UniProt functional annotation for Q9HCE7



	UniProt functional annotation for Q9HCE7

UniProt code: Q9HCE7.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA. Promotes ubiquitination and subsequent proteasomal degradation of MAVS (PubMed:23087404). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:10458166, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:21402695, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:23999003}.

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; Evidence={ECO:0000269|PubMed:19937093};

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with TRAF4. Interacts (via HECT domain) with FBXL15 (via LRR repeats). Interacts with SMAD7 and TGFBR1; SMAD7 recruits SMURF1 to TGFBR1 and regulates TGF-beta receptor degradation. Interacts with MAVS; the interaction is mediated by NDFIP1 (PubMed:23087404). {ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:21402695, ECO:0000269|PubMed:21572392, ECO:0000269|PubMed:23087404}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:21572392}. Cell membrane {ECO:0000269|PubMed:21572392}; Peripheral membrane protein {ECO:0000269|PubMed:21572392}; Cytoplasmic side {ECO:0000269|PubMed:21572392}.

Tissue specificity: Expressed in melanocytes (PubMed:23999003). {ECO:0000269|PubMed:23999003}.

Domain: The C2 domain mediates membrane localization and substrate selection. {ECO:0000269|PubMed:21402695}.

Ptm: Auto-ubiquitinated in presence of NDFIP1 (PubMed:23087404). Ubiquitinated by the SCF(FBXL15) complex at Lys-381 and Lys-383, leading to its degradation by the proteasome. Lys-383 is the primary ubiquitination site. {ECO:0000269|PubMed:21572392, ECO:0000269|PubMed:23087404}.

Sequence caution: Sequence=BAB13451.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA. Promotes ubiquitination and subsequent proteasomal degradation of MAVS (PubMed:23087404). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269\|PubMed:10458166, ECO:0000269\|PubMed:19937093, ECO:0000269\|PubMed:21402695, ECO:0000269\|PubMed:23087404, ECO:0000269\|PubMed:23999003}.


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; Evidence={ECO:0000269\|PubMed:19937093};
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with TRAF4. Interacts (via HECT domain) with FBXL15 (via LRR repeats). Interacts with SMAD7 and TGFBR1; SMAD7 recruits SMURF1 to TGFBR1 and regulates TGF-beta receptor degradation. Interacts with MAVS; the interaction is mediated by NDFIP1 (PubMed:23087404). {ECO:0000269\|PubMed:11163210, ECO:0000269\|PubMed:19937093, ECO:0000269\|PubMed:21402695, ECO:0000269\|PubMed:21572392, ECO:0000269\|PubMed:23087404}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:21572392}. Cell membrane {ECO:0000269\|PubMed:21572392}; Peripheral membrane protein {ECO:0000269\|PubMed:21572392}; Cytoplasmic side {ECO:0000269\|PubMed:21572392}.
Tissue specificity:		Expressed in melanocytes (PubMed:23999003). {ECO:0000269\|PubMed:23999003}.
Domain:		The C2 domain mediates membrane localization and substrate selection. {ECO:0000269\|PubMed:21402695}.
Ptm:		Auto-ubiquitinated in presence of NDFIP1 (PubMed:23087404). Ubiquitinated by the SCF(FBXL15) complex at Lys-381 and Lys-383, leading to its degradation by the proteasome. Lys-383 is the primary ubiquitination site. {ECO:0000269\|PubMed:21572392, ECO:0000269\|PubMed:23087404}.
Sequence caution:		Sequence=BAB13451.1; Type=Erroneous initiation; Evidence={ECO:0000305};