C1orf52

C1orf52
Identifiers
Aliases	C1orf52 , gm117, chromosome 1 open reading frame 52
External IDs	MGI: 1913671; HomoloGene: 11968; GeneCards: C1orf52; OMA:C1orf52 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1p22.3 Start 85,249,953 bp [1] End 85,259,672 bp [1]
Gene location (Mouse) Chr. Chromosome 3 (mouse) [2] Band 3|3 H2 Start 145,643,769 bp [2] End 145,650,584 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of arm pancreatic epithelial cell Brodmann area 46 amniotic fluid Brodmann area 23 thymus endothelial cell myocardium of left ventricle germinal epithelium tibia Top expressed in motor neuron medullary collecting duct facial motor nucleus Paneth cell condyle fossa medial ganglionic eminence sternocleidomastoid muscle renal corpuscle triceps brachii muscle More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 148423 66421 Ensembl ENSG00000162642 ENSMUSG00000036873 UniProt Q8N6N3 Q9CWU4 RefSeq (mRNA) NM_198077 NM_025555 NM_001356284 RefSeq (protein) NP_932343 NP_079831 NP_001343213 Location (UCSC) Chr 1: 85.25 – 85.26 Mb Chr 3: 145.64 – 145.65 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

Human C1orf52 gene neighborhood. B-cell lymphoma 10 (BCL10), B-cell lymphoma antisense 1 (BCL-AS1), dimethylarginine dimethylaminohydrolase 1 (DDAH1), and synapse defective Rho GTPase homolog 2 (SYDE2) genes are located in close proximity to C1orf52 on chromosome 1.

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

Conceptual translation of Human C1orf52. Splice sites between exons are indicated by blue text, the domain of unknown function (DUF4660) is in grey highlight, and pink text shows disordered regions.

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]

Human C1orf52 predicted tertiary structure labeled based on secondary structure. Alpha helixes are in red and coils are in grey.

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

Mutation rate of C1orf52 in comparison to Cytochrome C and Fibrinogen Alpha. All organisms used for C1orf52 mutation rate are on the table. Organsims shown for Cytochrome C and Fibrinogen Alpha are: Mus musculus, Gallus gallus, Alligator mississippiensis, Xenopus laevis, Danio rerio. Additional organisms shown for Cytochrome C: Pristis pectinata, Lampetra fluviatilis, Branchiostoma floridae, Styela clava.

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

1. GRCh38: Ensembl release 89: ENSG00000162642 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036873 – 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. "C1orf52 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2024-09-21.
6. "NCBI (National Center for Biotechnology Information) Gene Entry on C1orf52".
7. "C1orf52 Gene - Chromosome 1 Open Reading Frame 52".
8. 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.
9. 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.
10. 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.
11. "NCBI (National Center for Biotechnology Information) Nucleotide Entry on C1orf52". 5 April 2024.
12. "UPF0690 protein C1orf52 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-12.
13. "SAPS Sequence Statistics".
14. "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2024-09-21.
15. "I-TASSER server for protein structure and function prediction". zhanggroup.org. Retrieved 2024-12-04.
16. "iCn3D: Web-based 3D Structure Viewer". www.ncbi.nlm.nih.gov. Retrieved 2024-12-04.
17. "AlphaFold Protein Structure Database". www.sbg.bio.ic.ac.uk. Retrieved 2024-12-12.
18. "Home - GEO - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-12.
19. "PaxDb: Protein Abundance Database". pax-db.org. Retrieved 2024-12-04.
20. "MyHits Motif Scan". psort.hgc.jp. Retrieved 2024-12-12.
21. "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2024-12-03.
22. 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.
23. 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.
24. "GWAS Catalog". www.ebi.ac.uk. Retrieved 2024-12-03.