CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-019533
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
398SAPLEGAKDSPVRRAubiquitination[1]
407SPVRRAVKDTLSNPQubiquitination[1]
425PSPYNSPKPQHKVTQubiquitination[1]
429NSPKPQHKVTQSFLPubiquitination[1]
457FFIDHNTKTTTWEDPubiquitination[1]
467TWEDPRLKFPVHMRSubiquitination[1]
475FPVHMRSKTSLNPNDubiquitination[1]
508FYIDHNSKITQWEDPubiquitination[1]
592WIEFESEKGLDYGGVubiquitination[1]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 
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 GHLPPLAEDG 360
ASGSATNSNN HLIEPQIRRP RSLSSPTVTL SAPLEGAKDS PVRRAVKDTL SNPQSPQPSP 420
YNSPKPQHKV TQSFLPPGWE MRIAPNGRPF FIDHNTKTTT WEDPRLKFPV HMRSKTSLNP 480
NDLGPLPPGW EERIHLDGRT FYIDHNSKIT QWEDPRLQNP AITGPAVPYS REFKQKYDYF 540
RKKLKKPADI PNRFEMKLHR NNIFEESYRR IMSVKRPDVL KARLWIEFES EKGLDYGGVA 600
REWFFLLSKE MFNPYYGLFE YSATDNYTLQ INPNSGLCNE DHLSYFTFIG RVAGLAVFHG 660
KLLDGFFIRP FYKMMLGKQI TLNDMESVDS EYYNSLKWIL ENDPTELDLM FCIDEENFGQ 720
TYQVDLKPNG SEIMVTNENK REYIDLVIQW RFVNRVQKQM NAFLEGFTEL LPIDLIKIFD 780
ENELELLMCG LGDVDVNDWR QHSIYKNGYC PNHPVIQWFW KAVLLMDAEK RIRLLQFVTG 840
TSRVPMNGFA ELYGSNGPQL FTIEQWGSPE KLPRAHTCFN RLDLPPYETF EDLREKLLMA 900
VENAQGFEGV D 911 
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.