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IID00114
 UniprotQ96PU5
ProteinE3 ubiquitin-protein ligase NEDD4-like
GeneNEDD4L
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
 Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
975
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 1-154 Monomer :
 Evidence X-RAY 2nsq A Reference
       Region 2nsq A 1-5 disorder
       Region 2nsq A 6-35 order
       Region 2nsq A 36-39 disorder
       Region 2nsq A 40-120 order
       Region 2nsq A 121-125 disorder
       Region 2nsq A 126-154 order
Seq 385-417 Hetero dimer : IID00135Complex
 Evidence NMR 2lty A Reference
       Region 2lty A 385-417 order
Seq 386-420 Hetero dimer : IID00113Complex
 Evidence NMR 2lb2 A Reference
       Region 2lb2 A 386-420 order
Seq 496-535 Hetero dimer : IID00113Complex
 Evidence NMR 2laj A Reference
       Region 2laj A 496-535 order
Seq 496-539,945-957 Hetero dimer :
 Evidence NMR 2mpt B This complex is hetero dimer in the automatic decision, but is actually homo dimer. Reference
       Region 2mpt B 945-957 order
 Evidence NMR 2mpt A This complex is hetero dimer in the automatic decision, but is actually homo dimer. Reference
       Region 2mpt A 496-497 disorder
       Region 2mpt A 498-529 order
       Region 2mpt A 530-539 disorder
Seq 594-967 Homo dimer :
 Evidence X-RAY 2oni A Reference
       Region 2oni A 594-653 order
       Region 2oni A 654-654 disorder
       Region 2oni A 655-966 order
       Region 2oni A 967-967 disorder
Seq 594-975 Hetero dimer : P62987
 Evidence X-RAY 5hpk A Reference
       Region 5hpk A 594-653 order
       Region 5hpk A 654-658 disorder
       Region 5hpk A 659-969 order
       Region 5hpk A 970-975 disorder
Seq 596-975 Hetero trimer : P0CG48,P62837
 Evidence X-RAY 3jvz C Reference
       Region 3jvz C 596-970 order
       Region 3jvz C 971-975 disorder
 Evidence X-RAY 3jvz D Reference
       Region 3jvz D 596-969 order
       Region 3jvz D 970-975 disorder
 Evidence X-RAY 3jw0 C Reference
       Region 3jw0 C 596-970 order
       Region 3jw0 C 971-975 disorder
 Evidence X-RAY 3jw0 D Reference
       Region 3jw0 D 596-969 order
       Region 3jw0 D 970-975 disorder
Seqphosphorylation
    312-312 Phosphoserine
    318-318 Phosphothreonine
    342-342 Phosphoserine; by WNK1 and WNK4
    367-367 Phosphothreonine; by SGK1
    446-446 Phosphoserine
    448-448 Phosphoserine; by PKA and SGK1
    449-449 Phosphoserine; by WNK1 and WNK4
    464-464 Phosphoserine
    475-475 Phosphoserine
    479-479 Phosphoserine
    483-483 Phosphoserine
    487-487 Phosphoserine
Seqacetylation
    2-2 N-acetylalanine
 
Prediction
NeProc
Disorder 1-15,123-496,534-546
Order 16-122,497-533,547-975
ProS 8-15,123-155,164-176,196-223,247-255,316-323,333-345,352-356,385-417,430-458
AlphaFold
Disorder 1-7,14-17,37-38,99-99,120-126,156-193,205-207,226-383,418-499,509-509,528-528,530-548,562-563,582-588,590-593,595-595,656-661,687-691,782-783,968-975
Order 8-13,18-36,39-98,100-119,127-155,194-204,208-225,384-417,500-508,510-527,529-529,549-561,564-581,589-589,594-594,596-655,662-686,692-781,784-967
Pfam Hmmer
PF00168 22-109 1.8e-32
PF00397 195-224 3.7e-15
PF00397 387-416 2e-16
PF00397 499-528 3.5e-16
PF00397 550-579 9e-14
PF00632 669-974 5e-188
SEG 190-197 ,283-300 ,354-366 ,475-491 ,542-553
Function
Function in SwissProt
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 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338).
Biological Process
See also
Diagram with PDB data
SMAD7/SMURF2Solution structure of Smurf2 WW3 domain-Smad7 PY peptide complex
SMAD3/NEDD4LStructure of the second domain of human Nedd4L in complex with a phosphorylated pTPY motif derived from human Smad3