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Protein

Transcriptional coactivator YAP1

Gene

Yap1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization. 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 (PubMed:16461361).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-RNO-1251985. Nuclear signaling by ERBB4.
R-RNO-2028269. Signaling by Hippo.
R-RNO-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcriptional coactivator YAP1
Short name:
Yes-associated protein 1
Alternative name(s):
Protein yorkie homolog
Yes-associated protein YAP65 homolog
Gene namesi
Name:Yap1
Synonyms:Yap, Yap65
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi1306035. Yap1.

Subcellular locationi

  • 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. PTPN14 induces translocation from the nucleus to the cytoplasm.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003937721 – 469Transcriptional coactivator YAP1Add BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei46PhosphoserineCombined sources1
Modified residuei48PhosphothreonineBy similarity1
Modified residuei90PhosphoserineCombined sources1
Modified residuei94PhosphoserineCombined sources1
Modified residuei95PhosphothreonineCombined sources1
Modified residuei104PhosphothreonineCombined sources1
Modified residuei112Phosphoserine; by LATS1 and LATS2By similarity1
Modified residuei113PhosphoserineBy similarity1
Modified residuei116PhosphoserineBy similarity1
Modified residuei136Phosphothreonine; by MAPK8 and MAPK9By similarity1
Modified residuei146Phosphoserine; by LATS1 and LATS2By similarity1
Modified residuei271PhosphoserineBy similarity1
Modified residuei320PhosphoserineCombined sources1
Modified residuei333Phosphoserine; by MAPK8 and MAPK9By similarity1
Modified residuei347PhosphoserineBy similarity1
Modified residuei348PhosphoserineBy similarity1
Modified residuei354PhosphoserineBy similarity1
Modified residuei363Phosphoserine; by LATS1 and LATS2By similarity1
Modified residuei366Phosphoserine; by CK1By similarity1
Modified residuei369Phosphoserine; by CK1By similarity1
Modified residuei373Phosphotyrosine; by ABL1By similarity1
Modified residuei378Phosphothreonine; by MAPK8 and MAPK9By similarity1

Post-translational modificationi

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 regulation of apoptosis by YAP1 (By similarity).By similarity
Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ2EJA0.

PTM databases

iPTMnetiQ2EJA0.
PhosphoSitePlusiQ2EJA0.

Expressioni

Tissue specificityi

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

Inductioni

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

Gene expression databases

ExpressionAtlasiQ2EJA0. baseline and differential.

Interactioni

Subunit structurei

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 (By similarity). The phosphorylated form interacts with YWHAB. Interacts (via WW domains) with LATS1 (via PPxY motif 2). Interacts with LATS2. Interact (via WW domain 1) with ERBB4 (via PPxY motif 2). Interacts with TEAD1, TEAD2, TEAD3 and TEAD4. Interacts with TP73. Interacts with RUNX1. Interacts with HCK. 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).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ2EJA0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini153 – 186WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini212 – 245WW 2PROSITE-ProRule annotationAdd BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni273 – 469Transactivation domainAdd BLAST197

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili71 – 85By similarityAdd BLAST15
Coiled coili280 – 325Sequence analysisAdd BLAST46

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi3 – 34Pro-richAdd BLAST32

Domaini

The first coiled-coil region mediates most of the interaction with TEAD transcription factors.By similarity

Sequence similaritiesi

Belongs to the YAP1 family.Curated
Contains 2 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

GeneTreeiENSGT00510000046760.
HOGENOMiHOG000007854.
HOVERGENiHBG096677.
InParanoidiQ2EJA0.
KOiK16687.
OMAiMDPGQQP.
OrthoDBiEOG091G095A.

Family and domain databases

InterProiIPR001202. WW_dom.
[Graphical view]
PfamiPF00397. WW. 2 hits.
[Graphical view]
SMARTiSM00456. WW. 2 hits.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 2 hits.
PROSITEiPS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms may exist.
Isoform 1 (identifier: Q2EJA0-1) [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
MEPAQQPPPQ PAPQGPAPPS VSPAGTPAAP PAPPAGHQVV HVRGDSETDL
60 70 80 90 100
EALFNAVMNP KTANVPQTVP MRLRKLPDSF FKPPEPKSHS RQASTDAGTA
110 120 130 140 150
GALTPQHVRA HSSPASLQLG AGTLTASGVV SGPAATPAAQ HLRQSSFEIP
160 170 180 190 200
DDVPLPAGWE MAKTSSGQRY FLNHNDQTTT WQDPRKAMLS QLNVPTSASP
210 220 230 240 250
AVPQTLMNSA SGPLPDGWEQ AMTQDGEVYY INHKNKTTSW LDPRLDPRFA
260 270 280 290 300
MNQRITQSAP VKQPPPLAPQ SPQGGVLGGG SSNQQQQIQL QQLQMEKERL
310 320 330 340 350
RLKQQELFRQ ELALRSQLPS LEQDGGTQNA VSSPGMTQEL RTMTTNSSDP
360 370 380 390 400
FLNSGTYHSR DESTDSGLSM SSYSIPRTPD DFLNSVDEMD TGDTISQSTL
410 420 430 440 450
PSQQSRFPDY LEALPGTNVD LGTLEGDAMN IEGEELMPSL QEALSSEILD
460
VESVLAATKL DKESFLTWL
Length:469
Mass (Da):50,501
Last modified:March 21, 2006 - v1
Checksum:i98252AF782DE1907
GO
Isoform 2 (identifier: Q2EJA0-2) [UniParc]FASTAAdd to basket
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.

Show »
Length:354
Mass (Da):37,974
Checksum:i0F9DBE83022EE3C0
GO
Isoform 3 (identifier: Q2EJA0-3) [UniParc]FASTAAdd to basket
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.

Show »
Length:366
Mass (Da):39,174
Checksum:i9DBD84666239DE4D
GO
Isoform 4 (identifier: Q2EJA0-4) [UniParc]FASTAAdd to basket
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.

Show »
Length:350
Mass (Da):37,494
Checksum:i84320F844DD1D404
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039047311 – 366ELALR…ESTDS → AIRNINPSTANAPKCQTVRA GISSPQPVALTGAGWRDSEC SVFSRDDSGIEDNDNQ in isoform 3. 1 PublicationAdd BLAST56
Alternative sequenceiVSP_039048311 – 354ELALR…PFLNS → VRPQTVRAGISSPQPVALTG AGWRDSECSVFSRDDSGIED NDNQ in isoform 2. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_039049311 – 350ELALR…NSSDP → TVRAGISSPQPVALTGAGWR DSECSVFSRDDSGIEDNDNQ in isoform 4. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_039050351 – 469Missing in isoform 4. 1 PublicationAdd BLAST119
Alternative sequenceiVSP_039051355 – 469Missing in isoform 2. 1 PublicationAdd BLAST115
Alternative sequenceiVSP_039052367 – 469Missing in isoform 3. 1 PublicationAdd BLAST103

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ186896 mRNA. Translation: ABA33615.2.
DQ186897 mRNA. Translation: ABA33616.2.
DQ186898 mRNA. Translation: ABA33617.2.
DQ376007 mRNA. Translation: ABD32155.1.
RefSeqiNP_001029174.2. NM_001034002.2. [Q2EJA0-3]
XP_006242555.1. XM_006242493.3. [Q2EJA0-1]
UniGeneiRn.162978.

Genome annotation databases

EnsembliENSRNOT00000008074; ENSRNOP00000008074; ENSRNOG00000005933. [Q2EJA0-1]
ENSRNOT00000031189; ENSRNOP00000034369; ENSRNOG00000005933. [Q2EJA0-3]
ENSRNOT00000085285; ENSRNOP00000074302; ENSRNOG00000005933. [Q2EJA0-4]
GeneIDi363014.
KEGGirno:363014.
UCSCiRGD:1306035. rat. [Q2EJA0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ186896 mRNA. Translation: ABA33615.2.
DQ186897 mRNA. Translation: ABA33616.2.
DQ186898 mRNA. Translation: ABA33617.2.
DQ376007 mRNA. Translation: ABD32155.1.
RefSeqiNP_001029174.2. NM_001034002.2. [Q2EJA0-3]
XP_006242555.1. XM_006242493.3. [Q2EJA0-1]
UniGeneiRn.162978.

3D structure databases

ProteinModelPortaliQ2EJA0.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

iPTMnetiQ2EJA0.
PhosphoSitePlusiQ2EJA0.

Proteomic databases

PRIDEiQ2EJA0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000008074; ENSRNOP00000008074; ENSRNOG00000005933. [Q2EJA0-1]
ENSRNOT00000031189; ENSRNOP00000034369; ENSRNOG00000005933. [Q2EJA0-3]
ENSRNOT00000085285; ENSRNOP00000074302; ENSRNOG00000005933. [Q2EJA0-4]
GeneIDi363014.
KEGGirno:363014.
UCSCiRGD:1306035. rat. [Q2EJA0-1]

Organism-specific databases

CTDi10413.
RGDi1306035. Yap1.

Phylogenomic databases

GeneTreeiENSGT00510000046760.
HOGENOMiHOG000007854.
HOVERGENiHBG096677.
InParanoidiQ2EJA0.
KOiK16687.
OMAiMDPGQQP.
OrthoDBiEOG091G095A.

Enzyme and pathway databases

ReactomeiR-RNO-1251985. Nuclear signaling by ERBB4.
R-RNO-2028269. Signaling by Hippo.
R-RNO-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.

Miscellaneous databases

PROiQ2EJA0.

Gene expression databases

ExpressionAtlasiQ2EJA0. baseline and differential.

Family and domain databases

InterProiIPR001202. WW_dom.
[Graphical view]
PfamiPF00397. WW. 2 hits.
[Graphical view]
SMARTiSM00456. WW. 2 hits.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 2 hits.
PROSITEiPS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiYAP1_RAT
AccessioniPrimary (citable) accession number: Q2EJA0
Secondary accession number(s): Q3LRU4, Q3LRU5, Q3LRU6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 20, 2010
Last sequence update: March 21, 2006
Last modified: November 2, 2016
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.