Reviewed, UniProtKB/Swiss-Prot Q9EPK5 (WWTR1_MOUSE)

Names and origin

Protein names

Recommended name:
    WW domain-containing transcription regulator protein 1
Alternative name(s):
    Transcriptional coactivator with PDZ-binding motif

Gene names

Name:	Wwtr1
Synonyms:	Taz

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	395 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Functions as a transcriptional coactivator. Ref.1
Subunit structure	Binds to SLC9A3R2 via the PDZ motif at the plasma membrane. Binds to YWHAZ in vivo and in vitro through the phosphoserine-binding motif RSHSSP. Ref.1
Subcellular location	Nucleus. Cytoplasm. Note: Concentrates along specific portions of the plasma membrane, and accumulates in punctate nuclear bodies. When phosphorylated is retained in cytoplasm by YWHAZ. Ref.1
Tissue specificity	Highly expressed in kidney, heart, placenta and lung. Ref.1
Domain	The PDZ-binding motif is essential for stimulated gene transcription. It localizes the protein into both punctate nuclear foci and plasma membrane-associated complexes. Binds to transcription factors via its WW domain.
Post-translational modification	Phosphorylated. Phosphorylation results in the inhibition of transcriptional coactivation through YWHAZ-mediated nuclear export. Ref.1 Ref.4
Sequence similarities	Contains 1 WW domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cilium morphogenesis Inferred from mutant phenotype. Source: MGI glomerulus development Inferred from mutant phenotype. Source: MGI negative regulation of fat cell differentiation Inferred from genetic interaction. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI osteoblast differentiation Inferred from genetic interaction. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: MGI transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.1 Inferred from direct assay. Source: MGI transcription factor complex Inferred from direct assay. Source: MGI
Molecular function	protein homodimerization activity Inferred from direct assay. Source: UniProtKB transcription coactivator activity Inferred from direct assay. Source: UniProtKB transcription corepressor activity Inferred from genetic interaction. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-1211920,EBI-1211920
Crebbp	P45481	1	EBI-1211920,EBI-296306
KAT2B	Q92831	1	EBI-1211920,EBI-477430	From a different organism.
Nkx2-1	P23441	1	EBI-1211920,EBI-1223127	From a different organism.
TBX5	Q99593	1	EBI-1211920,EBI-297043	From a different organism.
Yap1	P46938	1	EBI-1211920,EBI-1211949

Alternative products

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

Isoform 1 (identifier: Q9EPK5-1)

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: Q9EPK5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MHNSTAPLSARLFPKGGSLLQTLFMGQSGSRGGCARLRLLCRLLAQWERPRPVPGIKM

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 395	395	WW domain-containing transcription regulator protein 1		PRO_0000076070
Regions
	Domain	124 – 157	34	WW
	Coiled coil	224 – 258	35	Potential
	Motif	389 – 395	7	PDZ-binding By similarity
Amino acid modifications
	Modified residue	87	1	Phosphoserine By similarity
	Modified residue	89	1	Phosphoserine Ref.1
	Modified residue	93	1	Phosphoserine Ref.4
Natural variations
	Alternative sequence	1	1	M → MHNSTAPLSARLFPKGGSLL QTLFMGQSGSRGGCARLRLL CRLLAQWERPRPVPGIKM in isoform 2.		VSP_026137
Experimental info
	Mutagenesis	89	1	S → A: Loss of YWHAZ binding with increased nuclear localization. Partial recovery of nuclear accumulation; when associated with deletion of 392-L--L-395. Ref.1
	Mutagenesis	392 – 395	4	Missing: Loss of SLC9A3R2 binding and reduced nuclear localization. Partial recovery of nuclear accumulation; when associated with A-89. Ref.1
	Sequence conflict	384	1	A → V in CAC17733. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 7, 2005. Version 2. Checksum: 1B8A7487D4CA341C	FASTA	395	43,620
	10 20 30 40 50 60 MNPSSVPHPL PPPGQQVIHV TQDLDTDLEA LFNSVMNPKP SSWRKKILPE SFFKEPDSGS 70 80 90 100 110 120 HSRQSSTDSS GGHPGPRLAG GAQHVRSHSS PASLQLGTGA GAAGGPAQQH AHLRQQSYDV 130 140 150 160 170 180 TDELPLPPGW EMTFTATGQR YFLNHIEKIT TWQDPRKVMN QPLNHVNLHP SITSTSVPQR 190 200 210 220 230 240 SMAVSQPNLA MNHQHQQVVA TSLSPQNHPT QNQPTGLMSV PNALTTQQQQ QQKLRLQRIQ 250 260 270 280 290 300 MERERIRMRQ EELMRQEAAL CRQLPMETET MAPVNTPAMS TDMRSVTNSS SDPFLNGGPY 310 320 330 340 350 360 HSREQSTDSG LGLGCYSVPT TPEDFLSNMD EMDTGENSGQ TPMTVNPQQT RFPDFLDCLP 370 380 390 GTNVDLGTLE SEDLIPLFND VESALNKSEP FLTWL
	Isoform 2. Checksum: 6A8D7114823BA29F	FASTA	452	49,834
	10 20 30 40 50 60 MHNSTAPLSA RLFPKGGSLL QTLFMGQSGS RGGCARLRLL CRLLAQWERP RPVPGIKMNP 70 80 90 100 110 120 SSVPHPLPPP GQQVIHVTQD LDTDLEALFN SVMNPKPSSW RKKILPESFF KEPDSGSHSR 130 140 150 160 170 180 QSSTDSSGGH PGPRLAGGAQ HVRSHSSPAS LQLGTGAGAA GGPAQQHAHL RQQSYDVTDE 190 200 210 220 230 240 LPLPPGWEMT FTATGQRYFL NHIEKITTWQ DPRKVMNQPL NHVNLHPSIT STSVPQRSMA 250 260 270 280 290 300 VSQPNLAMNH QHQQVVATSL SPQNHPTQNQ PTGLMSVPNA LTTQQQQQQK LRLQRIQMER 310 320 330 340 350 360 ERIRMRQEEL MRQEAALCRQ LPMETETMAP VNTPAMSTDM RSVTNSSSDP FLNGGPYHSR 370 380 390 400 410 420 EQSTDSGLGL GCYSVPTTPE DFLSNMDEMD TGENSGQTPM TVNPQQTRFP DFLDCLPGTN 430 440 450 VDLGTLESED LIPLFNDVES ALNKSEPFLT WL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins." Kanai F., Marignani P.A., Sarbassova D., Yagi R., Hall R.A., Donowitz M., Hisaminato A., Fujiwara T., Ito Y., Cantley L.C., Yaffe M.B. EMBO J. 19:6778-6791(2000) [PubMed: 11118213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SLC9A3R2 AND YWHAZ, PHOSPHORYLATION AT SER-89, TISSUE SPECIFICITY, MUTAGENESIS OF SER-89 AND 392-GLU--LEU-395.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Heart.
[3]	"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). Strain: FVB/N. Tissue: Mammary tumor.
[4]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ299430 mRNA. Translation: CAC17733.1. AK142299 mRNA. Translation: BAE25019.1. AK142720 mRNA. Translation: BAE25174.1. BC004640 mRNA. Translation: AAH04640.1. BC014727 mRNA. Translation: AAH14727.1.
IPI	IPI00320121. IPI00848891.
RefSeq	NP_001161753.1. NP_598545.2.
UniGene	Mm.405029
3D structure databases
SMR	Q9EPK5. Positions 118-157.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9EPK5. 7 interactions.
STRING	Q9EPK5.
PTM databases
PhosphoSite	Q9EPK5.
Genome annotation databases
Ensembl	ENSMUST00000029380; ENSMUSP00000029380; ENSMUSG00000027803; Mus musculus. [Genome view] ENSMUST00000120977; ENSMUSP00000113040; ENSMUSG00000027803; Mus musculus. [Genome view]
GeneID	97064.
KEGG	mmu:97064.
UCSC	uc008phb.1. mouse.
Organism-specific databases
CTD	97064.
MGI	MGI:1917649. Wwtr1.
Phylogenomic databases
eggNOG	roNOG10463.
HOGENOM	HBG714081.
HOVERGEN	Q9EPK5.
InParanoid	Q9EPK5.
OMA	AMSQPNL.
OrthoDB	EOG98GZPF.
PhylomeDB	Q9EPK5.
Gene expression databases
ArrayExpress	Q9EPK5.
Bgee	Q9EPK5.
CleanEx	MM_WWTR1.
Genevestigator	Q9EPK5.
GermOnline	ENSMUSG00000027803. Mus musculus.
Family and domain databases
InterPro	IPR001202. WW_Rsp5_WWP. [Graphical view]
Pfam	PF00397. WW. 1 hit. [Graphical view]
SMART	SM00456. WW. 1 hit. [Graphical view]
PROSITE	PS01159. WW_DOMAIN_1. 1 hit. PS50020. WW_DOMAIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	352477.
SOURCE	Search...

Entry information

Entry name

WWTR1_MOUSE

Accession

Primary (citable) accession number: Q9EPK5
Secondary accession number(s): Q3UQ69, Q3UQM0, Q99KI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2005
Last sequence update:	June 7, 2005
Last modified:	February 9, 2010
This is version 61 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)