CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-016823
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase NEDD4-like 
Protein Synonyms/Alias
 NEDD4.2; Nedd4-2 
Gene Name
 Nedd4l 
Gene Synonyms/Alias
 Kiaa0439; Nedd4b 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
53ESRILRVKVVSGIDLubiquitination[1]
491SAPLEGAKDSPIRRAubiquitination[1]
568FPVHMRSKASLNPNDubiquitination[1, 2]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [2] Synaptic protein ubiquitination in rat brain revealed by antibody-based ubiquitome analysis.
 Na CH, Jones DR, Yang Y, Wang X, Xu Y, Peng J.
 J Proteome Res. 2012 Sep 7;11(9):4722-32. [PMID: 22871113
Functional Description
 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, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. 
Sequence Annotation
 DOMAIN 35 137 C2.
 DOMAIN 221 254 WW 1.
 DOMAIN 414 447 WW 2.
 DOMAIN 526 559 WW 3.
 DOMAIN 577 610 WW 4.
 DOMAIN 669 1003 HECT.
 ACT_SITE 971 971 Glycyl thioester intermediate.
 MOD_RES 331 331 Phosphothreonine.
 MOD_RES 347 347 Phosphothreonine (By similarity).
 MOD_RES 371 371 Phosphoserine; by WNK1 and WNK4.
 MOD_RES 396 396 Phosphothreonine; by SGK1 (By
 MOD_RES 475 475 Phosphoserine.
 MOD_RES 477 477 Phosphoserine; by SGK1.
 MOD_RES 478 478 Phosphoserine; by WNK1 and WNK4 (By
 MOD_RES 493 493 Phosphoserine (By similarity).
 MOD_RES 508 508 Phosphoserine.
 MOD_RES 512 512 Phosphoserine.
 MOD_RES 516 516 Phosphoserine (By similarity).  
Keyword
 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Ligase; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1004 AA 
Protein Sequence
MSLCEAPVHV GDKELKYFQI PQMLSQLSLL ASHHSRGLEF SGGQGESRIL RVKVVSGIDL 60
AKKDIFGASD PYVKLSLYVA DENRELALVQ TKTIKKTLNP KWNEEFYFRV NPSNHRLLFE 120
VFDENRLTRD DFLGQVDVPL SHLPTEDPTM ERPYTFKDFL LRPRSHKSRV KGFLRLKMAY 180
MPKNGGQDEE NSEQRDDMEH GWEVVDSNDS ASQHQEELPP PPLPPGWEEK VDNLGRTYYV 240
NHNNRSTQWH RPSLMDVSSE SDNNIRQINQ EAAHRRFRSR RHISEDLEPE ASEGGGEGPE 300
PWETISEEMN MAGDSLSLAL PPPPASPVSR TSPQELSEEV SRRLQITPDS NGEQFSSLIQ 360
REPSSRLRSC SVTDTVAEQA HLPPPSTPTR RARSSTVTGG EEPTPSVAYV HTTPGLPSGW 420
EERKDAKGRT YYVNHNNRTT TWTRPIMQLA EDGASGSATN SNNHLVEPQI RRPRSLSSPT 480
VTLSAPLEGA KDSPIRRAVK DTLSNPQSPQ PSPYNSPKPQ HKVTQSFLPP GWEMRIAPNG 540
RPFFIDHNTK TTTWEDPRLK FPVHMRSKAS LNPNDLGPLP PGWEERIHLD GRTFYIDHNS 600
KITQWEDPRL QNPAITGPAV PYSREFKQKY DYFRKKLKKP ADIPNRFEMK LHRNNIFEES 660
YRRIMSVKRP DVLKARLWIE FESEKGLDYG GVAREWFFLL SKEMFNPYYG LFEYSATDNY 720
TLQINPNSGL CNEDHLSYFT FIGRVAGLAV FHGKLLDGFF IRPFYKMMLG KQITLNDMES 780
VDSEYYNSLK WILENDPTEL DLMFCIDEEN FGQTYQVDLK PNGSEIMVTN ENKREYIDLV 840
IQWRFVNRVQ KQMNAFLEGF TELLPIDLIK IFDENELELL MCGLGDVDVN DWRQHSIYKN 900
GYCPNHPVIQ WFWKAVLLMD AEKRIRLLQF VTGTSRVPMN GFAELYGSNG PQLFTIEQWG 960
SPEKLPRAHT CFNRLDLPPY ETFEDLREKL LMAVENAQGF EGVD 1004 
Gene Ontology
 GO:0005737; C:cytoplasm; IBA:RefGenome.
 GO:0005634; C:nucleus; IBA:RefGenome.
 GO:0019871; F:sodium channel inhibitor activity; IDA:MGI.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:MGI.
 GO:0010766; P:negative regulation of sodium ion transport; IDA:MGI.
 GO:0003085; P:negative regulation of systemic arterial blood pressure; IMP:MGI.
 GO:2001259; P:positive regulation of cation channel activity; IGI:MGI.
 GO:0010765; P:positive regulation of sodium ion transport; IGI:MGI.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
 GO:2000810; P:regulation of tight junction assembly; IDA:MGI.
 GO:0009651; P:response to salt stress; IMP:MGI.
 GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IDA:MGI. 
Interpro
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR020477; C2_dom.
 IPR018029; C2_membr_targeting.
 IPR024928; E3_ub_ligase_SMURF1.
 IPR000569; HECT.
 IPR001202; WW_dom. 
Pfam
 PF00168; C2
 PF00632; HECT
 PF00397; WW 
SMART
 SM00239; C2
 SM00119; HECTc
 SM00456; WW 
PROSITE
 PS50004; C2
 PS50237; HECT
 PS01159; WW_DOMAIN_1
 PS50020; WW_DOMAIN_2 
PRINTS
 PR00360; C2DOMAIN.