Q15561 (TEAD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcriptional enhancer factor TEF-3

Alternative name(s):
TEA domain family member 4
Short name=TEAD-4
Transcription factor 13-like 1
Transcription factor RTEF-1

Gene names

Name:	TEAD4
Synonyms:	RTEF1, TCF13L1, TEF3

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	434 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif. Ref.8 Ref.9
Subunit structure	Interacts with YAP1 and WWTR1/TAZ. Ref.8 Ref.9 Ref.10
Subcellular location	Nucleus.
Tissue specificity	Preferentially expressed in skeletal muscle. Lower levels in pancreas, placenta, and heart.
Sequence similarities	Contains 1 TEA DNA-binding domain.
Sequence caution	The sequence CAA64212.2 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical ATA isoleucine codon.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	hippo signaling cascade Inferred from direct assay Ref.8Ref.9. Source: UniProtKB muscle organ development Traceable author statement Ref.1. Source: ProtInc regulation of transcription from RNA polymerase II promoter Traceable author statement Ref.1. Source: ProtInc skeletal system development Traceable author statement PubMed 8662936. Source: ProtInc transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.8Ref.9. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
WWTR1	Q9GZV5	2	EBI-747736,EBI-747743

Alternative products

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

Isoform 1 (identifier: Q15561-1)

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: Q15561-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-129: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q15561-3)

The sequence of this isoform differs from the canonical sequence as follows:
     119-161: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 434	434	Transcriptional enhancer factor TEF-3		PRO_0000205937
Regions
	DNA binding	38 – 105	68	TEA
Natural variations
	Alternative sequence	1 – 129	129	Missing in isoform 2.		VSP_043099
	Alternative sequence	119 – 161	43	Missing in isoform 3.		VSP_045657
	Natural variant	323	1	P → S. Corresponds to variant rs11550887 [ dbSNP | Ensembl ].		VAR_052279
Experimental info
	Mutagenesis	266	1	D → A: Reduced transforming ability. Ref.10
	Mutagenesis	297	1	K → A: Important loss of interaction with YAP1 and complete loss of transforming ability. Ref.10
	Mutagenesis	299	1	W → A: Important loss of interaction with YAP1 and complete loss of transforming ability. Ref.10
	Mutagenesis	337	1	F → A: Reduced interaction with YAP1. Ref.10
	Mutagenesis	373	1	F → A: Reduced transforming ability. Ref.10
	Mutagenesis	380	1	L → A: Reduced transforming ability. Ref.10
	Mutagenesis	391	1	E → A: Reduced transforming ability. Ref.10
	Mutagenesis	393	1	F → A: Reduced transforming ability. Ref.10
	Mutagenesis	427	1	H → A: Reduced transforming ability. Ref.10
	Mutagenesis	429	1	Y → A or H: Loss of interaction with YAP1 and also activation by YAP1. Ref.8 Ref.10
	Mutagenesis	429	1	Y → A: Important loss of interaction with YAP1 and complete loss of transforming ability. Ref.8 Ref.10
	Sequence conflict	39	1	A → G in AAC50763. Ref.1
	Sequence conflict	149	1	A → R in AAC50763. Ref.1
	Sequence conflict	172	1	G → E in AAC50763. Ref.1
	Sequence conflict	218 – 220	3	SVA → RRG in AAC50763. Ref.1
	Sequence conflict	258 – 259	2	SD → LR in AAC50763. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 3. Checksum: 544DDFD86E88D9A8	FASTA	434	48,329
	10 20 30 40 50 60 MEGTAGTITS NEWSSPTSPE GSTASGGSQA LDKPIDNDAE GVWSPDIEQS FQEALAIYPP 70 80 90 100 110 120 CGRRKIILSD EGKMYGRNEL IARYIKLRTG KTRTRKQVSS HIQVLARRKA REIQAKLKDQ 130 140 150 160 170 180 AAKDKALQSM AAMSSAQIIS ATAFHSSMAL ARGPGRPAVS GFWQGALPGQ AGTSHDVKPF 190 200 210 220 230 240 SQQTYAVQPP LPLPGFESPA GPAPSPSAPP APPWQGRSVA SSKLWMLEFS AFLEQQQDPD 250 260 270 280 290 300 TYNKHLFVHI GQSSPSYSDP YLEAVDIRQI YDKFPEKKGG LKDLFERGPS NAFFLVKFWA 310 320 330 340 350 360 DLNTNIEDEG SSFYGVSSQY ESPENMIITC STKVCSFGKQ VVEKVETEYA RYENGHYSYR 370 380 390 400 410 420 IHRSPLCEYM INFIHKLKHL PEKYMMNSVL ENFTILQVVT NRDTQETLLC IAYVFEVSAS 430 EHGAQHHIYR LVKE
	Isoform 2 [UniParc]. Checksum: 6A3BDF596BCE7797	FASTA	305	34,158
	10 20 30 40 50 60 MAAMSSAQII SATAFHSSMA LARGPGRPAV SGFWQGALPG QAGTSHDVKP FSQQTYAVQP 70 80 90 100 110 120 PLPLPGFESP AGPAPSPSAP PAPPWQGRSV ASSKLWMLEF SAFLEQQQDP DTYNKHLFVH 130 140 150 160 170 180 IGQSSPSYSD PYLEAVDIRQ IYDKFPEKKG GLKDLFERGP SNAFFLVKFW ADLNTNIEDE 190 200 210 220 230 240 GSSFYGVSSQ YESPENMIIT CSTKVCSFGK QVVEKVETEY ARYENGHYSY RIHRSPLCEY 250 260 270 280 290 300 MINFIHKLKH LPEKYMMNSV LENFTILQVV TNRDTQETLL CIAYVFEVSA SEHGAQHHIY RLVKE
	Isoform 3 [UniParc]. Checksum: 68B36C4E607ADB1E	FASTA	391	44,058
	10 20 30 40 50 60 MEGTAGTITS NEWSSPTSPE GSTASGGSQA LDKPIDNDAE GVWSPDIEQS FQEALAIYPP 70 80 90 100 110 120 CGRRKIILSD EGKMYGRNEL IARYIKLRTG KTRTRKQVSS HIQVLARRKA REIQAKLKFW 130 140 150 160 170 180 QGALPGQAGT SHDVKPFSQQ TYAVQPPLPL PGFESPAGPA PSPSAPPAPP WQGRSVASSK 190 200 210 220 230 240 LWMLEFSAFL EQQQDPDTYN KHLFVHIGQS SPSYSDPYLE AVDIRQIYDK FPEKKGGLKD 250 260 270 280 290 300 LFERGPSNAF FLVKFWADLN TNIEDEGSSF YGVSSQYESP ENMIITCSTK VCSFGKQVVE 310 320 330 340 350 360 KVETEYARYE NGHYSYRIHR SPLCEYMINF IHKLKHLPEK YMMNSVLENF TILQVVTNRD 370 380 390 TQETLLCIAY VFEVSASEHG AQHHIYRLVK E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human RTEF-1, a transcriptional enhancer factor-1-related gene preferentially expressed in skeletal muscle: evidence for an ancient multigene family." Stewart A.F.R., Richard C.W. III, Suzow J., Stephan D., Weremowicz S., Morton C.C., Adra C.N. Genomics 37:68-76(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Heart.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Uterine endothelium.
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton 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].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[6]	"A novel family of developmentally regulated mammalian transcription factors containing the TEA/ATTS DNA binding domain." Jacquemin P., Hwang J.-J., Martial J.A., Dolle P., Davidson I. J. Biol. Chem. 271:21775-21785(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-434 (ISOFORM 1).
[7]	"Role of MCAT binding factors during muscle hypertrophy." Tsika R.W., Karasseva N.G., Tsika G.L. Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-391 (ISOFORM 3).
[8]	"TEAD mediates YAP-dependent gene induction and growth control." Zhao B., Ye X., Yu J., Li L., Li W., Li S., Yu J., Lin J.D., Wang C.Y., Chinnaiyan A.M., Lai Z.C., Guan K.L. Genes Dev. 22:1962-1971(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH YAP1, MUTAGENESIS OF TYR-429.
[9]	"TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition." Zhang H., Liu C.Y., Zha Z.Y., Zhao B., Yao J., Zhao S., Xiong Y., Lei Q.Y., Guan K.L. J. Biol. Chem. 284:13355-13362(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH WWTR1.
[10]	"Structural basis of YAP recognition by TEAD4 in the hippo pathway." Chen L., Chan S.W., Zhang X., Walsh M., Lim C.J., Hong W., Song H. Genes Dev. 24:290-300(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH YAP1, MUTAGENESIS OF ASP-266; LYS-297; TRP-299; PHE-337; PHE-373; LEU-380; GLU-391; PHE-393; HIS-427 AND TYR-429.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U63824 mRNA. Translation: AAC50763.1. BX640921 mRNA. Translation: CAE45959.1. AC005911 Genomic DNA. No translation available. AC125807 Genomic DNA. No translation available. AC131234 Genomic DNA. No translation available. CH471116 Genomic DNA. Translation: EAW88872.1. BC015497 mRNA. Translation: AAH15497.2. X94438 mRNA. Translation: CAA64212.2. Sequence problems. AY101179 mRNA. Translation: AAM89497.1.
IPI	IPI00216204. IPI00410573. IPI00410574.
RefSeq	NP_003204.2. NM_003213.3. NP_958849.1. NM_201441.2. NP_958851.1. NM_201443.2.
UniGene	Hs.94865.
3D structure databases
ProteinModelPortal	Q15561.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15561. 2 interactions.
STRING	9606.ENSP00000352926.
PTM databases
PhosphoSite	Q15561.
Polymorphism databases
DMDM	215274211.
Proteomic databases
PaxDb	Q15561.
PRIDE	Q15561.
Protocols and materials databases
DNASU	7004.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000397122; ENSP00000380311; ENSG00000197905.
GeneID	7004.
KEGG	hsa:7004.
UCSC	uc001qln.3. human.
Organism-specific databases
CTD	7004.
GeneCards	GC12P003068.
HGNC	HGNC:11717. TEAD4.
MIM	601714. gene.
neXtProt	NX_Q15561.
PharmGKB	PA36435.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG246992.
HOGENOM	HOG000253933.
HOVERGEN	HBG056905.
InParanoid	Q15561.
KO	K09448.
Enzyme and pathway databases
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q15561.
Bgee	Q15561.
CleanEx	HS_TEAD4.
Genevestigator	Q15561.
GermOnline	ENSG00000197905. Homo sapiens.
Family and domain databases
InterPro	IPR000818. TEA/ATTS. IPR016361. TEF. IPR027255. TEF-3. [Graphical view]
PANTHER	PTHR11834. PTHR11834. 1 hit.
Pfam	PF01285. TEA. 1 hit. [Graphical view]
PIRSF	PIRSF002603. TEF. 1 hit. PIRSF500722. TEF-3. 1 hit.
PRINTS	PR00065. TEADOMAIN.
SMART	SM00426. TEA. 1 hit. [Graphical view]
PROSITE	PS00554. TEA_1. 1 hit. PS51088. TEA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7004.
NextBio	27354.
SOURCE	Search...

Entry information

Entry name

TEAD4_HUMAN

Accession

Primary (citable) accession number: Q15561
Secondary accession number(s): H0Y308 , Q6MZR9, Q8NEV5, Q92883, Q96BK2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 112 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.