NEDD4L - NEDD4 like E3 ubiquitin protein ligase Gene

Also Known as RSP5; PVNH7; NEDD4-2; NEDD4.2; hNEDD4-2

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 23327

About NEDD4L

Cytogenetic location: 18q21.31 Genomic coordinates (GRCh38): 18:58,044,226-58,401,540 (from NCBI)

This gene has 62 transcripts (splice variants), 202 orthologues, 24 paralogues and is associated with 3 phenotypes. Broad expression in prostate (RPKM 13.1), kidney (RPKM 13.0) and 25 other tissues.

Summary

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]

NEDD4L Products (10)

mRNA	Protein	Name
NM_001144964.1	NP_001138436.1	E3 ubiquitin-protein ligase NEDD4-like isoform 2
NM_001144965.2	NP_001138437.1	E3 ubiquitin-protein ligase NEDD4-like isoform 2
NM_001144966.3	NP_001138438.1	E3 ubiquitin-protein ligase NEDD4-like isoform 2
NM_001144967.3	NP_001138439.1	E3 ubiquitin-protein ligase NEDD4-like isoform 1
NM_001144968.2	NP_001138440.1	E3 ubiquitin-protein ligase NEDD4-like isoform 4
NM_001144969.2	NP_001138441.1	E3 ubiquitin-protein ligase NEDD4-like isoform 5
NM_001144970.3	NP_001138442.1	E3 ubiquitin-protein ligase NEDD4-like isoform 6
NM_001144971.2	NP_001138443.1	E3 ubiquitin-protein ligase NEDD4-like isoform 6
NM_001243960.2	NP_001230889.1	E3 ubiquitin-protein ligase NEDD4-like isoform 7
NM_015277.6	NP_056092.2	E3 ubiquitin-protein ligase NEDD4-like isoform 3

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables potassium channel inhibitor activity	IDA IDA: Inferred from direct assay	21463633	GOA
enables potassium channel regulator activity	IDA IDA: Inferred from direct assay	17289006	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	11244092	GOA
enables sodium channel inhibitor activity	IDA IDA: Inferred from direct assay	15217910	GOA
enables sodium channel regulator activity	IDA IDA: Inferred from direct assay	11244092	GOA
enables transmembrane transporter binding	IPI IPI: Inferred from physical interaction	15217910	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in negative regulation of potassium ion transmembrane transport	IDA IDA: Inferred from direct assay	21463633	GOA
involved in negative regulation of potassium ion transmembrane transporter activity	IDA IDA: Inferred from direct assay	21463633	GOA
involved in negative regulation of protein localization to cell surface	IDA IDA: Inferred from direct assay	21463633	GOA
involved in negative regulation of sodium ion transmembrane transport	IDA IDA: Inferred from direct assay	15217910	GOA
involved in negative regulation of sodium ion transmembrane transporter activity	IDA IDA: Inferred from direct assay	15217910	GOA
involved in positive regulation of dendrite extension	IDA IDA: Inferred from direct assay	23999003	GOA
involved in proteasome-mediated ubiquitin-dependent protein catabolic process	IDA IDA: Inferred from direct assay	21463633	GOA
involved in protein K48-linked ubiquitination	IDA IDA: Inferred from direct assay	21463633	GOA
involved in protein ubiquitination	IDA IDA: Inferred from direct assay	15217910	GOA
involved in protein ubiquitination	IMP IMP: Inferred from mutant phenotype	27445338	GOA
involved in regulation of membrane depolarization	IDA IDA: Inferred from direct assay	15217910	GOA
involved in regulation of membrane potential	IDA IDA: Inferred from direct assay	17289006	GOA
involved in regulation of membrane repolarization	IDA IDA: Inferred from direct assay	21463633	GOA
involved in regulation of monoatomic ion transmembrane transport	IDA IDA: Inferred from direct assay	17289006	GOA
involved in regulation of potassium ion transmembrane transporter activity	IDA IDA: Inferred from direct assay	17289006	GOA
involved in regulation of protein stability	IMP IMP: Inferred from mutant phenotype	27445338	GOA
involved in regulation of sodium ion transmembrane transport	IDA IDA: Inferred from direct assay	11244092	GOA
involved in ubiquitin-dependent protein catabolic process	IDA IDA: Inferred from direct assay	21463633	GOA

Cellular Component GO Annotation	Evidence	References	Source
colocalizes with plasma membrane	IDA IDA: Inferred from direct assay	22879586	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

NEDD4L Protein Structure

HECT

0
200
400
600
800
975 a.a.

Protein Preferred Names	Protein Names
E3 ubiquitin-protein ligase NEDD4-like	HECT-type E3 ubiquitin transferase NED4L

NEDD4L Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	NEDD4L	Q96PU5	YWHAE	Homo sapiens	P62258	Crosslink	36931259
Intra	NEDD4L	Q96PU5	DAZAP2	Homo sapiens	Q15038	Validated Y2H	25416956
Intra	NEDD4L	Q96PU5	ENTREP1	Homo sapiens	Q15884	Y2H	34927784

Cross: Cross-species interaction Intra: Intraspecies interaction

NEDD4L Antibodies

Cat. No.	Product Name	Application	Reactivity
HY-P82765	NEDD4 Antibody (YA2510)	WB, IP	Human, Mouse, Rat
HY-P82765A	NEDD4 Antibody (YA2510)(PBS only)	WB, IP	Human, Mouse, Rat
HY-P86985	NEDD4L Antibody (YA6678)	WB, IP	Human

Related Diseases

Diseases	Alias
Periventricular Nodular Heterotopia 7	PVNH7
Periventricular Nodular Heterotopia	Periventricular Heterotopia Pvnh Familial Nodular Heterotopia Heterotopia, Periventricular Periventricular Heterotopia, X-Linked
Liddle Syndrome 1	Liddle Syndrome Pseudoaldosteronism Liddle'S Syndrome LIDLS1 Lidls Pseudohyperaldosteronism Pseudoprimary Hyperaldosteronism Pseudohyperaldosteronism Type 1 Liddles Syndrome
Hypertension, Essential	Essential Hypertension Hypertension High Blood Pressure Hypertension, Essential, Susceptibility To Hypertensive Disease Primary Hypertension EHT Hypertension, Salt-Sensitive Essential, Susceptibility To Hyperpiesia Idiopathic Hypertension Hypertensive Disorder Hypertension, Essential, Susceptibility To, 3 Hypertension, Essential 3 Hypertension, Essential, Salt-Sensitive Hypertension, Essential, Susceptibility To, 6 Hypertension, Essential 6 Hypertension, Salt-Sensitive Essential Hypertension, Susceptibility To Hypertension, Essential, Susceptibility To, 4 Hypertension, Essential 4 Hypertension, Essential, Susceptibility To, 2 Hypertension, Essential 2 Hypertension, Essential, Susceptibility To, 1 Hypertension, Essential 1 Hypertension, Essential, Susceptibility To, 5 Hypertension, Essential 5 Htn Vascular Hypertensive Disorder Systemic Primary Arterial Hypertension Hbp - [High Blood Pressure] Systemic Arterial Hypertensive Disorder Elevated Blood Pressure Arterial Hypertension Nos Hypertension Nos Benign Hypertension Systemic Arterial Hypertension Systemic Hypertension Artery Htn Benign Htn Vascular Htn Vascular Hypertension Cholesterol Hypertension Cholesterol Htn Idiopathic Htn Malignant Hypertension Malignant Htn Raised Blood Pressure Cardiovascular Hypertension Primary Htn - [Hypertension] High Arterial Tension High Blood Pressure Disorder Ht - [Hypertension] Htn - [Hypertension] Hypertensive Vascular Disease Hypertensive Vascular Degeneration
Long Qt Syndrome	Romano-Ward Syndrome Long Q-T Syndrome Lqt Qt Syndrome, Long Congenital Long Qt Syndrome Familial Long Qt Syndrome
Dyslexia
Brugada Syndrome	Sudden Unexpected Nocturnal Death Syndrome Sudden Unexplained Nocturnal Death Syndrome Bangungut Brugada Type Idiopathic Ventricular Fibrillation Pokkuri Death Syndrome Sunds Idiopathic Ventricular Fibrillation, Brugada Type Sudden Unexplained Death Dream Disease Right Bundle Branch Block, St Segment Elevation, And Sudden Death Syndrome Sudden Unexplained Death Syndrome Suds Sunds - [Sudden Unexplained Nocturnal Death Syndrome]
Pure Autonomic Failure	Orthostatic Hypotension Idiopathic Orthostatic Hypotension Postural Hypotension Bradbury-Eggleston Syndrome Bradbury Eggleston Syndrome Hypotension, Orthostatic Hypotension, Postural Paf Pure Dysautonomia Pure Idiopatic Dysautonomia Hypotension Orthostatic Primary Orthostatic Hypotension Chronic Orthostatic Hypotension
Renal Tubular Transport Disease	Renal Tubular Transport, Inborn Errors Inborn Renal Tubular Transport Disorder
Pseudohypoaldosteronism, Type I, Autosomal Recessive	Autosomal Recessive Pseudohypoaldosteronism Type 1 PHA1B Pseudohypoaldosteronism Type 1 Pseudohypoaldosteronism, Type I Generalized Pha1 Generalized Pseudohypoaldosteronism Type 1 Pseudohypoaldosteronism Type 1 Autosomal Recessive Pha1 Pseudohypoaldosteronism Pha I, Autosomal Recessive Autosomal Recessive Pha 1 Pseudohypoaldosteronism Type 1, Recessive Pseudohypoaldosteronism Type I Autosomal Recessive Pha1 Pha Type 1 Pseudohypoaldosteronism 1, Autosomal Recessive Multisystem Pseudohypoaldosteronism Pha Type I, Autosomal Recessive Pseudohypoaldosteronism Type I, Autosomal Recessive
Conn'S Syndrome	Cushing Syndrome Hyperaldosteronism Primary Hyperaldosteronism Hypercortisolism Primary Aldosteronism Cushing'S Syndrome Adrenal Gland Hyperfunction Conn Syndrome Hyperadrenalism Ectopic Acth Syndrome Hyperadrenocorticism Cushing Disease Cushing'S Disease Adrenal Cortex Adenoma Corticotroph Pituitary Adenoma Pituitary Corticotroph Micro-Adenoma Pituitary-Dependent Cushing Syndrome Pituitary Acth Hypersecretion Acth Syndrome, Ectopic Acth-Secreting Pituitary Adenoma Adrenal Hyperfunction Resulting From Pituitary Acth Excess Ectopic Adrenocorticotropic Hormone Syndrome Nodular Primary Adrenocortical Dysplasia Pituitary Dependent Cushing Syndrome Pituitary Cushing Syndrome Pituitary-Dependant Cushing Syndrome Pituitary-Dependant Hypercortisolism Pituitary-Dependant Hypercortisolism Disorder Aldosteronism Primary Acth Syndrome Ectopic Adrenal Cushing'S Syndrome Adrenal Cortical Adenoma Cushing Syndrome Nos Cortisol Hypersecretion Corticoadrenal Hypersecretion Cushing Syndrome Secondary To Ectopic Acth-Secretion Ectopic Cushing Syndrome Hypercortisolism Due To Nonpituitary Tumour Ectopic Acth - [Adrenocorticotropic Hormone] Secretion Ectopic Acth - [Adrenocorticotropic Hormone] Secretion Causing Cushing Syndrome Idiopathic Aldosteronism Aldosteronism Primary Aldosteronism Due To Bilateral Adrenal Hyperplasia Primary Aldosteronism Due To Adrenal Hyperplasia

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (3)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-RS09180	NEDD4L Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS17116	Nedd4l Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS23561	Nedd4l Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Felis catus	NEDD4L	VGNC	VGNC:68450
Rattus norvegicus	NEDD4L	RGD	RGD:735047
Bos taurus	NEDD4L	VGNC	VGNC:31983
Macaca mulatta	NEDD4L	VGNC	VGNC:75303
Mus musculus	NEDD4L	MGD	MGI:1933754
Canis familiaris	NEDD4L	VGNC	VGNC:43721
Others	NEDD4L	NCBI