C1QL1

C1QL1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4D7Y, 4QQ2
Identifiers
Aliases	C1QL1, C1QRF, C1QTNF14, CRF, complement component 1, q subcomponent-like 1, complement C1q like 1, CTRP14
External IDs	OMIM: 611586 MGI: 1344400 HomoloGene: 4867 GeneCards: C1QL1
Gene location (Human) Chr. Chromosome 17 (human) Band 17q21.31 Start 44,959,693 bp End 44,968,303 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 E1 Start 102,830,090 bp End 102,837,514 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in amygdala hypothalamus nucleus accumbens hippocampus proper prefrontal cortex caudate nucleus dorsolateral prefrontal cortex substantia nigra Brodmann area 9 ganglionic eminence Top expressed in inferior olivary nucleus corpus callosum submandibular gland optic nerve cochlear nuclei superior frontal gyrus morula adrenal gland internal capsule ventral tegmental area More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding signaling receptor binding molecular function Cellular component cytoplasm extracellular region collagen climbing fiber presynapse synaptic cleft cellular component Biological process locomotory behavior maintenance of synapse structure neuron remodeling motor learning Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10882 23829 Ensembl ENSG00000131094 ENSMUSG00000045532 UniProt O75973 O88992 RefSeq (mRNA) NM_006688 NM_011795 RefSeq (protein) NP_006679 NP_035925 Location (UCSC) Chr 17: 44.96 – 44.97 Mb Chr 11: 102.83 – 102.84 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

The complement component 1, q subcomponent-like 1 (or C1QL1) is encoded by a gene located at chromosome 17q21.31. It is a secreted protein and is 258 amino acids in length. The protein is widely expressed but its expression is highest in the brain and may also be involved in regulation of motor control. The pre-mRNA of this protein is subject to RNA editing.

Protein function

Its physiological function is unknown. It is a member of the C1Q domain proteins which have important signalling roles in inflammation and in adaptive immunity.

RNA editing

Editing type

The pre-mRNA of this protein is subject to A to I RNA editing, which is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cell's translational machinery. There are three members of the ADAR family: ADARs 1-3, with ADAR 1 and ADAR 2 being the only enzymatically active members. ADAR 3 is thought to have a regulatory role in the brain. ADAR 1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain. The double-stranded regions of RNA are formed by base-pairing between residues in a region complementary to the region of the editing site. This complementary region is usually found in a neighbouring intron but can also be located in an exonic sequence. The region that pairs with the editing region is known as an Editing Complementary Sequence (ECS).

Editing sites

The candidate editing sites were determined experimentally by comparison of cDNA sequences and genomically encoded DNA from the same individual to avoid single nucleotide polymorphisms (SNPs). Two of the three editing sites found in mouse gene were found in the human transcript. However, only the Q/R site was detected in all RNA, with the T/A site detected just once. Both sites are found within exon 1.

Q/R site

This site is found in exon 1 at position 66. Editing results in a codon change from a Glutamine codon to an Arginine codon.

T/A site

This site is also found in exon 1, at position 63. It was only detected in one genomic sample indicating that the edited residue may be an SNP. However, the secondary structure of the RNA is predicted, around the editing site, to be highly conserved in mice and humans. This indicates that the T/A site may still be shown to be a site of A to I RNA editing. Editing at this site would result in an amino acid change from a Threonine to an Alanine.

The ECS is also predicted to be found within exon 1 at a location 5' to the editing region.

Editing regulation

Editing is differentially expressed in the cerebellum and cortex. This regulation is also present in mice suggesting conservation of editing regulation. No editing has been detected in human lung, heart, kidney or spleen tissue.

Evolutionary conservation

The sequence of exon 1 is highly conserved in mammalian species and editing of the pre-mRNA of this protein is likely to occur in mice, rat, dog and cow as well as humans. Even though the ECS is not conserved in non-mammals, an alternative ECS has been predicted in Zebrafish with a similar structure but in a different location. The Ecs is found downstream of the editing sites.

Effects on Protein structure

These predicted editing sites result in the translation of an Arginine instead of a Glutamine at the Q/R site and an Alanine instead of a Threonine at the T/A site. These codon changes are nonsynomonous. Since the editing sites are located just before a collagen like trimerization domain, editing may effect protein oligomerization. This region is also likely to be a protease domain. It is not known if the amino acid changes caused by editing could have an effect on these domains.

Further reading

• Sie CP, Maas S (2009). "Conserved recoding RNA editing of vertebrate C1q-related factor C1QL1". FEBS Lett. 583 (7): 1171–4. doi:10.1016/j.febslet.2009.02.044. PMID 19275900. S2CID 33286445.
• Davila S, Froeling FE, Tan A, et al. (2010). "New genetic associations detected in a host response study to hepatitis B vaccine". Genes Immun. 11 (3): 232–8. doi:10.1038/gene.2010.1. PMID 20237496. S2CID 11183658.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Bérubé NG, Swanson XH, Bertram MJ, et al. (1999). "Cloning and characterization of CRF, a novel C1q-related factor, expressed in areas of the brain involved in motor function". Brain Res. Mol. Brain Res. 63 (2): 233–40. doi:10.1016/S0169-328X(98)00278-2. PMID 9878755.

External links

• DARNED (DAtabase of RNa EDiting in humans)
• Human C1QL1 genome location and C1QL1 gene details page in the UCSC Genome Browser.