SMURF1

Protein SMURF1

Identifiers
SMAD specific E3 ubiquitin protein ligase 1
HUGO:SMURF1 hgnc_id:HGNC:16807 HGNC:16807 ENTREZ:57154 UNIPROT:Q9HCE7
HUGO:SMURF1, HGNC:16807, ENTREZ:57154, GENECARDS:GC07M098627, UNIPROT:Q9HCE7
HUGO:SMURF1 HGNC:16807 ENTREZ:57154 UNIPROT:Q9HCE7 GENECARDS:SMURF1 REACTOME:414424 ATLASONC:GC_SMURF1 WIKI:SMURF1

Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / GROWTH_FACTORS_SIGNALING_PATHWAYS
EMT Senescence / EMT_REGULATORS
EMT Senescence / CELL_CELL_ADHESIONS
EMT Senescence / TIGHT_JUNCTIONS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / WNT_NON_CANONICAL

References
CASCADE:TGFB
PMID:15265520
SMAD7 has been shown to interact with the E3 ubiquitin ligases Smurf 1 and Smurf 2, recruiting them to T??R complexes and inducing the degradation of activated T??RI
PMID:14722617
Overexpression of Smurf1 and Smurf2 further significantly reduced the levels of T??RI protein in normal fibroblasts treated with TGF-??1
PMID:21572392
SMURF1 is an E3 ubiquitin ligase
SMURF1 performs a crucial role in the regulation of the BMP signalling pathway in both embryonic development and bone remodelling.
PMID:15761148
PARD6A interacts with TGFB receptors and is phsophorylated by TGFBRIII.
Phosphorylation of Par6 is required for TGFB-dependent EMT in mammary gland epithelial cells
This phosphorylation stimulates the interaction of PARD6A with the E3 ubiquitin ligase Smurf1.
Smurf1, in turn, targets GTPase RhoA for degradation, thereby leading to a loss of tight junctions.
TGFB regulation of the Par6-Smurf1-RhoA pathway is required for EMT.
PMID:14657501
Smurf1 functions as an effector of the polarity complex by mediating localized ubiquitination and degradation of RhoA in cellular protrusions.
Atypical protein kinase C (aPKCZ), an effector of the Cdc42/Rac1-PAR6 polarity complex, recruited Smurf1 to cellular protrusions, where it controlled the local level of RhoA.
PMID:22949611
Signaling molecules act directly on polarity proteins, bypassing transcription factors such as Snail and Zeb1:
TGFBRI binds to the tight junction protein Occludin and locally assembles into a complex containing Par6.
Activated TGFBRII phosphorylates Par6, which binds to Smurf1 and causes RhoA ubiquitylation and the dissolution of junctions.
PMID:14744429
RhoA is the prototypical member of the Rho GTPase family, which regulates many cellular processes, including cellular adhesion, motility, and polarity
Need more reference 34-36 from PMID15761148: RhoA is an important modulator of cell junction formation and stability.

SMURF1@Cytoplasm

References
s_wnc1_re111( Survival ):
Rspo is required for clathrin-mediated endocytosis
PMID:21397842
It has been shown that Dvl polymers are not associated with vesicles, therefore endocytosis of the complex is likely to be after Dvl polymerisation.
PMID:16263762

Modifications:
In compartment: Cytoplasm

SMURF1@Cytoplasm

In compartment: Cytosol

SMURF1@Cytosol

In compartment: Nucleus

SMURF1@Nucleus

Participates in complexes:
In compartment: Cytoplasm

In compartment: Cytosol

PARD6A|S345_pho:SMURF1@Cytosol

Participates in reactions:
As Reactant or Product:

As Catalyser:

TGFBR1@Cytosol → degraded
em_emtc_emtc_s2907 → RHOA|ubi@Cytosol