P19484 (TFEB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor EB

Alternative name(s):
Class E basic helix-loop-helix protein 35
Short name=bHLHe35

Gene names

Name:	TFEB
Synonyms:	BHLHE35

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	476 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor that specifically recognizes and binds E-box sequences (3'-CANNTG-5'). Efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF. In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4+ T-cells and thymus-dependent humoral immunity. Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression. It thereby plays a central role in expression of lysosomal genes. Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer. Plays a role in the signal transduction processes required for normal vascularization of the placenta. Ref.9
Subunit structure	Homodimer and heterodimer; with TFE3 or MITF.
Subcellular location	Cytoplasm. Nucleus. Note: Mainly present in the cytoplasm. Under aberrant lysosomal storage conditions, it translocates from the cytoplasm to the nucleus.
Domain	The leucin zipper region is essential for homo- or heterodimerization and high-affinity DNA binding. DNA binding is mediated by the basic region. Ref.5
Post-translational modification	Sumoylated; does not affect dimerization with MITF. Ref.6
Sequence similarities	Belongs to the MiT/TFE family. Contains 1 basic helix-loop-helix (bHLH) domain.
Sequence caution	The sequence AAA36730.1 differs from that shown. Reason: Erroneous initiation. The sequence CAE77681.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	embryonic placenta development Inferred from sequence or structural similarity. Source: UniProtKB humoral immune response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.9. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay Ref.9. Source: UniProtKB
Molecular function	sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.9. Source: UniProtKB transcription regulatory region DNA binding Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P19484-1)

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 2 (identifier: P19484-2)

The sequence of this isoform differs from the canonical sequence as follows:
     72-156: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 476	476	Transcription factor EB		PRO_0000127473
Regions
	Domain	249 – 289	41	Helix-loop-helix motif
	Domain	298 – 319	22	Leucine-zipper
	DNA binding	233 – 248	16	Basic motif Ref.5 Ref.9
	Region	156 – 165	10	Strong transcription activation domain Potential
	Compositional bias	10 – 44	35	Gln-rich
	Compositional bias	35 – 44	10	Poly-Gln
	Compositional bias	366 – 414	49	Pro-rich
Amino acid modifications
	Modified residue	109	1	Phosphoserine Ref.7 Ref.8
	Modified residue	114	1	Phosphoserine Ref.7 Ref.8
	Modified residue	122	1	Phosphoserine Ref.7 Ref.8
	Modified residue	133	1	Phosphoserine Ref.7
	Modified residue	134	1	Phosphoserine Ref.7
	Modified residue	138	1	Phosphoserine Ref.7
	Modified residue	142	1	Phosphoserine Ref.7
	Modified residue	467	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	72 – 156	85	Missing in isoform 2.		VSP_002159
Experimental info
	Sequence conflict	106	1	A → AA in AAA36730. Ref.1
	Sequence conflict	113 – 141	29	GSPKP…NSAPN → ALRNPHQPPPQGCELDTCCP PPLATVLPI in AAA36730. Ref.1
	Sequence conflict	168 – 170	3	DDV → TMS in AAA36730. Ref.1
	Sequence conflict	415 – 476	62	EPLAP…EGDVL → DRN Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 29, 2001. Version 3. Checksum: 093AE3B79C760D99	FASTA	476	52,865
	10 20 30 40 50 60 MASRIGLRMQ LMREQAQQEE QRERMQQQAV MHYMQQQQQQ QQQQLGGPPT PAINTPVHFQ 70 80 90 100 110 120 SPPPVPGEVL KVQSYLENPT SYHLQQSQHQ KVREYLSETY GNKFAAHISP AQGSPKPPPA 130 140 150 160 170 180 ASPGVRAGHV LSSSAGNSAP NSPMAMLHIG SNPERELDDV IDNIMRLDDV LGYINPEMQM 190 200 210 220 230 240 PNTLPLSSSH LNVYSSDPQV TASLVGVTSS SCPADLTQKR ELTDAESRAL AKERQKKDNH 250 260 270 280 290 300 NLIERRRRFN INDRIKELGM LIPKANDLDV RWNKGTILKA SVDYIRRMQK DLQKSRELEN 310 320 330 340 350 360 HSRRLEMTNK QLWLRIQELE MQARVHGLPT TSPSGMNMAE LAQQVVKQEL PSEEGPGEAL 370 380 390 400 410 420 MLGAEVPDPE PLPALPPQAP LPLPTQPPSP FHHLDFSHSL SFGGREDEGP PGYPEPLAPG 430 440 450 460 470 HGSPFPSLSK KDLDLMLLDD SLLPLASDPL LSTMSPEASK ASSRRSSFSM EEGDVL
	Isoform 2 [UniParc]. Checksum: 9B43BAA84C5517B2	FASTA	391	43,803
	10 20 30 40 50 60 MASRIGLRMQ LMREQAQQEE QRERMQQQAV MHYMQQQQQQ QQQQLGGPPT PAINTPVHFQ 70 80 90 100 110 120 SPPPVPGEVL KLDDVIDNIM RLDDVLGYIN PEMQMPNTLP LSSSHLNVYS SDPQVTASLV 130 140 150 160 170 180 GVTSSSCPAD LTQKRELTDA ESRALAKERQ KKDNHNLIER RRRFNINDRI KELGMLIPKA 190 200 210 220 230 240 NDLDVRWNKG TILKASVDYI RRMQKDLQKS RELENHSRRL EMTNKQLWLR IQELEMQARV 250 260 270 280 290 300 HGLPTTSPSG MNMAELAQQV VKQELPSEEG PGEALMLGAE VPDPEPLPAL PPQAPLPLPT 310 320 330 340 350 360 QPPSPFHHLD FSHSLSFGGR EDEGPPGYPE PLAPGHGSPF PSLSKKDLDL MLLDDSLLPL 370 380 390 ASDPLLSTMS PEASKASSRR SSFSMEEGDV L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A helix-loop-helix protein related to the immunoglobulin E box-binding proteins." Carr C.S., Sharp P.A. Mol. Cell. Biol. 10:4384-4388(1990) [PubMed: 2115126] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: B-cell.
[2]	"Regulation of the MiTF/TFE bHLH-LZ transcription factors through restricted spatial expression and alternative splicing of functional domains." Kuiper R.P., Schepens M., Thijssen J., Schoenmakers E.F.P.M., Geurts van Kessel A. Nucleic Acids Res. 32:2315-2322(2004) [PubMed: 15118077] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Kidney.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-476 (ISOFORM 2). Tissue: Brain and Lung.
[5]	"TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family." Fisher D.E., Carr C.S., Parent L.A., Sharp P.A. Genes Dev. 5:2342-2352(1991) [PubMed: 1748288] [Abstract] Cited for: DNA-BINDING, INTERACTION WITH TFE3, DOMAIN.
[6]	"Sumoylation of MITF and its related family members TFE3 and TFEB." Miller A.J., Levy C., Davis I.J., Razin E., Fisher D.E. J. Biol. Chem. 280:146-155(2005) [PubMed: 15507434] [Abstract] Cited for: SUMOYLATION, INTERACTION WITH MITF.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-109; SER-114; SER-122; SER-133; SER-134; SER-138 AND SER-142, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-109; SER-114; SER-122 AND SER-467, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"A gene network regulating lysosomal biogenesis and function." Sardiello M., Palmieri M., di Ronza A., Medina D.L., Valenza M., Gennarino V.A., Di Malta C., Donaudy F., Embrione V., Polishchuk R.S., Banfi S., Parenti G., Cattaneo E., Ballabio A. Science 325:473-477(2009) [PubMed: 19556463] [Abstract] Cited for: FUNCTION, DNA-BINDING.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	M33782 mRNA. Translation: AAA36730.1. Different initiation. AJ608786 mRNA. Translation: CAE77681.1. Different initiation. AL035588 Genomic DNA. Translation: CAD92604.1. BC006225 mRNA. Translation: AAH06225.2. BC032448 mRNA. Translation: AAH32448.1.
IPI	IPI00385436. IPI00465427.
PIR	A35658.
RefSeq	NP_001161299.1. NM_001167827.1. NP_009093.1. NM_007162.2.
UniGene	Hs.485360. Hs.715310.
3D structure databases
ProteinModelPortal	P19484.
SMR	P19484. Positions 233-319.
ModBase	Search...
Protein-protein interaction databases
IntAct	P19484. 1 interaction.
STRING	P19484.
PTM databases
PhosphoSite	P19484.
Polymorphism databases
DMDM	19856774.
Proteomic databases
PRIDE	P19484.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000230323; ENSP00000230323; ENSG00000112561. ENST00000343317; ENSP00000343948; ENSG00000112561. ENST00000358871; ENSP00000351742; ENSG00000112561. ENST00000373033; ENSP00000362124; ENSG00000112561. ENST00000403298; ENSP00000384203; ENSG00000112561.
GeneID	7942.
KEGG	hsa:7942.
UCSC	uc003oqr.1. human. uc003oqs.1. human.
Organism-specific databases
CTD	7942.
GeneCards	GC06M041698.
H-InvDB	HIX0005869.
HGNC	HGNC:11753. TFEB.
MIM	600744. gene.
neXtProt	NX_P19484.
PharmGKB	PA36468.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12887.
HOVERGEN	HBG006768.
InParanoid	P19484.
OrthoDB	EOG469QTV.
PhylomeDB	P19484.
Gene expression databases
ArrayExpress	P19484.
Bgee	P19484.
CleanEx	HS_TFEB.
Genevestigator	P19484.
GermOnline	ENSG00000112561. Homo sapiens.
Family and domain databases
InterPro	IPR024097. bHLH_ZIP_TF. IPR021802. bHLH_ZIP_TF_MiT/TFE. IPR011598. HLH_DNA-bd. IPR024098. TFEB. [Graphical view]
Gene3D	G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
KO	K15590.
PANTHER	PTHR10014. PTHR10014. 1 hit. PTHR10014:SF9. PTHR10014:SF9. 1 hit.
Pfam	PF11851. DUF3371. 1 hit. 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...
Other
NextBio	30462.
SOURCE	Search...

Entry information

Entry name

TFEB_HUMAN

Accession

Primary (citable) accession number: P19484
Secondary accession number(s): Q709B3 , Q7Z6P9, Q9BRJ5, Q9UJD8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	August 29, 2001
Last modified:	January 25, 2012
This is version 121 of the entry and version 3 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.