ATX1L_MOUSE
ID ATX1L_MOUSE Reviewed; 687 AA.
AC P0C7T6;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Ataxin-1-like;
DE AltName: Full=Brother of ataxin-1;
GN Name=Atxn1l; Synonyms=Boat;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16121196; DOI=10.1038/sj.emboj.7600785;
RA Mizutani A., Wang L., Rajan H., Vig P.J.S., Alaynick W.A., Thaler J.P.,
RA Tsai C.-C.;
RT "Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-
RT 1.";
RL EMBO J. 24:3339-3351(2005).
RN [3]
RP INTERACTION WITH ATXN1 AND CIC.
RX PubMed=17322884; DOI=10.1038/ng1977;
RA Bowman A.B., Lam Y.C., Jafar-Nejad P., Chen H.-K., Richman R., Samaco R.C.,
RA Fryer J.D., Kahle J.J., Orr H.T., Zoghbi H.Y.;
RT "Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing
RT incorporation of polyglutamine-expanded ataxin-1 into native complexes.";
RL Nat. Genet. 39:373-379(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-282 AND SER-359, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND IDENTIFICATION IN A
RP COMPLEX WITH CIC AND ATXN1.
RX PubMed=28288114; DOI=10.1038/ng.3808;
RA Lu H.C., Tan Q., Rousseaux M.W., Wang W., Kim J.Y., Richman R., Wan Y.W.,
RA Yeh S.Y., Patel J.M., Liu X., Lin T., Lee Y., Fryer J.D., Han J.,
RA Chahrour M., Finnell R.H., Lei Y., Zurita-Jimenez M.E., Ahimaz P.,
RA Anyane-Yeboa K., Van Maldergem L., Lehalle D., Jean-Marcais N.,
RA Mosca-Boidron A.L., Thevenon J., Cousin M.A., Bro D.E., Lanpher B.C.,
RA Klee E.W., Alexander N., Bainbridge M.N., Orr H.T., Sillitoe R.V.,
RA Ljungberg M.C., Liu Z., Schaaf C.P., Zoghbi H.Y.;
RT "Disruption of the ATXN1-CIC complex causes a spectrum of neurobehavioral
RT phenotypes in mice and humans.";
RL Nat. Genet. 49:527-536(2017).
CC -!- FUNCTION: Chromatin-binding factor that repress Notch signaling in the
CC absence of Notch intracellular domain by acting as a CBF1 corepressor.
CC Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-
CC mediated repression (By similarity). Can suppress the cytotoxicity of
CC ATXN1 in spinocerebellar ataxia type 1 (SCA1) (PubMed:16121196). In
CC concert with CIC and ATXN1, involved in brain development
CC (PubMed:28288114). {ECO:0000250|UniProtKB:P0C7T5,
CC ECO:0000269|PubMed:16121196, ECO:0000269|PubMed:28288114}.
CC -!- SUBUNIT: Homodimer. Interacts (via AXH domain) with NCOR2 (By
CC similarity). Interacts with ATXN1 and CIC. Directly interacts with
CC RBPJ; this interaction is disrupted in the presence of Notch
CC intracellular domain. Competes with ATXN1 for RBPJ-binding (By
CC similarity). Found in a complex with CIC and ATXN1 (PubMed:28288114).
CC {ECO:0000250|UniProtKB:P0C7T5, ECO:0000269|PubMed:28288114}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16121196}. Cell
CC projection, dendrite {ECO:0000269|PubMed:16121196}. Note=Forms nuclear
CC foci. Colocalizes with NCOR2 and HDAC3. Distributed beyond the nucleus
CC into the cell body and dendrites in Purkinje cells and in inferior
CC olive cells.
CC -!- TISSUE SPECIFICITY: Expressed in the cortex and hypothalamus (at
CC protein level). Expressed in neuronal cells. Highly expressed in
CC Purkinje cells of cerebellum. {ECO:0000269|PubMed:16121196,
CC ECO:0000269|PubMed:28288114}.
CC -!- DISRUPTION PHENOTYPE: Mice with conditional knockouts of either ATXN1-
CC ATXN1L or CIC in the developing forebrain exhibit intellectual
CC disability, hyperactivity, social-behavioral deficits and reduced
CC thickness of upper cortical layers. {ECO:0000269|PubMed:28288114}.
CC -!- MISCELLANEOUS: Its overexpression suppresses the ataxia caused by
CC polyglutamine-expanded Atxn1. Competes with mutant Atxn1 and wild-type
CC Atxn1 for association with CIC. Decreased association of mutant Atxn1
CC into its CIC-containing complexes decreases the levels of mutant Atxn1-
CC containing CIC complexes, suppressing pathology, while promoting
CC aggregation and thus increasing nuclear inclusions.
CC -!- SIMILARITY: Belongs to the ATXN1 family. {ECO:0000305}.
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DR EMBL; AC132138; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS40474.1; -.
DR RefSeq; NP_001074399.1; NM_001080930.1.
DR RefSeq; XP_011246741.1; XM_011248439.2.
DR RefSeq; XP_011246742.1; XM_011248440.2.
DR RefSeq; XP_011246743.1; XM_011248441.2.
DR RefSeq; XP_017168386.1; XM_017312897.1.
DR AlphaFoldDB; P0C7T6; -.
DR SMR; P0C7T6; -.
DR BioGRID; 206522; 3.
DR STRING; 10090.ENSMUSP00000090850; -.
DR iPTMnet; P0C7T6; -.
DR PhosphoSitePlus; P0C7T6; -.
DR EPD; P0C7T6; -.
DR jPOST; P0C7T6; -.
DR MaxQB; P0C7T6; -.
DR PaxDb; P0C7T6; -.
DR PeptideAtlas; P0C7T6; -.
DR PRIDE; P0C7T6; -.
DR ProteomicsDB; 273627; -.
DR Antibodypedia; 67440; 90 antibodies from 14 providers.
DR Ensembl; ENSMUST00000093162; ENSMUSP00000090850; ENSMUSG00000069895.
DR Ensembl; ENSMUST00000212605; ENSMUSP00000148324; ENSMUSG00000069895.
DR GeneID; 52335; -.
DR KEGG; mmu:52335; -.
DR UCSC; uc009njh.1; mouse.
DR CTD; 342371; -.
DR MGI; MGI:3694797; Atxn1l.
DR VEuPathDB; HostDB:ENSMUSG00000069895; -.
DR eggNOG; KOG4053; Eukaryota.
DR GeneTree; ENSGT00390000005939; -.
DR HOGENOM; CLU_434497_0_0_1; -.
DR InParanoid; P0C7T6; -.
DR OMA; RGMPVFY; -.
DR OrthoDB; 249631at2759; -.
DR PhylomeDB; P0C7T6; -.
DR TreeFam; TF350643; -.
DR BioGRID-ORCS; 52335; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Atxn1l; mouse.
DR PRO; PR:P0C7T6; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P0C7T6; protein.
DR Bgee; ENSMUSG00000069895; Expressed in ascending aorta and 216 other tissues.
DR ExpressionAtlas; P0C7T6; baseline and differential.
DR Genevisible; P0C7T6; MM.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI.
DR GO; GO:0007612; P:learning; IMP:UniProtKB.
DR GO; GO:0048286; P:lung alveolus development; IMP:MGI.
DR GO; GO:0007613; P:memory; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:1902035; P:positive regulation of hematopoietic stem cell proliferation; IMP:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0035176; P:social behavior; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI.
DR InterPro; IPR020997; Ataxin-1_N.
DR InterPro; IPR043404; ATAXIN1-like.
DR InterPro; IPR003652; Ataxin_AXH_dom.
DR InterPro; IPR036096; Ataxin_AXH_dom_sf.
DR PANTHER; PTHR13392; PTHR13392; 1.
DR Pfam; PF12547; ATXN-1_C; 1.
DR Pfam; PF08517; AXH; 1.
DR SMART; SM00536; AXH; 1.
DR SUPFAM; SSF102031; SSF102031; 1.
DR PROSITE; PS51148; AXH; 1.
PE 1: Evidence at protein level;
KW Cell projection; DNA-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..687
FT /note="Ataxin-1-like"
FT /id="PRO_0000343710"
FT DOMAIN 455..586
FT /note="AXH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00496"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 20..197
FT /note="Interaction with NCOR2 and ATXN1"
FT /evidence="ECO:0000250"
FT REGION 20..197
FT /note="Self-association"
FT /evidence="ECO:0000250"
FT REGION 185..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 261..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 356..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 587..649
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..217
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..287
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..373
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 328
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P0C7T5"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 687 AA; 73374 MW; 952C394FFB6B8300 CRC64;
MKPVHERSQE CLPPKKRDLP VTSEDMGRTT SCSTNHTPSS DASEWSRGVV VAGQSQTGAR
VSLGGDGTEA ITGLTVDQYG MLYKVAVPPA TFSPTGLPSV VNMSPLPPTF NVASSLIQHP
GIHYPPVHYA QLPSTSLQFI GSPYSLPYAV PPNFLPSPLL SPSANLATTH LPHFVPYASL
LAEEATPPPQ AASPAQSFNK SSSATSPPGQ LPHHSNTQPL DLAPGRMPIY YQMSRLPAGY
TLHETSTAGA SPILTPQEGQ SALEAAAANG QRQRERNVRR ESEALDSASS KGESQGLVPV
VECMADGQLF SGSQTPRVEV AAPAHRGTPD TDLEVQRVVG ALASQDYRVV AAQRKDEPSP
LNLSHHNLDH QGEGRGSARN PTELVEKSQA RVFYPQSHQE PVKHRPLPKA MVVANGNLVP
TGTDPSLLPV GSEILVASSL DLQARATFPD KEPTPPPVTS SHLPSHFMKG AIIQLATGEL
KRVEDLQTQD FVRSAEVSGG LKIDSSTVVD IQESQWPGFV MLHFVVGEQQ SKVSIEVPPE
HPFFVYGQGW SSCSPGRTAQ LFSLPCHRLQ VGDVCISISL QSLNSNSVSQ ASCAPPGQLG
TPRERPERTV LGPRDLCDSE GKNQPSGEGS RVGEPSQPEP GAQACWPAPS FQRFSMQGEE
ARAAMLRPSF IPQEVKLSIE GRSNAGK
