Alternative titles; symbolsC1q- AND TUMOR NECROSIS FACTOR-RELATED PROTEIN 10; C1QTNF10CTRP10HGNC Approved Gene Symbol: C1QL2Cytogenetic location: 2q14.2 Geno...
Alternative titles; symbols
HGNC Approved Gene Symbol: C1QL2
Cytogenetic location: 2q14.2 Genomic coordinates (GRCh38): 2:119,156,242-119,158,750 (from NCBI)
C1QL2 belongs to a large family of multimeric secreted proteins with a signature globular domain homologous to C1QA (120550). These proteins also share structural homology with TNF (191160) family members. C1QL2 forms homotrimers and higher-order oligomers (Wong et al., 2008).
▼ Cloning and Expression
By searching databases with the globular C1q domain of adiponectin (ADIPOQ; 605441), Wong et al. (2008) identified mouse and human C1QL2, which they termed CTRP10. The predicted 287-amino acid human protein contains a signal peptide, followed by a short N-terminal variable region, a collagen domain with 15 gly-X-Y repeats, and a C-terminal globular domain homologous to C1Q. Mouse and human CTRP10 share 81%, 100%, and 100% identity in their N-terminal variable regions, collagen domains, and C-terminal globular domains, respectively. Real-time PCR analysis of mouse tissues revealed highest Ctrp10 expression in eye, followed by placenta and brain. Limited expression was detected in adipose tissue, with lower expression still in lymph node and testis, and no detectable expression in other tissues examined. Expression levels of Ctrp10 were slightly higher in male compared with female mice, in contrast to adiponectin, which is expressed at much higher levels in female mice. Expression of Ctrp10 was significantly higher in stromal cells than in adipocytes in adipose tissues. Immunoblot analysis confirmed the predicted lack of N-linked glycosylation sites in CTRP10, which was expressed as a 37-kD glycoprotein with carbohydrate moieties localized to the N-terminal variable region.
Bolliger et al. (2011) stated that all 4 mammalian C1QL proteins have the same domain structure, consisting of an N-terminal signal peptide, followed by a short cysteine loop domain, a central collagen-like sequence, and a C-terminal globular C1q (gC1q) domain. Biochemical analyses showed that all 4 mouse C1ql proteins formed higher-order oligomers via interactions within their gC1q domains and/or their collagenous and cysteine loop domains.
Using quantitative RT-PCR, Martinelli et al. (2016) showed that C1ql3 (615227) was broadly expressed in mouse brain, including in all cortical areas tested. C1ql1 (611586) was detected at low levels in most mouse brain regions examined except hindbrain, whereas C1ql2 was only expressed at high levels in hippocampus.
▼ Gene Function
Wong et al. (2008) found that human CTRP10 formed trimers and higher-order oligomers that required its N-terminal cys residues. They observed higher expression of Ctrp10 in obese (ob/ob) mice than in age-matched controls at 8 weeks of age, but no significant differences in expression were observed at 12 weeks of age.
By immunoprecipitation analysis, Bolliger et al. (2011) showed that all mouse C1ql proteins interacted with human BAI3 (602684). The interactions required divalent cations, most likely Ca(2+). Binding was mediated by the gC1q domains of the C1ql proteins and the thrombospondin repeats of BAI3. Treatment of cultured mouse primary hippocampal neurons with recombinant gC1q domains of C1ql proteins decreased synapse density, but did not alter overall neuron size, dendrite length, or dendritic branching.
Martinelli et al. (2016) showed that expression of C1ql genes promoted excitatory synapse density in cultured mouse neurons, whereas knockdown decreased it and prevented increased synaptogenesis.
▼ Gene Structure
Wong et al. (2008) determined that the CTRP10 gene spans 2.65 kb and contains 2 exons.
Wong et al. (2008) stated that the CTRP10 gene maps to chromosome 2q14.2.