ASCL1_HUMAN
ID ASCL1_HUMAN Reviewed; 236 AA.
AC P50553; A8K3C4; Q9BQ30;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Achaete-scute homolog 1 {ECO:0000303|PubMed:8390674};
DE Short=ASH-1 {ECO:0000303|PubMed:8390674};
DE Short=hASH1 {ECO:0000303|PubMed:8390674};
DE AltName: Full=Class A basic helix-loop-helix protein 46 {ECO:0000312|HGNC:HGNC:738};
DE Short=bHLHa46 {ECO:0000312|HGNC:HGNC:738};
GN Name=ASCL1 {ECO:0000312|HGNC:HGNC:738};
GN Synonyms=ASH1, BHLHA46 {ECO:0000312|HGNC:HGNC:738},
GN HASH1 {ECO:0000303|PubMed:8390674};
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].
RC TISSUE=Thyroid carcinoma;
RX PubMed=8390674; DOI=10.1073/pnas.90.12.5648;
RA Ball D.W., Azzoli C.G., Baylin S.B., Chi D., Dou S., Donis-Keller H.,
RA Cumaraswamy A., Borges M., Nelkin B.D.;
RT "Identification of a human achaete-scute homolog highly expressed in
RT neuroendocrine tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5648-5652(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [5]
RP INTERACTION WITH TCF3.
RX PubMed=10903890; DOI=10.1006/bbrc.2000.3090;
RA Persson P., Joegi A., Grynfeld A., Paahlman S., Axelson H.;
RT "HASH-1 and E2-2 are expressed in human neuroblastoma cells and form a
RT functional complex.";
RL Biochem. Biophys. Res. Commun. 274:22-31(2000).
CC -!- FUNCTION: Transcription factor that plays a key role in neuronal
CC differentiation: acts as a pioneer transcription factor, accessing
CC closed chromatin to allow other factors to bind and activate neural
CC pathways. Directly binds the E box motif (5'-CANNTG-3') on promoters
CC and promotes transcription of neuronal genes. The combination of three
CC transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to
CC reprogram fibroblasts and other somatic cells into induced neuronal
CC (iN) cells in vitro. Plays a role at early stages of development of
CC specific neural lineages in most regions of the CNS, and of several
CC lineages in the PNS. Essential for the generation of olfactory and
CC autonomic neurons. Acts synergistically with FOXN4 to specify the
CC identity of V2b neurons rather than V2a from bipotential p2 progenitors
CC during spinal cord neurogenesis, probably through DLL4-NOTCH signaling
CC activation. Involved in the regulation of neuroendocrine cell
CC development in the glandular stomach (By similarity).
CC {ECO:0000250|UniProtKB:Q02067}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Forms a heterodimer with TCF3. {ECO:0000269|PubMed:10903890}.
CC -!- INTERACTION:
CC P50553; P15923: TCF3; NbExp=3; IntAct=EBI-957042, EBI-769630;
CC P50553; P15884: TCF4; NbExp=7; IntAct=EBI-957042, EBI-533224;
CC P50553; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-957042, EBI-741480;
CC P50553; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-957042, EBI-947187;
CC P50553; A0A024R8A9: USP20; NbExp=3; IntAct=EBI-957042, EBI-14096082;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q02067}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ASCL1ID713ch12q23.html";
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DR EMBL; L08424; AAA58376.1; -; mRNA.
DR EMBL; AK290539; BAF83228.1; -; mRNA.
DR EMBL; CH471054; EAW97703.1; -; Genomic_DNA.
DR EMBL; BC001638; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC002341; AAH02341.1; -; mRNA.
DR EMBL; BC003134; AAH03134.1; -; mRNA.
DR EMBL; BC004425; AAH04425.1; -; mRNA.
DR EMBL; BC031299; AAH31299.1; -; mRNA.
DR CCDS; CCDS31886.1; -.
DR PIR; A48279; A48279.
DR RefSeq; NP_004307.2; NM_004316.3.
DR AlphaFoldDB; P50553; -.
DR SMR; P50553; -.
DR BioGRID; 106921; 36.
DR IntAct; P50553; 6.
DR STRING; 9606.ENSP00000266744; -.
DR iPTMnet; P50553; -.
DR PhosphoSitePlus; P50553; -.
DR BioMuta; ASCL1; -.
DR DMDM; 20455478; -.
DR PaxDb; P50553; -.
DR PeptideAtlas; P50553; -.
DR PRIDE; P50553; -.
DR Antibodypedia; 18050; 536 antibodies from 40 providers.
DR DNASU; 429; -.
DR Ensembl; ENST00000266744.4; ENSP00000266744.3; ENSG00000139352.4.
DR GeneID; 429; -.
DR KEGG; hsa:429; -.
DR MANE-Select; ENST00000266744.4; ENSP00000266744.3; NM_004316.4; NP_004307.2.
DR UCSC; uc001tjr.5; human.
DR CTD; 429; -.
DR DisGeNET; 429; -.
DR GeneCards; ASCL1; -.
DR HGNC; HGNC:738; ASCL1.
DR HPA; ENSG00000139352; Tissue enhanced (brain, choroid plexus, liver, pituitary gland).
DR MalaCards; ASCL1; -.
DR MIM; 100790; gene.
DR neXtProt; NX_P50553; -.
DR OpenTargets; ENSG00000139352; -.
DR Orphanet; 99803; Haddad syndrome.
DR PharmGKB; PA26416; -.
DR VEuPathDB; HostDB:ENSG00000139352; -.
DR eggNOG; KOG4029; Eukaryota.
DR GeneTree; ENSGT00940000162483; -.
DR HOGENOM; CLU_063523_3_0_1; -.
DR InParanoid; P50553; -.
DR OMA; QLIPPAC; -.
DR OrthoDB; 1131543at2759; -.
DR PhylomeDB; P50553; -.
DR TreeFam; TF322889; -.
DR PathwayCommons; P50553; -.
DR Reactome; R-HSA-9031628; NGF-stimulated transcription.
DR SignaLink; P50553; -.
DR SIGNOR; P50553; -.
DR BioGRID-ORCS; 429; 28 hits in 1105 CRISPR screens.
DR GeneWiki; ASCL1; -.
DR GenomeRNAi; 429; -.
DR Pharos; P50553; Tbio.
DR PRO; PR:P50553; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P50553; protein.
DR Bgee; ENSG00000139352; Expressed in ganglionic eminence and 114 other tissues.
DR Genevisible; P50553; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IBA:GO_Central.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0061104; P:adrenal chromaffin cell differentiation; IEA:Ensembl.
DR GO; GO:0061103; P:carotid body glomus cell differentiation; IEA:Ensembl.
DR GO; GO:0048469; P:cell maturation; IEA:Ensembl.
DR GO; GO:0071259; P:cellular response to magnetism; IEA:Ensembl.
DR GO; GO:0021954; P:central nervous system neuron development; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0021892; P:cerebral cortex GABAergic interneuron differentiation; IEP:UniProtKB.
DR GO; GO:0021902; P:commitment of neuronal cell to specific neuron type in forebrain; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0060487; P:lung epithelial cell differentiation; NAS:UniProtKB.
DR GO; GO:0061100; P:lung neuroendocrine cell differentiation; IEA:Ensembl.
DR GO; GO:0097475; P:motor neuron migration; IEA:Ensembl.
DR GO; GO:0050883; P:musculoskeletal movement, spinal reflex action; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0007400; P:neuroblast fate determination; IEA:Ensembl.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0022008; P:neurogenesis; IDA:UniProtKB.
DR GO; GO:0048666; P:neuron development; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR GO; GO:0048663; P:neuron fate commitment; ISS:UniProtKB.
DR GO; GO:0048665; P:neuron fate specification; ISS:UniProtKB.
DR GO; GO:0003358; P:noradrenergic neuron development; ISS:UniProtKB.
DR GO; GO:0003359; P:noradrenergic neuron fate commitment; IMP:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0060166; P:olfactory pit development; IEA:Ensembl.
DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
DR GO; GO:0048935; P:peripheral nervous system neuron development; IEA:Ensembl.
DR GO; GO:0045787; P:positive regulation of cell cycle; IEA:Ensembl.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IEA:Ensembl.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0030856; P:regulation of epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0060165; P:regulation of timing of subpallium neuron differentiation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0070849; P:response to epidermal growth factor; IEA:Ensembl.
DR GO; GO:0051593; P:response to folic acid; IEA:Ensembl.
DR GO; GO:0010226; P:response to lithium ion; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IEP:UniProtKB.
DR GO; GO:0007423; P:sensory organ development; IBA:GO_Central.
DR GO; GO:0021527; P:spinal cord association neuron differentiation; IEA:Ensembl.
DR GO; GO:0021530; P:spinal cord oligodendrocyte cell fate specification; IEA:Ensembl.
DR GO; GO:0061102; P:stomach neuroendocrine cell differentiation; IEA:Ensembl.
DR GO; GO:0060163; P:subpallium neuron fate commitment; IEA:Ensembl.
DR GO; GO:0061549; P:sympathetic ganglion development; ISS:UniProtKB.
DR GO; GO:0048485; P:sympathetic nervous system development; NAS:UniProtKB.
DR GO; GO:0060579; P:ventral spinal cord interneuron fate commitment; ISS:UniProtKB.
DR GO; GO:0021750; P:vestibular nucleus development; IEA:Ensembl.
DR DisProt; DP01942; -.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR015660; MASH1/Ascl1a-like.
DR PANTHER; PTHR13935; PTHR13935; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Developmental protein; Differentiation;
KW DNA-binding; Neurogenesis; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..236
FT /note="Achaete-scute homolog 1"
FT /id="PRO_0000127126"
FT DOMAIN 118..170
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..68
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 156
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q02067"
FT VARIANT 158
FT /note="E -> G (in dbSNP:rs1803157)"
FT /id="VAR_013179"
FT CONFLICT 62
FT /note="Q -> QQQ (in Ref. 1; AAA58376)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 236 AA; 25454 MW; A7D784329305B49A CRC64;
MESSAKMESG GAGQQPQPQP QQPFLPPAAC FFATAAAAAA AAAAAAAQSA QQQQQQQQQQ
QQAPQLRPAA DGQPSGGGHK SAPKQVKRQR SSSPELMRCK RRLNFSGFGY SLPQQQPAAV
ARRNERERNR VKLVNLGFAT LREHVPNGAA NKKMSKVETL RSAVEYIRAL QQLLDEHDAV
SAAFQAGVLS PTISPNYSND LNSMAGSPVS SYSSDEGSYD PLSPEEQELL DFTNWF
