P17542 (TAL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Class A basic helix-loop-helix protein 17
Short name=bHLHa17
Stem cell protein
T-cell leukemia/lymphoma protein 5

Gene names

Name:	TAL1
Synonyms:	BHLHA17, SCL, TCL5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	331 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Implicated in the genesis of hemopoietic malignancies. It may play an important role in hemopoietic differentiation. Serves as a positive regulator of erythroid differentiation By similarity. Ref.7
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein. Forms heterodimers with TCF3. Binds to the LIM domain containing protein LMO2 and to DRG1. Can assemble in a complex with LDB1 and LMO2. Component of a TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3 By similarity.
Subcellular location	Nucleus By similarity.
Tissue specificity	Leukemic stem cell.
Domain	The helix-loop-helix domain is necessary and sufficient for the interaction with DRG1.
Post-translational modification	Phosphorylated on serine residues. Phosphorylation of Ser-122 is strongly stimulated by hypoxia By similarity. Ref.8 Ubiquitinated; subsequent to hypoxia-dependent phosphorylation of Ser-122, ubiquitination targets the protein for rapid degradation via the ubiquitin system. This process may be characteristic for microvascular endothelial cells, since it could not be observed in large vessel endothelial cells By similarity.
Involvement in disease	A chromosomal aberration involving TAL1 may be a cause of some T-cell acute lymphoblastic leukemias (T-ALL). Translocation t(1;14)(p32;q11) with T-cell receptor alpha chain (TCRA) genes.
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Proto-oncogene
Ligand	DNA-binding
Molecular function	Developmental protein
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: Compara astrocyte fate commitment Inferred from electronic annotation. Source: Compara basophil differentiation Inferred from expression pattern PubMed 7678994. Source: BHF-UCL cell fate commitment Inferred from sequence or structural similarity. Source: BHF-UCL definitive hemopoiesis Inferred from electronic annotation. Source: Compara embryonic hemopoiesis Inferred from sequence or structural similarity. Source: UniProtKB erythrocyte differentiation Inferred from mutant phenotype Ref.7. Source: BHF-UCL erythrocyte maturation Inferred from electronic annotation. Source: Compara hemangioblast cell differentiation Inferred from electronic annotation. Source: Compara hematopoietic stem cell differentiation Inferred from electronic annotation. Source: Compara locomotory behavior Inferred from electronic annotation. Source: Compara megakaryocyte development Inferred from electronic annotation. Source: Compara megakaryocyte differentiation Inferred from expression pattern PubMed 7678994. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara platelet formation Inferred from electronic annotation. Source: Compara positive regulation of cell division Inferred from mutant phenotype PubMed 20855495. Source: BHF-UCL positive regulation of chromatin assembly or disassembly Inferred from mutant phenotype PubMed 20855495. Source: BHF-UCL positive regulation of erythrocyte differentiation Inferred from direct assay PubMed 20028976. Source: UniProtKB positive regulation of mitotic cell cycle Inferred from mutant phenotype PubMed 20855495. Source: BHF-UCL positive regulation of protein complex assembly Inferred from direct assay PubMed 20855495. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 20855495. Source: BHF-UCL regulation of cell proliferation Inferred from electronic annotation. Source: Compara regulation of mast cell differentiation Inferred from electronic annotation. Source: Compara regulation of stem cell maintenance Inferred from electronic annotation. Source: Compara spinal cord association neuron differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	nuclear chromatin Inferred from direct assay PubMed 20855495. Source: BHF-UCL transcription factor complex Inferred from direct assay PubMed 15920471. Source: BHF-UCL
Molecular_function	E-box binding Inferred from direct assay PubMed 20855495. Source: BHF-UCL RNA polymerase II distal enhancer sequence-specific DNA binding Inferred from electronic annotation. Source: Compara chromatin binding Inferred from direct assay PubMed 16763211. Source: MGI sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 19497860. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Lmo2	P25801	5	EBI-1753878,EBI-3903256	From a different organism.
TCF3	P15923	4	EBI-1753878,EBI-769630

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: The splicing pattern is cell-lineage dependent.

Isoform PP42-TAL1 (identifier: P17542-1)

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 PP39-TAL1 (identifier: P17542-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.

Isoform PP22-TAL1 (identifier: P17542-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-175: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 331	331	T-cell acute lymphocytic leukemia protein 1		PRO_0000127454
Regions
	Domain	187 – 239	53	bHLH
	Compositional bias	89 – 132	44	Pro-rich
	Compositional bias	263 – 274	12	Poly-Gly
Amino acid modifications
	Modified residue	122	1	Phosphoserine Ref.9
Natural variations
	Alternative sequence	1 – 175	175	Missing in isoform PP22-TAL1.		VSP_002154
	Alternative sequence	1 – 25	25	Missing in isoform PP39-TAL1.		VSP_002153

Sequences

	Sequence		Length	Mass (Da)
	Isoform PP42-TAL1 [UniParc]. Last modified November 1, 1991. Version 2. Checksum: 33BBE31589DBB7C7	FASTA	331	34,271
	10 20 30 40 50 60 MTERPPSEAA RSDPQLEGRD AAEASMAPPH LVLLNGVAKE TSRAAAAEPP VIELGARGGP 70 80 90 100 110 120 GGGPAGGGGA ARDLKGRDAA TAEARHRVPT TELCRPPGPA PAPAPASVTA ELPGDGRMVQ 130 140 150 160 170 180 LSPPALAAPA APGRALLYSL SQPLASLGSG FFGEPDAFPM FTTNNRVKRR PSPYEMEITD 190 200 210 220 230 240 GPHTKVVRRI FTNSRERWRQ QNVNGAFAEL RKLIPTHPPD KKLSKNEILR LAMKYINFLA 250 260 270 280 290 300 KLLNDQEEEG TQRAKTGKDP VVGAGGGGGG GGGGAPPDDL LQDVLSPNSS CGSSLDGAAS 310 320 330 PDSYTEEPAP KHTARSLHPA MLPAADGAGP R
	Isoform PP39-TAL1 [UniParc]. Checksum: 4457C743678771FE	FASTA	306	31,617
	10 20 30 40 50 60 MAPPHLVLLN GVAKETSRAA AAEPPVIELG ARGGPGGGPA GGGGAARDLK GRDAATAEAR 70 80 90 100 110 120 HRVPTTELCR PPGPAPAPAP ASVTAELPGD GRMVQLSPPA LAAPAAPGRA LLYSLSQPLA 130 140 150 160 170 180 SLGSGFFGEP DAFPMFTTNN RVKRRPSPYE MEITDGPHTK VVRRIFTNSR ERWRQQNVNG 190 200 210 220 230 240 AFAELRKLIP THPPDKKLSK NEILRLAMKY INFLAKLLND QEEEGTQRAK TGKDPVVGAG 250 260 270 280 290 300 GGGGGGGGGA PPDDLLQDVL SPNSSCGSSL DGAASPDSYT EEPAPKHTAR SLHPAMLPAA DGAGPR
	Isoform PP22-TAL1 [UniParc]. Checksum: 5BC0D5F12E261CDE	FASTA	156	16,548
	10 20 30 40 50 60 MEITDGPHTK VVRRIFTNSR ERWRQQNVNG AFAELRKLIP THPPDKKLSK NEILRLAMKY 70 80 90 100 110 120 INFLAKLLND QEEEGTQRAK TGKDPVVGAG GGGGGGGGGA PPDDLLQDVL SPNSSCGSSL 130 140 150 DGAASPDSYT EEPAPKHTAR SLHPAMLPAA DGAGPR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The SCL gene is formed from a transcriptionally complex locus." Aplan P.D., Begley C.G., Bertness V., Nussmeier M., Ezquerra A., Coligan J., Kirsch I.R. Mol. Cell. Biol. 10:6426-6435(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Coding sequences of the tal-1 gene are disrupted by chromosome translocation in human T cell leukemia." Chen Q., Yang C.Y.C., Tsan J.T., Xia Y., Ragab A.H., Peiper S.C., Carroll A., Baer R. J. Exp. Med. 172:1403-1408(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 106-148.
[5]	"The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif." Begley C.G., Aplan P.D., Denning S.M., Haynes B.F., Waldmann T.A., Kirsch I.R. Proc. Natl. Acad. Sci. U.S.A. 86:10128-10132(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 118-331. Tissue: Bone marrow.
[6]	"The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein." Chen Q., Cheng J.-T., Tsai L.H., Schneider N., Buchanan G., Carroll A., Crist W., Ozanne B., Siciliano M.J., Baer R. EMBO J. 9:415-424(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 181-331.
[7]	"The SCL gene product: a positive regulator of erythroid differentiation." Aplan P.D., Nakahara K., Orkin S.H., Kirsch I.R. EMBO J. 11:4073-4081(1992) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Products of the TAL1 oncogene: basic helix-loop-helix proteins phosphorylated at serine residues." Cheng J.-T., Hsu H.-L., Hwang L.-Y., Baer R. Oncogene 8:677-683(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[9]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	M61108 mRNA. Translation: AAA36600.1. M61103 Genomic DNA. No translation available. M61104 Genomic DNA. No translation available. M61105 Genomic DNA. No translation available. M63572 Genomic DNA. No translation available. M63589, M63576, M63584 Genomic DNA. Translation: AAA36599.1. AL135960 Genomic DNA. Translation: CAB72103.1. CH471059 Genomic DNA. Translation: EAX06875.1. CH471059 Genomic DNA. Translation: EAX06876.1. CH471059 Genomic DNA. Translation: EAX06877.1. X58621 Genomic DNA. Translation: CAA41476.1. Sequence problems. X58622 Genomic DNA. Translation: CAA41477.1. M29038 mRNA. Translation: AAA36598.1. X51990 mRNA. Translation: CAA36246.1.
IPI	IPI00218206. IPI00471993. IPI00747776.
PIR	A36358. I38253.
RefSeq	NP_003180.1. NM_003189.2.
UniGene	Hs.705618.
3D structure databases
ProteinModelPortal	P17542.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-40640N.
IntAct	P17542. 12 interactions.
MINT	MINT-2801392.
STRING	9606.ENSP00000294339.
PTM databases
PhosphoSite	P17542.
Polymorphism databases
DMDM	134305.
Proteomic databases
PaxDb	P17542.
PRIDE	P17542.
Protocols and materials databases
DNASU	6886.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000294339; ENSP00000294339; ENSG00000162367. ENST00000371884; ENSP00000360951; ENSG00000162367.
GeneID	6886.
KEGG	hsa:6886.
UCSC	uc001cqx.2. human.
Organism-specific databases
CTD	6886.
GeneCards	GC01M047681.
H-InvDB	HIX0029300.
HGNC	HGNC:11556. TAL1.
HPA	CAB017805.
MIM	187040. gene.
neXtProt	NX_P17542.
Orphanet	99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKB	PA36326.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG307510.
HOGENOM	HOG000113414.
HOVERGEN	HBG005018.
KO	K09068.
OrthoDB	EOG4TMR2R.
PhylomeDB	P17542.
Gene expression databases
ArrayExpress	P17542.
Bgee	P17542.
CleanEx	HS_TAL1.
Genevestigator	P17542.
GermOnline	ENSG00000162367. Homo sapiens.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. [Graphical view]
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6886.
NextBio	26909.
PMAP-CutDB	P17542.
SOURCE	Search...

Entry information

Entry name

TAL1_HUMAN

Accession

Primary (citable) accession number: P17542
Secondary accession number(s): D3DQ24

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	November 1, 1991
Last modified:	May 1, 2013
This is version 142 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.