O93507 (TAL1_DANRE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
T-cell acute lymphocytic leukemia protein 1 homolog
Short name=TAL-1

Alternative name(s):
Stem cell protein
Short name=zSCL

Gene names

Name:	tal1
Synonyms:	scl, tal-1
ORF Names:	si:ch211-135j1.3

Organism

Danio rerio (Zebrafish) (Brachydanio rerio)

Taxonomic identifier

7955 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Actinopterygii › Neopterygii › Teleostei › Ostariophysi › Cypriniformes › Cyprinidae › Danio

Protein attributes

Sequence length	324 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor that plays a pivotal role in hemopoietic and endothelial development, acting synergistically with lmo2 and downstream of clo. Specifies mesodermal precursors to a hemangioblast cell fate. Hemangioblasts are bipotential precursors of blood and endothelium, and in the absence of hemopoietic induction cues such as gata1, tal1/scl-lmo2-induced hemangioblasts differentiate into endothelial cells. Isoform alpha and isoform beta are redundant for the initiation of primitive hemopoiesis but have distinct roles in the regulation of primitive erythroid differentiation and definitive hemopoietic stem cell specification, most likely due to differences in expression levels. Specification of definitive hemopoietic stem cells requires isoform beta. DNA binding is required for erythroid maturation, but not for its other hemopoietic functions. Endothelial roles include development of the dorsal aorta, the site of definitive hemopoiesis in the embryo. Required for angiogenesis but not angioblast specification. Has an additional role in endocardium formation during heart development. May play a role in central nervous system development. Ref.1 Ref.2 Ref.3 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Subcellular location	Nucleus By similarity UniProtKB P22091.
Tissue specificity	Expressed in hemopoietic and endothelial lineages. Isoform beta emerges first, expressing in the entire anterior and posterior lateral mesoderm (ALM and PLM respectively), and in the ventral wall of the dorsal aorta, where definitive hemopoiesis begins. Isoform alpha expresses later as two pairs of stripes in the PLM and ALM, and becomes restricted to the intermediate cell mass (ICM) by the 18-somite stage. The ICM is the key site of primitive hemopoiesis, giving rise to the erythroid lineage. Also expressed in all stages of endocardial cell migration and in the developing midbrain, hindbrain and spinal cord. In adults, expressed in the main hemopoietic organs, namely the kidney (where isoform alpha is the predominant isoform) and the spleen. Also expressed in the liver, gill and gonads. Ref.1 Ref.2 Ref.3 Ref.6 Ref.8 Ref.14
Developmental stage	Expression of isoform beta begins at the 1-2 somite stage, peaks at the 11-18 somite stage, and is maintained at a lower level in the adult kidney. Isoform alpha isn't expressed until the 4-somite stage, after which expression levels rapidly increase. Ref.3
Sequence similarities	Contains 1 basic helix-loop-helix (bHLH) domain.
Sequence caution	The sequence AAC41264.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAC41264.1 differs from that shown. Reason: Frameshift at positions 129, 130, 138 and 303.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	angiogenesis Inferred from mutant phenotype Ref.11. Source: UniProtKB artery morphogenesis Inferred from mutant phenotype Ref.10. Source: UniProtKB definitive hemopoiesis Inferred from mutant phenotype Ref.11Ref.10Ref.3. Source: UniProtKB embryonic heart tube development Inferred from mutant phenotype Ref.14. Source: ZFIN endocardium formation Inferred from mutant phenotype Ref.14. Source: UniProtKB heart morphogenesis Inferred from genetic interaction. Source: ZFIN hemangioblast cell differentiation Inferred from mutant phenotype Ref.9Ref.1. Source: UniProtKB hemopoietic stem cell differentiation Inferred from mutant phenotype Ref.3. Source: UniProtKB lateral mesoderm development Inferred from mutant phenotype. Source: ZFIN nucleate erythrocyte development Inferred from mutant phenotype Ref.3. Source: ZFIN positive regulation of endothelial cell differentiation Inferred from mutant phenotype Ref.1. Source: ZFIN regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW thyroid gland development Inferred from mutant phenotype. Source: ZFIN transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW vasculogenesis Inferred from mutant phenotype Ref.2. Source: UniProtKB
Cellular component	nucleus Inferred by curator Ref.12. Source: UniProtKB
Molecular function	DNA binding Inferred from mutant phenotype Ref.12. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform alpha Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 (identifier: O93507-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform beta Ref.3 (identifier: O93507-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-118: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 324	324	T-cell acute lymphocytic leukemia protein 1 homolog		PRO_0000320003
Regions
	Domain	198 – 238	41	Helix-loop-helix motif
	DNA binding	185 – 197	13	Basic motif
Natural variations
	Alternative sequence	1 – 118	118	Missing in isoform beta. Ref.3		VSP_052683
Experimental info
	Mutagenesis	193 – 195	3	RER → AAA: Abolishes DNA binding. Ref.12
	Sequence conflict	16	1	A → T in CAC95157. Ref.4
	Sequence conflict	20	1	A → T in CAC95157. Ref.4
	Sequence conflict	79	1	A → V in AAC41264. Ref.2
	Sequence conflict	116 – 117	2	DT → EI in AAC41264. Ref.2
	Sequence conflict	123	1	S → I in AAC41264. Ref.2
	Sequence conflict	127	1	F → Y in AAC41264. Ref.2
	Sequence conflict	135	1	L → F in AAC41264. Ref.2
	Sequence conflict	143	1	L → F in AAC41264. Ref.2
	Sequence conflict	283	1	S → T in AAC41264. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform alpha [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 28B98591156C40F6	FASTA	324	35,705
	10 20 30 40 50 60 MMEKLKSEQF PLSPSAEGCA SPPRGDGDAR GKQEGTTAET GEHRLPEELN GVAKETAHHA 70 80 90 100 110 120 TELKKEVAVI ELSRRGGSAD IKGRELKAEL SHKVQTTELC RPPIPLPLPP RDPLSDTRMV 130 140 150 160 170 180 QLSPPAFPLP ARAMLYSNMT TPLATINSGF AGDAEQYGMY PSNRVKRRPA PYEVEINDGS 190 200 210 220 230 240 QPKIVRRIFT NSRERWRQQN VNGAFAELRK LIPTHPPDKK LSKNEILRLA MKYINFLAKL 250 260 270 280 290 300 LNDQDDMVGG EAPARANRDS RDATLVRDDL LQEMLSPNSS CGSLLDGDAS PESFTEDQDS 310 320 SVESRPSARG LHHSSLPLDG NAQR
	Isoform beta [UniParc]. Checksum: 153FB5F7D105772D	FASTA	206	22,925
	10 20 30 40 50 60 MVQLSPPAFP LPARAMLYSN MTTPLATINS GFAGDAEQYG MYPSNRVKRR PAPYEVEIND 70 80 90 100 110 120 GSQPKIVRRI FTNSRERWRQ QNVNGAFAEL RKLIPTHPPD KKLSKNEILR LAMKYINFLA 130 140 150 160 170 180 KLLNDQDDMV GGEAPARANR DSRDATLVRD DLLQEMLSPN SSCGSLLDGD ASPESFTEDQ 190 200 DSSVESRPSA RGLHHSSLPL DGNAQR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The SCL gene specifies haemangioblast development from early mesoderm." Gering M., Rodaway A.R.F., Goettgens B., Patient R.K., Green A.R. EMBO J. 17:4029-4045(1998) [PubMed: 9670018] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION, TISSUE SPECIFICITY. Tissue: Embryo.
[2]	"SCL/Tal-1 transcription factor acts downstream of cloche to specify hematopoietic and vascular progenitors in zebrafish." Liao E.C., Paw B.H., Oates A.C., Pratt S.J., Postlethwait J.H., Zon L.I. Genes Dev. 12:621-626(1998) [PubMed: 9499398] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION, TISSUE SPECIFICITY. Tissue: Angioblast.
[3]	"Distinct functions for different scl isoforms in zebrafish primitive and definitive hematopoiesis." Qian F., Zhen F., Xu J., Huang M., Li W., Wen Z. PLoS Biol. 5:1110-1119(2007) [PubMed: 17472439] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[4]	The Danio rerio sequencing project at the Sanger Institute Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AB and Tuebingen.
[5]	NIH - Zebrafish Gene Collection (ZGC) project Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). Tissue: Embryo.
[6]	"Distinct 5' SCL enhancers direct transcription to developing brain, spinal cord, and endothelium: neural expression is mediated by GATA factor binding sites." Sinclair A.M., Goettgens B., Barton L.M., Stanley M.L., Pardanaud L., Klaine M., Gering M., Bahn S., Sanchez M.-J., Bench A.J., Fordham J.L., Bockamp E.-O., Green A.R. Dev. Biol. 209:128-142(1999) [PubMed: 10208748] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Hhex and scl function in parallel to regulate early endothelial and blood differentiation in zebrafish." Liao W., Ho C.-Y., Yan Y.L., Postlethwait J.H., Stainier D.Y.R. Development 127:4303-4313(2000) [PubMed: 11003831] [Abstract] Cited for: FUNCTION.
[8]	"Regulation of the stem cell leukemia (SCL) gene: a tale of two fishes." Barton L.M., Goettgens B., Gering M., Gilbert J.G.R., Grafham D., Rogers J., Bentley D., Patient R.K., Green A.R. Proc. Natl. Acad. Sci. U.S.A. 98:6747-6752(2001) [PubMed: 11381108] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Lmo2 and Scl/Tal1 convert non-axial mesoderm into haemangioblasts which differentiate into endothelial cells in the absence of Gata1." Gering M., Yamada Y., Rabbitts T.H., Patient R.K. Development 130:6187-6199(2003) [PubMed: 14602685] [Abstract] Cited for: FUNCTION.
[10]	"Scl is required for dorsal aorta as well as blood formation in zebrafish embryos." Patterson L.J., Gering M., Patient R.K. Blood 105:3502-3511(2005) [PubMed: 15644413] [Abstract] Cited for: FUNCTION.
[11]	"Zebrafish scl functions independently in hematopoietic and endothelial development." Dooley K.A., Davidson A.J., Zon L.I. Dev. Biol. 277:522-536(2005) [PubMed: 15617691] [Abstract] Cited for: FUNCTION.
[12]	"Distinct roles for SCL in erythroid specification and maturation in zebrafish." Juarez M.A., Su F., Chun S., Kiel M.J., Lyons S.E. J. Biol. Chem. 280:41636-41644(2005) [PubMed: 16210319] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF 193-ARG--ARG-195.
[13]	"The transcription factors Scl and Lmo2 act together during development of the hemangioblast in zebrafish." Patterson L.J., Gering M., Eckfeldt C.E., Green A.R., Verfaillie C.M., Ekker S.C., Patient R.K. Blood 109:2389-2398(2007) [PubMed: 17090656] [Abstract] Cited for: FUNCTION.
[14]	"Early endocardial morphogenesis requires Scl/Tal1." Bussmann J., Bakkers J., Schulte-Merker S. PLoS Genet. 3:1425-1437(2007) [PubMed: 17722983] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF038873 mRNA. Translation: AAC36057.1. AF045432 mRNA. Translation: AAC41264.1. Sequence problems. EF488003 mRNA. Translation: ABO77946.1. EF488004 mRNA. Translation: ABO77947.1. AL592495 Genomic DNA. Translation: CAC95157.2. BX664601, BX322568 Genomic DNA. Translation: CAK04103.1. BX322568, BX664601 Genomic DNA. Translation: CAK11011.1. BC068324 mRNA. Translation: AAH68324.1.
IPI	IPI00493592. IPI00972632.
RefSeq	NP_998402.1. NM_213237.1.
UniGene	Dr.75812.
3D structure databases
ProteinModelPortal	O93507.
ModBase	Search...
Protein-protein interaction databases
STRING	O93507.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSDART00000083063; ENSDARP00000077498; ENSDARG00000019930.
GeneID	30766.
KEGG	dre:30766.
Organism-specific databases
CTD	6886.
ZFIN	ZDB-GENE-980526-501. tal1.
Phylogenomic databases
eggNOG	fiNOG05366.
GeneTree	ENSGT00590000082747.
HOVERGEN	HBG005018.
InParanoid	O93507.
OrthoDB	EOG4TMR2R.
Gene expression databases
ArrayExpress	O93507.
Bgee	O93507.
Family and domain databases
InterPro	IPR011598. HLH_DNA-bd. [Graphical view]
Gene3D	G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
KO	K09068.
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. HLH. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

TAL1_DANRE

Accession

Primary (citable) accession number: O93507
Secondary accession number(s): A4UTQ6, O57562, Q90W24

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program