CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-019532
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; NEDL3 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
129MERPYTFKDFLLRPRubiquitination[1]
462SAPLEGAKDSPVRRAubiquitination[2]
471SPVRRAVKDTLSNPQubiquitination[1, 2]
521FFIDHNTKTTTWEDPubiquitination[1]
531TWEDPRLKFPVHMRSubiquitination[1]
539FPVHMRSKTSLNPNDubiquitination[2]
656WIEFESEKGLDYGGVubiquitination[2, 3]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572] 
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 7 109 C2.
 DOMAIN 193 226 WW 1.
 DOMAIN 385 418 WW 2.
 DOMAIN 497 530 WW 3.
 DOMAIN 548 581 WW 4.
 DOMAIN 640 974 HECT.
 ACT_SITE 942 942 Glycyl thioester intermediate.
 MOD_RES 302 302 Phosphothreonine (By similarity).
 MOD_RES 318 318 Phosphothreonine.
 MOD_RES 342 342 Phosphoserine; by WNK1 and WNK4.
 MOD_RES 367 367 Phosphothreonine; by SGK1 (Probable).
 MOD_RES 446 446 Phosphoserine.
 MOD_RES 448 448 Phosphoserine; by PKA and SGK1.
 MOD_RES 449 449 Phosphoserine; by WNK1 and WNK4.
 MOD_RES 464 464 Phosphoserine.
 MOD_RES 479 479 Phosphoserine.
 MOD_RES 483 483 Phosphoserine.
 MOD_RES 487 487 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Host-virus interaction; Ligase; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 975 AA 
Protein Sequence
MATGLGEPVY GLSEDEGESR ILRVKVVSGI DLAKKDIFGA SDPYVKLSLY VADENRELAL 60
VQTKTIKKTL NPKWNEEFYF RVNPSNHRLL FEVFDENRLT RDDFLGQVDV PLSHLPTEDP 120
TMERPYTFKD FLLRPRSHKS RVKGFLRLKM AYMPKNGGQD EENSDQRDDM EHGWEVVDSN 180
DSASQHQEEL PPPPLPPGWE EKVDNLGRTY YVNHNNRTTQ WHRPSLMDVS SESDNNIRQI 240
NQEAAHRRFR SRRHISEDLE PEPSEGGDVP EPWETISEEV NIAGDSLGLA LPPPPASPGS 300
RTSPQELSEE LSRRLQITPD SNGEQFSSLI QREPSSRLRS CSVTDAVAEQ GHLPPPSAPA 360
GRARSSTVTG GEEPTPSVAY VHTTPGLPSG WEERKDAKGR TYYVNHNNRT TTWTRPIMQL 420
AEDGASGSAT NSNNHLIEPQ IRRPRSLSSP TVTLSAPLEG AKDSPVRRAV KDTLSNPQSP 480
QPSPYNSPKP QHKVTQSFLP PGWEMRIAPN GRPFFIDHNT KTTTWEDPRL KFPVHMRSKT 540
SLNPNDLGPL PPGWEERIHL DGRTFYIDHN SKITQWEDPR LQNPAITGPA VPYSREFKQK 600
YDYFRKKLKK PADIPNRFEM KLHRNNIFEE SYRRIMSVKR PDVLKARLWI EFESEKGLDY 660
GGVAREWFFL LSKEMFNPYY GLFEYSATDN YTLQINPNSG LCNEDHLSYF TFIGRVAGLA 720
VFHGKLLDGF FIRPFYKMML GKQITLNDME SVDSEYYNSL KWILENDPTE LDLMFCIDEE 780
NFGQTYQVDL KPNGSEIMVT NENKREYIDL VIQWRFVNRV QKQMNAFLEG FTELLPIDLI 840
KIFDENELEL LMCGLGDVDV NDWRQHSIYK NGYCPNHPVI QWFWKAVLLM DAEKRIRLLQ 900
FVTGTSRVPM NGFAELYGSN GPQLFTIEQW GSPEKLPRAH TCFNRLDLPP YETFEDLREK 960
LLMAVENAQG FEGVD 975 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0019871; F:sodium channel inhibitor activity; IEA:Compara.
 GO:0017080; F:sodium channel regulator activity; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; NAS:UniProtKB.
 GO:0006883; P:cellular sodium ion homeostasis; NAS:UniProtKB.
 GO:0007588; P:excretion; NAS:UniProtKB.
 GO:0034220; P:ion transmembrane transport; TAS:Reactome.
 GO:0010766; P:negative regulation of sodium ion transport; IEA:Compara.
 GO:0003085; P:negative regulation of systemic arterial blood pressure; IEA:Compara.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:Reactome.
 GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
 GO:2001259; P:positive regulation of cation channel activity; IEA:Compara.
 GO:0045807; P:positive regulation of endocytosis; NAS:UniProtKB.
 GO:0010765; P:positive regulation of sodium ion transport; IEA:Compara.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
 GO:0042391; P:regulation of membrane potential; IDA:BHF-UCL.
 GO:1901016; P:regulation of potassium ion transmembrane transporter activity; IDA:BHF-UCL.
 GO:0042176; P:regulation of protein catabolic process; NAS:UniProtKB.
 GO:2000810; P:regulation of tight junction assembly; IEA:Compara.
 GO:0010038; P:response to metal ion; IDA:UniProtKB.
 GO:0009651; P:response to salt stress; IEA:Compara.
 GO:0006814; P:sodium ion transport; NAS:UniProtKB.
 GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
 GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IEA:Compara.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW.
 GO:0030104; P:water homeostasis; NAS:UniProtKB. 
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.