UniProt functional annotation for Q8CFI0



	UniProt functional annotation for Q8CFI0

UniProt code: Q8CFI0.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF- beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1. Plays a role in dendrite formation by melanocytes (By similarity). Involved in the regulation of TOR signaling (By similarity). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (By similarity). {ECO:0000250|UniProtKB:Q96PU5, ECO:0000269|PubMed:11149908, ECO:0000269|PubMed:11244092, ECO:0000269|PubMed:11742982, ECO:0000269|PubMed:12424229, ECO:0000269|PubMed:15123669}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.26;

Activity regulation: Activated by NDFIP1- and NDFIP2-binding. Interacts with SGK1. {ECO:0000250}.

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with SMAD2, SMAD3, SMAD6 and SMAD7 (By similarity). Interacts with CLCN5 (By similarity). The phosphorylated form interacts with 14-3-3 proteins (By similarity). Interacts via its WW domains with SCNN1A, SCNN1B, SCNN1G, SCN1A, SCN2A, SCN3A, SCN5A, SCN8A, SCN9A and SCN10A (PubMed:11244092., PubMed:11742982, PubMed:12424229, PubMed:15123669). Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase (PubMed:12050153). Interacts with TNK2 (By similarity). Interacts (via C2 domain) with NPC2 (By similarity). Interacts with ARRDC4 (By similarity). Interacts with KCNQ1; promotes internalization of KCNQ1 (By similarity). Interacts (via domains WW1, 3 and 4) with USP36; the interaction inhibits ubiquitination of, at least, NTRK1, KCNQ2 and KCNQ3 by NEDD4L (By similarity). Interacts with PRRG4 (via cytoplasmic domain) (By similarity). {ECO:0000250|UniProtKB:Q96PU5, ECO:0000269|PubMed:11244092, ECO:0000269|PubMed:11742982, ECO:0000269|PubMed:12050153, ECO:0000269|PubMed:12424229, ECO:0000269|PubMed:14993279, ECO:0000269|PubMed:15123669}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:12050153}. Golgi apparatus {ECO:0000250|UniProtKB:Q96PU5}. Endosome, multivesicular body {ECO:0000250|UniProtKB:Q96PU5}.

Tissue specificity: Highly expressed in liver and kidney. Also expressed in heart, brain and lung. Isoform 1 is expressed in kidney, lung and gut. Isoform 3 is ubiquitously expressed. {ECO:0000269|PubMed:11149908, ECO:0000269|PubMed:11244092}.

Developmental stage: In the developing brain, it is homogenously distributed in the cortical plate, ventricular zone and ganglionic eminences at 15 dpc. A peak of expression in the cortex is observed at 16.5 dpc. {ECO:0000269|PubMed:27694961}.

Ptm: Phosphorylated; which impairs interaction with SCNN. Interaction with YWHAH inhibits dephosphorylation (By similarity). Aldosterone induces Ser-477 phosphorylation by SGK1. {ECO:0000250, ECO:0000269|PubMed:11742982, ECO:0000269|PubMed:15958725}.

Ptm: Auto-ubiquitinated. Deubiquitinated by USP36, no effect on NEDD4L protein levels. Both proteins interact and regulate each other's ubiquitination levels. {ECO:0000250|UniProtKB:Q96PU5}.

Sequence caution: Sequence=BAC31307.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF- beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1. Plays a role in dendrite formation by melanocytes (By similarity). Involved in the regulation of TOR signaling (By similarity). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (By similarity). {ECO:0000250\|UniProtKB:Q96PU5, ECO:0000269\|PubMed:11149908, ECO:0000269\|PubMed:11244092, ECO:0000269\|PubMed:11742982, ECO:0000269\|PubMed:12424229, ECO:0000269\|PubMed:15123669}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.26;
Activity regulation:		Activated by NDFIP1- and NDFIP2-binding. Interacts with SGK1. {ECO:0000250}.
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with SMAD2, SMAD3, SMAD6 and SMAD7 (By similarity). Interacts with CLCN5 (By similarity). The phosphorylated form interacts with 14-3-3 proteins (By similarity). Interacts via its WW domains with SCNN1A, SCNN1B, SCNN1G, SCN1A, SCN2A, SCN3A, SCN5A, SCN8A, SCN9A and SCN10A (PubMed:11244092., PubMed:11742982, PubMed:12424229, PubMed:15123669). Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase (PubMed:12050153). Interacts with TNK2 (By similarity). Interacts (via C2 domain) with NPC2 (By similarity). Interacts with ARRDC4 (By similarity). Interacts with KCNQ1; promotes internalization of KCNQ1 (By similarity). Interacts (via domains WW1, 3 and 4) with USP36; the interaction inhibits ubiquitination of, at least, NTRK1, KCNQ2 and KCNQ3 by NEDD4L (By similarity). Interacts with PRRG4 (via cytoplasmic domain) (By similarity). {ECO:0000250\|UniProtKB:Q96PU5, ECO:0000269\|PubMed:11244092, ECO:0000269\|PubMed:11742982, ECO:0000269\|PubMed:12050153, ECO:0000269\|PubMed:12424229, ECO:0000269\|PubMed:14993279, ECO:0000269\|PubMed:15123669}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:12050153}. Golgi apparatus {ECO:0000250\|UniProtKB:Q96PU5}. Endosome, multivesicular body {ECO:0000250\|UniProtKB:Q96PU5}.
Tissue specificity:		Highly expressed in liver and kidney. Also expressed in heart, brain and lung. Isoform 1 is expressed in kidney, lung and gut. Isoform 3 is ubiquitously expressed. {ECO:0000269\|PubMed:11149908, ECO:0000269\|PubMed:11244092}.
Developmental stage:		In the developing brain, it is homogenously distributed in the cortical plate, ventricular zone and ganglionic eminences at 15 dpc. A peak of expression in the cortex is observed at 16.5 dpc. {ECO:0000269\|PubMed:27694961}.
Ptm:		Phosphorylated; which impairs interaction with SCNN. Interaction with YWHAH inhibits dephosphorylation (By similarity). Aldosterone induces Ser-477 phosphorylation by SGK1. {ECO:0000250, ECO:0000269\|PubMed:11742982, ECO:0000269\|PubMed:15958725}.
Ptm:		Auto-ubiquitinated. Deubiquitinated by USP36, no effect on NEDD4L protein levels. Both proteins interact and regulate each other's ubiquitination levels. {ECO:0000250\|UniProtKB:Q96PU5}.
Sequence caution:		Sequence=BAC31307.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};