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

Summary

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: mouse all
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Genomic context

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_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D7S756 (e-PCR)
- UniSTS:23374

NoName (e-PCR)
- UniSTS:489946

STS-N34389 (e-PCR)
- UniSTS:42734

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

EC 2.3.2.27

NP_079090.2

EC 2.3.2.27

XP_011514882.1

EC 2.3.2.27

XP_016868132.1

EC 2.3.2.27

XP_024302704.1

EC 2.3.2.27

XP_024302705.1

EC 2.3.2.27

XP_024302706.1

EC 2.3.2.27

XP_047276811.1

EC 2.3.2.27

XP_054215022.1

EC 2.3.2.27

XP_054215023.1

EC 2.3.2.27

XP_054215024.1

EC 2.3.2.27

XP_054215025.1

EC 2.3.2.27

XP_054215026.1

EC 2.3.2.27

XP_054215027.1

EC 2.3.2.27

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)

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
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

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

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

107744142..107761667

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_060931.1 Alternate T2T-CHM13v2.0

Range

109062577..109080102

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054359047.1 → XP_054215022.1 E3 ubiquitin-protein ligase Hakai isoform X1
XM_054359048.1 → XP_054215023.1 E3 ubiquitin-protein ligase Hakai isoform X2
XM_054359049.1 → XP_054215024.1 E3 ubiquitin-protein ligase Hakai isoform X3
XM_054359051.1 → XP_054215026.1 E3 ubiquitin-protein ligase Hakai isoform X3
XM_054359050.1 → XP_054215025.1 E3 ubiquitin-protein ligase Hakai isoform X3
XM_054359052.1 → XP_054215027.1 E3 ubiquitin-protein ligase Hakai isoform X4

UniProtKB/TrEMBL

B4DDV7