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Overview

Uniprot IDQ62940
Protein NameE3 ubiquitin-protein ligase NEDD4
Gene NameNedd4
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
442 MQDDPRSKIPAHLRG

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. Specifically ubiquitinates 'Lys-63' in target proteins (By similarity). Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Promotes ubiquitination of RAPGEF2. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Is involved in ubiquitination of ERBB4 intracellular domain E4ICD (By similarity). Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development (PubMed:20159449). Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (By similarity). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (By similarity). Ubiquitinates DAZAP2, leading to its proteasomal degradation (By similarity). Ubiquitinates POLR2A (By similarity). Functions as a platform to recruit USP13 to form an NEDD4-USP13 deubiquitination complex that plays a critical role in cleaving the 'Lys-48'-linked ubiquitin chains of VPS34 and then stabilizing VPS34, thus promoting the formation of autophagosomes (By similarity)

Protein Sequence

10 MAADDTEAPV 20 LSEDEVWEFC 30 LDKNEEGGGS 40 PGSDVTDTCE 50 PPCGCWELNP 60 SSLEEEHVLF 70 TAESIISSFN 80 NDDTRVVRVK 90 VIAGIGLAKK 100 DILGASDPYV 110 RVTLYDPMSG 120 VLTSVQTKTI 130 KKSLNPKWNE 140 EILFRVLPQQ 150 HRILFEVFDE 160 NRLTRDDFLG 170 QVDVPLYPLP 180 TENPRMERPY 190 TFKDFVLHPR 200 SHKSRVKGYL 210 RLKMTYLPKN 220 GSDDENADQA 230 EELEPGWVVL 240 DQPDAATHLQ 250 HPPEPSPLPP 260 GWEERQDVLG 270 RTYYVNHESR 280 TTQWKRPSPE 290 DDLTDDENGD 300 IQLQAHGAFT 310 TRRQISEDVD 320 GPDNHESPEN 330 WEIVREDENT 340 IYSGQAVQSP 350 PSGHPDVQVR 360 LAEELDTRLT 370 MYGNPATSQP 380 VTSSNHSSRG 390 GSSQTCIFEE 400 QPTLPVLLPT 410 SSGLPPGWEE 420 KQDDRGRSYY 430 VDHNSKTTTW 440 SKPTMQDDPR 450 SKIPAHLRGK 460 TPVDSNDLGP 470 LPPGWEERTH 480 TDGRVFFINH 490 NIKKTQWEDP 500 RMQNVAITGP 510 AEPYSRDYKR 520 KYEFFRRKLK 530 KQTDIPNKFE 540 MKLRRANILE 550 DSYRRIMGVK 560 RADFLKARLW 570 IEFDGEKGLD 580 YGGVAREWFF 590 LISKEMFNPY 600 YGLFEYSATE 610 DNYTLQINPN 620 SGLCNEDHLS 630 YFKFIGRVAG 640 MAVYHGKLLD 650 GFFIRPFYKM 660 MLQKLITLHD 670 MESVDSEYYS 680 SLRWILENDP 690 TELDLRFIID 700 EELFGQTHQH 710 ELKTGGSEVV 720 VTNKNKKEYI 730 YLVIQWRFVN 740 RIQKQMAAFK 750 EGFFELIPQD 760 LIKIFDENEL 770 ELLMCGLGDV 780 DVNDWREHTK 790 YKNGYSLNHQ 800 VIHWFWKAVL 810 MMDSEKRIRL 820 LQFVTGTSRV 830 PMNGFAELYG 840 SNGPQSFTVE 850 QWGTPDKLPR 860 AHTCFNRLDL 870 PPYESFDELW 880 DKLQMAIENT QGFDGVD

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005938 cell cortex
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0098978 glutamatergic synapse
Cellular Component GO:0005794 Golgi apparatus
Cellular Component GO:0000151 ubiquitin ligase complex
Molecular Function GO:0031698 beta-2 adrenergic receptor binding
Molecular Function GO:0016248 channel inhibitor activity
Molecular Function GO:0019899 enzyme binding
Molecular Function GO:0035255 ionotropic glutamate receptor binding
Molecular Function GO:0050815 phosphoserine residue binding
Molecular Function GO:0050816 phosphothreonine residue binding
Molecular Function GO:0019870 potassium channel inhibitor activity
Molecular Function GO:0070064 proline-rich region binding
Molecular Function GO:0019904 protein domain specific binding
Molecular Function GO:0070063 RNA polymerase binding
Molecular Function GO:0019871 sodium channel inhibitor activity
Molecular Function GO:0044325 transmembrane transporter binding
Molecular Function GO:0043130 ubiquitin binding
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:0004842 ubiquitin-protein transferase activity
Biological Process GO:0002250 adaptive immune response
Biological Process GO:0048514 blood vessel morphogenesis
Biological Process GO:0034644 cellular response to UV
Biological Process GO:0006974 DNA damage response
Biological Process GO:0003197 endocardial cushion development
Biological Process GO:0006955 immune response
Biological Process GO:0007041 lysosomal transport
Biological Process GO:1903765 negative regulation of potassium ion export across plasma membrane
Biological Process GO:0010766 negative regulation of sodium ion transport
Biological Process GO:0000122 negative regulation of transcription by RNA polymerase II
Biological Process GO:0030948 negative regulation of vascular endothelial growth factor receptor signaling pathway
Biological Process GO:0007528 neuromuscular junction development
Biological Process GO:0031175 neuron projection development
Biological Process GO:0042921 nuclear receptor-mediated glucocorticoid signaling pathway
Biological Process GO:0003151 outflow tract morphogenesis
Biological Process GO:0046824 positive regulation of nucleocytoplasmic transport
Biological Process GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Process GO:0045732 positive regulation of protein catabolic process
Biological Process GO:0050847 progesterone receptor signaling pathway
Biological Process GO:0070534 protein K63-linked ubiquitination
Biological Process GO:0006513 protein monoubiquitination
Biological Process GO:0006622 protein targeting to lysosome
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0032801 receptor catabolic process
Biological Process GO:0031623 receptor internalization
Biological Process GO:0048814 regulation of dendrite morphogenesis
Biological Process GO:0042391 regulation of membrane potential
Biological Process GO:0099149 regulation of postsynaptic neurotransmitter receptor internalization
Biological Process GO:0099576 regulation of protein catabolic process at postsynapse, modulating synaptic transmission
Biological Process GO:0050807 regulation of synapse organization
Biological Process GO:0140252 regulation protein catabolic process at postsynapse
Biological Process GO:0014894 response to denervation involved in regulation of muscle adaptation
Biological Process GO:0042110 T cell activation
Biological Process GO:0006511 ubiquitin-dependent protein catabolic process
Biological Process GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
Cellular Component GO:0016020 membrane
Cellular Component GO:0005902 microvillus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0099524 postsynaptic cytosol
Cellular Component GO:0032991 protein-containing complex

Reference

[1] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.