Reviewed, UniProtKB/Swiss-Prot P19532 (TFE3_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcription factor E3

Gene names

Name:

TFE3

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	575 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Positive-acting transcription factor that binds to the immunoglobulin enchancer MUE3 motif. It also binds very well to a USF/MLTF site. Binding of TFE3 to DNA induces DNA binding.
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein.
Subcellular location	Nucleus.
Tissue specificity	Ubiquitous in fetal and adult tissues.
Involvement in disease	Chromosomal aberrations involving TFE3 are recurrent in alveolar soft part sarcoma (ASPS) [MIM:606243]. Translocation t(X;17)(p11;q25) with ASPSCR1 forms a ASPSCR1-TFE3 fusion protein. Ref.7 Ref.8 Chromosomal aberrations involving TFE3 may be a cause of papillary renal cell carcinoma (PRCC) [MIM:605074]. Translocation t(X;1)(p11.2;q21.2) with PRCC; translocation t(X;1)(p11.2;p34) with PSF; inversion inv(X)(p11.2;q12) that fuses NONO to TFE3. Ref.4 Ref.5 Chromosomal aberrations involving TFE3 are recurrent in alveolar soft part sarcoma (ASPS). Translocation t(X;17)(p11;q25) with ASPSCR1 forms a ASPSCR1-TFE3 fusion protein.
Sequence similarities	Belongs to the MiT/TFE family. Contains 1 basic helix-loop-helix (bHLH) domain.
Sequence caution	The sequence CAA35714.1 differs from that shown. Reason: Frameshift at position 557. The sequence CAA65800.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct transcription factor activity Non-traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACLY	P53396	1	EBI-1048957,EBI-1042794
AKR1B1	P15121	1	EBI-1048957,EBI-1052491
CLTC	Q00610	1	EBI-1048957,EBI-354967
CUL2	Q13617	1	EBI-1048957,EBI-456179
EIF3A	Q14152	1	EBI-1048957,EBI-366617
EPRS	P07814	1	EBI-1048957,EBI-355315
NEDD8	Q15843	1	EBI-1048957,EBI-716247
PFAS	O15067	1	EBI-1048957,EBI-1052653
PHB2	Q99623	1	EBI-1048957,EBI-358348
RPL38	P63173	1	EBI-1048957,EBI-359141
TRIM28	Q13263	1	EBI-1048957,EBI-78139
VARS	P26640	1	EBI-1048957,EBI-355765

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 575	575	Transcription factor E3		PRO_0000127471
Regions
	Domain	360 – 400	41	Helix-loop-helix motif
	Domain	409 – 430	22	Leucine-zipper Potential
	DNA binding	344 – 359	16	Basic motif
	Region	260 – 271	12	Strong transcription activation domain Potential
Sites
	Site	178 – 179	2	Breakpoint for translocation to form PRCC-TFE3 oncogene
	Site	260 – 261	2	Breakpoint for translocation to form ASPSCR1-TFE3 oncogene
	Site	295 – 296	2	Breakpoint for translocation to form NONO-TFE3, PSF-TFE3 and ASPSCR1-TFE3 oncogenes
Amino acid modifications
	Modified residue	568	1	Phosphoserine By similarity
Natural variations
	Natural variant	96	1	S → C: dbSNP rs5953258.		VAR_027501
	Natural variant	313	1	T → A: dbSNP rs3027470.		VAR_027502
Experimental info
	Sequence conflict	172	1	V → M in CAA65800. Ref.5
	Sequence conflict	219	1	P → S in CAA65800. Ref.5
	Sequence conflict	222	1	P → K in CAA35714. Ref.6
	Sequence conflict	229	1	P → L in CAA65800. Ref.5
	Sequence conflict	443	1	P → G in CAA35714. Ref.6
	Sequence conflict	455	1	A → T in CAA65800. Ref.5
	Sequence conflict	455	1	A → T in CAA35714. Ref.6
	Sequence conflict	475	1	A → R in CAA35714. Ref.6
	Sequence conflict	575	1	S → M in CAA65800. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P19532-1 [UniParc]. Last modified November 13, 2007. Version 4. Checksum: EF1F11AB624C6BE1	FASTA	575	61,521
	10 20 30 40 50 60 MSHAAEPARD GVEASAEGPR AVFVLLEERR PADSAQLLSL NSLLPESGIV ADIELENVLD 70 80 90 100 110 120 PDSFYELKSQ PLPLRSSLPI SLQATPATPA TLSASSSAGG SRTPAMSSSS SSRVLLRQQL 130 140 150 160 170 180 MRAQAQEQER RERREQAAAA PFPSPAPASP AISVVGVSAG GHTLSRPPPA QVPREVLKVQ 190 200 210 220 230 240 THLENPTRYH LQQARRQQVK QYLSTTLGPK LASQALTPPP GPASAQPLPA PEAAHTTGPT 250 260 270 280 290 300 GSAPNSPMAL LTIGSSSEKE IDDVIDEIIS LESSYNDEML SYLPGGTTGL QLPSTLPVSG 310 320 330 340 350 360 NLLDVYSSQG VATPAITVSN SCPAELPNIK REISETEAKA LLKERQKKDN HNLIERRRRF 370 380 390 400 410 420 NINDRIKELG TLIPKSSDPE MRWNKGTILK ASVDYIRKLQ KEQQRSKDLE SRQRSLEQAN 430 440 450 460 470 480 RSLQLRIQEL ELQAQIHGLP VPPTPGLLSL ATTSASDSLK PEQLDIEEEG RPGAATFHVG 490 500 510 520 530 540 GGPAQNAPHQ QPPAPPSDAL LDLHFPSDHL GDLGDPFHLG LEDILMEEEE GVVGGLSGGA 550 560 570 LSPLRAASDP LLSSVSPAVS KASSRRSSFS MEEES

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma." Clark J., Lu Y.-J., Sidhar S.K., Parker C., Gill S., Smedley D., Hamoudi R., Linehan W.M., Shipley J., Cooper C.S. Oncogene 15:2233-2239(1997) [PubMed: 9393982] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH PSF AND NONO.
[2]	Clark J. Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas." Weterman M.A.J., Wilbrink M., Geurts van Kessel A. Proc. Natl. Acad. Sci. U.S.A. 93:15294-15298(1996) [PubMed: 8986805] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-219, CHROMOSOMAL TRANSLOCATION WITH PRCC.
[5]	"The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene." Sidhar S.K., Clark J., Gill S., Hamoudi R., Crew A.J., Gwilliam R., Ross M., Linehan W.M., Birdsall S., Shipley J., Cooper C.S. Hum. Mol. Genet. 5:1333-1338(1996) [PubMed: 8872474] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 149-575, CHROMOSOMAL TRANSLOCATION WITH PRCC. Tissue: Monocyte.
[6]	"TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif." Beckmann H., Su L.-K., Kadesch T. Genes Dev. 4:167-179(1990) [PubMed: 2338243] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 212-575. Tissue: Leukemia.
[7]	"Fusion of a novel gene, RCC17, to the TFE3 gene in t(X;17)(p11.2;q25.3)-bearing papillary renal cell carcinomas." Heimann P., El Housni H., Ogur G., Weterman M.A.J., Petty E.M., Vassart G. Cancer Res. 61:4130-4135(2001) [PubMed: 11358836] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH ASPSCR1.
[8]	"The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25." Ladanyi M., Lui M.Y., Antonescu C.R., Krause-Boehm A., Meindl A., Argani P., Healey J.H., Ueda T., Yoshikawa H., Meloni-Ehrig A., Sorensen P.H.B., Mertens F., Mandahl N., van den Berghe H., Sciot R., Dal Cin P., Bridge J. Oncogene 20:48-57(2001) [PubMed: 11244503] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH ASPSCR1, INVOLVEMENT IN ASPS.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	X96717 mRNA. Translation: CAA65478.1. BX572102 Genomic DNA. No translation available. X99721 Genomic DNA. Translation: CAA68061.1. X97160, X97161, X97162 Genomic DNA. Translation: CAA65800.1. Sequence problems. X51330 mRNA. Translation: CAA35714.1. Sequence problems.
IPI	IPI00019490.
PIR	A34596.
RefSeq	NP_006512.2.
UniGene	Hs.714810
3D structure databases
HSSP	HSSP built from PDB template 1AN4 based on UniProtKB P22415.
ModBase	Search...
Protein-protein interaction databases
IntAct	P19532. 41 interactions.
Proteomic databases
PRIDE	P19532.
Genome annotation databases
Ensembl	ENSG00000068323. Homo sapiens. [Contig view]
GeneID	7030.
KEGG	hsa:7030.
Organism-specific databases
GeneCards	GC0XM048771.
HGNC	HGNC:11752. TFE3.
MIM	314310. gene. 605074. phenotype. 606243. phenotype.
Orphanet	163699. Alveolar soft-part sarcoma. 47044. Renal cell carcinoma, papillary, familial.
PharmGKB	PA36467.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P19532.
HOVERGEN	P19532.
OMA	P19532. TATFHAG.
Enzyme and pathway databases
Pathway_Interaction_DB	smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
Gene expression databases
ArrayExpress	P19532.
Bgee	P19532.
CleanEx	HS_TFE3.
GermOnline	ENSG00000068323. Homo sapiens.
Family and domain databases
InterPro	IPR001092. HLH_basic. IPR011598. HLH_DNA_bd. [Graphical view]
Gene3D	G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
PROSITE	PS50888. HLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	27465.
SOURCE	Search...

Entry information

Entry name

TFE3_HUMAN

Accession

Primary (citable) accession number: P19532
Secondary accession number(s): A8MZL6 , Q92757, Q92758, Q99964

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	November 13, 2007
Last modified:	June 16, 2009
This is version 99 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)