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Q2EJA0 (YAP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 49. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Yorkie homolog
Alternative name(s):
65 kDa Yes-associated protein
Short name=YAP65
Gene names
Name:Yap1
Synonyms:Yap, Yap65
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length469 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role 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 STK3/MST2 and STK4/MST1, 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. Plays a key role to control cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction By similarity. Isoform 2, isoform 3 and isoform 4 (lacking the C-terminal transactivation domain) can attenuate p73-mediated cell death signaling in transcriptional repression-induced atypical death (TRIAD) of neurons. Ref.1

Subunit structure

Binds to the SH3 domain of the YES kinase. Binds to WBP1 and WBP2. Binds, in vitro, through the WW1 domain, to neural isoforms of ENAH that contain the PPSY motif. The phosphorylated form interacts with YWHAB. Interacts (via WW domains) with LATS1 (via PPxY motif 2). Interacts with LATS2. Interacts (via WW domain 1) with isoform 2 of ERBB4 (via PPxY motif 2). Interacts with TEAD1, TEAD2, TEAD3 and TEAD4 By similarity. Interacts with TP73 and HCK By similarity. Interacts with RUNX1 By similarity. Interacts (via WW domains) with PTPN14 (via PPxY motif 2); this interaction leads to the cytoplasmic sequestration of YAP1 and inhibits its transcriptional coactivator activity By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Note: Both phosphorylation and cell density can regulate its subcellular localization. Phosphorylation sequesters it in the cytoplasm by inhibiting its translocation into the nucleus. At low density, predominantly nuclear and is translocated to the cytoplasm at high density By similarity.

Tissue specificity

Isoform 3 is highly-specific to cortical neurons. Ref.1

Induction

Down-regulated by alpha-amanitin (AMA). Ref.1

Post-translational modification

Phosphorylated by LATS1 and LATS2; leading to cytoplasmic translocation and inactivation. Phosphorylated by ABL1; leading to YAP1 stabilization, enhanced interaction with TP73 and recruitment onto proapoptotic genes; in response to DNA damage. Phosphorylation at Ser-366 and Ser-369 by CK1 is triggered by previous phosphorylation at Ser-363 by LATS proteins and leads to YAP1 ubiquitination by SCF(beta-TRCP) E3 ubiquitin ligase and subsequent degradation By similarity. Phosphorylated at Thr-104, Thr-136, Ser-333 and Thr-378 by MAPK8/JNK1 and MAPK9/JNK2, which is required for the regukation of apoptosis by YAP1 By similarity.

Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase By similarity.

Sequence similarities

Belongs to the YORKIE family.

Contains 2 WW domains.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms may exist.
Isoform 1 (identifier: Q2EJA0-1)

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: Q2EJA0-2)

Also known as: Neuron-specific YAPdeltaC insert25 isoform;

The sequence of this isoform differs from the canonical sequence as follows:
     311-354: ELALRSQLPS...TNSSDPFLNS → VRPQTVRAGI...DSGIEDNDNQ
     355-469: Missing.
Isoform 3 (identifier: Q2EJA0-3)

Also known as: Neuron-specific YAPdeltaC insert61 isoform;

The sequence of this isoform differs from the canonical sequence as follows:
     311-366: ELALRSQLPS...YHSRDESTDS → AIRNINPSTA...DSGIEDNDNQ
     367-469: Missing.
Isoform 4 (identifier: Q2EJA0-4)

Also known as: Neuron-specific YAPdeltaC insert13 isoform;

The sequence of this isoform differs from the canonical sequence as follows:
     311-350: ELALRSQLPS...RTMTTNSSDP → TVRAGISSPQ...DSGIEDNDNQ
     351-469: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 469469Yorkie homolog
PRO_0000393772

Regions

Domain153 – 18634WW 1
Domain212 – 24534WW 2
Region273 – 469197Transactivation domain
Compositional bias3 – 3432Pro-rich

Amino acid modifications

Modified residue461Phosphoserine; by LATS1 and LATS2 By similarity
Modified residue481Phosphothreonine By similarity
Modified residue941Phosphoserine; by LATS1 and LATS2 By similarity
Modified residue1041Phosphothreonine; by MAPK8 and MAPK9 By similarity
Modified residue1121Phosphoserine; by LATS1 and LATS2 By similarity
Modified residue1131Phosphoserine By similarity
Modified residue1161Phosphoserine By similarity
Modified residue1361Phosphothreonine; by MAPK8 and MAPK9 By similarity
Modified residue1461Phosphoserine; by LATS1 and LATS2 By similarity
Modified residue2711Phosphoserine By similarity
Modified residue3331Phosphoserine; by MAPK8 and MAPK9 By similarity
Modified residue3631Phosphoserine; by LATS1 and LATS2 By similarity
Modified residue3661Phosphoserine; by CK1 By similarity
Modified residue3691Phosphoserine; by CK1 By similarity
Modified residue3731Phosphotyrosine; by ABL1 By similarity
Modified residue3781Phosphothreonine; by MAPK8 and MAPK9 By similarity

Natural variations

Alternative sequence311 – 36656ELALR…ESTDS → AIRNINPSTANAPKCQTVRA GISSPQPVALTGAGWRDSEC SVFSRDDSGIEDNDNQ in isoform 3.
VSP_039047
Alternative sequence311 – 35444ELALR…PFLNS → VRPQTVRAGISSPQPVALTG AGWRDSECSVFSRDDSGIED NDNQ in isoform 2.
VSP_039048
Alternative sequence311 – 35040ELALR…NSSDP → TVRAGISSPQPVALTGAGWR DSECSVFSRDDSGIEDNDNQ in isoform 4.
VSP_039049
Alternative sequence351 – 469119Missing in isoform 4.
VSP_039050
Alternative sequence355 – 469115Missing in isoform 2.
VSP_039051
Alternative sequence367 – 469103Missing in isoform 3.
VSP_039052

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 21, 2006. Version 1.
Checksum: 98252AF782DE1907

FASTA46950,501
        10         20         30         40         50         60 
MEPAQQPPPQ PAPQGPAPPS VSPAGTPAAP PAPPAGHQVV HVRGDSETDL EALFNAVMNP 

        70         80         90        100        110        120 
KTANVPQTVP MRLRKLPDSF FKPPEPKSHS RQASTDAGTA GALTPQHVRA HSSPASLQLG 

       130        140        150        160        170        180 
AGTLTASGVV SGPAATPAAQ HLRQSSFEIP DDVPLPAGWE MAKTSSGQRY FLNHNDQTTT 

       190        200        210        220        230        240 
WQDPRKAMLS QLNVPTSASP AVPQTLMNSA SGPLPDGWEQ AMTQDGEVYY INHKNKTTSW 

       250        260        270        280        290        300 
LDPRLDPRFA MNQRITQSAP VKQPPPLAPQ SPQGGVLGGG SSNQQQQIQL QQLQMEKERL 

       310        320        330        340        350        360 
RLKQQELFRQ ELALRSQLPS LEQDGGTQNA VSSPGMTQEL RTMTTNSSDP FLNSGTYHSR 

       370        380        390        400        410        420 
DESTDSGLSM SSYSIPRTPD DFLNSVDEMD TGDTISQSTL PSQQSRFPDY LEALPGTNVD 

       430        440        450        460 
LGTLEGDAMN IEGEELMPSL QEALSSEILD VESVLAATKL DKESFLTWL

« Hide

Isoform 2 (Neuron-specific YAPdeltaC insert25 isoform) [UniParc].

Checksum: 0F9DBE83022EE3C0
Show »

FASTA35437,974
Isoform 3 (Neuron-specific YAPdeltaC insert61 isoform) [UniParc].

Checksum: 9DBD84666239DE4D
Show »

FASTA36639,174
Isoform 4 (Neuron-specific YAPdeltaC insert13 isoform) [UniParc].

Checksum: 84320F844DD1D404
Show »

FASTA35037,494

References

[1]"Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73."
Hoshino M., Qi M.-L., Yoshimura N., Tagawa K., Wada Y.-I., Enokido Y., Marubuchi S., Harjes P., Arai N., Oyanagi K., Blandino G., Sudol M., Rich T., Kanazawa I., Wanker E.E., Saitoe M., Okazawa H.
J. Cell Biol. 172:589-604(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, INDUCTION, TISSUE SPECIFICITY.
Strain: Wistar.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		DQ186896 mRNA. Translation: ABA33615.2.
DQ186897 mRNA. Translation: ABA33616.2.
DQ186898 mRNA. Translation: ABA33617.2.
DQ376007 mRNA. Translation: ABD32155.1.
IPIIPI00188053.
IPI00777070.
IPI00780976.
IPI00958532.
RefSeqNP_001029174.2. NM_001034002.2.
UniGeneRn.162978.

3D structure databases

ProteinModelPortalQ2EJA0.
SMRQ2EJA0. Positions 147-192, 212-244.
ModBaseSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000034369.

PTM databases

PhosphoSiteQ2EJA0.

Proteomic databases

PaxDbQ2EJA0.
PRIDEQ2EJA0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID363014.
KEGGrno:363014.
UCSCRGD:1306035. rat.

Organism-specific databases

CTD10413.
RGD1306035. Yap1.

Phylogenomic databases

eggNOGCOG5021.
HOGENOMHOG000007854.
HOVERGENHBG096677.
KOK16687.

Gene expression databases

GenevestigatorQ2EJA0.

Family and domain databases

InterProIPR001202. WW_dom.
[Graphical view]
PfamPF00397. WW. 2 hits.
[Graphical view]
SMARTSM00456. WW. 2 hits.
[Graphical view]
SUPFAMSSF51045. WW_Rsp5_WWP. 2 hits.
PROSITEPS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio682129.

Entry information

Entry nameYAP1_RAT
AccessionPrimary (citable) accession number: Q2EJA0
Secondary accession number(s): Q3LRU4, Q3LRU5, Q3LRU6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 20, 2010
Last sequence update: March 21, 2006
Last modified: May 1, 2013
This is version 49 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents