C1orf52
| C1orf52 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | C1orf52, gm117, chromosome 1 open reading frame 52 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 1913671; HomoloGene: 11968; GeneCards: C1orf52; OMA:C1orf52 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Chromosome 1 open reading frame 52 is a protein in humans encoded by the C1orf52 gene. C1orf52 is localized in the nucleus and ubiquitously expressed in human tissues.[5]
Gene
C1orf52 is located on the minus strand at 1p22.3.[6] The gene is 9,720 base pairs and has 3 exons.[7]
Gene neighborhood
The gene neighborhood of C1orf52 consists of B-cell lymphoma 10 (BCL10), B-cell lymphoma antisense 1 (BCL-AS1), dimethylarginine dimethylaminohydrolase 1 (DDAH1), and synapse defective Rho GTPase homolog 2 (SYDE2).[6] The BCL10 gene encodes the BCL10 scaffolding protein that controls immune and pro-inflammatory pathways by connecting antigen receptor signaling to NF-kB activation in B cells and T cells.[8] DDAH1 regulates intracellular ROS levels and apoptosis sensitivity via a SOD2-dependent pathway.[9] SYDE2 converts Rho-type GTPases into an inactive guanosine diphosphate-bound state.[10]
Transcript
Including untranslated regions, the mRNA is 3254 nucleotides long.[11]
Transcript variants
There is a transcript variant that includes an additional exon.[6] This alternate exon in the coding region in variant 2 results in a frameshift and early stop codon. This transcript does not form the C1orf52 protein because the product is significantly truncated and the transcript is a candidate for nonsense-mediated decay.
| Exons | 1 | 2 | 3 | 4 | Protein Length (amino acids) |
| Transcript Variant 1 | 306 | - | 199 | 2750 | 182 |
| Transcript Variant 2 | 306 | 127 | 199 | 2750 | none |
Protein
The C1orf52 protein consists of 182 amino acids with a molecular weight of 20 kDa and an isoelectric point of 5 pI.[7] The protein contains a domain of unknown function (DUF4660), also known as pFAM15559, that is 98 amino acids long. The domain of unknown function is flanked by two disordered regions, which make up the majority of the protein.[12] Compared to other proteins, C1orf52 is lysine and histidine deficient as well as glutamine and proline rich.[13]
No protein isoforms of C1orf52 have been reported.[14]
Structure
There is a high amount of disorder in the secondary and tertiary protein structure, with very few predicted alpha helixes or beta sheets.[15][17]
Regulation
Gene
C1orf52 is ubiquitously expressed at high levels in human tissues, with higher abundance in bone marrow, brain regions, and immune organs (thymus and thyroid), with lower expression in digestive organs.[6][18]
Protein
The C1orf52 protein has 21 times the average abundance in humans compared to other proteins.[19] There are 3 phosphorylation sites identified through mass spectrometry.[12] Within the cell, C1orf52 is localized to the nucleus and contains a bipartite nuclear localization signal.[20]
Homology
Paralogs
No paralogs of C1orf52 have been identified in the human genome.[14]
Orthologs
C1orf52 orthologs are in all common classes of vertebrates. Orthologs are also in invertebrates including sponges, marine tunicate, and lancelets. Orthologs were not found in insects, fungi, plants or protists.
| Genus and Species | Common Name | Taxonomic Order | Date of Divergence from Humans (MYA) | Assession Number | Sequence Length | Sequence Identity to Humans | Sequence Similarity to Humans |
|---|---|---|---|---|---|---|---|
| Homo Sapiens | Human | Primate | 0 | NP_932343.1 | 182 | 100% | 100% |
| Mus musculus | House Mouse | Rodentia | 87 | NP_079831.1 | 180 | 85.2% | 89.0% |
| Ornithorhynchus anatinus | Platypus | Monotreme | 180 | XP_028917768.1 | 191 | 61.7% | 71.0% |
| Harpia harpyja | Harpy Owl | Accipitriformes | 319 | XP_052658103.1 | 183 | 64.6% | 75.1% |
| Gallus gallus | Chicken | Galliformes | 319 | NP_001264489.2 | 183 | 63.0% | 71.4% |
| Taeniopygia guttata | Zebra finch | Passeriformes | 319 | XP_030134956.3 | 183 | 62.1% | 73.2% |
| Gopherus evgoodei | Goode’s thornscrub tortoise | Testudines | 319 | XP_038601107.1 | 187 | 64.7% | 73.3% |
| Alligator mississippiensis | Alligator | Crocodilia | 319 | XP_014450079.3 | 187 | 62.6% | 70.5% |
| Protobothrops mucrosquamatus | Pit viper | Squamata | 319 | XP_015668904.1 | 187 | 61.5% | 69.7% |
| Microcaecilia unicolor | Tiny Cayenne Caecilian | Gymnophiona | 352 | XP_030062820.1 | 184 | 62.2% | 72.0% |
| Xenopus laevis | African clawed frog | Anura | 352 | NP_001089243.1 | 171 | 60.9% | 70.8% |
| Pleurodeles waltl | Iberian ribbed newt | Urodela | 352 | KAJ1114225.1 | 182 | 57.1% | 67.9% |
| Protopterus annectens | West African Lung Fish | Ceratodontiformes | 408 | XP_043941971.1 | 181 | 53.5% | 70.1% |
| Polypterus senegalus | Gray bichir | Polypteriformes | 429 | XP_039591352 | 188 | 54.3% | 64.5% |
| Danio rerio | Zebrafish | Cypriniformes | 429 | NP_956836.1 | 214 | 45.9% | 58.3% |
| Pristis pectinata | Smalltooth Sawfish | Rhinopristiformes | 462 | XP_051869055.1 | 205 | 44.9% | 58.9% |
| Lampetra fluviatilis | European river lamprey | Petromyzontiformes | 563 | CAL5931002.1 | 242 | 26.7% | 36.0% |
| Branchiostoma floridae | Flordia Lancelet | Amphioxiformes | 581 | XP_035684389.1 | 234 | 24.7% | 37.7% |
| Styela clava | Sea squirt | Stolidobranchia | 596 | XP_039271545.1 | 236 | 25.4% | 39.9% |
| Geodia barretti | Deep Sea Sponge | Tetractinellida | 758 | CAI8039110.1 | 221 | 27.1% | 38.1% |
Evolution
The C1orf52 gene appears most distantly in sea sponges which diverged from humans approximately 758 million years ago.[21] C1orf52 evolves moderately quickly at a rate of 3.8 times faster than slowly evolving Cytochrome C and 0.61 times the rate of fast evolving Fibrinogen Alpha.[14]
Interacting proteins
High throughput affinity capture-mass spectrometry supports a physical association between C1orf52 and MAD1L1 (Mitotic Arrest Deficient 1 Like 1), DENN Domain Containing 2D (DENND2D), Differentially expressed in FDCP 6 homolog (DEF6), Insulin gene enhancer protein ISL2 (ISL2), and LIM/homeobox protein 4 (LHX4).[22] [23]
Clinical Significance
Single nucleotide polymorphisms within the second intron of human C1orf52 have been linked to metabolic syndrome, high density lipoprotein cholesterol levels, response to levetiracetam in genetic generalized epilepsy, multiple sclerosis, body mass index, and protein quantitative trait (liver).[24]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000162642 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036873 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "C1orf52 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2024-09-21.
- ^ a b c d "NCBI (National Center for Biotechnology Information) Gene Entry on C1orf52".
- ^ a b "C1orf52 Gene - Chromosome 1 Open Reading Frame 52".
- ^ Luo Y, Wu J, Zou J, Cao Y, He Y, Ling H, et al. (August 2019). "BCL10 in cell survival after DNA damage". Clinica Chimica Acta; International Journal of Clinical Chemistry. 495: 301–308. doi:10.1016/j.cca.2019.04.077. PMID 31047877.
- ^ Gao Q, Ni P, Wang Y, Huo P, Zhang X, Wang S, et al. (May 2024). "DDAH1 promotes neurogenesis and neural repair in cerebral ischemia". Acta Pharmaceutica Sinica. B. 14 (5): 2097–2118. doi:10.1016/j.apsb.2024.02.001. PMC 11119513. PMID 38799640.
{{cite journal}}: CS1 maint: overridden setting (link) - ^ Kouchi Z, Kojima M (March 2022). "Function of SYDE C2-RhoGAP family as signaling hubs for neuronal development deduced by computational analysis". Scientific Reports. 12 (1): 4325. Bibcode:2022NatSR..12.4325K. doi:10.1038/s41598-022-08147-7. PMC 8918327. PMID 35279680.
- ^ "NCBI (National Center for Biotechnology Information) Nucleotide Entry on C1orf52". 5 April 2024.
- ^ a b "UPF0690 protein C1orf52 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-12.
- ^ "SAPS Sequence Statistics".
- ^ a b c "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2024-09-21.
- ^ a b "I-TASSER server for protein structure and function prediction". zhanggroup.org. Retrieved 2024-12-04.
- ^ "iCn3D: Web-based 3D Structure Viewer". www.ncbi.nlm.nih.gov. Retrieved 2024-12-04.
- ^ "AlphaFold Protein Structure Database". www.sbg.bio.ic.ac.uk. Retrieved 2024-12-12.
- ^ "Home - GEO - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-12.
- ^ "PaxDb: Protein Abundance Database". pax-db.org. Retrieved 2024-12-04.
- ^ "MyHits Motif Scan". psort.hgc.jp. Retrieved 2024-12-12.
- ^ "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2024-12-03.
- ^ 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.
{{cite journal}}: CS1 maint: overridden setting (link) - ^ Huttlin EL, Ting L, Bruckner RJ, Gebreab F, Gygi MP, Szpyt J, et al. (July 2015). "The BioPlex Network: A Systematic Exploration of the Human Interactome". Cell. 162 (2): 425–440. doi:10.1016/j.cell.2015.06.043. PMC 4617211. PMID 26186194.
{{cite journal}}: CS1 maint: overridden setting (link) - ^ "GWAS Catalog". www.ebi.ac.uk. Retrieved 2024-12-03.