C1QL1

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.[5] The protein is widely expressed but its expression is highest in the brain and may also be involved in regulation of motor control.[6] The pre-mRNA of this protein is subject to RNA editing.[7]

C1QL1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesC1QL1, C1QRF, C1QTNF14, CRF, complement component 1, q subcomponent-like 1, complement C1q like 1, CTRP14
External IDsOMIM: 611586 MGI: 1344400 HomoloGene: 4867 GeneCards: C1QL1
Orthologs
SpeciesHumanMouse
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 MbChr 11: 102.83 – 102.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[8]

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.[7] 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.[7]

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.[7]

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.[7]

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.[7]

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.[7] 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.[7]

References

  1. GRCh38: Ensembl release 89: ENSG00000131094 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000045532 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. C1QL1 Gene - GeneCards | C1QRF Protein | C1QRF Antibody
  6. Bérubé NG, Swanson XH, Bertram MJ, et al. (January 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.
  7. Sie CP, Maas S (April 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.
  8. Ghai R, Waters P, Roumenina LT, et al. (2007). "C1q and its growing family". Immunobiology. 212 (4–5): 253–66. doi:10.1016/j.imbio.2006.11.001. PMID 17544811.

Further reading

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