This gene encodes an E3 ubiquitin-ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation. A related pseudogene has been identified on chromosome X. Alternative splicing results in a non-coding transcript... See more...

Aliases for CBLL1 Gene

Aliases for CBLL1 Gene

  • Cbl Proto-Oncogene Like 1 2 3 5
  • RNF188 2 3 4
  • HAKAI 2 3 4
  • Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence-Like 1 2 3
  • Casitas B-Lineage Lymphoma-Transforming Sequence-Like Protein 1 3 4
  • Cbl Proto-Oncogene Like 1, E3 Ubiquitin Protein Ligase 2 3
  • RING-Type E3 Ubiquitin Transferase Hakai 3 4
  • E3 Ubiquitin-Protein Ligase Hakai 3 4
  • RING Finger Protein 188 3 4
  • C-Cbl-Like Protein 1 3 4
  • Cbl Proto-Oncogene-Like 1, E3 Ubiquitin Protein Ligase 2
  • Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase-Like 1 3
  • Casitas B-Lineage Lymphoma-Like 2
  • E-Cadherin Binding Protein E7 3
  • EC 2.3.2.27 4
  • FLJ23109 2
  • EC 6.3.2 50
  • CBLL1 5

External Ids for CBLL1 Gene

Previous GeneCards Identifiers for CBLL1 Gene

  • GC07P106931
  • GC07P106945
  • GC07P106978
  • GC07P107171
  • GC07P107385
  • GC07P101746

Summaries for CBLL1 Gene

Entrez Gene Summary for CBLL1 Gene

  • This gene encodes an E3 ubiquitin-ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation. A related pseudogene has been identified on chromosome X. Alternative splicing results in a non-coding transcript variant. [provided by RefSeq, Aug 2011]

GeneCards Summary for CBLL1 Gene

CBLL1 (Cbl Proto-Oncogene Like 1) is a Protein Coding gene. Diseases associated with CBLL1 include Wilms Tumor 1 and Gastric Cancer, Hereditary Diffuse. Among its related pathways are Remodeling of Adherens Junctions and Listeria monocytogenes entry into host cells. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and ligase activity. An important paralog of this gene is CBLL2.

UniProtKB/Swiss-Prot Summary for CBLL1 Gene

  • E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1 (By similarity). Targets CDH1 for endocytosis and degradation (By similarity). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Its function in the WMM complex is unknown (PubMed:29507755).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CBLL1 Gene

Genomics for CBLL1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CBLL1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CBLL1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CBLL1

Top Transcription factor binding sites by QIAGEN in the CBLL1 gene promoter:
  • AML1a
  • AP-1
  • c-Fos
  • c-Jun
  • CUTL1
  • FosB
  • Fra-1
  • JunB
  • JunD
  • Spz1

Genomic Locations for CBLL1 Gene

Latest Assembly
chr7:107,743,836-107,764,997
(GRCh38/hg38)
Size:
21,162 bases
Orientation:
Plus strand

Previous Assembly
chr7:107,384,587-107,402,112
(GRCh37/hg19 by Entrez Gene)
Size:
17,526 bases
Orientation:
Plus strand

chr7:107,384,142-107,402,112
(GRCh37/hg19 by Ensembl)
Size:
17,971 bases
Orientation:
Plus strand

Genomic View for CBLL1 Gene

Genes around CBLL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CBLL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CBLL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CBLL1 Gene

Proteins for CBLL1 Gene

  • Protein details for CBLL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q75N03-HAKAI_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase Hakai
    Protein Accession:
    Q75N03
    Secondary Accessions:
    • B7ZM03
    • Q8TAJ4
    • Q9H5S6

    Protein attributes for CBLL1 Gene

    Size:
    491 amino acids
    Molecular mass:
    54519 Da
    Quaternary structure:
    • Homodimer (By similarity). Interacts with tyrosine-phosphorylated SRC substrates (By similarity). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29507755). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29507755). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29507755). Also component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3 (PubMed:24100041).

    Alternative splice isoforms for CBLL1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CBLL1 Gene

Selected DME Specific Peptides for CBLL1 Gene

Q75N03:
  • YGRMIPCKHVFCYDCAILHEKKGDKMCPGC
  • HPHHIMPPQQHYAPPPPPPPPISHP
  • GLDVRRRIPIKLISK
  • HPPQAAGTPH
  • SMAPPPPR
  • PVQRIEQC
  • PPYMNHPPPGPPP
  • APPPITPPPGHIIAQ
  • QHVPHEH
  • HSNLITVPIQDDSNSGARE
  • WPAPRGPPP
  • EDQGTLSPPFTQPGGMSPG
  • RGSLFMCSIVQGCKRTYLSQRDLQAHINHRHMRA
  • APPPHHYNP

Post-translational modifications for CBLL1 Gene

Domains & Families for CBLL1 Gene

Gene Families for CBLL1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for CBLL1 Gene

Suggested Antigen Peptide Sequences for CBLL1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ57701, highly similar to Homo sapiens Cas-Br-M (murine) ecotropic retroviral transforming sequence-like 1 (CBLL1), mRNA (B4DDV7_HUMAN)
  • c-Cbl-like protein 1 (HAKAI_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q75N03

UniProtKB/Swiss-Prot:

HAKAI_HUMAN :
  • The HYB domain forms a phosphotyrosine-binding pocket upon dimerization, and mediates as well the recognition of its flanking acidic amino acids.
  • Belongs to the Hakai family.
Domain:
  • The HYB domain forms a phosphotyrosine-binding pocket upon dimerization, and mediates as well the recognition of its flanking acidic amino acids.
Family:
  • Belongs to the Hakai family.
genes like me logo Genes that share domains with CBLL1: view

Function for CBLL1 Gene

Molecular function for CBLL1 Gene

UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1 (By similarity). Targets CDH1 for endocytosis and degradation (By similarity). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Its function in the WMM complex is unknown (PubMed:29507755).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q9JIY2};.

Enzyme Numbers (IUBMB) for CBLL1 Gene

Phenotypes From GWAS Catalog for CBLL1 Gene

Gene Ontology (GO) - Molecular Function for CBLL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity TAS 14996930
GO:0005515 protein binding IPI 11836526
GO:0016740 transferase activity IEA --
GO:0042802 identical protein binding IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with CBLL1: view
genes like me logo Genes that share phenotypes with CBLL1: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CBLL1

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for CBLL1 Gene

Localization for CBLL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CBLL1 Gene

Nucleus speckle. Nucleus, nucleoplasm. Cytoplasm. Note=Mainly nuclear with some fraction located in the cytoplasm. ZC3H13 is required to anchor component of the MACOM subcomplex, such as VIRMA, in the nucleus. {ECO:0000250 UniProtKB:Q9JIY2}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CBLL1 gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 2
cytoskeleton 2
endosome 2
lysosome 2
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear speckles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CBLL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000151 ubiquitin ligase complex IC 14996930
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IEA --
GO:0005737 cytoplasm ISS --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with CBLL1: view

Pathways & Interactions for CBLL1 Gene

genes like me logo Genes that share pathways with CBLL1: view

Pathways by source for CBLL1 Gene

1 Qiagen pathway for CBLL1 Gene
  • Remodeling of Adherens Junctions

UniProtKB/Swiss-Prot Q75N03-HAKAI_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for CBLL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007162 negative regulation of cell adhesion IEA,ISS --
GO:0007275 multicellular organism development IEA --
GO:0016567 protein ubiquitination IEA,TAS 14996930
GO:0030155 regulation of cell adhesion IBA 21873635
GO:0030335 positive regulation of cell migration IEA,ISS --
genes like me logo Genes that share ontologies with CBLL1: view

No data available for SIGNOR curated interactions for CBLL1 Gene

Drugs & Compounds for CBLL1 Gene

No Compound Related Data Available

Transcripts for CBLL1 Gene

mRNA/cDNA for CBLL1 Gene

2 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CBLL1

Alternative Splicing Database (ASD) splice patterns (SP) for CBLL1 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b
SP1: - - -
SP2: - -
SP3:
SP4:
SP5: - -
SP6: -

Relevant External Links for CBLL1 Gene

GeneLoc Exon Structure for
CBLL1

Expression for CBLL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CBLL1 Gene

Protein differential expression in normal tissues from HIPED for CBLL1 Gene

This gene is overexpressed in CD8 Tcells (15.7), Peripheral blood mononuclear cells (13.6), and CD4 Tcells (10.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CBLL1 Gene



Protein tissue co-expression partners for CBLL1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CBLL1

SOURCE GeneReport for Unigene cluster for CBLL1 Gene:

Hs.592271

Evidence on tissue expression from TISSUES for CBLL1 Gene

  • Lung(4.4)
  • Nervous system(4.2)
  • Intestine(2.5)
  • Skin(2.3)
  • Kidney(2.3)
  • Muscle(2.2)
  • Lymph node(2.2)
  • Heart(2)
genes like me logo Genes that share expression patterns with CBLL1: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for CBLL1 Gene

Orthologs for CBLL1 Gene

This gene was present in the common ancestor of animals.

Orthologs for CBLL1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CBLL1 29 30
  • 99.73 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CBLL1 29 30
  • 96.74 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CBLL1 29 30
  • 95.52 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia -- 30
  • 95 (a)
ManyToMany
-- 30
  • 55 (a)
ManyToMany
Rat
(Rattus norvegicus)
Mammalia Cbll1 29
  • 93.85 (n)
Mouse
(Mus musculus)
Mammalia Cbll1 29 16 30
  • 93.75 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 87 (a)
OneToMany
Chicken
(Gallus gallus)
Aves CBLL1 29 30
  • 81.67 (n)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 84 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia cbll1 29
  • 78.67 (n)
Str.16186 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.3484 29
Zebrafish
(Danio rerio)
Actinopterygii cbll1 30
  • 69 (a)
ManyToMany
CU041386.1 30
  • 65 (a)
ManyToMany
LOC100002706 29
  • 64.81 (n)
zgc55308 29
Fruit Fly
(Drosophila melanogaster)
Insecta Hakai 30
  • 23 (a)
OneToMany
Species where no ortholog for CBLL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for CBLL1 Gene

ENSEMBL:
Gene Tree for CBLL1 (if available)
TreeFam:
Gene Tree for CBLL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CBLL1: view image
Alliance of Genome Resources:
Additional Orthologs for CBLL1

Paralogs for CBLL1 Gene

Paralogs for CBLL1 Gene

(1) SIMAP similar genes for CBLL1 Gene using alignment to 6 proteins:

  • HAKAI_HUMAN
  • B7ZM03_HUMAN
  • C9J2P9_HUMAN
  • C9K074_HUMAN
  • F8WEM5_HUMAN
  • L8ECK4_HUMAN

Pseudogenes.org Pseudogenes for CBLL1 Gene

genes like me logo Genes that share paralogs with CBLL1: view

Variants for CBLL1 Gene

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CBLL1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Variation tolerance for CBLL1 Gene

Residual Variation Intolerance Score: 6.08% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.54; 11.62% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CBLL1 Gene

Human Gene Mutation Database (HGMD)
CBLL1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CBLL1
Leiden Open Variation Database (LOVD)
CBLL1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot , Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP and Structural Variations from Database of Genomic Variants (DGV) for CBLL1 Gene

Disorders for CBLL1 Gene

MalaCards: The human disease database

(2) MalaCards diseases for CBLL1 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
wilms tumor 1
  • wt1
gastric cancer, hereditary diffuse
  • hdgc
- elite association - COSMIC cancer census association via MalaCards
Search CBLL1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CBLL1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CBLL1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CBLL1 Gene

Publications for CBLL1 Gene

  1. VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. (PMID: 29507755) Yue Y … Liu J (Cell discovery 2018) 3 4
  2. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 40
  3. The DNA sequence of human chromosome 7. (PMID: 12853948) Hillier LW … Wilson RK (Nature 2003) 3 4
  4. E-cadherin and Hakai: signalling, remodeling or destruction? (PMID: 11944035) Pece S … Gutkind JS (Nature cell biology 2002) 2 3
  5. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. (PMID: 11836526) Fujita Y … Birchmeier W (Nature cell biology 2002) 2 3

Products for CBLL1 Gene

Sources for CBLL1 Gene