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CBLL1 Cbl proto-oncogene like 1 [ Homo sapiens (human) ]

Gene ID: 79872, updated on 2-Nov-2024

Summary

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Official Symbol
CBLL1provided by HGNC
Official Full Name
Cbl proto-oncogene like 1provided by HGNC
Primary source
HGNC:HGNC:21225
See related
Ensembl:ENSG00000105879 MIM:606872; AllianceGenome:HGNC:21225
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HAKAI; RNF188
Summary
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]
Expression
Ubiquitous expression in colon (RPKM 9.2), testis (RPKM 4.9) and 25 other tissues See more
Orthologs
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Genomic context

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See CBLL1 in Genome Data Viewer
Location:
7q22.3
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (107744142..107761667)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (109062577..109080102)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (107384587..107402112)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene BANF1 pseudogene 5 Neighboring gene SLC26A4 antisense RNA 1 Neighboring gene MPRA-validated peak6681 silencer Neighboring gene solute carrier family 26 member 4 Neighboring gene Sharpr-MPRA regulatory region 3291 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:107383176-107383695 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:107383696-107384214 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26495 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26496 Neighboring gene CBLL1 antisense RNA 1 Neighboring gene solute carrier family 26 member 3 Neighboring gene GFI1 motif-containing MPRA enhancer 278 Neighboring gene phosphatidylinositol glycan anchor biosynthesis class C pseudogene 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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

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Related articles in PubMed

  1. E3 ubiquitin ligase Hakai regulates cell growth and invasion, and increases the chemosensitivity to cisplatin in non‑small‑cell lung cancer cells. Liu Z, et al. Int J Mol Med, 2018 Aug. PMID 29786107
  2. Stratification of Colorectal Patients Based on Survival Analysis Shows the Value of Consensus Molecular Subtypes and Reveals the CBLL1 Gene as a Biomarker of CMS2 Tumours. Alfonsín G, et al. Int J Mol Sci, 2024 Feb 5. PMID 38339195, Free PMC Article
  3. CBLL1 is hypomethylated and correlates with cortical thickness in transgender men before gender affirming hormone treatment. Fernández R, et al. Sci Rep, 2023 Dec 7. PMID 38062063, Free PMC Article
  4. E-cadherin and Hakai: signalling, remodeling or destruction? Pece S, et al. Nat Cell Biol, 2002 Apr. PMID 11944035
  5. Newest findings on the oldest oncogene; how activated src does it. Frame MC. J Cell Sci, 2004 Mar 1. PMID 14996930

See all (68) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion.
    Title: CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion.
  2. Stratification of Colorectal Patients Based on Survival Analysis Shows the Value of Consensus Molecular Subtypes and Reveals the CBLL1 Gene as a Biomarker of CMS2 Tumours.
    Title: Stratification of Colorectal Patients Based on Survival Analysis Shows the Value of Consensus Molecular Subtypes and Reveals the CBLL1 Gene as a Biomarker of CMS2 Tumours.
  3. CBLL1 is hypomethylated and correlates with cortical thickness in transgender men before gender affirming hormone treatment.
    Title: CBLL1 is hypomethylated and correlates with cortical thickness in transgender men before gender affirming hormone treatment.
  4. Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease.
    Title: Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease.
  5. Downregulation of long non-coding RNA XIST inhibits cell proliferation, migration, invasion and EMT by regulating miR-212-3p/CBLL1 axis in non-small cell lung cancer cells.
    Title: Downregulation of long non-coding RNA XIST inhibits cell proliferation, migration, invasion and EMT by regulating miR-212-3p/CBLL1 axis in non-small cell lung cancer cells.
  6. Study have demonstrated that CBLL1 is highly expressed in non-small lung cancer (NSCLC) cancer tissues compared with corresponding normal lung tissues, and correlated with tumor size. Moreover, CBLL1 promotes the cell proliferation by inducing the G0/G1-S transition and cell invasion by increasing degradation of extracellular matrices of NSCLC cells.
    Title: CBLL1 is highly expressed in non-small cell lung cancer and promotes cell proliferation and invasion.
  7. we have detected the presence of micrometastasis in the lung mice, further confirming Hakai role during tumour metastasis in vivo. These results lead to the consideration of Hakai as a potential new therapeutic target to block tumour development and metastasis
    Title: Hakai overexpression effectively induces tumour progression and metastasis in vivo.
  8. The present study demonstrated for the first time that knockdown of Hakai inhibited the proliferation, migration and invasion of nonsmallcell lung cancer cells, and sensitized nonsmallcell lung cancer cells to cisplatin.
    Title: E3 ubiquitin ligase Hakai regulates cell growth and invasion, and increases the chemosensitivity to cisplatin in non‑small‑cell lung cancer cells.
  9. findings suggest that the E3 ubiquitin-ligase, such as Hakai, may be a better target than proteasome for using novel specific inhibitors in tumor subtypes that follow EMT.
    Title: Proteomic Analysis of the E3 Ubiquitin-Ligase Hakai Highlights a Role in Plasticity of the Cytoskeleton Dynamics and in the Proteasome System.
  10. These results suggest that stabilization of delta-catenin by Hakai is dependent on Src.
    Title: Hakai, an E3-ligase for E-cadherin, stabilizes δ-catenin through Src kinase.
Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ23109, MGC163401, MGC163403

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables identical protein binding IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin-protein transferase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell-cell adhesion IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in mRNA processing IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of cell adhesion ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of cell migration ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of endocytosis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein ubiquitination IEA
Inferred from Electronic Annotation
more info
  
involved_in protein ubiquitination TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of cell adhesion IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
part_of RNA N6-methyladenosine methyltransferase complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of RNA N6-methyladenosine methyltransferase complex IPI
Inferred from Physical Interaction
more info
 PubMed 
located_in cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nuclear speck IDA
Inferred from Direct Assay
more info
  
located_in nucleus NAS
Non-traceable Author Statement
more info
 PubMed 
part_of ubiquitin ligase complex IC
Inferred by Curator
more info
 PubMed 

General protein information

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Preferred Names
E3 ubiquitin-protein ligase Hakai
Names
Cas-Br-M (murine) ecotropic retroviral transforming sequence-like 1
Cbl proto-oncogene like 1, E3 ubiquitin protein ligase
Cbl proto-oncogene, E3 ubiquitin protein ligase-like 1
E-cadherin binding protein E7
RING finger protein 188
RING-type E3 ubiquitin transferase Hakai
c-Cbl-like protein 1
casitas B-lineage lymphoma-transforming sequence-like protein 1
NP_001271220.1
NP_079090.2
XP_011514882.1
XP_016868132.1
XP_024302704.1
XP_024302705.1
XP_024302706.1
XP_047276811.1
XP_054215022.1
XP_054215023.1
XP_054215024.1
XP_054215025.1
XP_054215026.1
XP_054215027.1

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

  1. NM_001284291.2 → NP_001271220.1  E3 ubiquitin-protein ligase Hakai isoform 2

    See identical proteins and their annotated locations for NP_001271220.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region. The encoded isoform (2) is shorter than isoform (1).
    Source sequence(s)
    AC002467, AI055864, BC144176
    Consensus CDS
    CCDS64754.1
    UniProtKB/TrEMBL
    A0A8V8TMY5
    Related
    ENSP00000222597.2, ENST00000222597.7
    Conserved Domains (1) summary
    cd16508
    Location:106 → 147
    RING-HC_HAKAI_like; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins

  2. NM_024814.4 → NP_079090.2  E3 ubiquitin-protein ligase Hakai isoform 1

    See identical proteins and their annotated locations for NP_079090.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AC002467, AI055864, BC130529
    Consensus CDS
    CCDS5747.1
    UniProtKB/Swiss-Prot
    B7ZM03, Q75N03, Q8TAJ4, Q9H5S6
    UniProtKB/TrEMBL
    A0A8V8TMY5
    Related
    ENSP00000401277.2, ENST00000440859.8
    Conserved Domains (1) summary
    cd16508
    Location:107 → 148
    RING-HC_HAKAI_like; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins

RNA

  1. NR_024199.3 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) includes an alternate exon which introduces a stop codon and renders the transcript a candidate for nonsense-mediated decay (NMD).
    Source sequence(s)
    AC002467, AI055864, DB033469

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    107744142..107761667
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017012643.2 → XP_016868132.1  E3 ubiquitin-protein ligase Hakai isoform X1

    UniProtKB/TrEMBL
    A0A8V8TMY5
    Conserved Domains (2) summary
    cd16508
    Location:147 → 188
    RING-HC_HAKAI_like; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins
    pfam18408
    Location:201 → 232
    zf_Hakai; C2H2 Hakai zinc finger domain

  2. XM_047420855.1 → XP_047276811.1  E3 ubiquitin-protein ligase Hakai isoform X2

  3. XM_024446936.2 → XP_024302704.1  E3 ubiquitin-protein ligase Hakai isoform X3

    UniProtKB/TrEMBL
    A0A8V8TMY5
    Conserved Domains (1) summary
    cd16508
    Location:57 → 98
    RING-HC_HAKAI_like; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins

  4. XM_024446938.2 → XP_024302706.1  E3 ubiquitin-protein ligase Hakai isoform X3

    UniProtKB/TrEMBL
    A0A8V8TMY5
    Conserved Domains (1) summary
    cd16508
    Location:57 → 98
    RING-HC_HAKAI_like; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins

  5. XM_024446937.2 → XP_024302705.1  E3 ubiquitin-protein ligase Hakai isoform X3

    UniProtKB/TrEMBL
    A0A8V8TMY5
    Conserved Domains (1) summary
    cd16508
    Location:57 → 98
    RING-HC_HAKAI_like; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Hakai, zinc finger protein 645 (ZNF645), and similar proteins

  6. XM_011516580.4 → XP_011514882.1  E3 ubiquitin-protein ligase Hakai isoform X4

    See identical proteins and their annotated locations for XP_011514882.1

    UniProtKB/TrEMBL
    B4DDV7
    Conserved Domains (1) summary
    pfam13923
    Location:1 → 27
    zf-C3HC4_2; Zinc finger, C3HC4 type (RING finger)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    109062577..109080102
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054359047.1 → XP_054215022.1  E3 ubiquitin-protein ligase Hakai isoform X1

  2. XM_054359048.1 → XP_054215023.1  E3 ubiquitin-protein ligase Hakai isoform X2

  3. XM_054359049.1 → XP_054215024.1  E3 ubiquitin-protein ligase Hakai isoform X3

  4. XM_054359051.1 → XP_054215026.1  E3 ubiquitin-protein ligase Hakai isoform X3

  5. XM_054359050.1 → XP_054215025.1  E3 ubiquitin-protein ligase Hakai isoform X3

  6. XM_054359052.1 → XP_054215027.1  E3 ubiquitin-protein ligase Hakai isoform X4

    UniProtKB/TrEMBL
    B4DDV7
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q75N03.1 GenPept UniProtKB/Swiss-Prot:Q75N03

Gene LinkOut

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