BioPAX pathway converted from "Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9" in the Reactome database.

2.7.11

Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9

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: 9835017

nucleoplasmGO0005654p-2S-SMAD2/3:SMAD4 [nucleoplasm]

p-2S-SMAD2/3:SMAD4

Reactome DB_ID: 9835009

UniProt:O70437Smad4

Reactomehttp://www.reactome.orgRattus norvegicus

NCBI Taxonomy10116UniProtO70437

Chain Coordinates

EQUAL

552

EQUAL

Converted from EntitySet in Reactome

Reactome DB_ID: 9835015

p-2S-SMAD2/3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityphospho-Smad3 [nucleoplasm]phospho-Smad2 [nucleoplasm]

UniProtP84025UniProtO70436Reactome Database ID Release 759835017Database 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=9835017ReactomeR-RNO-173511

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-173511.1

Reactome DB_ID: 29358

ATP(4-) [ChEBI:30616]

ATP(4-)

Adenosine 5'-triphosphateatpATP

ChEBI30616

Reactome DB_ID: 9882416

p-T,2S-SMAD2/3:SMAD4 [nucleoplasm]

p-T,2S-SMAD2/3:SMAD4

Reactome DB_ID: 9835009

EQUAL

552

EQUAL

Converted from EntitySet in Reactome

Reactome DB_ID: 9882414

p-T,2S-SMAD2/3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityphospho-Smad3 [nucleoplasm]phospho-Smad2 [nucleoplasm]

Reactome Database ID Release 759882416Database 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=9882416ReactomeR-RNO-2176487

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-2176487.1

Reactome DB_ID: 113582

ADP(3-) [ChEBI:456216]

ADP(3-)

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

ChEBI456216PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 9829640

P-TEFb complex [nucleoplasm]

P-TEFb complex

Reactome DB_ID: 9829624

UniProt:Q641Z4Cdk9

UniProtQ641Z4

EQUAL

372

EQUAL

Converted from EntitySet in Reactome

Reactome DB_ID: 9829638

CCNT1,CCNT2,CCNK [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityCcnk [nucleoplasm]Ccnt2 [nucleoplasm]Ccnt1 [nucleoplasm]

UniProtA1L1L5UniProtD3ZGL6UniProtD3ZC98Reactome Database ID Release 759829640Database 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=9829640ReactomeR-RNO-112431

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-112431.1GO0004674

GO molecular function

Reactome Database ID Release 759882417Database 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=9882417Reactome Database ID Release 759882419Database 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=9882419ReactomeR-RNO-2176475

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-2176475.1CDK8 in complex with cyclin C (CDK8:CCNC) and CDK9 in complex with cyclin T (CDK9:CCNT) are able to phosphorylate the linker region of SMAD2 and SMAD3. In SMAD3, CDK8/CDK9 preferentially targets threonine residue T179, although serine residues S208 and S213 can also be phosphorylated. In SMAD2, CDK8/9 preferentially targets threonine residue T220 (corresponds to T190 in the short isoform of SMAD2, SMAD2-2). Phosphorylation of serine residues that correspond to serines S208 and S213 of SMAD3 has not been examined. Phosphorylation of the linker region of SMAD2 and SMAD3 by CDK8/CDK9 enhances transcriptional activity of SMAD2/3:SMAD4 complex, but also primes SMAD2 and SMAD3 for ubiquitination and subsequent degradation (Alarcon et al. 2009).

19914168Pubmed2009Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathwaysAlarcon, CZaromytidou, AIXi, QGao, SYu, JFujisawa, SBarlas, AMiller, ANManova-Todorova, KMacias, MJSapkota, GPan, DMassague, JCell 139:757-69inferred by electronic annotationIEAGOIEA