ITCH - itchy E3 ubiquitin protein ligase Gene

Homo sapiens

Also known as AIF4; AIP4; ADMFD; NAPP1

Gene ID: 83737 | Gene type: protein coding

About ITCH

Cytogenetic location: 20q11.22 Genomic coordinates (GRCh38): 20:34,363,273-34,511,773 (from NCBI)

This gene has 19 transcripts (splice variants), 285 orthologues, 24 paralogues and is associated with 3 phenotypes. Ubiquitous expression in testis (RPKM 12.7), esophagus (RPKM 11.6) 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 plays a role in multiple cellular processes including erythroid and lymphoid cell differentiation and the regulation of immune responses. Mutations in this gene are a cause of syndromic multisystem autoimmune disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

ITCH Products(5)

mRNA	Protein	Name
NM_001257137.3	NP_001244066.1	E3 ubiquitin-protein ligase Itchy homolog isoform 1
NM_001257138.3	NP_001244067.1	E3 ubiquitin-protein ligase Itchy homolog isoform 3
NM_001324197.2	NP_001311126.1	E3 ubiquitin-protein ligase Itchy homolog isoform 1
NM_001324198.2	NP_001311127.1	E3 ubiquitin-protein ligase Itchy homolog isoform 2
NM_031483.7	NP_113671.3	E3 ubiquitin-protein ligase Itchy homolog isoform 2

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	Reference	Source
enables CXCR chemokine receptor binding	IPI IPI: Inferred from physical interaction	19116316	GOA
enables arrestin family protein binding	IPI IPI: Inferred from physical interaction	23886940	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	9647693	GOA
enables ribonucleoprotein complex binding	IPI IPI: Inferred from physical interaction	19881509	GOA
enables ubiquitin protein ligase activity	IDA IDA: Inferred from direct assay	15678106	GOA
enables ubiquitin protein ligase activity	IMP IMP: Inferred from mutant phenotype	15051726	GOA
enables ubiquitin-like protein ligase binding	IPI IPI: Inferred from physical interaction	24790097	GOA
enables ubiquitin-protein transferase activity	EXP EXP: Inferred from Experiment	34999730	GOA
enables ubiquitin-ubiquitin ligase activity	IDA IDA: Inferred from direct assay	29378950	GOA

Biological Process GO Annotation	Evidence	Reference	Source
involved in negative regulation of apoptotic process	IMP IMP: Inferred from mutant phenotype	20068034	GOA
involved in negative regulation of cytoplasmic pattern recognition receptor signaling pathway	IDA IDA: Inferred from direct assay	27736772	GOA
involved in negative regulation of defense response to virus	IMP IMP: Inferred from mutant phenotype	19881509	GOA
involved in positive regulation of receptor catabolic process	IMP IMP: Inferred from mutant phenotype	24790097	GOA
involved in proteasome-mediated ubiquitin-dependent protein catabolic process	IDA IDA: Inferred from direct assay	29378950	GOA
involved in proteasome-mediated ubiquitin-dependent protein catabolic process	IMP IMP: Inferred from mutant phenotype	22009753	GOA
involved in protein K29-linked ubiquitination	IDA IDA: Inferred from direct assay	17028573	GOA
involved in protein K48-linked ubiquitination	IDA IDA: Inferred from direct assay	19881509	GOA
involved in protein K63-linked ubiquitination	IDA IDA: Inferred from direct assay	18718448	GOA
involved in protein autoubiquitination	IMP IMP: Inferred from mutant phenotype	24790097	GOA
involved in protein branched polyubiquitination	IDA IDA: Inferred from direct assay	29378950	GOA
involved in protein monoubiquitination	IDA IDA: Inferred from direct assay	34927784	GOA
involved in protein ubiquitination	IDA IDA: Inferred from direct assay	17592138	GOA
involved in protein ubiquitination	IMP IMP: Inferred from mutant phenotype	24790097	GOA
involved in receptor internalization	IMP IMP: Inferred from mutant phenotype	34927784	GOA
acts upstream of or within ubiquitin-dependent protein catabolic process	IDA IDA: Inferred from direct assay	15678106	GOA
involved in ubiquitin-dependent protein catabolic process	IMP IMP: Inferred from mutant phenotype	22009753	GOA

Cellular Component GO Annotation	Evidence	Reference	Source
located in cytoplasmic vesicle	IDA IDA: Inferred from direct assay	22009753	GOA
colocalizes with early endosome	IDA IDA: Inferred from direct assay	24790097	GOA
is active in plasma membrane	IDA IDA: Inferred from direct assay	34927784	GOA
located in plasma membrane	IDA IDA: Inferred from direct assay	14602072	GOA
part of protein-containing complex	IDA IDA: Inferred from direct assay	24790097	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

ITCH Protein Structure

HECT

0
200
400
600
800
903 a.a.

Protein Preferred Names

Protein Names

E3 ubiquitin-protein ligase Itchy homolog

HECT-type E3 ubiquitin transferase Itchy homolog

ITCH Protein-protein interaction Information

Type Cross Intra	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	Reference
Intra	ITCH	Q96J02	TTYH3	Homo sapiens	Q9C0H2	Phage Display	37219487
Intra	ITCH	Q96J02	CYLD	Homo sapiens	Q9NQC7	Anti Tag CoIP	22057290
Intra	ITCH	Q96J02	TP63	Homo sapiens	Q9H3D4	Anti Bait CoIP	16908849
Intra	ITCH	Q96J02	ARRDC1	Homo sapiens	Q8N5I2	Y2H	23236378
Intra	ITCH	Q96J02	MLANA	Homo sapiens	Q16655	Phage Display	37219487
Intra	ITCH	Q96J02	SGK3	Homo sapiens	Q96BR1	IF	16888620
Intra	ITCH	Q96J02	SGK3	Homo sapiens	Q96BR1	Pull Down	16888620
Intra	ITCH	Q96J02	GLI1	Homo sapiens	P08151	Pull Down	20818436
Intra	ITCH	Q96J02	PI4K2A	Homo sapiens	Q9BTU6	IF	23146885
Intra	ITCH	Q96J02	PI4K2A	Homo sapiens	Q9BTU6	Pull Down	23146885
Intra	ITCH	Q96J02	TP73	Homo sapiens	O15350	Anti Bait CoIP	15678106
Intra	ITCH	Q96J02	TP73	Homo sapiens	O15350	Phage Display	37219487
Intra	ITCH	Q96J02	TP73	Homo sapiens	O15350	Pull Down	17592138
Intra	ITCH	Q96J02	TP73	Homo sapiens	O15350-1	Pull Down	15678106
Intra	ITCH	Q96J02	TP73	Homo sapiens	O15350-1	Anti Tag CoIP	15678106
Intra	ITCH	Q96J02	RNF11	Homo sapiens	Q9Y3C5	Anti Tag CoIP	20676133
Cross	ITCH	Q96J02	M	Isfahan virus	Q5K2K5	Phage Display	37100772
Intra	ITCH	Q96J02	N4BP1	Homo sapiens	O75113	Pull Down	17592138
Intra	ITCH	Q96J02	N4BP1	Homo sapiens	O75113	Anti Tag CoIP	17592138
Intra	ITCH	Q96J02	TP73	Homo sapiens	O15350-8	Anti Tag CoIP	15678106
Intra	ITCH	Q96J02	TMEM51	Homo sapiens	Q9NW97	Phage Display	37219487
Intra	ITCH	Q96J02	TP53BP2	Homo sapiens	Q13625	Anti Bait CoIP	25436413
Intra	ITCH	Q96J02	SNX9	Homo sapiens	Q9Y5X1	Anti Tag CoIP	20491914
Intra	ITCH	Q96J02	ENTREP1	Homo sapiens	Q15884	Y2H	34927784
Cross	ITCH	Q96J02	VP40	Sudan ebolavirus	Q5XX06	Phage Display	37100772
Cross	ITCH	Q96J02	VP40	Lake Victoria marburgvirus	Q6UY67	Phage Display	37100772
Cross	ITCH	Q96J02	VP40	Lake Victoria marburgvirus	Q1PDC8	Phage Display	37100772
Cross	ITCH	Q96J02	VP40	Lake Victoria marburgvirus	Q1PD51	Phage Display	37100772
Cross	ITCH	Q96J02	VP40	Lake Victoria marburgvirus	Q03040	Phage Display	37100772
Cross	ITCH	Q96J02	VP40	Lake Victoria marburgvirus	P35260	Phage Display	37100772
Cross	ITCH	Q96J02	M	Vesicular stomatitis Indiana virus	Q8B0I2	Phage Display	37100772
Cross	ITCH	Q96J02	M	Vesicular stomatitis Indiana virus	Q8B0H7	Phage Display	37100772
Cross	ITCH	Q96J02	M	Vesicular stomatitis Indiana virus	Q8B0H2	Phage Display	37100772
Cross	ITCH	Q96J02	M	Vesicular stomatitis Indiana virus	P04876	Phage Display	37100772
Cross	ITCH	Q96J02	M	Vesicular stomatitis Indiana virus	P03519	Phage Display	37100772

Cross: Cross-species interaction Intra: Intraspecies interaction

Recombinant ITCH Proteins

Cat. No.	Product Name	Accession	Purity
HY-P75894	ITCH/AIP4 Protein, Human (solution)	NP_113671.3 (N-G&P, R485-E862)	≥95%
HY-P75894A	ITCH/AIP4 Protein, Human	Q96J02-2/NP_113671.3 (R485-E862)	≥95%

Related Diseases

Diseases

Alias

Autoimmune Disease, Multisystem, With Facial Dysmorphism

Syndromic Multisystem Autoimmune Disease Due To Itch Deficiency	ADMFD
Syndromic Multisystem Autoimmune Disease

Itch E3 Ubiquitin Ligase Deficiency

Autoimmune Disease, Syndromic Multisystem

Syndromic Multisystem Autoimmune Disease

Autoimmune Disease

Autoimmune Diseases	Autoimmune Hypersensitivity Disease
Hypersensitivity Reaction Type Ii Disease	Type Ii Hypersensitivity Reaction Disease

Influenza

Flu	Influenza With Non-Respiratory Manifestation
Influenza With Other Manifestations	Influenza, Human
Influenza, Susceptibility To	Seasonal Influenza, Virus Identified

Immunodeficiency 58

IMD58	Severe Combined Immunodeficiency Due To Carmil2 Deficiency
Combined Immunodeficiency Due To Carmil2 Deficiency	Combined Immunodeficiency Due To Rltpr Deficiency

Spastic Paraplegia 20, Autosomal Recessive

Troyer Syndrome	SPG20
Spastic Paraparesis, Childhood-Onset, With Distal Muscle Wasting	Spastic Paraplegia, Autosomal Recessive, Troyer Type
Autosomal Recessive Spastic Paraplegia Type 20	Autosomal Recessive Hereditary Spastic Paraplegia
Spastic Paraplegia 20	Cross-Mckusick Syndrome
Autosomal Recessive Spastic Paraplegia 20	Autosomal Recessive Spastic Paraplegia Troyer Type
Childhood-Onset Spastic Paraparesis With Distal Muscle Wasting	Hereditary Spastic Paraplegia 20
Spastic Paraplegia Type 20	Hereditary Spastic Paraplegia
Childhood-Onset Spastic Paraparesis-Distal Muscle Wasting Syndrome	Spastic Paraparesis Childhood-Onset With Distal Muscle Wasting
Spastic Paraplegia Autosomal Recessive Troyer Type	Trs
Spastic Paraplegia Hereditary Autosomal Recessive	Spastic Paraplegia, Hereditary

Ectodermal Dysplasia

Congenital Ectodermal Defect	Congenital Ectodermal Dysplasia
Ectodermal Dysplasia Syndrome	Dysplasia, Ectodermal

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

Approval

Bioactive Molecules (3)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-B0548A	Hydroxyzine dihydrochloride	Antagonist	99.81%	Unkown
HY-B1183	Hydrocortisone acetate	Agonist	99.14%	Yes
HY-B0548	Hydroxyzine	Antagonist	99.60%	Unkown

Inhibitory Antibodies (2)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-P99025	Lebrikizumab	Inhibitor	99.90%	Unkown
HY-P99162	Nemolizumab	Inhibitor	/	Unkown

Clinical Phase

Bioactive Molecules (2)

Cat. No.	Product Name	Effect	Purity	Phase
HY-106566	Alclometasone dipropionate		≥96.0%	Phase 2
HY-14939	Vapitadine		/	Phase 2

Pre-clinical Phase

Bioactive Molecules (26)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-129047	Trypsin	Activator	/	Unkown
HY-103368	Eact	Activator	98.14%	Unkown
HY-148244	MS47134		99.88%	Unkown
HY-118069	(R)-ZINC-3573	Agonist	99.81%	Unkown
HY-103320A	Calhex 231 hydrochloride	Inhibitor	99.81%	Unkown
HY-147051	MRGPRX4 modulator-2		99.64%	Unkown
HY-129047A	Trypsin (MS grade)	Activator	95.00%	Unkown
HY-145997	MRGPRX4 modulator-1		99.09%	Unkown
HY-136642	Fluocinolone		99.66%	Yes
HY-148949	Kallikrein 5-IN-2		98.69%	Unkown
HY-B1144A	Chlormidazole hydrochloride	Inhibitor	98.98%	Unkown
HY-103320B	(1R,2R)-Calhex 231 hydrochloride		99.07%	Unkown
HY-145153	S-777469	Agonist	98.83%	Unkown
HY-108425	AMG8379	Antagonist	/	Unkown
HY-108425B	(Rac)-AMG8379	Antagonist	/	Unkown
HY-103320	Calhex 231	Antagonist	/	Unkown
HY-108425A	AMG8380	Antagonist	/	Unkown
HY-124356	Alcaftadine carboxylic acid		/	Unkown
HY-135495	AM-0466	Inhibitor	/	Unkown
HY-143481	Nav1.8-IN-2	Inhibitor	/	Unkown
HY-157496	EP3 antagonist 7	Antagonist	/	Unkown
HY-163840	GFRα2/3-IN-1		/	Unkown
HY-P1192	GR-73632	Agonist	99.98%	Unkown
HY-P5357	SFNGGP-NH2		/	Unkown
HY-RS06943	ITCH Human Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown
HY-N12040	γ-Isofagarine		/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Canis familiaris	ITCH	VGNC	VGNC:42117
Macaca mulatta	ITCH	VGNC	VGNC:73589
Rattus norvegicus	ITCH	RGD	RGD:1359556
Bos taurus	ITCH	VGNC	VGNC:30307
Mus musculus	ITCH	MGD	MGI:1202301
Felis catus	ITCH	VGNC	VGNC:80122
Others	ITCH	NCBI

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