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ITCH itchy E3 ubiquitin protein ligase [ Homo sapiens (human) ]

Gene ID: 83737, updated on 1-Aug-2020

Summary

Official Symbol
ITCHprovided by HGNC
Official Full Name
itchy E3 ubiquitin protein ligaseprovided by HGNC
Primary source
HGNC:HGNC:13890
See related
Ensembl:ENSG00000078747 MIM:606409
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AIF4; AIP4; ADMFD; NAPP1
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]
Expression
Ubiquitous expression in testis (RPKM 12.7), esophagus (RPKM 11.6) and 25 other tissues See more
Orthologs

Genomic context

See ITCH in Genome Data Viewer
Location:
20q11.22
Exon count:
31
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 20 NC_000020.11 (34363273..34511773)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (32951041..33099198)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene agouti signaling protein Neighboring gene exportin for tRNA pseudogene 1 Neighboring gene density regulated re-initiation and release factor pseudogene Neighboring gene adenosylhomocysteinase Neighboring gene uncharacterized LOC107985381 Neighboring gene cell division cycle 42 pseudogene 1 Neighboring gene microRNA 644a Neighboring gene ferredoxin 1 pseudogene 1 Neighboring gene dynein light chain roadblock-type 1 Neighboring gene microtubule associated protein 1 light chain 3 alpha

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Nef nef HIV-1 Nef co-localizes with CXCR4, AIP4, NEDD4, CD63/LAMP-1-positive vesicles, and HRS/VPS27-positive ESCRT-0 structures in HeLa cells PubMed
nef The Lys residues (K327/331/333) in the C-terminal tail of CXCR4 and the catalytic Cys830 in the HECT domain of AIP4 are critically required for HIV-1 Nef-mediated downregulation of CXCR4 PubMed
nef HIV-1 Nef dramatically enhances the binding of AIP4 with CXCR4 and alanine substitutions at positions Q297 and N329 of AIP4 eliminate this binding PubMed
nef HIV-1 Nef-mediated CXCR4 downregulation is dependent on ubiquitinylation, which is mediated by the E3 ubiquitin ligase AIP4 PubMed
nef HIV-1 Nef co-localizes with E3 ubiquitin ligases AIP4 and NEDD4. HIV-1 Nef induced degradation of GNAI2 involves AIP4 and NEDD4 through recruitment of AIP4 and NEDD4 by Nef PubMed
Vif vif HIV-1 Vif, through amino acids 20-128, binds to the WW domains of hNedd4 and AIP4, two HECT E3 ubiquitin ligases PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CXCR chemokine receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
arrestin family protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ribonucleoprotein complex binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin protein ligase activity TAS
Traceable Author Statement
more info
 
ubiquitin-like protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin-protein transferase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
ubiquitin-protein transferase activity NAS
Non-traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
Notch signaling pathway TAS
Traceable Author Statement
more info
 
apoptotic process IEA
Inferred from Electronic Annotation
more info
 
defense response to virus IEA
Inferred from Electronic Annotation
more info
 
inflammatory response NAS
Non-traceable Author Statement
more info
PubMed 
innate immune response IEA
Inferred from Electronic Annotation
more info
 
negative regulation of JNK cascade ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of NF-kappaB transcription factor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of defense response to virus IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of type I interferon production TAS
Traceable Author Statement
more info
 
nucleotide-binding oligomerization domain containing signaling pathway TAS
Traceable Author Statement
more info
 
positive regulation of protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of receptor catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
proteasome-mediated ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein K29-linked ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein K29-linked ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein K48-linked ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein K48-linked ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein K63-linked ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein K63-linked ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein autoubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein polyubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein ubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of cell growth NAS
Non-traceable Author Statement
more info
PubMed 
regulation of hematopoietic stem cell differentiation TAS
Traceable Author Statement
more info
 
regulation of protein deubiquitination ISS
Inferred from Sequence or Structural Similarity
more info
 
ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
ubiquitin-dependent protein catabolic process NAS
Non-traceable Author Statement
more info
PubMed 
viral entry into host cell TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
colocalizes_with early endosome IDA
Inferred from Direct Assay
more info
PubMed 
early endosome membrane IEA
Inferred from Electronic Annotation
more info
 
extracellular exosome HDA PubMed 
intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
 
membrane HDA PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
E3 ubiquitin-protein ligase Itchy homolog
Names
HECT-type E3 ubiquitin transferase Itchy homolog
NFE2-associated polypeptide 1
atrophin-1 interacting protein 4
itchy E3 ubiquitin protein ligase homolog
NP_001244066.1
NP_001244067.1
NP_001311126.1
NP_001311127.1
NP_113671.3
XP_005260627.1
XP_011527381.1
XP_016883578.1
XP_016883579.1
XP_016883580.1
XP_016883581.1
XP_024307773.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_023206.1 RefSeqGene

    Range
    4980..153137
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_354

mRNA and Protein(s)

  1. NM_001257137.3NP_001244066.1  E3 ubiquitin-protein ligase Itchy homolog isoform 1

    See identical proteins and their annotated locations for NP_001244066.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1). Both variants 1 and 4 encode the same isoform (1).
    Source sequence(s)
    AA730741, AL109923, AL356299, AL705688, BC011571, BG928040
    Consensus CDS
    CCDS58768.1
    UniProtKB/Swiss-Prot
    Q96J02
    Related
    ENSP00000262650.5, ENST00000262650.10
    Conserved Domains (3) summary
    cd04021
    Location:17140
    C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase
    COG5021
    Location:359903
    HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]
    pfam00397
    Location:328357
    WW; WW domain
  2. NM_001257138.3NP_001244067.1  E3 ubiquitin-protein ligase Itchy homolog isoform 3

    See identical proteins and their annotated locations for NP_001244067.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks two internal exons and initiates translation at a downstream, in-frame start codon, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AA730741, AF038564, AK304090, AL109923, AL356299, AL705688, BG928040
    Consensus CDS
    CCDS58769.1
    UniProtKB/Swiss-Prot
    Q96J02
    Related
    ENSP00000445608.1, ENST00000535650.7
    Conserved Domains (3) summary
    COG5021
    Location:208752
    HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]
    pfam00397
    Location:177206
    WW; WW domain
    cl14603
    Location:130
    C2; C2 domain
  3. NM_001324197.2NP_001311126.1  E3 ubiquitin-protein ligase Itchy homolog isoform 1

    Status: REVIEWED

    Source sequence(s)
    AL109923, AL356299, BG928040
    Consensus CDS
    CCDS58768.1
    UniProtKB/Swiss-Prot
    Q96J02
    Related
    ENSP00000499786.1, ENST00000665346.1
    Conserved Domains (3) summary
    cd04021
    Location:17140
    C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase
    COG5021
    Location:359903
    HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]
    pfam00397
    Location:328357
    WW; WW domain
  4. NM_001324198.2NP_001311127.1  E3 ubiquitin-protein ligase Itchy homolog isoform 2

    Status: REVIEWED

    Source sequence(s)
    AL109923, AL356299, BG928040
    Consensus CDS
    CCDS13234.1
    UniProtKB/Swiss-Prot
    Q96J02
    Related
    ENSP00000499685.1, ENST00000660337.1
    Conserved Domains (3) summary
    cd04021
    Location:17140
    C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase
    COG5021
    Location:318862
    HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]
    pfam00397
    Location:287316
    WW; WW domain
  5. NM_031483.7NP_113671.3  E3 ubiquitin-protein ligase Itchy homolog isoform 2

    See identical proteins and their annotated locations for NP_113671.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1. Both variants 2 and 5 encode the same isoform (2).
    Source sequence(s)
    AA730741, AK315212, AL109923, AL356299, AL705688, BG928040
    Consensus CDS
    CCDS13234.1
    UniProtKB/Swiss-Prot
    Q96J02
    Related
    ENSP00000363998.4, ENST00000374864.9
    Conserved Domains (3) summary
    cd04021
    Location:17140
    C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase
    COG5021
    Location:318862
    HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]
    pfam00397
    Location:287316
    WW; WW domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20200522

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p13 Primary Assembly

    Range
    34363273..34511773
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017028090.1XP_016883579.1  E3 ubiquitin-protein ligase Itchy homolog isoform X2

    Related
    ENSP00000499526.1, ENST00000670516.1
  2. XM_005260570.1XP_005260627.1  E3 ubiquitin-protein ligase Itchy homolog isoform X4

    Conserved Domains (2) summary
    COG5021
    Location:148692
    HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]
    pfam00397
    Location:117146
    WW; WW domain
  3. XM_017028091.1XP_016883580.1  E3 ubiquitin-protein ligase Itchy homolog isoform X3

    UniProtKB/Swiss-Prot
    Q96J02
    Conserved Domains (3) summary
    COG5021
    Location:208752
    HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]
    pfam00397
    Location:177206
    WW; WW domain
    cl14603
    Location:130
    C2; C2 domain
  4. XM_017028092.2XP_016883581.1  E3 ubiquitin-protein ligase Itchy homolog isoform X6

  5. XM_024452005.1XP_024307773.1  E3 ubiquitin-protein ligase Itchy homolog isoform X1

    Conserved Domains (3) summary
    cd04021
    Location:17140
    C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase
    COG5021
    Location:359903
    HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]
    pfam00397
    Location:328357
    WW; WW domain
  6. XM_017028089.1XP_016883578.1  E3 ubiquitin-protein ligase Itchy homolog isoform X1

    UniProtKB/Swiss-Prot
    Q96J02
    Conserved Domains (3) summary
    cd04021
    Location:17140
    C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase
    COG5021
    Location:359903
    HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]
    pfam00397
    Location:328357
    WW; WW domain
  7. XM_011529079.1XP_011527381.1  E3 ubiquitin-protein ligase Itchy homolog isoform X5

    Conserved Domains (4) summary
    smart00456
    Location:268299
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:361689
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00078
    Location:337690
    HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
    pfam00397
    Location:229258
    WW; WW domain

RNA

  1. XR_001754418.1 RNA Sequence

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