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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NEDD4L Gene

protein-coding GIFtS: 66
GCID: GC18P055711

neural precursor cell expressed, developmentally down-regulated...

(Previous names: neural precursor cell expressed, developmentally down-regulated...)

Explore 16 diseases affiliated with
NEDD4L via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like, E3 Ubiquitin Protein Ligase¹ ²		HNEDD4-2¹
RSP5¹ ² ⁵		Ubiquitin-Protein Ligase Rsp5²
KIAA0439¹ ³ ⁵		EC 6.3.2.-³
NEDD4-2¹ ²		NEDL3³
NEDD4.2² ³		Nedd4-2³
Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like¹		EC 6.3.2⁸
E3 Ubiquitin-Protein Ligase NEDD4-Like²

External Ids:	HGNC: 7728¹	Entrez Gene: 23327²	Ensembl: ENSG00000049759⁷	OMIM: 606384⁵	UniProtKB: Q96PU5³

Export aliases for NEDD4L gene to outside databases

Previous GC identifers: GC18P055746 GC18P055496 GC18P053860 GC18P053862 GC18P052421

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NEDD4L:

This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases

transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for

lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a

critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium

channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension.

Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. (provided by

RefSeq, Mar 2012)

UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5

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. 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

Gene Wiki entry for NEDD4L

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000018.9 NC_018929.1 NT_025028.14

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the NEDD4L gene promoter:
HEN1 POU2F1 c-Myb Hand1 Evi-1 RSRFC4 E47 GATA-1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: NEDD4L promoter sequence

Search SABiosciences Chromatin IP Primers for NEDD4L

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NEDD4L

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 18q21 Ensembl cytogenetic band: 18q21.31 HGNC cytogenetic band: 18q21

NEDD4L Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NEDD4L gene location

GeneLoc information about chromosome 18 GeneLoc Exon Structure

GeneLoc location for GC18P055711: view genomic region (about GC identifiers)

Start:	55,711,599 bp from pter	End:	56,068,772 bp from pter
Size:	357,174 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5 (See protein sequence)

Recommended Name: E3 ubiquitin-protein ligase NEDD4-like

Size: 975 amino acids; 111932 Da

Subunit: Interacts with UBE2E3 (By similarity). Interacts with NDFIP1 and NDFIP2 (By similarity); this interaction

activates the E3 ubiquitin-protein ligase. Interacts via its WW domains with SCNN1A, SCNN1B, SCNN1G, SCN1A, SCN2A,

SCN3A, SCN5A, SCN8A, SCN9A, SCN10A and CLCN5. Interacts with SMAD2, SMAD3, SMAD6 and SMAD7. The phosphorylated form

interacts with 14-3-3 proteins. Interacts with Epstein-Barr virus LMP2A. Interacts with TNK2. Interacts with WNK1.

Interacts with SGK1. Interacts (via C2 domain) with NPC2

Subcellular location: Cytoplasm. Note=May be recruited to exosomes by NDFIP1

Sequence caution: Sequence=BAA23711.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;

Sequence=BAA23711.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact;

6/7 PDB 3D structures from and Proteopedia for NEDD4L (see all 7):

2LAJ (3D)

2LB2 (3D)

2LTY (3D)

2NSQ (3D)

2ONI (3D)

3JVZ (3D)

Secondary accessions: O43165 Q3LSM7 Q7Z5F1 Q7Z5F2 Q7Z5N3 Q8N5A7 Q8WUU9 Q9BW58 Q9H2W4 Q9NT88

Alternative splicing: 8 isoforms: Q96PU5-1 Q96PU5-2 Q96PU5-3 Q96PU5-4 Q96PU5-5 Q96PU5-6 Q96PU5-7 Q96PU5-9

(No experimental confirmation available)

Explore the universe of human proteins at neXtProt for NEDD4L: NX_Q96PU5

Post-translational modifications:

Phosphorylated by SGK1 or PKA; which impairs interaction with SCNN. Interaction with YWHAH inhibits dephosphorylation¹

Auto-ubiquitinated¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q96PU5

4/11 DME Specific Peptides for NEDD4L (Q96PU5) (see all 11)

PLPPGWE

TQWEDPR

NPYYGLF

RLLQFVTG

NEDD4L Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (10 alternative transcripts):

NP_001138436.1 NP_001138437.1 NP_001138438.1 NP_001138439.1 NP_001138440.1 NP_001138441.1 NP_001138442.1 NP_001138443.1

NP_001230889.1 NP_056092.2

ENSEMBL proteins:

ENSP00000348847 ENSP00000383199 ENSP00000465669 ENSP00000372301 ENSP00000256830

ENSP00000466776 ENSP00000393395 ENSP00000350569 ENSP00000468546 ENSP00000405440

ENSP00000466789 ENSP00000389406 ENSP00000467072 ENSP00000467768 ENSP00000468332

ENSP00000256832 ENSP00000411947

Reactome Protein details: Q96PU5
Human Recombinant Protein Products:

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	Novus Biologicals NEDD4L Proteins Novus Biologicals NEDD4L Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for NEDD4L

Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005622	intracellular	IC	11244092
GO:0005634	nucleus	IBA	--
GO:0005654	nucleoplasm	TAS	--
GO:0005737	cytoplasm	IBA	--
GO:0005829	cytosol	TAS	--

NEDD4L for ontologies About GeneDecksing

NEDD4L Antibody Products:

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	Abcam antibodies for NEDD4L
	Uscn Antibodies for NEDD4L
	Search ThermoFisher Antibodies for NEDD4L

Assay Products for NEDD4L:

	Browse Kits and Assays available from EMD Millipore
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	Uscn ELISAs and CLIAs for NEDD4L

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

NEDD4L for domains About GeneDecksing

5/7 InterPro domains/families (see all 7):

IPR008973 C2_Ca/lipid-bd_dom_CaLB

IPR024928 E3_ub_ligase_SMURF1

IPR018029 C2_membr_targeting

IPR001202 WW_Rsp5_WWP

IPR020477 C2_dom

Graphical View of Domain Structure for InterPro Entry Q96PU5

ProtoNet protein and cluster: Q96PU5

3 Blocks protein families:

IPB000008 C2 domain

IPB000569 HECT domain (Ubiquitin-protein ligase)

IPB002349 WW domain signature

UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5

Similarity: Contains 1 C2 domain

Similarity: Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain

Similarity: Contains 4 WW domains

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5

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. 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

Enzyme regulation: Activated by NDFIP1- and NDFIP2-binding

Induction: By androgens in prostate, and by albumin in kidney

Genatlas biochemistry entry for NEDD4L:

neural precursor cell expressed gene 4-like,developmentally down-regulated 4-like

Enzyme Numbers (IUBMB): EC 6.3.2.-¹ EC 6.3.2²

miRNA Products:		OriGene 3'-UTR Clone (see all 9): NEDD4L Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NEDD4L
		8/145 QIAGEN miScript miRNA Assays for microRNAs that regulate NEDD4L (see all 145):
		hsa-miR-579 hsa-miR-26a-2* hsa-miR-193a-3p hsa-miR-106a hsa-miR-519a hsa-miR-200b hsa-miR-92b hsa-miR-130b

		SwitchGear 3'UTR luciferase reporter plasmid: NEDD4L 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for NEDD4L (see all 7) OriGene shRNA RFP: NEDD4L Browse OriGene siRNA
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NEDD4L

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for NEDD4L

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for NEDD4L (see all 12) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for NEDD4L (see all 9) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NEDD4L

Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004842	ubiquitin-protein ligase activity	NAS	11244092
GO:0005515	protein binding	IPI	19664597
GO:0017080	sodium channel regulator activity	IDA	11244092
GO:0019871	sodium channel inhibitor activity	IEA	--

NEDD4L for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for NEDD4L:

Synthetic lethal with Ras

Animal Models:
Mouse knock-out Nedd4l^tm1.2Blyg for NEDD4L
10 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Nedd4l):

behavior/neurological	cardiovascular system	digestive/alimentary	homeostasis/metabolism	immune system
mortality/aging	muscle	no phenotypic analysis	renal/urinary system	respiratory system

NEDD4L for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/15 super-pathways (see all 15) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Antigen processing: Ubiquitination & Proteasome degradation

	Antigen processing: Ubiquitination & Proteasome degradation	1.00			Polyubiquitination of substrate	0.75
	Class I MHC mediated antigen processing & presentation	0.83			Ubiquitin mediated proteolysis	0.36

Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer

	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1.00			Downregulation of SMAD2/3:SMAD4 transcriptional activity	0.56
	Signaling by TGF-beta Receptor Complex	0.61

Immune System

Immune System

1.00

Adaptive Immune System

0.59

Ion channel transport

Ion channel transport

1.00

Stimuli-sensing channels

0.49

Generic Transcription Pathway

Generic Transcription Pathway

1.00

Gene Expression

0.46

Pathway sources
See GeneCards unified pathways
Show all pathways

2 Cell Signaling Technology (CST) Pathways for NEDD4L

	TGF-beta/Smad Signaling
	Protein Stability

2 BioSystems Pathways for NEDD4L

	TGF-beta receptor signaling
	Neurotrophic factor-mediated Trk receptor signaling

5/16 Reactome Pathways for NEDD4L (see all 16)

	TGF-beta receptor signaling activates SMADs
	Stimuli-sensing channels
	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
	Transmembrane transport of small molecules
	Antigen processing: Ubiquitination & Proteasome degradation

1 PharmGKB Pathway for NEDD4L

Diuretics Pathway, Pharmacodynamics

3 Kegg Pathways (Kegg details for NEDD4L):

	Ubiquitin mediated proteolysis
	Endocytosis
	Aldosterone-regulated sodium reabsorption

UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5

Pathway: Protein modification; protein ubiquitination

NEDD4L for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for NEDD4L

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/208 Interacting proteins for NEDD4L (Q96PU5^{2, 3} ENSP00000383199⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 208)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
LAPTM5	Q13571²^,³, ENSP00000294507⁴	MINT-62184 I2D: score=3 STRING: ENSP00000294507
RNF11	Q9Y3C5²^,³, ENSP00000242719⁴	MINT-60888 I2D: score=3 STRING: ENSP00000242719
SCNN1B	P51168²^,³, ENSP00000345751⁴	MINT-8290136 I2D: score=3 STRING: ENSP00000345751
SMAD2	Q15796²^,³, ENSP00000262160⁴	MINT-61615 I2D: score=2 STRING: ENSP00000262160
MED28	Q9H204²^,³, ENSP00000237380⁴	MINT-7041937 I2D: score=1 STRING: ENSP00000237380

About this table

Gene Ontology (GO): 5/27 biological process terms (GO ID links to tree view) (see all 27): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	TAS	--
GO:0003085	negative regulation of systemic arterial blood pressure	IEA	--
GO:0006351	transcription, DNA-dependent	TAS	--
GO:0006367	transcription initiation from RNA polymerase II promoter	TAS	--
GO:0006814	sodium ion transport	NAS	11244092

NEDD4L for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

NEDD4L for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for NEDD4L

4 HMDB Compounds for NEDD4L About this table

Compound	Synonyms	CAS #	PubMed Ids
Adenosine monophosphate	5'-AMP (see all 28)	61-19-8	--
Adenosine triphosphate	5'-(tetrahydrogen triphosphate) Adenosine (see all 24)	56-65-5	--
Phosphoric acid	acide phosphorique (FRENCH) (see all 20)	7664-38-2	--
Pyrophosphate	(4-)Diphosphoric acid ion (see all 10)	14000-31-8	--

3 Novoseek chemical compound relationships for NEDD4L gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
sodium	64.4	23	16338225 (5), 18687683 (3), 12522688 (2), 18498246 (1) (see all 12)
glutamate	0	1	12911626 (1)
cysteine	0	1	10066826 (1)

1 PharmGKB related drug/compound annotation for NEDD4L gene

Drug/compound	PharmGKB Annotation
hydrochlorothiazide	CA

About this table

Search CenterWatch for drugs/clinical trials and news about NEDD4L / NED4L

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for NEDD4L gene (10 alternative transcripts):

NM_001144964.1 NM_001144965.1 NM_001144966.2 NM_001144967.2 NM_001144968.1 NM_001144969.1 NM_001144970.2 NM_001144971.1

NM_001243960.1 NM_015277.5

Unigene Cluster for NEDD4L:

Neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase

Hs.185677 [show with all ESTs]

Unigene Representative Sequence: NM_001144967

18/37 Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 37):

ENST00000356462(uc002lgz.3) ENST00000400345(uc002lgy.3) ENST00000589054

ENST00000382850(uc002lgx.3) ENST00000256830(uc002lha.1 uc002lhh.2 uc010dpm.1)

ENST00000590694 ENST00000591989 ENST00000591579 ENST00000592846 ENST00000585363

ENST00000588516 ENST00000585594 ENST00000587547 ENST00000435432(uc002lhb.2)

ENST00000357895(uc002lhc.2 uc002lhd.2 uc002lhe.2) ENST00000586263

ENST00000456173(uc002lhf.3) ENST00000588494

miRNA Products:		OriGene 3'-UTR Clone (see all 9): NEDD4L Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NEDD4L
		8/145 QIAGEN miScript miRNA Assays for microRNAs that regulate NEDD4L (see all 145):
		hsa-miR-579 hsa-miR-26a-2* hsa-miR-193a-3p hsa-miR-106a hsa-miR-519a hsa-miR-200b hsa-miR-92b hsa-miR-130b

		SwitchGear 3'UTR luciferase reporter plasmid: NEDD4L 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NEDD4L

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for NEDD4L Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat NEDD4L
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat NEDD4L
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat NEDD4L

Additional cDNA sequence:

AB007899.1 AB071179.1 AF070601.1 AF210730.1 AF385931.1 AK091189.1 AK096812.1 AK130420.1

AK294963.1 AK300444.1 AL137469.1 AY112983.1 AY112984.2 AY112985.2 AY243313.1 AY243314.1

AY243316.1 AY243317.1 AY243318.1 AY243319.1 AY243321.1 AY243322.1 AY256662.1 AY312514.1

AY751751.1 BC000621.2 BC019345.1 BC032597.1 DQ181796.1

24/39 DOTS entries (see all 39):

DT.100820119 DT.121086464 DT.117979 DT.95113158 DT.101977753 DT.100820117 DT.40206821 DT.100820114

DT.212759 DT.100820116 DT.100820113 DT.101984926 DT.101969416 DT.40246153 DT.75193154 DT.100000871

DT.101960611 DT.101964807 DT.40189222 DT.100805131 DT.92432739 DT.75147786 DT.91849864 DT.102833453

24/284 AceView cDNA sequences (see all 284):

AY312514 AI202695 BG496356 AW613877 AI373225 AW025620 AW195564 AI264097

CB108717 AK091189 BM694251 BQ220579 BQ000605 CK725192 AY243319 BP340588

AK130420 H06012 CB152874 BX486688 AA026694 AI261929 BM674388 BQ679080

GeneLoc Exon Structure

5/20 Alternative Splicing Database (ASD) splice patterns (SP) for NEDD4L (see all 20) About this scheme

ExUns:	1a	·	1b	·	1c	^	2	^	3	^	4	^	5	^	6a	·	6b	^	7a	·	7b	^	8	^	9	^	10	^	11a	·	11b	^	12	^	13	^	14	^	15	^	16	^	17	^	18	^	19a	·	19b	^	20	^
SP1:																	-						-		-		-
SP2:																							-		-
SP3:																							-		-		-
SP4:							-		-		-		-		-		-						-		-		-
SP5:											-		-		-		-						-		-		-

ExUns:	21a	·	21b	^	22a	·	22b	^	23	^	24	^	25a	·	25b	^	26	^	27	^	28	^	29	^	30	^	31	^	32	^	33	^	34	^	35	^	36	^	37a	·	37b	^	38a	·	38b	^	39	^	40a	·	40b	·
SP1:			-		-																-																		-				-
SP2:	-		-		-																-																		-				-
SP3:			-		-																-																		-				-
SP4:			-		-																-																		-				-
SP5:			-		-																-																		-				-

ExUns:	40c	·	40d	·	40e	·	40f
SP1:
SP2:
SP3:
SP4:
SP5:

ECgene alternative splicing isoforms for NEDD4L

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

NEDD4L expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

NEDD4L expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

5 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Gut Tube

Midgut

Midgut Endoderm Cells

Endoderm

Neural Tube

Spinal Neural Tube Cells

Neural Ectoderm

Gut Tube

Kidney

Presumptive Spinal Cord

Spinal Cord

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

Posterior foregut-like cells (A scalable, suspensi...)

See NEDD4L Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for NEDD4L

SOURCE GeneReport for Unigene cluster: Hs.185677

UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5

Tissue specificity: Ubiquitously expressed, with highest levels in prostate, pancreas and kidney

SABiosciences Expression via Pathway-Focused PCR Array including NEDD4L:

Ubiquitin Ligases in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for NEDD4L gene from 8/30 species (see all 30) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	NEDD4L¹	neural precursor cell expressed, developmentally down-regulated more	82.36(n) 94.05(a)		374119 XM_424462.3 XP_424462.3
lizard (Anolis carolinensis)	Reptilia	NEDD4L⁶	--	91(a)	1 ↔ 1	GL343213.1(2569142-2653113)
African clawed frog (Xenopus laevis)	Amphibia	Xl.206²	Xenopus laevis mRNA for Nedd4 protein	79.02(n)		AJ000085.1
zebrafish (Danio rerio)	Actinopterygii	Dr.26117²	Transcribed sequence with moderate similarity to protein more	77.48(n)		CD605190.1
fruit fly (Drosophila melanogaster)	Insecta	Nedd4³	protein ubiquitination ubiquitin-protein ligase	46(a)		--
worm (Caenorhabditis elegans)	Secernentea	Y92H12A.2³	--	47(a)		I(1543634-1555890) --
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	RSP5¹	Rsp5p	51.97(n) 46.6(a)		856862 NP_011051.3
soybean (Glycine max)	eudicotyledons	46766445²	--	69.22(n)

ENSEMBL Gene Tree for NEDD4L (if available)
TreeFam Gene Tree for NEDD4L (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for NEDD4L gene

HECW2² HACE1² WWP2² KIAA0317² SMURF2² HECW1² SMURF1² ITCH²

NEDD4² WWP1²

17 SIMAP similar genes for NEDD4L using alignment to 9 protein entries: NED4L_HUMAN (see all proteins):

DKFZp564H223 HUWE1 SMURF2 UBE3A WWP2 WWP1

NEDD4 WWC2 HECTD1 HECW1 SMURF1 UBE3B

KIAA0317 ITCH HECTD2 HACE1 PLEKHA5

NEDD4L for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 18 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs112593000^1,2	C,	--	55709659(+)	`AATGCGTGTGT/- GTGTG`	3	--	us2k¹		1		CSA	2
rs58187125^1,2	C	--	55709664(+)	`GTGTG-/TGTGTG TGAGA`	3	--	us2k¹		1		NA	2
rs5021419^1,2	C	--	55709676(+)	`gtgtgA/Tgtgtg`	3	--	us2k¹		1		NA	2
rs75390257^1,2	C	--	55709682(+)	`GTGTGA/TGAGAG`	3	--	us2k¹		3		WA CSA	5
rs191954254^1,2		--	55709809(+)	`GGAGTA/GCAGTG`	3	--	us2k¹		0	--	--	--	--
rs141099809^1,2		--	55709838(+)	`GCAACA/CTCCGC`	3	--	us2k¹		0	--	--	--	--
rs72536240^1,2	C,	--	55709966(+)	`GGCCAG/-GCTGG`	3	--	us2k¹		1		CSA	2
rs34088423^1,2	C	--	55709967(+)	`CCAGCG/-TGGTC`	3	--	us2k¹		1		NA	2
rs183868461^1,2		--	55710001(+)	`CGCCCA/GCCTCA`	3	--	us2k¹		0	--	--	--	--
rs187411827^1,2		--	55710129(+)	`ATAGTC/TCTCCA`	3	--	us2k¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for NEDD4L (55711599 - 55961599 bp, first 250kb of NEDD4L)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 15 variations for NEDD4L
7 CNVs: 102680 38373 50014 67370 3169 102679 10533
8 Indels: 26074 102681 11965 42339 45669 61627 26075 67369
Human Gene Mutation Database (HGMD): NEDD4L

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

NEDD4L for disorders           About GeneDecksing

OMIM gene information: 606384    OMIM disorders: --

16 diseases for NEDD4L:    About MalaCards

essential hypertension hypertension orthostatic hypotension liddle syndrome

gallbladder cancer nephropathy aldosteronism prostate cancer

ischemia obesity sarcoma cerebritis

prostatitis immunodeficiency malaria neuronitis

2 diseases from the University of Copenhagen DISEASES database for NEDD4L:

Liddle syndrome Hypertension

3 Novoseek disease relationships for NEDD4L gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
liddles syndrome	90.6	4	19007435 (1), 18691017 (1), 16477034 (1)
essential hypertension	51.8	3	16103266 (2), 18293164 (1)
hypotension orthostatic	30.2	3	16103266 (2)

Genetic Association Database (GAD): NEDD4L
Human Genome Epidemiology (HuGE) Navigator: NEDD4L (13 documents)

Export disorders for NEDD4L gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for NEDD4L gene, integrated from 9 sources (see all 189):
(articles sorted by number of sources associating them with NEDD4L)

Utopia: connect your pdf to the dynamic
world of online information

NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a homologue of the mouse Nedd4-2 gene. (PubMed id 11840194)^{1, 2, 9} Chen H.... McInnis M.G. (2001)
Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK) ubiquitination and degradation. (PubMed id 15576372)^{1, 2, 9} Zhou R. and Snyder P.M. (2005)
cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na(+) channel through convergent phosphorylation of Nedd4- 2. (PubMed id 15328345)^{1, 2, 9} Snyder P.M.... Steines J.C. (2004)
Nedd4-2 isoforms ubiquitinate individual epithelial s odium channel subunits and reduce surface expression and function of the epithe lial sodium channel. (PubMed id 18322022)^{1, 3, 9} Raikwar N.S. and Thomas C.P. (2008)
Association of NEDD4L ubiquitin ligase with essential hypertension. (PubMed id 16103266)^{1, 4, 9} Russo C.J....Baldwin C.T. (2005)
Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel. (PubMed id 11696533)^{1, 2, 9} Snyder P.M.... Thomas B.C. (2002)
Identification of NPC2 protein as interaction molecul e with C2 domain of human Nedd4L. (PubMed id 19664597)^{1, 2, 9} Araki N....Umemura S. (2009)
A naturally occurring human Nedd4-2 variant displays impaired ENaC regulation in Xenopus laevis oocytes. (PubMed id 15140763)^{1, 2, 9} Fouladkou F....Staub O. (2004)
Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B. (PubMed id 12911626)^{1, 2, 9} Boehmer C.... Lang F. (2003)
Androgens differentially regulate the expression of NEDD4L transcripts in LNCaP human prostate cancer cells. (PubMed id 14615060)^{1, 2, 9} Qi H.... Labrie C. (2003)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 23327	HGNC: 7728	AceView: NEDD4L	Ensembl:ENSG00000049759	euGenes: HUgn23327
ECgene: NEDD4L	Kegg: 23327	H-InvDB: NEDD4L

(According to HUGE)
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HUGE: KIAA0439

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for NEDD4L	Pharmacogenomics, SNPs, Pathways

Intellectual Property for NEDD4L gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for NEDD4L gene:
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GeneCards and IP:
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neural precursor cell expressed, developmentally down-regulated...

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