UPF0602
| UPF0602 Protein C4orf47 | |||||||
|---|---|---|---|---|---|---|---|
 AlphaFold prediction of UPF0602 protein c4orf47's tertiary structure[1] | |||||||
| Identifiers | |||||||
| Symbol | c4orf47 | ||||||
| Alt. symbols | LOC441054 | ||||||
| HGNC | 34346 | ||||||
| RefSeq | NM_00107829 | ||||||
| UniProt | A7E2U8 | ||||||
| Other data | |||||||
| Locus | Chr. 4 q35.1 | ||||||
| |||||||
UPF0602 is a protein in humans that is encoded by the chromosome 4 open reading frame 47 (c4orf47) gene.[2]
Gene
[edit]The c4orf47 gene is positioned at 4q35.1 on the plus strand and spans 44,602 base pairs in length (185,405,227...185,449,828). The gene is made up of 12 exons and 11 introns.[3]
There is overlap with two other genes which reside on the negative strand. These genes are UFM1 specific peptidase 2 (UFSP2) and Coiled-coil domain containing 110 (CCDC110)
Another alias for the c4orf47 gene is LOC441054
Transcript
[edit]Transcript variant 1 is the longest experimentally validated variant of c4orf47 mRNA and it encodes for UPF0602 protein isoform 1. This variant contains a total of 8 exons with an upstream in-frame stop codon located within the first exon, a disordered region, and a domain of unknown function. The mRNA is 1,333 nucleotides long and encodes for a 309 amino acid polypeptide.[4]
Transcript variant 2 differs in the 5' UTR, uses an alternate translation start site, and lacks two alternate exons in the 5' coding region compared to variant 1. The encoded protein isoform (2) is shorter and has a distinct N-terminus compared to protein isoform 1. The mRNA is 1,037 nucleotides long and encodes for a 183 amino acid polypeptide.[5]
C4orf47 mRNA is ubiquitously expressed in all tissue, with higher expression occurring within the choroid plexus, retina, fallopian tubes, and testis.[6]
Protein
[edit]UPF0602 protein isoform 1 has a molecular weight of 34.4kDa and a predicted isoelectric point of 9.64 pI.[7] It contains the domain of unknown function known as DUF4586.[8] this domain belongs to pfam15239 which is the only member of protein superfamily cl21099.[9]
This protein contains a higher than average quantity of basic amino acids relative to its size and contains two repeat sections.[7]
| Location | Amino Acids |
|---|---|
| 145 - 148 | PGKK |
| 235 - 238 | PGKK |
| 164 - 168 | SHSAD |
| 252 - 256 | SHSAD |
Localization
[edit]This protein contains no signal peptide and has been shown to localize within the cell to cytoplasmic microtubules, centrosomes, and non-motile cilia.[10][3][11][12]
Expression
[edit]UPF0602 is ubiquitously expressed in all tissue, with higher expression occurring within the lungs, fallopian tubes, and testis. The lungs and fallopian tubes see the greatest protein abundance within ciliated cells. Specifically in the tip of cilia and the cilia axoneme. Within the testis, protein abundance is highest in elongated or late spermatid.[6][10]
Homology
[edit]UPF0602 protein has no paralogs. However, homologs are found within most ciliated eukaryotes. Exceptions include all reptiles except turtles, salamanders, and lobe-finned fishes other than the West Indian Coelacanth. A UPF0602 protein homolog is also found within Chytridiomycetes, a class of fungi.
The following table represents a small selection of homologs found using BLAST.[13]
| Genus and Species | Common Name | Taxonomic Group | Estimated Divergence (MYA) | Accession Number | Sequence Length (aa) | Sequence Identity (%) | Sequence Similarity (%) |
|---|---|---|---|---|---|---|---|
| Homo sapiens | Human | Primates | 0 | NP_001107829.1 | 309 | 100 | 100 |
| Gallus gallus | Domestic chicken | Aves | 312 | XP_004936032.2 | 311 | 67.2 | 78.8 |
| Chrysemys picta bellii | Painted turtle | Reptilia | 312 | XP_005282053.1 | 311 | 66.6 | 79.7 |
| Rhinatrema bivittatum | Two-lined caecilian | Amphibia | 351.8 | XP_029442782.1 | 308 | 61.1 | 74.3 |
| Xenophus tropicalis | Western clawed frog | Amphibia | 351.8 | XP_002934310.1 | 307 | 58.3 | 75.1 |
| Latimeria chalumnae | West Indian coelacanth | Coelacanthiformes | 413 | XP_014353738.1 | 311 | 55 | 70.4 |
| Danio rerio | Zebrafish | Actinopterygii | 435 | NP_001038879.1 | 312 | 54.5 | 70.2 |
| Rhinocodon typus | Whale shark | Chondrichthyes | 473 | XP_020367910.1 | 319 | 50.2 | 63.3 |
| Lytechinus variegatus | Green sea urchin | Temnopleuroida | 684 | XP_041485424.1 | 316 | 52.8 | 67.1 |
| Pomacea canaliculata | Channeled applesnail | Mollusca | 797 | XP_025090509.1 | 321 | 51.1 | 67 |
| Amphibalanus amphitrite | Acorn barnacle | Arthropoda | 797 | KAF0292396.1 | 334 | 30.8 | 47.9 |
| Powellomyces hirtus | Chytrids | Chytridiomycetes | 1017 | TPX58729.1 | 353 | 32.3 | 45.3 |
Evolution
[edit]The c4orf47 gene has been evolving at a relatively slow rate when compared to the evolutionary rates of Fibrinogen Alpha and Cytochrome C. This suggests there is a conserved function for the encoded protein.
Function
[edit]The function this protein carries out within the cell are not well understood by the scientific community, however evidence suggests it is related to cilia and flagella assembly.[10][14]
Interacting proteins
[edit]High throughput evidence supports physical interaction between UPF0602 protein and nucleophosmin (NPM1),[15] as well as with ubiquitin-specific peptidase 9, Y-linked (USP9Y).[14]
Clinical significance
[edit]Single nucleotide polymorphisms (SNPs) within regions of the UFSP2 gene overlapping c4orf47 have been linked to Beukes hip dysplasia, Spondyloepimetaphyseal dysplasia, Di Rocco type, microcephaly, and other developmental anomalies.[16][17][18]
References
[edit]- ^ "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk.
- ^ "UPF0602 protein C4orf47 isoform 1 [Homo sapiens] - Protein". National Center for Biotechnology Information. Retrieved 4 October 2021.
- ^ a b "C4orf47 chromosome 4 open reading frame 47 [Homo sapiens (human)] - Gene". National Center for Biotechnology Information.
- ^ "Homo sapiens chromosome 4 open reading frame 47 (C4orf47), transcript variant 1, mRNA". National Center for Biotechnology Information. 2 July 2021.
- ^ "Homo sapiens chromosome 4 open reading frame 47 (C4orf47), transcript variant 2, mRNA". National Center for Biotechnology Information. 18 December 2020.
- ^ a b "Tissue expression of C4orf47 - Summary". Human Protein Atlas. Retrieved 18 December 2021.
- ^ a b "SAPS < Sequence Statistics". European Bioinformatics Institute. Retrieved 18 December 2021.
- ^ "UPF0602 protein C4orf47 isoform 1 [Homo sapiens] - Protein". National Center for Biotechnology Information.
- ^ "CDD Conserved Protein Domain Family: DUF4586". National Center for Biotechnology Information.
- ^ a b c Urizar-Arenaza I, Osinalde N, Akimov V, Puglia M, Muñoa-Hoyos I, Gómez-Giménez B, et al. (September 2020). "Kappa- opioid receptor regulates human sperm functions via SPANX-A/D protein family". Reproductive Biology. 20 (3): 300–306. doi:10.1016/j.repbio.2020.07.003. PMID 32684427. S2CID 220652968.
- ^ Firat-Karalar EN, Sante J, Elliott S, Stearns T (October 2014). "Proteomic analysis of mammalian sperm cells identifies new components of the centrosome". Journal of Cell Science. 127 (Pt 19): 4128–4133. doi:10.1242/jcs.157008. PMC 4179487. PMID 25074808.
- ^ Sigg MA, Menchen T, Lee C, Johnson J, Jungnickel MK, Choksi SP, et al. (December 2017). "Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways". Developmental Cell. 43 (6): 744–762.e11. doi:10.1016/j.devcel.2017.11.014. PMC 5752135. PMID 29257953.
- ^ "BLAST: Basic Local Alignment Search Tool". National Center for Biotechnology Information. Retrieved 15 December 2021.
- ^ a b Huttlin EL, Bruckner RJ, Navarrete-Perea J, Cannon JR, Baltier K, Gebreab F, et al. (May 2021). "Dual proteome-scale networks reveal cell-specific remodeling of the human interactome". Cell. 184 (11): 3022–3040.e28. doi:10.1016/j.cell.2021.04.011. PMC 8165030. PMID 33961781.
- ^ Fasci D, van Ingen H, Scheltema RA, Heck AJ (October 2018). "Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei". Molecular & Cellular Proteomics. 17 (10): 2018–2033. doi:10.1074/mcp.RA118.000924. PMC 6166682. PMID 30021884.
- ^ Watson CM, Crinnion LA, Gleghorn L, Newman WG, Ramesar R, Beighton P, Wallis GA (September 2015). "Identification of a mutation in the ubiquitin-fold modifier 1-specific peptidase 2 gene, UFSP2, in an extended South African family with Beukes hip dysplasia". South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde. 105 (7): 558–563. doi:10.7196/SAMJnew.7917. PMID 26428751.
- ^ Di Rocco M, Rusmini M, Caroli F, Madeo A, Bertamino M, Marre-Brunenghi G, Ceccherini I (March 2018). "Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation". Clinical Genetics. 93 (3): 671–674. doi:10.1111/cge.13134. PMID 28892125. S2CID 3587666.
- ^ Ni M, Afroze B, Xing C, Pan C, Shao Y, Cai L, et al. (May 2021). "A pathogenic UFSP2 variant in an autosomal recessive form of pediatric neurodevelopmental anomalies and epilepsy". Genetics in Medicine. 23 (5): 900–908. doi:10.1038/s41436-020-01071-z. PMC 8105169. PMID 33473208.