.1; XM_006501313.2. DR RefSeq; XP_006501377.1; XM_006501314.2. DR RefSeq; XP_006501379.1; XM_006501316.2. DR RefSeq; XP_006501380.1; XM_006501317.3. DR RefSeq; XP_006501381.1; XM_006501318.3. DR RefSeq; XP_006501382.1; XM_006501319.3. DR AlphaFoldDB; Q64321; -. DR SMR; Q64321; -. DR BioGRID; 204677; 324. DR IntAct; Q64321; 4. DR MINT; Q64321; -. DR STRING; 10090.ENSMUSP00000103058; -. DR iPTMnet; Q64321; -. DR PhosphoSitePlus; Q64321; -. DR MaxQB; Q64321; -. DR PaxDb; 10090-ENSMUSP00000029677; -. DR ProteomicsDB; 275339; -. DR Antibodypedia; 20407; 319 antibodies from 38 providers. DR Ensembl; ENSMUST00000029677.9; ENSMUSP00000029677.9; ENSMUSG00000028042.16. DR Ensembl; ENSMUST00000107432.8; ENSMUSP00000103055.2; ENSMUSG00000028042.16. DR Ensembl; ENSMUST00000107433.8; ENSMUSP00000103056.2; ENSMUSG00000028042.16. DR Ensembl; ENSMUST00000107435.8; ENSMUSP00000103058.2; ENSMUSG00000028042.16. DR GeneID; 22724; -. DR KEGG; mmu:22724; -. DR UCSC; uc008pza.1; mouse. DR AGR; MGI:102755; -. DR CTD; 51043; -. DR MGI; MGI:102755; Zbtb7b. DR VEuPathDB; HostDB:ENSMUSG00000028042; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000160219; -. DR HOGENOM; CLU_025627_0_0_1; -. DR InParanoid; Q64321; -. DR OMA; SPEHHEL; -. DR OrthoDB; 783166at2759; -. DR PhylomeDB; Q64321; -. DR TreeFam; TF331824; -. DR BioGRID-ORCS; 22724; 4 hits in 79 CRISPR screens. DR ChiTaRS; Zbtb7b; mouse. DR PRO; PR:Q64321; -. DR Proteomes; UP000000589; Chromosome 3. DR RNAct; Q64321; Protein. DR Bgee; ENSMUSG00000028042; Expressed in granulocyte and 185 other cell types or tissues. DR ExpressionAtlas; Q64321; baseline and differential. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:0001217; F:DNA-binding transcription repressor activity; IMP:UniProtKB. DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI. DR GO; GO:1990845; P:adaptive thermogenesis; IMP:UniProtKB. DR GO; GO:0007595; P:lactation; IMP:UniProtKB. DR GO; GO:0043377; P:negative regulation of CD8-positive, alpha-beta T cell differentiation; IMP:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:MGI. DR GO; GO:0051141; P:negative regulation of NK T cell proliferation; IMP:UniProtKB. DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; IMP:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0001865; P:NK T cell differentiation; IMP:UniProtKB. DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IMP:UniProtKB. DR GO; GO:0043372; P:positive regulation of CD4-positive, alpha-beta T cell differentiation; IMP:UniProtKB. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IMP:UniProtKB. DR GO; GO:2000640; P:positive regulation of SREBP signaling pathway; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0043376; P:regulation of CD8-positive, alpha-beta T cell differentiation; IMP:MGI. DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI. DR GO; GO:0045622; P:regulation of T-helper cell differentiation; IMP:MGI. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0032868; P:response to insulin; IMP:UniProtKB. DR CDD; cd18327; BTB_POZ_ZBTB7B_ZBTB15; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 4. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR011333; SKP1/BTB/POZ_sf. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR46105; AGAP004733-PA; 1. DR PANTHER; PTHR46105:SF4; ZINC FINGER AND BTB DOMAIN-CONTAINING PROTEIN 7B; 1. DR Pfam; PF00651; BTB; 1. DR Pfam; PF00096; zf-C2H2; 2. DR SMART; SM00225; BTB; 1. DR SMART; SM00355; ZnF_C2H2; 4. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 2. DR SUPFAM; SSF54695; POZ domain; 1. DR PROSITE; PS50097; BTB; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4. DR Genevisible; Q64321; MM. PE 1: Evidence at protein level; KW Acetylation; Developmental protein; Differentiation; Disease variant; KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..544 FT /note="Zinc finger and BTB domain-containing protein 7B" FT /id="PRO_0000047720" FT DOMAIN 34..115 FT /note="BTB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037" FT ZN_FING 350..372 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 378..400 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 406..428 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 434..458 FT /note="C2H2-type 4; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 171..221 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 244..314 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 348..404 FT /note="Required for interaction with and acetylation by FT EP300" FT /evidence="ECO:0000269|PubMed:20810990" FT REGION 465..493 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 507..544 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 185..201 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 150 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15156" FT MOD_RES 210 FT /note="N6-acetyllysine; by EP300; alternate" FT /evidence="ECO:0000269|PubMed:20810990" FT MOD_RES 216 FT /note="N6-acetyllysine; by EP300; alternate" FT /evidence="ECO:0000269|PubMed:20810990" FT MOD_RES 339 FT /note="N6-acetyllysine; by EP300; alternate" FT /evidence="ECO:0000269|PubMed:20810990" FT MOD_RES 373 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O15156" FT CROSSLNK 210 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:20810990" FT CROSSLNK 216 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:20810990" FT CROSSLNK 339 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:20810990" FT VARIANT 102 FT /note="L -> R (in helpless)" FT /evidence="ECO:0000269|PubMed:23105140" FT VARIANT 389 FT /note="R -> G (in HD; disrupts sequence-specific FT DNA-binding; no effect on homodimerization or interaction FT with HDAC4 and HDAC5)" FT /evidence="ECO:0000269|PubMed:15729333, FT ECO:0000269|PubMed:22730529, ECO:0000269|PubMed:24880459" FT MUTAGEN 21 FT /note="L->S: Fails to repress CD8 expression. Abolishes FT interaction with HDAC4 and HDAC5. No effect on FT homodimerization and DNA binding." FT /evidence="ECO:0000269|PubMed:22730529" FT MUTAGEN 27..28 FT /note="QR->AL: Fails to repress CD8 expression. Abolishes FT interaction with HDAC4 and HDAC5. No effect on FT homodimerization and DNA binding." FT /evidence="ECO:0000269|PubMed:22730529" FT MUTAGEN 207 FT /note="K->R: No effect on acetylation levels. Slightly FT decreases acetylation levels; when associated with R-210. FT Slightly decreases acetylation levels; when associated with FT R-216." FT /evidence="ECO:0000269|PubMed:20810990" FT MUTAGEN 210 FT /note="K->R: Slightly decreases acetylation levels. No FT effect on protein stability. Slightly decreases acetylation FT levels; when associated with R-207. Slightly decreases FT acetylation levels and increases protein stability; when FT associated with R-216. Increases protein stability; when FT associated with R-339. Decreases acetylation levels; when FT associated with R-216 and R-343. Abolishes acetylation FT levels and ubiquitination and highly increases protein FT stability; when associated with R-216 and R-339." FT /evidence="ECO:0000269|PubMed:20810990" FT MUTAGEN 216 FT /note="K->R: Slightly decreases acetylation levels. No FT effect on protein stability. Slightly decreases acetylation FT levels; when associated with R-207. Slightly decreases FT acetylation levels and increases protein stability; when FT associated with R-210. Increases protein stability; when FT associated with R-339. Decreases acetylation levels; when FT associated with R-210 and R-343. Abolishes acetylation FT levels and ubiquitination and highly increases protein FT stability; when associated with R-210 and R-339." FT /evidence="ECO:0000269|PubMed:20810990" FT MUTAGEN 339 FT /note="K->R: Slightly decreases acetylation levels. FT Slightly increases protein stability. Slightly decreases FT acetylation levels; when associated with R-343. Increases FT protein stability; when associated with R-210 or R-216. FT Abolishes acetylation levels and ubiquitination and highly FT increases protein stability; when associated with R-210 and FT R-216." FT /evidence="ECO:0000269|PubMed:20810990" FT MUTAGEN 343 FT /note="K->R: No effect on acetylation levels. Slightly FT decreases acetylation levels; when associated with R-339. FT Decreases acetylation levels; when associated with R-210 FT and R-216." FT /evidence="ECO:0000269|PubMed:20810990" FT CONFLICT 268 FT /note="A -> T (in Ref. 2; AAA61956/CAA85307)" FT /evidence="ECO:0000305" SQ SEQUENCE 544 AA; 58918 MW; 5A43F10AE2970709 CRC64; MGSPEDDLIG IPFPDHSSEL LSCLNEQRQL GHLCDLTIRT QGLEYRTHRA VLAACSHYFK KLFTEGGGGT VMGTGGGGTA SGGAGAGVCE LDFVGPEALG ALLEFAYTAT LTTSSANMPA VLQAARLLEI PCVIAACMEI LQGSGLEAPS PDEDDCERAR QYLEAFATAT TTASTSGMPN GEDSPPQVPL LPPPPPPPRP VARRSRKPRK AFLQTKGARA NHLVPEAPTV LTHPLTYEEE EMVGRLGNSG GSGLGDSYSP PTGAASPAEG PLNYEVFEGE EEEEEMAYPP GYGLAQSNEP SLSPEELGSD EDPIDPDLMA YLSSLHQDAL TPGLDGQDKL VRKRRSQMPQ ECPVCHKIIH GAGKLPRHMR THTGEKPFAC EVCGVRFTRN DKLKIHMRKH TGERPYSCPH CPARFLHSYD LKNHMHLHTG DRPYECHLCH KAFAKEDHLQ RHLKGQNCLE VRTRRRRKDD VAAPHYPPPS TTTSSPAGLD LSNGHLDTFH LSLARFWEQS ATTGPPVTTQ GPPEEEEEEG TPTTPQAEGA MESS //