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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 193-226 Hetero tetramer : IID00842Complex
 Evidence X-RAY 7lp3 A Reference
       Region 7lp3 A 193-226 order
 Evidence X-RAY 7lp3 C Reference
       Region 7lp3 C 193-226 order
Seq 338-347 Hetero octamer : IID00816Complex
 Evidence X-RAY 6zbt E Reference
       Region 6zbt E 338-344 order
       Region 6zbt E 345-347 disorder
 Evidence X-RAY 6zbt F Reference
       Region 6zbt F 338-344 order
       Region 6zbt F 345-347 disorder
 Evidence X-RAY 6zbt G Reference
       Region 6zbt G 338-338 disorder
       Region 6zbt G 339-344 order
       Region 6zbt G 345-347 disorder
 Evidence X-RAY 6zbt H Reference
       Region 6zbt H 338-338 disorder
       Region 6zbt H 339-344 order
       Region 6zbt H 345-347 disorder
Seq 385-417 Hetero dimer : IID00135Complex
 Evidence NMR 2lty A Reference
       Region 2lty A 385-417 order
Seq 385-418 Hetero hexamer : IID00842Complex
 Evidence X-RAY 7lp2 A Reference
       Region 7lp2 A 385-385 disorder
       Region 7lp2 A 386-418 order
 Evidence X-RAY 7lp2 C Reference
       Region 7lp2 C 385-385 disorder
       Region 7lp2 C 386-418 order
 Evidence X-RAY 7lp2 E Reference
       Region 7lp2 E 385-417 order
       Region 7lp2 E 418-418 disorder
Seq 386-420 Hetero dimer : IID00113Complex
 Evidence NMR 2lb2 A Reference
       Region 2lb2 A 386-420 order
Seq 444-453 Hetero octamer : IID00816Complex
 Evidence X-RAY 6zc9 E Reference
       Region 6zc9 E 444-450 order
       Region 6zc9 E 451-453 disorder
 Evidence X-RAY 6zc9 F Reference
       Region 6zc9 F 444-444 disorder
       Region 6zc9 F 445-449 order
       Region 6zc9 F 450-453 disorder
 Evidence X-RAY 6zc9 G Reference
       Region 6zc9 G 444-444 disorder
       Region 6zc9 G 445-449 order
       Region 6zc9 G 450-453 disorder
 Evidence X-RAY 6zc9 H Reference
       Region 6zc9 H 444-450 order
       Region 6zc9 H 451-453 disorder
Seq 493-539 Hetero dimer : IID00842Complex
 Evidence NMR 7lp5 A Reference
       Region 7lp5 A 493-539 order
       Region 7lp5 A 536-539 high_rmsd
Seq 493-539 Monomer :
 Evidence X-RAY 7lp1 A Reference
       Region 7lp1 A 494-532 order
 Evidence NMR 7lp4 A Reference
       Region 7lp4 A 493-539 order
       Region 7lp4 A 493-496 high_rmsd
       Region 7lp4 A 529-539 high_rmsd
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 A Reference
       Region 2mpt A 496-497 disorder
       Region 2mpt A 498-529 order
       Region 2mpt A 530-539 disorder
 Evidence NMR 2mpt B Reference
       Region 2mpt B 945-957 order
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
SeqProS predicted 338-344 This region is predicted to be disordered by NeProc and AlphaFold (pLDDT < 68.5). Hetero octamer : IID00816Complex
       Region 6zbt E 338-344 order
       Region 6zbt F 338-344 order
       Region 6zbt G 339-344 order
       Region 6zbt H 339-344 order
SeqProS predicted 444-450 This region is predicted to be disordered by NeProc and AlphaFold (pLDDT < 68.5). Hetero octamer : IID00816Complex
       Region 6zc9 E 444-450 order
       Region 6zc9 F 445-449 order
       Region 6zc9 G 445-449 order
       Region 6zc9 H 444-450 order
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
    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
    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 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 (PubMed:31959741, PubMed:33608556, PubMed:20064473). Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation (PubMed:15496141). Downregulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels (PubMed:28820317, PubMed:31959741). 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). 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 (PubMed:33608556).
Biological Process
Diagram with PDB data
NEDD4L/YWHAGStructure of 14-3-3 gamma in complex with Nedd4-2 14-3-3 binding motif Ser342
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
AMOT/NEDD4LStructure of Nedd4L WW3 domain