BioPAX pathway converted from "ABL1 phosphorylates YAP1" in the Reactome database.

2.7.10

ABL1 phosphorylates YAP1

This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>

Reactome DB_ID: 9869281

nucleoplasmGO0005654

UniProt:Q2EJA0 Yap1

Yap1

Yap1Yap65YapFUNCTION 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).SUBUNIT 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. Interacts (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).TISSUE SPECIFICITY Isoform 3 is highly-specific to cortical neurons.INDUCTION Down-regulated by alpha-amanitin (AMA).DOMAIN The first coiled-coil region mediates most of the interaction with TEAD transcription factors.PTM 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).PTM Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase.SIMILARITY Belongs to the YAP1 family.

Reactomehttp://www.reactome.orgRattus norvegicus

NCBI Taxonomy10116UniProtQ2EJA0

Chain Coordinates

EQUAL

504

EQUAL

Reactome DB_ID: 29358

ATP(4-) [ChEBI:30616]

ATP(4-)

Adenosine 5'-triphosphateatpATP

ChEBI30616

Reactome DB_ID: 9922855

O4'-phospho-L-tyrosine at 407 (in Homo sapiens)

407

EQUAL

O4'-phospho-L-tyrosine [MOD:00048]

EQUAL

504

EQUAL

Reactome DB_ID: 113582

ADP(3-) [ChEBI:456216]

ADP(3-)

ADP trianion5'-O-[(phosphonatooxy)phosphinato]adenosineADP

ChEBI456216PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 9900712

UniProt:E9PT20Abl1

UniProtE9PT20

O-phospho-L-serine at 456 (in Homo sapiens)

456

EQUAL

O-phospho-L-serine [MOD:00046]

EQUAL

1130

EQUAL

GO0004713

GO molecular function

Reactome Database ID Release 759900720Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9900720Reactome Database ID Release 759922857Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9922857ReactomeR-RNO-8956659

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-8956659.1In response to DNA damage, ABL1 phosphorylates YAP1 on tyrosine residue Y407 (corresponds to Y357 in the YAP1 splicing isoform 3, known as YAP1-1beta, which was used in the study by Levy, Adamovich et al. 2008).

18280240Pubmed2008Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damageLevy, DanAdamovich, YaaritReuven, NinaShaul, YosefMol. Cell 29:350-61inferred by electronic annotationIEAGOIEA