Q8CFI0
uniprot
Q8CFI0
canonical
activity_regulation
ACTIVITY REGULATION: Activated by NDFIP1- and NDFIP2-binding. {ECO:0000250|UniProtKB:Q96PU5}.
uniprot
proteins
amino_acid_sequence
MSLCEAPVHVGDKELKYFQIPQMLSQLSLLASHHSRGLEFSGGQGESRILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYMPKNGGQDEENSEQRDDMEHGWEVVDSNDSASQHQEELPPPPLPPGWEEKVDNLGRTYYVNHNNRSTQWHRPSLMDVSSESDNNIRQINQEAAHRRFRSRRHISEDLEPEASEGGGEGPEPWETISEEMNMAGDSLSLALPPPPASPVSRTSPQELSEEVSRRLQITPDSNGEQFSSLIQREPSSRLRSCSVTDTVAEQAHLPPPSTPTRRARSSTVTGGEEPTPSVAYVHTTPGLPSGWEERKDAKGRTYYVNHNNRTTTWTRPIMQLAEDGASGSATNSNNHLVEPQIRRPRSLSSPTVTLSAPLEGAKDSPIRRAVKDTLSNPQSPQPSPYNSPKPQHKVTQSFLPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRLKFPVHMRSKASLNPNDLGPLPPGWEERIHLDGRTFYIDHNSKITQWEDPRLQNPAITGPAVPYSREFKQKYDYFRKKLKKPADIPNRFEMKLHRNNIFEESYRRIMSVKRPDVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILENDPTELDLMFCIDEENFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSNGPQLFTIEQWGSPEKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFEGVD
uniprot
proteins
ec_number
2.3.2.26
uniprot
proteins
ec_number
2.3.2.36
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repair. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Down-regulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels. 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 (PubMed:15123669). 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. Plays a role in antiviral innate immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked ubiquitination of TRAF3 (By similarity). Ubiquitinates TTYH2 and TYYH3 and regulates protein levels of TTYH2 (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}.
uniprot
proteins
mass_dalton
115419
uniprot
proteins
mutagenesis
MUTAGEN 371; /note="S->A: Weakly reduces phosphorylation by SGK1."; /evidence="ECO:0000269|PubMed:11742982"; MUTAGEN 477; /note="S->A: Strongly reduces phosphorylation by SGK1."; /evidence="ECO:0000269|PubMed:11742982"; MUTAGEN 971; /note="C->S: Abolishes activity."; /evidence="ECO:0000269|PubMed:11149908
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000305}.
uniprot
proteins
post_translational_modification
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}.
uniprot
proteins
pubmed
11149908
uniprot
proteins
pubmed
11244092
uniprot
proteins
pubmed
11742982
uniprot
proteins
pubmed
12050153
uniprot
proteins
pubmed
12424229
uniprot
proteins
pubmed
14993279
uniprot
proteins
pubmed
15123669
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15958725
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
27694961
uniprot
proteins
sequence_length
1004
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12050153}. Golgi apparatus {ECO:0000250|UniProtKB:Q96PU5}. Endosome, multivesicular body {ECO:0000250|UniProtKB:Q96PU5}.
uniprot
proteins