CFAP70 (cilia and flagella associated protein 70)

2019-01-01   Jean Loup Huret  

jean-loup.huret@atlasgeneticsoncology.org

Identity

HGNC
LOCATION
10q22.1; on reverse strand
LOCUSID
ALIAS
TTC18
FUSION GENES

Abstract

Review on CFAP70, a poorly known gene and protein, with data on DNA, on the protein encoded, and where the gene is implicated.

DNA/RNA

Transcription

Various transcripts (see below).

Proteins

Description

Various isoforms have been described:
According to Vega: 3 protein coding transcripts: CFAP70-001: 3691 base pairs (bp), coding for a protein of 590 amino acids (aa); CFAP70-006: 1710bp, 498 aa; CFAP70-002: 1403bp, 361 aa
According to Uniprot: Isoform 1 (Q5T0N1-1), canonical sequence: 1,121 aa, 125,721 Da; Isoform 2 (Q5T0N1-2): 1,091 aa, 122,269 Da; Isoform 3 (Q5T0N1-3): 119 aa, 12,999 Da; Isoform 4 (Q5T0N1-6): 195 aa, 22,338 Da; Isoform 5 (Q5T0N1-7): 225 aa, 25,790 Da.
According to Ensembl: Protein ENSP00000310829: the transcript has 28 exons, 3703bp, 1121 aa, 33 domains; Protein ENSP00000347781: the transcript has 28 exons, 3691bp, 590 aa, 32 domains; Protein ENSP00000409527; the transcript has 12 exons, 1710bp, 498 aa, 23 domains; Protein ENSP00000343650: the transcript has 12 exons, 1403bp, 361 aa, 13 domains; Protein ENSP00000378334; the transcript has 9 exons, 1222bp, 179 aa, 13 domains.
Domains in the canonical sequence (Q5T0N1-1 in UniProt): 1121 aa.
there are 8 tetratricopeptide repeats (TRP): TPR 1, aa 635-668, TPR 2: aa 669-702, TPR 3 : aa 704-736, TPR 4: aa 929-962, TPR 5: aa 963-996, TPR 6: aa 1000-1033, TPR 7: aa 1035-1066 and TPR 8: aa 1068-1100. The TPR sequence contains about 34 amino acids, with a consensus sequence of small and large hydrophobic amino acids; small hydrophobic amino acids are often found at positions 8, 20, and 27, and large ones at positions 4, 7, and 24. Three-dimensional structure shows that the TPR motif contains two antiparallel α-helical subdomains (termed helix A and helix B), equivalent in length. TPR adopts a helix-turn-helix arrangement. They self-associate via a "knobs and holes" mechanism (Das et al., 1998; DAndrea and Regan 2003; Cerveny et al., 2013; SMART).
Atlas Image
Figure 1 CFAP70 protein and domains.

Expression

CFAP70 is expressed in adrenal gland, bronchus, testis, sperm flagella and in cilia of glandular cells in fallopian tube, and endometrium, according to The Human Protein Atlas.

Localisation

CFAP70 localizes on the epithelial cilia and sperm flagella. It associates tightly to the ciliary axoneme (Shamoto et al., 2018).

Function

Tetratricopeptide repeats are found in at least 149 proteins (PFAM). Tetratricopeptide repeat containing proteins are involved in protein-protein interactions and the assembly of multiprotein complexes, cell cycle, transcription, mitochondrial protein transport, and neurogenesis.
CFAP70 binds to the axoneme of motile cilia and flagella in close proximity to the outer dynein arms and regulates outer dynein arms activity. It is the N-terminus of CFAP70 which localizes at the base of the outer dynein arms and not the tetratricopeptide repeats. Knockdown of CFAP70 causes a reduction in ciliary motility (Shamoto et al., 2018).

Implicated in

Top note
Low or high expression of CFAP70 is not a prognostic indicator in any cancer tested (The Human Protein Atlas).
Entity name
Breast adenocarcinoma
Note
The fusion gene DNAJC9/CFAP70 (10q22-10q22) has been found in breast adenocarcinoma (Gao et al. 2018).
The fusion gene CFAP70/ MCU (10q22-10q22) has been found in a breast cancer cell line (Klijn et al. 2015).
Entity name
Uterus corpus adenocarcinoma
Note
The fusion gene P4HA1/CFAP70 (10q22-10q22) has been found in uterus corpus adenocarcinoma (Hu et al. 2018).
Entity name
Lung squamous cell carcinoma
Note
The fusion gene ECD/CFAP70 (10q22-10q22) has been found in lung squamous cell carcinoma (Yoshihara et al. 2015).
Entity name
Thyroid adenocarcinoma
Note
The fusion gene MRPS16/CFAP70 (10q22-10q22) has been found in thyroid adenocarcinoma (Yoshihara et al. 2015).

Article Bibliography

Pubmed IDLast YearTitleAuthors
232640492013Tetratricopeptide repeat motifs in the world of bacterial pathogens: role in virulence mechanisms.Cerveny L et al
146596972003TPR proteins: the versatile helix.D'Andrea LD et al
94827161998The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions.Das AK et al
296176622018Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.Gao Q et al
290999512018TumorFusions: an integrative resource for cancer-associated transcript fusions.Hu X et al
254856192015A comprehensive transcriptional portrait of human cancer cell lines.Klijn C et al
301585082018CFAP70 Is a Novel Axoneme-Binding Protein That Localizes at the Base of the Outer Dynein Arm and Regulates Ciliary Motility.Shamoto N et al
255005442015The landscape and therapeutic relevance of cancer-associated transcript fusions.Yoshihara K et al

Other Information

Locus ID:

NCBI: 118491
MIM: 618661
HGNC: 30726
Ensembl: ENSG00000156042

Variants:

dbSNP: 118491
ClinVar: 118491
TCGA: ENSG00000156042
COSMIC: CFAP70

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000156042ENST00000310715Q5T0N1
ENSG00000156042ENST00000340329X6R507
ENSG00000156042ENST00000355577A0A087WSW1
ENSG00000156042ENST00000394865A0A0A0MS55
ENSG00000156042ENST00000433268X6RID7

Expression (GTEx)

0
5
10
15
20
25

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
316218622019CFAP70 mutations lead to male infertility due to severe astheno-teratozoospermia. A case report.25
316218622019CFAP70 mutations lead to male infertility due to severe astheno-teratozoospermia. A case report.25
163854512006A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.83
163854512006A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.83

Citation

Jean Loup Huret

CFAP70 (cilia and flagella associated protein 70)

Atlas Genet Cytogenet Oncol Haematol. 2019-01-01

Online version: http://atlasgeneticsoncology.org/gene/61764/haematological-explorer/css/gene-fusions/?id=61764