MultifacetedProtDB - Bologna Biocomputing Group

EC number	EC number description
2.3.2.26	Transferases; Acyltransferases; Aminoacyltransferases; HECT-type E3 ubiquitin transferase
2.3.2.36	Transferases; Acyltransferases; Aminoacyltransferases; RING-type E3 ubiquitin transferase (cysteine targeting)

Structure

PDB	Resolution (Å)	PDB name
2LAJ		Third WW domain of human Nedd4L in complex with doubly phosphorylated human smad3 derived peptide
2LB2		Structure of the second domain of human Nedd4L in complex with a phosphorylated pTPY motif derived from human Smad3
2LTY		NEDD4L WW2 domain in complex with a Smad7 derived peptide
2MPT		WW3 domain of Nedd4L in complex with its HECT domain PY motif
2NSQ	1.85	Crystal structure of the C2 domain of the human E3 ubiquitin-protein ligase NEDD4-like protein
2ONI	2.2	Catalytic Domain of the Human NEDD4-like E3 Ligase
3JVZ	3.3	E2~Ubiquitin-HECT
3JW0	3.1	E2~Ubiquitin-HECT
5HPK	2.431	System-wide modulation of HECT E3 ligases with selective ubiquitin variant probes: NEDD4L and UbV NL.1
6ZBT	1.79949	Structure of 14-3-3 gamma in complex with Nedd4-2 14-3-3 binding motif Ser342
6ZC9	1.89896	Structure of 14-3-3 gamma in complex with Nedd4-2 14-3-3 binding motif Ser448
7LP1	1.35	Structure of Nedd4L WW3 domain
7LP2	1.88	Structure of Nedd4L WW3 domain
7LP3	1.61	Structure of Nedd4L WW3 domain
7LP4		Structure of Nedd4L WW3 domain
7LP5		Structure of Nedd4L WW3 domain
7NMZ	2.303	Structure of 14-3-3 eta in complex with Nedd4-2(335-455) containing two 14-3-3 binding motifs Ser342 and Ser448

GO term

GO ontology	GO term	GO description
Biological Process	GO:0030154	cell differentiation
Biological Process	GO:0034220	monoatomic ion transmembrane transport
Biological Process	GO:1901380	negative regulation of potassium ion transmembrane transport
Biological Process	GO:1901017	negative regulation of potassium ion transmembrane transporter activity
Biological Process	GO:2000009	negative regulation of protein localization to cell surface
Biological Process	GO:1902306	negative regulation of sodium ion transmembrane transport
Biological Process	GO:2000650	negative regulation of sodium ion transmembrane transporter activity
Biological Process	GO:2001288	positive regulation of caveolin-mediated endocytosis
Biological Process	GO:1903861	positive regulation of dendrite extension
Biological Process	GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process	GO:0070936	protein K48-linked ubiquitination
Biological Process	GO:0016567	protein ubiquitination
Biological Process	GO:0048814	regulation of dendrite morphogenesis
Biological Process	GO:0003254	regulation of membrane depolarization
Biological Process	GO:0042391	regulation of membrane potential
Biological Process	GO:0060306	regulation of membrane repolarization
Biological Process	GO:0034765	regulation of monoatomic ion transmembrane transport
Biological Process	GO:1901016	regulation of potassium ion transmembrane transporter activity
Biological Process	GO:0031647	regulation of protein stability
Biological Process	GO:1902305	regulation of sodium ion transmembrane transport
Biological Process	GO:0006511	ubiquitin-dependent protein catabolic process
Biological Process	GO:0086005	ventricular cardiac muscle cell action potential
Molecular Function	GO:0019870	potassium channel inhibitor activity
Molecular Function	GO:0015459	potassium channel regulator activity
Molecular Function	GO:0019871	sodium channel inhibitor activity
Molecular Function	GO:0017080	sodium channel regulator activity
Molecular Function	GO:0044325	transmembrane transporter binding
Molecular Function	GO:0061630	ubiquitin protein ligase activity
Molecular Function	GO:0004842	ubiquitin-protein transferase activity
Cellular Component	GO:0005794	Golgi apparatus
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0070062	extracellular exosome
Cellular Component	GO:0005771	multivesicular body
Cellular Component	GO:0005654	nucleoplasm

InterPro / Pfam

InterPro	InterPro name
IPR000008	C2 domain
IPR000569	HECT domain
IPR001202	WW domain
IPR024928	E3 ubiquitin-protein ligase, SMURF1 type
IPR035892	C2 domain superfamily
IPR035983	HECT, E3 ligase catalytic domain
IPR036020	WW domain superfamily

Pfam	Pfam name
PF00168	C2 domain
PF00397	WW domain
PF00632	HECT-domain (ubiquitin-transferase)

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-162588	Budding and maturation of HIV virion	Leaf	R-HSA-1643685	Disease
R-HSA-2173788	Downregulation of TGF-beta receptor signaling	Leaf	R-HSA-162582	Signal Transduction
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity	Leaf	R-HSA-74160	Gene expression (Transcription)
R-HSA-2672351	Stimuli-sensing channels	Internal node	R-HSA-382551	Transport of small molecules
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation	Leaf	R-HSA-168256	Immune System

Subcellular location

Location	ECO term	Pubmed
Cytoplasm	ECO:0000269	PubMed:15496141
Cytoplasm	ECO:0000269	PubMed:18819914
Cytoplasm	ECO:0000269	PubMed:27694961
Endosome, multivesicular body	ECO:0000269	PubMed:26363003
Golgi apparatus	ECO:0000269	PubMed:26363003

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000201	Pierre-Robin sequence
HP:0000268	Dolichocephaly
HP:0000276	Long face
HP:0000308	Microretrognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000463	Anteverted nares
HP:0000490	Deeply set eye
HP:0000520	Proptosis
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000666	Horizontal nystagmus
HP:0000678	Dental crowding
HP:0000750	Delayed speech and language development
HP:0000963	Thin skin
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001629	Ventricular septal defect
HP:0001643	Patent ductus arteriosus
HP:0001654	Abnormal heart valve morphology
HP:0001659	Aortic regurgitation
HP:0001762	Talipes equinovarus
HP:0001892	Abnormal bleeding
HP:0002020	Gastroesophageal reflux
HP:0002021	Pyloric stenosis
HP:0002079	Hypoplasia of the corpus callosum
HP:0002121	Generalized non-motor (absence) seizure
HP:0002126	Polymicrogyria
HP:0002188	Delayed CNS myelination
HP:0002190	Choroid plexus cyst
HP:0002194	Delayed gross motor development
HP:0002282	Gray matter heterotopia
HP:0002521	Hypsarrhythmia
HP:0002539	Cortical dysplasia
HP:0002650	Scoliosis
HP:0002999	Patellar dislocation
HP:0003196	Short nose
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003834	Shoulder dislocation
HP:0004209	Clinodactyly of the 5th finger
HP:0004691	2-3 toe syndactyly
HP:0004942	Aortic aneurysm
HP:0006380	Knee flexion contracture
HP:0007165	Periventricular heterotopia
HP:0007359	Focal-onset seizure
HP:0008936	Axial hypotonia
HP:0009471	Contracture of the proximal interphalangeal joint of the 3rd finger
HP:0009540	Contracture of the proximal interphalangeal joint of the 2nd finger
HP:0010705	4-5 finger syndactyly
HP:0010712	1-4 toe syndactyly
HP:0011968	Feeding difficulties
HP:0012469	Infantile spasms
HP:0012639	Abnormal nervous system morphology
HP:0020049	Exodeviation
HP:0032388	Periventricular nodular heterotopia
HP:0032988	Persistent head lag
HP:0034391	Elbow contracture
HP:0100704	Cerebral visual impairment
HP:0100790	Hernia

Tissue and cell type

Tissue	Cell type	Expression level	Reliability
adrenal gland	glandular cells	Low	Approved
appendix	glandular cells	Medium	Approved
appendix	lymphoid tissue	Low	Approved
breast	glandular cells	Low	Approved
bronchus	respiratory epithelial cells	Medium	Approved
cerebral cortex	neuronal cells	Medium	Approved
cervix	glandular cells	Medium	Approved
colon	glandular cells	Medium	Approved
colon	peripheral nerve/ganglion	Medium	Approved
duodenum	glandular cells	Medium	Approved
endometrium 1	glandular cells	Low	Approved
endometrium 2	glandular cells	Medium	Approved
epididymis	glandular cells	Low	Approved
fallopian tube	glandular cells	Medium	Approved
gallbladder	glandular cells	Medium	Approved
heart muscle	cardiomyocytes	Low	Approved
kidney	cells in tubules	Medium	Approved
lung	macrophages	Low	Approved
lymph node	germinal center cells	Low	Approved
nasopharynx	respiratory epithelial cells	Low	Approved
ovary	follicle cells	Low	Approved
pancreas	exocrine glandular cells	Medium	Approved
placenta	decidual cells	Medium	Approved
placenta	trophoblastic cells	Medium	Approved
prostate	glandular cells	Medium	Approved
rectum	glandular cells	Medium	Approved
seminal vesicle	glandular cells	Medium	Approved
small intestine	glandular cells	Medium	Approved
stomach 1	glandular cells	Medium	Approved
stomach 2	glandular cells	Medium	Approved
thyroid gland	glandular cells	Medium	Approved
tonsil	germinal center cells	Low	Approved
tonsil	squamous epithelial cells	Low	Approved
urinary bladder	urothelial cells	Low	Approved

Summary of Q96PU5

Gene: NEDD4L, KIAA0439, NEDL3
Protein: E3 ubiquitin-protein ligase NEDD4-like

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of Q96PU5

Gene: NEDD4L, KIAA0439, NEDL3 Protein: E3 ubiquitin-protein ligase NEDD4-like

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: NEDD4L, KIAA0439, NEDL3
Protein: E3 ubiquitin-protein ligase NEDD4-like