CAND2 Gene (Cullin-Associated and Neddylation-Dissociated 2)

A key regulator of cullin-RING ubiquitin ligase (CRL) assembly and activity, involved in cell cycle control and tumorigenesis.

Gene Information Card

Symbol CAND2
Full Name Cullin-Associated and Neddylation-Dissociated 2
Gene Type Protein coding
Chromosomal Location 3p24.3
NCBI Gene ID 23066 ncbi.nlm.nih.gov/gene/23066
Ensembl ID ENSG00000144713
UniProt ID Q9H6Q4
OMIM ID 611745
HGNC ID 30689
Aliases TIP120B, TIP120B, CAND2, FLJ10324

Description

CAND2 (cullin-associated and neddylation-dissociated 2) encodes a protein that binds to cullin-RING ubiquitin ligase (CRL) complexes, inhibiting their activity by preventing neddylation and substrate recruitment. It plays a role in cell cycle progression, DNA damage response, and is implicated in various cancers. The gene is located on chromosome 3p24.3 and is expressed in multiple tissues.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Breast cancer CAND2 overexpression may disrupt CRL-mediated degradation of cell cycle regulators, promoting proliferation. COSMIC; PMID: 25691885
Colorectal cancer Mutations in CAND2 have been identified in tumor samples, potentially altering CRL assembly and contributing to genomic instability. COSMIC; PMID: 26691986
Lung cancer Altered CAND2 expression correlates with poor prognosis; functional studies suggest role in modulating p53 pathway via CRL. ClinVar; PMID: 28270531

Expression Profile

Tissue Expression
Tissue nTPM level
Testis 12.5 Medium
Brain 8.3 Low
Lung 6.1 Low
Liver 4.7 Low
Kidney 5.9 Low
Cell Line Expression
Cell Line nTPM Notes
HEK293 10.2 Embryonic kidney cell line
HeLa 8.9 Cervical cancer cell line
A549 7.4 Lung carcinoma cell line
MCF7 6.8 Breast cancer cell line
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1234C>T (p.Arg412*) Nonsense 0.02% (COSMIC) Loss of function; truncated protein unable to bind cullins
c.567G>A (p.Gly189Arg) Missense 0.01% (ClinVar) Unknown; predicted damaging by SIFT
c.2101_2102insA Frameshift 0.005% (COSMIC) Loss of function; premature stop codon
Mutation functional classification

Loss of Function (LOF)

Nonsense and frameshift mutations lead to truncated CAND2 protein, impairing its ability to regulate CRL neddylation and substrate degradation.

Gain of Function (GOF)

No confirmed gain-of-function mutations reported in curated databases.

Dominant Negative (DN)

Missense mutations in the cullin-binding domain may produce a dominant-negative effect by sequestering cullins without functional regulation.

Pathways

• hsa04120: Ubiquitin mediated proteolysis
• hsa04110: Cell cycle
• hsa05200: Pathways in cancer

Protein Summary

The CAND2 protein (UniProt Q9H6Q4) is a 120 kDa protein that contains a conserved cullin-binding domain. It binds to unneddylated cullins, preventing their association with the E2 ubiquitin-conjugating enzyme and thereby inhibiting CRL activity. This regulation is critical for proper cell cycle progression and DNA repair. CAND2 is widely expressed, with highest levels in testis. Mutations in CAND2 are associated with loss of function in cancer, and its expression is altered in several tumor types.

Related Products

Product name Cat.No. Species Gene ID
CAND2 Knockout HEK293 Cell Line EDJ-KQ7806 Human 23066 Details Get a Quote
CAND2 Knockout A-549 Cell Line EDJ-KQ33325 Human 23066 Details Get a Quote
CAND2 Knockout HeLa Cell Line EDJ-KQ55682 Human 23066 Details Get a Quote
CAND2 Knockout HCT 116 Cell Line EDJ-KQ72623 Human 23066 Details Get a Quote
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