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

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-103320A	Calhex 231 hydrochloride	Inhibitor	99.81%	Unkown
HY-118069	(R)-ZINC-3573	Agonist	99.81%	Unkown
HY-147051	MRGPRX4 modulator-2		99.64%	Unkown
HY-145997	MRGPRX4 modulator-1		99.09%	Unkown
HY-129047A	Trypsin (MS grade)	Activator	95.00%	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-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-124356	Alcaftadine carboxylic acid		/	Unkown
HY-135495	AM-0466		/	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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