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TAL1_DANRE
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   03-AUG-2022, entry version 140.
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, ECO:0000303|PubMed:9670018},
GN   tal-1 {ECO:0000312|EMBL:AAC41264.1}; 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};
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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   STRING; 7955.ENSDARP00000077498; -.
DR   PaxDb; O93507; -.
DR   DNASU; 30766; -.
DR   Ensembl; ENSDART00000083063; ENSDARP00000077498; ENSDARG00000019930. [O93507-1]
DR   GeneID; 30766; -.
DR   KEGG; dre:30766; -.
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; PMGKECK; -.
DR   OrthoDB; 1453623at2759; -.
DR   PhylomeDB; O93507; -.
DR   TreeFam; TF315153; -.
DR   Reactome; R-DRE-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR   PRO; PR:O93507; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 22.
DR   Bgee; ENSDARG00000019930; Expressed in mesoderm and 74 other tissues.
DR   GO; GO:0005634; C:nucleus; IC:UniProtKB.
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   Gene3D; 4.10.280.10; -; 1.
DR   InterPro; IPR011598; bHLH_dom.
DR   InterPro; IPR036638; HLH_DNA-bd_sf.
DR   InterPro; IPR040238; TAL-like.
DR   PANTHER; PTHR13864; PTHR13864; 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   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   COMPBIAS        27..49
FT                   /note="Basic and acidic residues"
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
 
 
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