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Q15561

- TEAD4_HUMAN

UniProt

Q15561 - TEAD4_HUMAN

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Protein

Transcriptional enhancer factor TEF-3

Gene

TEAD4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi38 – 10568TEAPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: UniProtKB-KW
  2. sequence-specific DNA binding transcription factor activity Source: UniProtKB

GO - Biological processi

  1. gene expression Source: Reactome
  2. hippo signaling Source: UniProtKB
  3. muscle organ development Source: ProtInc
  4. regulation of transcription from RNA polymerase II promoter Source: ProtInc
  5. skeletal system development Source: ProtInc
  6. transcription initiation from RNA polymerase II promoter Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_116145. PPARA activates gene expression.
REACT_118713. YAP1- and WWTR1 (TAZ)-stimulated gene expression.

Names & Taxonomyi

Protein namesi
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 namesi
Name:TEAD4
Synonyms:RTEF1, TCF13L1, TEF3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:11717. TEAD4.

Subcellular locationi

GO - Cellular componenti

  1. nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi266 – 2661D → A: Reduced transforming ability. 1 Publication
Mutagenesisi297 – 2971K → A: Important loss of interaction with YAP1 and complete loss of transforming ability. 1 Publication
Mutagenesisi299 – 2991W → A: Important loss of interaction with YAP1 and complete loss of transforming ability. 1 Publication
Mutagenesisi337 – 3371F → A: Reduced interaction with YAP1. 1 Publication
Mutagenesisi373 – 3731F → A: Reduced transforming ability. 1 Publication
Mutagenesisi380 – 3801L → A: Reduced transforming ability. 1 Publication
Mutagenesisi391 – 3911E → A: Reduced transforming ability. 1 Publication
Mutagenesisi393 – 3931F → A: Reduced transforming ability. 1 Publication
Mutagenesisi427 – 4271H → A: Reduced transforming ability. 1 Publication
Mutagenesisi429 – 4291Y → A or H: Loss of interaction with YAP1 and also activation by YAP1. 2 Publications
Mutagenesisi429 – 4291Y → A: Important loss of interaction with YAP1 and complete loss of transforming ability. 2 Publications

Organism-specific databases

PharmGKBiPA36435.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 434434Transcriptional enhancer factor TEF-3PRO_0000205937Add
BLAST

Proteomic databases

MaxQBiQ15561.
PaxDbiQ15561.
PRIDEiQ15561.

PTM databases

PhosphoSiteiQ15561.

Expressioni

Tissue specificityi

Preferentially expressed in skeletal muscle. Lower levels in pancreas, placenta, and heart.

Gene expression databases

BgeeiQ15561.
CleanExiHS_TEAD4.
ExpressionAtlasiQ15561. baseline and differential.
GenevestigatoriQ15561.

Organism-specific databases

HPAiHPA056896.

Interactioni

Subunit structurei

Interacts with YAP1 and WWTR1/TAZ.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
WWTR1Q9GZV52EBI-747736,EBI-747743

Protein-protein interaction databases

BioGridi112863. 18 interactions.
IntActiQ15561. 3 interactions.
MINTiMINT-1460562.
STRINGi9606.ENSP00000352926.

Structurei

3D structure databases

ProteinModelPortaliQ15561.
SMRiQ15561. Positions 35-113, 217-433.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Contains 1 TEA DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG246992.
GeneTreeiENSGT00390000008670.
HOGENOMiHOG000253933.
HOVERGENiHBG056905.
InParanoidiQ15561.
KOiK09448.
PhylomeDBiQ15561.

Family and domain databases

InterProiIPR000818. TEA/ATTS.
IPR016361. TEF.
IPR027255. TEF-3.
[Graphical view]
PANTHERiPTHR11834. PTHR11834. 1 hit.
PfamiPF01285. TEA. 1 hit.
[Graphical view]
PIRSFiPIRSF002603. TEF. 1 hit.
PIRSF500722. TEF-3. 1 hit.
PRINTSiPR00065. TEADOMAIN.
SMARTiSM00426. TEA. 1 hit.
[Graphical view]
PROSITEiPS00554. TEA_1. 1 hit.
PS51088. TEA_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q15561-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MEGTAGTITS NEWSSPTSPE GSTASGGSQA LDKPIDNDAE GVWSPDIEQS
60 70 80 90 100
FQEALAIYPP CGRRKIILSD EGKMYGRNEL IARYIKLRTG KTRTRKQVSS
110 120 130 140 150
HIQVLARRKA REIQAKLKDQ AAKDKALQSM AAMSSAQIIS ATAFHSSMAL
160 170 180 190 200
ARGPGRPAVS GFWQGALPGQ AGTSHDVKPF SQQTYAVQPP LPLPGFESPA
210 220 230 240 250
GPAPSPSAPP APPWQGRSVA SSKLWMLEFS AFLEQQQDPD TYNKHLFVHI
260 270 280 290 300
GQSSPSYSDP YLEAVDIRQI YDKFPEKKGG LKDLFERGPS NAFFLVKFWA
310 320 330 340 350
DLNTNIEDEG SSFYGVSSQY ESPENMIITC STKVCSFGKQ VVEKVETEYA
360 370 380 390 400
RYENGHYSYR IHRSPLCEYM INFIHKLKHL PEKYMMNSVL ENFTILQVVT
410 420 430
NRDTQETLLC IAYVFEVSAS EHGAQHHIYR LVKE
Length:434
Mass (Da):48,329
Last modified:November 25, 2008 - v3
Checksum:i544DDFD86E88D9A8
GO
Isoform 2 (identifier: Q15561-2) [UniParc]FASTAAdd to Basket

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

Note: No experimental confirmation available.

Show »
Length:305
Mass (Da):34,158
Checksum:i6A3BDF596BCE7797
GO
Isoform 3 (identifier: Q15561-3) [UniParc]FASTAAdd to Basket

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

Note: No experimental confirmation available.

Show »
Length:391
Mass (Da):44,058
Checksum:i68B36C4E607ADB1E
GO

Sequence cautioni

The sequence CAA64212.2 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical ATA isoleucine codon.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti39 – 391A → G in AAC50763. (PubMed:8921372)Curated
Sequence conflicti149 – 1491A → R in AAC50763. (PubMed:8921372)Curated
Sequence conflicti172 – 1721G → E in AAC50763. (PubMed:8921372)Curated
Sequence conflicti218 – 2203SVA → RRG in AAC50763. (PubMed:8921372)Curated
Sequence conflicti258 – 2592SD → LR in AAC50763. (PubMed:8921372)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti323 – 3231P → S.
Corresponds to variant rs11550887 [ dbSNP | Ensembl ].
VAR_052279

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 129129Missing in isoform 2. 1 PublicationVSP_043099Add
BLAST
Alternative sequencei119 – 16143Missing in isoform 3. 1 PublicationVSP_045657Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31729.1. [Q15561-1]
CCDS31730.1. [Q15561-3]
CCDS41737.1. [Q15561-2]
RefSeqiNP_003204.2. NM_003213.3. [Q15561-1]
NP_958849.1. NM_201441.2. [Q15561-3]
NP_958851.1. NM_201443.2. [Q15561-2]
UniGeneiHs.94865.

Genome annotation databases

EnsembliENST00000397122; ENSP00000380311; ENSG00000197905. [Q15561-2]
GeneIDi7004.
KEGGihsa:7004.
UCSCiuc001qln.3. human. [Q15561-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS31729.1. [Q15561-1 ]
CCDS31730.1. [Q15561-3 ]
CCDS41737.1. [Q15561-2 ]
RefSeqi NP_003204.2. NM_003213.3. [Q15561-1 ]
NP_958849.1. NM_201441.2. [Q15561-3 ]
NP_958851.1. NM_201443.2. [Q15561-2 ]
UniGenei Hs.94865.

3D structure databases

ProteinModelPortali Q15561.
SMRi Q15561. Positions 35-113, 217-433.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112863. 18 interactions.
IntActi Q15561. 3 interactions.
MINTi MINT-1460562.
STRINGi 9606.ENSP00000352926.

PTM databases

PhosphoSitei Q15561.

Proteomic databases

MaxQBi Q15561.
PaxDbi Q15561.
PRIDEi Q15561.

Protocols and materials databases

DNASUi 7004.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000397122 ; ENSP00000380311 ; ENSG00000197905 . [Q15561-2 ]
GeneIDi 7004.
KEGGi hsa:7004.
UCSCi uc001qln.3. human. [Q15561-1 ]

Organism-specific databases

CTDi 7004.
GeneCardsi GC12P003068.
HGNCi HGNC:11717. TEAD4.
HPAi HPA056896.
MIMi 601714. gene.
neXtProti NX_Q15561.
PharmGKBi PA36435.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG246992.
GeneTreei ENSGT00390000008670.
HOGENOMi HOG000253933.
HOVERGENi HBG056905.
InParanoidi Q15561.
KOi K09448.
PhylomeDBi Q15561.

Enzyme and pathway databases

Reactomei REACT_116145. PPARA activates gene expression.
REACT_118713. YAP1- and WWTR1 (TAZ)-stimulated gene expression.

Miscellaneous databases

ChiTaRSi TEAD4. human.
GeneWikii TEAD4.
GenomeRNAii 7004.
NextBioi 27354.
PROi Q15561.
SOURCEi Search...

Gene expression databases

Bgeei Q15561.
CleanExi HS_TEAD4.
ExpressionAtlasi Q15561. baseline and differential.
Genevestigatori Q15561.

Family and domain databases

InterProi IPR000818. TEA/ATTS.
IPR016361. TEF.
IPR027255. TEF-3.
[Graphical view ]
PANTHERi PTHR11834. PTHR11834. 1 hit.
Pfami PF01285. TEA. 1 hit.
[Graphical view ]
PIRSFi PIRSF002603. TEF. 1 hit.
PIRSF500722. TEF-3. 1 hit.
PRINTSi PR00065. TEADOMAIN.
SMARTi SM00426. TEA. 1 hit.
[Graphical view ]
PROSITEi PS00554. TEA_1. 1 hit.
PS51088. TEA_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiTEAD4_HUMAN
AccessioniPrimary (citable) accession number: Q15561
Secondary accession number(s): H0Y308
, Q6MZR9, Q8NEV5, Q92883, Q96BK2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 25, 2008
Last modified: November 26, 2014
This is version 127 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3