ID TAL1_DANRE Reviewed; 324 AA. AC O93507; A4UTQ6; O57562; Q90W24; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 02-SEP-2026, entry version 155. DE RecName: Full=T-cell acute lymphocytic leukemia protein 1 homolog; DE Short=TAL-1; DE AltName: Full=Stem cell protein; DE Short=zSCL; GN Name=tal1 {ECO:0000312|ZFIN:ZDB-GENE-980526-501}; GN Synonyms=scl {ECO:0000303|PubMed:17472439, GN ECO:0000303|PubMed:9670018}, tal-1 {ECO:0000312|EMBL:AAC41264.1}; GN ORFNames=si:ch211-135j1.3; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Danionidae; Danioninae; Danio. OX NCBI_TaxID=7955; RN [1] {ECO:0000305, ECO:0000312|EMBL:AAC36057.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Embryo {ECO:0000269|PubMed:9670018}; RX PubMed=9670018; DOI=10.1093/emboj/17.14.4029; RA Gering M., Rodaway A.R.F., Goettgens B., Patient R.K., Green A.R.; RT "The SCL gene specifies haemangioblast development from early mesoderm."; RL EMBO J. 17:4029-4045(1998). RN [2] {ECO:0000305, ECO:0000312|EMBL:AAC41264.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Angioblast {ECO:0000269|PubMed:9499398}; RX PubMed=9499398; DOI=10.1101/gad.12.5.621; RA Liao E.C., Paw B.H., Oates A.C., Pratt S.J., Postlethwait J.H., Zon L.I.; RT "SCL/Tal-1 transcription factor acts downstream of cloche to specify RT hematopoietic and vascular progenitors in zebrafish."; RL Genes Dev. 12:621-626(1998). RN [3] {ECO:0000305, ECO:0000312|EMBL:ABO77946.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA), FUNCTION, TISSUE RP SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=17472439; DOI=10.1371/journal.pbio.0050132; RA Qian F., Zhen F., Xu J., Huang M., Li W., Wen Z.; RT "Distinct functions for different scl isoforms in zebrafish primitive and RT definitive hematopoiesis."; RL PLoS Biol. 5:1110-1119(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Tuebingen; RX PubMed=23594743; DOI=10.1038/nature12111; RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M., RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I., RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J., RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y., RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B., RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S., RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M., RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J., RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G., RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P., RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S., RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N., RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J., RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J., RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D., RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S., RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E., RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A., RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P., RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J., RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E., RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C., RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C., RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M., RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F., RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M., RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M., RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C., RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.; RT "The zebrafish reference genome sequence and its relationship to the human RT genome."; RL Nature 496:498-503(2013). RN [5] {ECO:0000305, ECO:0000312|EMBL:CAK04103.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RC TISSUE=Embryo {ECO:0000312|EMBL:AAH68324.1}; RG NIH - Zebrafish Gene Collection (ZGC) project; RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases. RN [6] {ECO:0000305} RP TISSUE SPECIFICITY. RX PubMed=10208748; DOI=10.1006/dbio.1999.9236; RA Sinclair A.M., Goettgens B., Barton L.M., Stanley M.L., Pardanaud L., RA Klaine M., Gering M., Bahn S., Sanchez M.-J., Bench A.J., Fordham J.L., RA Bockamp E.-O., Green A.R.; RT "Distinct 5' SCL enhancers direct transcription to developing brain, spinal RT cord, and endothelium: neural expression is mediated by GATA factor binding RT sites."; RL Dev. Biol. 209:128-142(1999). RN [7] {ECO:0000305} RP FUNCTION. RX PubMed=11003831; DOI=10.1242/dev.127.20.4303; RA Liao W., Ho C.-Y., Yan Y.L., Postlethwait J.H., Stainier D.Y.R.; RT "Hhex and scl function in parallel to regulate early endothelial and blood RT differentiation in zebrafish."; RL Development 127:4303-4313(2000). RN [8] {ECO:0000305} RP TISSUE SPECIFICITY. RX PubMed=11381108; DOI=10.1073/pnas.101532998; RA Barton L.M., Goettgens B., Gering M., Gilbert J.G.R., Grafham D., RA Rogers J., Bentley D., Patient R.K., Green A.R.; RT "Regulation of the stem cell leukemia (SCL) gene: a tale of two fishes."; RL Proc. Natl. Acad. Sci. U.S.A. 98:6747-6752(2001). RN [9] {ECO:0000305} RP FUNCTION. RX PubMed=14602685; DOI=10.1242/dev.00875; RA Gering M., Yamada Y., Rabbitts T.H., Patient R.K.; RT "Lmo2 and Scl/Tal1 convert non-axial mesoderm into haemangioblasts which RT differentiate into endothelial cells in the absence of Gata1."; RL Development 130:6187-6199(2003). RN [10] {ECO:0000305} RP FUNCTION. RX PubMed=15644413; DOI=10.1182/blood-2004-09-3547; RA Patterson L.J., Gering M., Patient R.K.; RT "Scl is required for dorsal aorta as well as blood formation in zebrafish RT embryos."; RL Blood 105:3502-3511(2005). RN [11] {ECO:0000305} RP FUNCTION. RX PubMed=15617691; DOI=10.1016/j.ydbio.2004.09.004; RA Dooley K.A., Davidson A.J., Zon L.I.; RT "Zebrafish scl functions independently in hematopoietic and endothelial RT development."; RL Dev. Biol. 277:522-536(2005). RN [12] {ECO:0000305} RP FUNCTION, AND MUTAGENESIS OF 193-ARG--ARG-195. RX PubMed=16210319; DOI=10.1074/jbc.m507998200; RA Juarez M.A., Su F., Chun S., Kiel M.J., Lyons S.E.; RT "Distinct roles for SCL in erythroid specification and maturation in RT zebrafish."; RL J. Biol. Chem. 280:41636-41644(2005). RN [13] {ECO:0000305} RP FUNCTION. RX PubMed=17090656; DOI=10.1182/blood-2006-02-003087; RA Patterson L.J., Gering M., Eckfeldt C.E., Green A.R., Verfaillie C.M., RA Ekker S.C., Patient R.K.; RT "The transcription factors Scl and Lmo2 act together during development of RT the hemangioblast in zebrafish."; RL Blood 109:2389-2398(2007). RN [14] {ECO:0000305} RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=17722983; DOI=10.1371/journal.pgen.0030140; RA Bussmann J., Bakkers J., Schulte-Merker S.; RT "Early endocardial morphogenesis requires Scl/Tal1."; RL PLoS Genet. 3:1425-1437(2007). CC -!- FUNCTION: Transcription factor that plays a pivotal role in hemopoietic CC and endothelial development, acting synergistically with lmo2 and CC downstream of clo. Specifies mesodermal precursors to a hemangioblast CC cell fate. Hemangioblasts are bipotential precursors of blood and CC endothelium, and in the absence of hemopoietic induction cues such as CC gata1, tal1/scl-lmo2-induced hemangioblasts differentiate into CC endothelial cells. Isoform alpha and isoform beta are redundant for the CC initiation of primitive hemopoiesis but have distinct roles in the CC regulation of primitive erythroid differentiation and definitive CC hemopoietic stem cell specification, most likely due to differences in CC expression levels. Specification of definitive hemopoietic stem cells CC requires isoform beta. DNA binding is required for erythroid CC maturation, but not for its other hemopoietic functions. Endothelial CC roles include development of the dorsal aorta, the site of definitive CC hemopoiesis in the embryo. Required for angiogenesis but not angioblast CC specification. Has an additional role in endocardium formation during CC heart development. May play a role in central nervous system CC development. {ECO:0000269|PubMed:11003831, ECO:0000269|PubMed:14602685, CC ECO:0000269|PubMed:15617691, ECO:0000269|PubMed:15644413, CC ECO:0000269|PubMed:16210319, ECO:0000269|PubMed:17090656, CC ECO:0000269|PubMed:17472439, ECO:0000269|PubMed:17722983, CC ECO:0000269|PubMed:9499398, ECO:0000269|PubMed:9670018}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P22091, CC ECO:0000255|PROSITE-ProRule:PRU00981}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=alpha {ECO:0000269|PubMed:17472439, ECO:0000269|PubMed:9499398, CC ECO:0000269|PubMed:9670018}; CC IsoId=O93507-1; Sequence=Displayed; CC Name=beta {ECO:0000269|PubMed:17472439}; CC IsoId=O93507-2; Sequence=VSP_052683; CC -!- TISSUE SPECIFICITY: Expressed in hemopoietic and endothelial lineages. CC Isoform beta emerges first, expressing in the entire anterior and CC posterior lateral mesoderm (ALM and PLM respectively), and in the CC ventral wall of the dorsal aorta, where definitive hemopoiesis begins. CC Isoform alpha expresses later as two pairs of stripes in the PLM and CC ALM, and becomes restricted to the intermediate cell mass (ICM) by the CC 18-somite stage. The ICM is the key site of primitive hemopoiesis, CC giving rise to the erythroid lineage. Also expressed in all stages of CC endocardial cell migration and in the developing midbrain, hindbrain CC and spinal cord. In adults, expressed in the main hemopoietic organs, CC namely the kidney (where isoform alpha is the predominant isoform) and CC the spleen. Also expressed in the liver, gill and gonads. CC {ECO:0000269|PubMed:10208748, ECO:0000269|PubMed:11381108, CC ECO:0000269|PubMed:17472439, ECO:0000269|PubMed:17722983, CC ECO:0000269|PubMed:9499398, ECO:0000269|PubMed:9670018}. CC -!- DEVELOPMENTAL STAGE: Expression of isoform beta begins at the 1-2 CC somite stage, peaks at the 11-18 somite stage, and is maintained at a CC lower level in the adult kidney. Isoform alpha isn't expressed until CC the 4-somite stage, after which expression levels rapidly increase. CC {ECO:0000269|PubMed:17472439}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC41264.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAC41264.1; Type=Frameshift; 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; AF038873; AAC36057.1; -; mRNA. DR EMBL; AF045432; AAC41264.1; ALT_SEQ; mRNA. DR EMBL; EF488003; ABO77946.1; -; mRNA. DR EMBL; EF488004; ABO77947.1; -; mRNA. DR EMBL; AL592495; CAC95157.2; -; Genomic_DNA. DR EMBL; BX664601; CAK04103.1; -; Genomic_DNA. DR EMBL; BX322568; CAK04103.1; JOINED; Genomic_DNA. DR EMBL; BX322568; CAK11011.1; -; Genomic_DNA. DR EMBL; BX664601; CAK11011.1; JOINED; Genomic_DNA. DR EMBL; BC068324; AAH68324.1; -; mRNA. DR RefSeq; NP_998402.1; NM_213237.1. [O93507-1] DR AlphaFoldDB; O93507; -. DR SMR; O93507; -. DR FunCoup; O93507; 1417. DR STRING; 7955.ENSDARP00000077498; -. DR PaxDb; 7955-ENSDARP00000077498; -. DR DNASU; 30766; -. DR Ensembl; ENSDART00000083063; ENSDARP00000077498; ENSDARG00000019930. [O93507-1] DR GeneID; 30766; -. DR KEGG; dre:30766; -. DR AGR; ZFIN:ZDB-GENE-980526-501; -. DR CTD; 6886; -. DR ZFIN; ZDB-GENE-980526-501; tal1. DR eggNOG; KOG4029; Eukaryota. DR GeneTree; ENSGT00940000159889; -. DR HOGENOM; CLU_059203_0_0_1; -. DR InParanoid; O93507; -. DR OMA; SKWAMEP; -. DR OrthoDB; 10069510at2759; -. DR PhylomeDB; O93507; -. DR Reactome; R-DRE-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs. DR PRO; PR:O93507; -. DR Proteomes; UP000000437; Chromosome 22. DR Bgee; ENSDARG00000019930; Expressed in mesoderm and 74 other cell types or tissues. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; IMP:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. 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; IBA:GO_Central. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:ZFIN. DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB. DR GO; GO:0048844; P:artery morphogenesis; IMP:UniProtKB. DR GO; GO:0001568; P:blood vessel development; IMP:ZFIN. DR GO; GO:0060216; P:definitive hemopoiesis; IMP:UniProtKB. DR GO; GO:0035050; P:embryonic heart tube development; IMP:ZFIN. DR GO; GO:0035162; P:embryonic hemopoiesis; IMP:ZFIN. DR GO; GO:0060214; P:endocardium formation; IMP:UniProtKB. DR GO; GO:0003160; P:endocardium morphogenesis; IMP:ZFIN. DR GO; GO:0030218; P:erythrocyte differentiation; IGI:ZFIN. DR GO; GO:0007507; P:heart development; IGI:ZFIN. DR GO; GO:0003007; P:heart morphogenesis; IGI:ZFIN. DR GO; GO:0060217; P:hemangioblast cell differentiation; IDA:ZFIN. DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IMP:UniProtKB. DR GO; GO:0030097; P:hemopoiesis; IDA:ZFIN. DR GO; GO:0048368; P:lateral mesoderm development; IMP:ZFIN. DR GO; GO:0030099; P:myeloid cell differentiation; IEP:UniProtKB. DR GO; GO:0048823; P:nucleate erythrocyte development; IMP:ZFIN. DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IMP:ZFIN. DR GO; GO:0060215; P:primitive hemopoiesis; IDA:ZFIN. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0019827; P:stem cell population maintenance; IMP:ZFIN. DR GO; GO:0030878; P:thyroid gland development; IMP:ZFIN. DR GO; GO:0001570; P:vasculogenesis; IDA:ZFIN. DR CDD; cd19706; bHLH_TS_TAL1; 1. DR FunFam; 4.10.280.10:FF:000015; T-cell acute lymphocytic leukemia 1; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR040238; TAL-like. DR PANTHER; PTHR13864:SF27; T-CELL ACUTE LYMPHOCYTIC LEUKEMIA PROTEIN 1 HOMOLOG; 1. DR PANTHER; PTHR13864; T-CELL ACUTE LYMPHOCYTIC LEUKEMIA/STEM CELL LEUKEMIA-RELATED; 1. DR Pfam; PF00010; HLH; 1. DR SMART; SM00353; HLH; 1. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR PROSITE; PS50888; BHLH; 1. PE 1: Evidence at protein level; KW Alternative splicing; Angiogenesis; Developmental protein; Differentiation; KW DNA-binding; Nucleus; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..324 FT /note="T-cell acute lymphocytic leukemia protein 1 homolog" FT /id="PRO_0000320003" FT DOMAIN 185..237 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT REGION 1..49 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 276..324 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..118 FT /note="Missing (in isoform beta)" FT /evidence="ECO:0000303|PubMed:17472439" FT /id="VSP_052683" FT MUTAGEN 193..195 FT /note="RER->AAA: Abolishes DNA binding." FT /evidence="ECO:0000269|PubMed:16210319" FT CONFLICT 16 FT /note="A -> T (in Ref. 4; CAC95157)" FT /evidence="ECO:0000305" FT CONFLICT 20 FT /note="A -> T (in Ref. 4; CAC95157)" FT /evidence="ECO:0000305" FT CONFLICT 79 FT /note="A -> V (in Ref. 2; AAC41264)" FT /evidence="ECO:0000305" FT CONFLICT 116..117 FT /note="DT -> EI (in Ref. 2; AAC41264)" FT /evidence="ECO:0000305" FT CONFLICT 123 FT /note="S -> I (in Ref. 2; AAC41264)" FT /evidence="ECO:0000305" FT CONFLICT 127 FT /note="F -> Y (in Ref. 2; AAC41264)" FT /evidence="ECO:0000305" FT CONFLICT 135 FT /note="L -> F (in Ref. 2; AAC41264)" FT /evidence="ECO:0000305" FT CONFLICT 143 FT /note="L -> F (in Ref. 2; AAC41264)" FT /evidence="ECO:0000305" FT CONFLICT 283 FT /note="S -> T (in Ref. 2; AAC41264)" FT /evidence="ECO:0000305" SQ SEQUENCE 324 AA; 35705 MW; 28B98591156C40F6 CRC64; MMEKLKSEQF PLSPSAEGCA SPPRGDGDAR GKQEGTTAET GEHRLPEELN GVAKETAHHA TELKKEVAVI ELSRRGGSAD IKGRELKAEL SHKVQTTELC RPPIPLPLPP RDPLSDTRMV QLSPPAFPLP ARAMLYSNMT TPLATINSGF AGDAEQYGMY PSNRVKRRPA PYEVEINDGS QPKIVRRIFT NSRERWRQQN VNGAFAELRK LIPTHPPDKK LSKNEILRLA MKYINFLAKL LNDQDDMVGG EAPARANRDS RDATLVRDDL LQEMLSPNSS CGSLLDGDAS PESFTEDQDS SVESRPSARG LHHSSLPLDG NAQR //