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Achaete-scute homolog 1 (ASH-1) (hASH1) (Class A basic helix-loop-helix protein 46) (bHLHa46)

 ASCL1_HUMAN             Reviewed;         236 AA.
P50553; A8K3C4; Q9BQ30;
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
02-MAY-2002, sequence version 2.
23-MAY-2018, entry version 169.
RecName: Full=Achaete-scute homolog 1 {ECO:0000303|PubMed:8390674};
Short=ASH-1 {ECO:0000303|PubMed:8390674};
Short=hASH1 {ECO:0000303|PubMed:8390674};
AltName: Full=Class A basic helix-loop-helix protein 46 {ECO:0000312|HGNC:HGNC:738};
Short=bHLHa46 {ECO:0000312|HGNC:HGNC:738};
Name=ASCL1 {ECO:0000312|HGNC:HGNC:738};
Synonyms=ASH1, BHLHA46 {ECO:0000312|HGNC:HGNC:738},
HASH1 {ECO:0000303|PubMed:8390674};
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Thyroid carcinoma;
PubMed=8390674; DOI=10.1073/pnas.90.12.5648;
Ball D.W., Azzoli C.G., Baylin S.B., Chi D., Dou S., Donis-Keller H.,
Cumaraswamy A., Borges M., Nelkin B.D.;
"Identification of a human achaete-scute homolog highly expressed in
neuroendocrine tumors.";
Proc. Natl. Acad. Sci. U.S.A. 90:5648-5652(1993).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
INTERACTION WITH TCF3.
PubMed=10903890; DOI=10.1006/bbrc.2000.3090;
Persson P., Joegi A., Grynfeld A., Paahlman S., Axelson H.;
"HASH-1 and E2-2 are expressed in human neuroblastoma cells and form a
functional complex.";
Biochem. Biophys. Res. Commun. 274:22-31(2000).
-!- FUNCTION: Transcription factor that plays a key role in neuronal
differentiation: acts as a pioneer transcription factor, accessing
closed chromatin to allow other factors to bind and activate
neural pathways. Directly binds the E box motif (5'-CANNTG-3') on
promoters and promotes transcription of neuronal genes. The
combination of three transcription factors, ASCL1, POU3F2/BRN2 and
MYT1L, is sufficient to reprogram fibroblasts and other somatic
cells into induced neuronal (iN) cells in vitro. Plays a role at
early stages of development of specific neural lineages in most
regions of the CNS, and of several lineages in the PNS. Essential
for the generation of olfactory and autonomic neurons. Acts
synergistically with FOXN4 to specify the identity of V2b neurons
rather than V2a from bipotential p2 progenitors during spinal cord
neurogenesis, probably through DLL4-NOTCH signaling activation.
{ECO:0000250|UniProtKB:Q02067}.
-!- SUBUNIT: Efficient DNA binding requires dimerization with another
bHLH protein. Forms a heterodimer with TCF3.
{ECO:0000269|PubMed:10903890}.
-!- INTERACTION:
P15923:TCF3; NbExp=3; IntAct=EBI-957042, EBI-769630;
P15884:TCF4; NbExp=7; IntAct=EBI-957042, EBI-533224;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q02067}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/ASCL1ID713ch12q23.html";
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EMBL; L08424; AAA58376.1; -; mRNA.
EMBL; AK290539; BAF83228.1; -; mRNA.
EMBL; CH471054; EAW97703.1; -; Genomic_DNA.
EMBL; BC001638; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; BC002341; AAH02341.1; -; mRNA.
EMBL; BC003134; AAH03134.1; -; mRNA.
EMBL; BC004425; AAH04425.1; -; mRNA.
EMBL; BC031299; AAH31299.1; -; mRNA.
CCDS; CCDS31886.1; -.
PIR; A48279; A48279.
RefSeq; NP_004307.2; NM_004316.3.
UniGene; Hs.703025; -.
ProteinModelPortal; P50553; -.
SMR; P50553; -.
BioGrid; 106921; 6.
IntAct; P50553; 6.
STRING; 9606.ENSP00000266744; -.
iPTMnet; P50553; -.
PhosphoSitePlus; P50553; -.
BioMuta; ASCL1; -.
DMDM; 20455478; -.
PaxDb; P50553; -.
PeptideAtlas; P50553; -.
PRIDE; P50553; -.
DNASU; 429; -.
Ensembl; ENST00000266744; ENSP00000266744; ENSG00000139352.
GeneID; 429; -.
KEGG; hsa:429; -.
UCSC; uc001tjr.5; human.
CTD; 429; -.
DisGeNET; 429; -.
EuPathDB; HostDB:ENSG00000139352.3; -.
GeneCards; ASCL1; -.
HGNC; HGNC:738; ASCL1.
HPA; HPA029217; -.
MalaCards; ASCL1; -.
MIM; 100790; gene.
neXtProt; NX_P50553; -.
OpenTargets; ENSG00000139352; -.
Orphanet; 99803; Haddad syndrome.
PharmGKB; PA26416; -.
eggNOG; KOG4029; Eukaryota.
eggNOG; ENOG411227D; LUCA.
GeneTree; ENSGT00530000063321; -.
HOGENOM; HOG000013056; -.
HOVERGEN; HBG050590; -.
InParanoid; P50553; -.
KO; K09067; -.
OMA; ELMRCKR; -.
OrthoDB; EOG091G0OB6; -.
PhylomeDB; P50553; -.
TreeFam; TF322889; -.
SignaLink; P50553; -.
SIGNOR; P50553; -.
GeneWiki; ASCL1; -.
GenomeRNAi; 429; -.
PRO; PR:P50553; -.
Proteomes; UP000005640; Chromosome 12.
Bgee; ENSG00000139352; -.
CleanEx; HS_ASCL1; -.
Genevisible; P50553; HS.
GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0090575; C:RNA polymerase II transcription factor complex; IBA:GO_Central.
GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
GO; GO:0003700; F:DNA binding transcription factor activity; IDA:UniProtKB.
GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; ISA:NTNU_SB.
GO; GO:0000989; F:transcription factor activity, transcription factor binding; ISS:UniProtKB.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0061104; P:adrenal chromaffin cell differentiation; IEA:Ensembl.
GO; GO:0061103; P:carotid body glomus cell differentiation; IEA:Ensembl.
GO; GO:0048469; P:cell maturation; IEA:Ensembl.
GO; GO:0071259; P:cellular response to magnetism; IEA:Ensembl.
GO; GO:0021954; P:central nervous system neuron development; IEA:Ensembl.
GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
GO; GO:0021892; P:cerebral cortex GABAergic interneuron differentiation; IEP:UniProtKB.
GO; GO:0021902; P:commitment of neuronal cell to specific neuron type in forebrain; IEA:Ensembl.
GO; GO:0060487; P:lung epithelial cell differentiation; NAS:UniProtKB.
GO; GO:0061100; P:lung neuroendocrine cell differentiation; IEA:Ensembl.
GO; GO:0050883; P:musculoskeletal movement, spinal reflex action; IEA:Ensembl.
GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0007400; P:neuroblast fate determination; IEA:Ensembl.
GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
GO; GO:0022008; P:neurogenesis; IDA:UniProtKB.
GO; GO:0048666; P:neuron development; ISS:UniProtKB.
GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
GO; GO:0048663; P:neuron fate commitment; ISS:UniProtKB.
GO; GO:0048665; P:neuron fate specification; ISS:UniProtKB.
GO; GO:0001764; P:neuron migration; IEA:Ensembl.
GO; GO:0003358; P:noradrenergic neuron development; ISS:UniProtKB.
GO; GO:0003359; P:noradrenergic neuron fate commitment; IMP:UniProtKB.
GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
GO; GO:0060166; P:olfactory pit development; IEA:Ensembl.
GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
GO; GO:0045787; P:positive regulation of cell cycle; IEA:Ensembl.
GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IEA:Ensembl.
GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
GO; GO:0030856; P:regulation of epithelial cell differentiation; IEA:Ensembl.
GO; GO:0010468; P:regulation of gene expression; ISS:UniProtKB.
GO; GO:0007346; P:regulation of mitotic cell cycle; IEA:Ensembl.
GO; GO:0060165; P:regulation of timing of subpallium neuron differentiation; IEA:Ensembl.
GO; GO:0070849; P:response to epidermal growth factor; IEA:Ensembl.
GO; GO:0051593; P:response to folic acid; IEA:Ensembl.
GO; GO:0010226; P:response to lithium ion; IEA:Ensembl.
GO; GO:0032526; P:response to retinoic acid; IEP:UniProtKB.
GO; GO:0021527; P:spinal cord association neuron differentiation; IEA:Ensembl.
GO; GO:0021530; P:spinal cord oligodendrocyte cell fate specification; IEA:Ensembl.
GO; GO:0061102; P:stomach neuroendocrine cell differentiation; IEA:Ensembl.
GO; GO:0060163; P:subpallium neuron fate commitment; IEA:Ensembl.
GO; GO:0061549; P:sympathetic ganglion development; ISS:UniProtKB.
GO; GO:0048485; P:sympathetic nervous system development; NAS:UniProtKB.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0060579; P:ventral spinal cord interneuron fate commitment; ISS:UniProtKB.
GO; GO:0021750; P:vestibular nucleus development; IEA:Ensembl.
CDD; cd00083; HLH; 1.
Gene3D; 4.10.280.10; -; 1.
InterPro; IPR011598; bHLH_dom.
InterPro; IPR036638; HLH_DNA-bd_sf.
InterPro; IPR015660; MASH1/Ascl1a-like.
PANTHER; PTHR13935; PTHR13935; 1.
Pfam; PF00010; HLH; 1.
SMART; SM00353; HLH; 1.
SUPFAM; SSF47459; SSF47459; 1.
PROSITE; PS50888; BHLH; 1.
1: Evidence at protein level;
Acetylation; Activator; Complete proteome; Developmental protein;
Differentiation; DNA-binding; Neurogenesis; Nucleus; Polymorphism;
Reference proteome; Transcription; Transcription regulation.
CHAIN 1 236 Achaete-scute homolog 1.
/FTId=PRO_0000127126.
DOMAIN 118 170 bHLH. {ECO:0000255|PROSITE-
ProRule:PRU00981}.
COMPBIAS 33 47 Poly-Ala.
COMPBIAS 51 62 Poly-Gln.
MOD_RES 156 156 N6-acetyllysine.
{ECO:0000250|UniProtKB:Q02067}.
VARIANT 158 158 E -> G (in dbSNP:rs1803157).
/FTId=VAR_013179.
CONFLICT 62 62 Q -> QQQ (in Ref. 1; AAA58376).
{ECO:0000305}.
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


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