CCDC200

---

Coiled-coil domain-containing protein 200 (CCDC200) is a human protein, also known as LINC00854 and TMEM106A-AS1, that has the highest expression in the kidneys. The CCDC200 transcript variant 1 (NM_001363254) is a gene that has 727 base pairs (bp), is located on the minus strand of chromosome 17 (17q21.31), has 4 exons, and encodes a protein that is 168 amino acids long. This protein has an isoelectric point of 9.3 and a molecular weight of ~19.4 kilodaltons (kDa). It also contains an evolutionarily conserved coiled-coil region and is predicted to be localized in the nucleus. While CCDC200 is a highly conserved protein with many orthologs, dating as far back as 319 million years ago (mya),  no human paralogs have been found yet for this protein.

When CCDC200 was knocked out, an increase in viral infection as well as a change in host and pathogen interactions was observed, suggesting potential roles in immune response.

Gene

Figure 1. The gene neighborhood of CCDC200 includes upstream (TMEM106A and NBR1) and downstream (RNU2-1) genes.

Figure 2. Depicts chromosome 17 and provides a visual representation of where the CCDC200 gene is located (marked by a red band).

The human CCDC200 gene is located on chromosome 17, at position 17q21.31, on the minus strand and has 4 exons, spanning 4998 bp. The gene neighborhood of CCDC200 includes upstream (TMEM106A and NBR1) and downstream (RNU2-1) genes.

Transcript

The CCDC200 gene has one isoform and two splice variants that are different based on their coding potential. Transcript variant 1 has 3 introns and encodes for the CCDC200 protein, while transcript variant 2 (NR_047479) is labeled as a non-coding RNA (see Figure 3).

Tissue Expression

According to RNA sequencing data of total RNA from 20 different human tissues, biased expression in the kidneys was found with low expression located in the lungs, stomach, uterus, spleen, and thymus. When comparing the highest tissue expression, in reads per kilobase million (or RPKM), for kidneys (3.28) and in skeletal muscle (0.049), there was a ~67-fold difference.

Figure 3. Shows the two variants of CCDC200 that exist, one that encodes for the CCDC200 protein and one that is a non-coding RNA. This article primarily discusses isoform 1, which is located at the top of the figure.

Proteins

General Information:

The Human CCDC200 protein (NP_001350183.1) contains 168 amino acids with an isoelectric point of 9.3 and a molecular weight is 19.4 kDa. This aligns with CCDC200’s distant mammalian orthologs (such as Mus musculus) that has an isoelectric point of 9.6 and a molecular weight of 19.4 kDa. This protein is glutamine and proline-rich, which can play a role in characterizing proteins as intrinsically disordered proteins (IDPs) due to limiting the formation of alpha helices or beta sheets. This protein is also phenylalanine and glycine-deficient, suggesting that this protein in unlikely a transmembrane protein.

Species	Accession	Molecular Weight (kDa)	Isoelectric Point
Homo Sapiens	NP_001350183.1	19.4	9.3
Mus musculus	NP_001359474.1	19.4	9.6
Bos taurus	XP_024836665.1	17.7	9.0

Table 1. CCDC200 Protein Characteristics Shown in Humans and Close Mammalian Orthologs

Primary

The human CCDC200 protein is predicted to have nuclear localization signals in their N-terminal and C-terminal regions. The protein is also predicted to be sub-cellularly localized to the nucleus with a 52.2% chance and is further supported with similar results when compared to Mus musculus (56.5%).

There is a coiled-coil region is predicted to be found from residues 16-50 and intrinsically disordered regions found at 23-168. The protein is also predicted to have a polyampholyte region (31-52), an area of low complexity (70-82), proline-rich regions (83-94 & 104-117), and polar regions (124-138 & 145-168).

Figure 4. The annotated primary structure of CCDC200 shows domains, disordered regions, motifs, and phosphorylation sites (using InterPro and DTU HealthTech). The boxes show domains, regions, and motifs spanning different amino acid residues: the coiled-coil region is in royal blue (16-50), the polyampholyte motif in purple (31-52), the low-complexity region in red (70-82), the proline-rich regions in teal (84-95 & 103-116), the polar regions are in green (124-138 & 145-168), and the disordered region is marked (23-168). The different phosphorylation sites with highest probabilities are marked at their respective locations.

Post-Translational Modification

The human CCDC200 protein is predicted to contain various phosphorylation, ubiquitination, and sumoylation motifs.

Secondary and Tertiary Protein Structure

Predicted secondary structures of human CCDC200 show that the N-terminal region is more disordered compared to the rest of the protein.

Figure 5. Predicted tertiary structure of human CCDC200 (C-score -3.48 and cluster density of 0.0267) shows an alpha-helical structure (at N-terminus) with a disordered region located towards the C-terminal region. Confidence score (C-score) refers to how accurate the predicted model is on a scale from [-5,2]

Regulation

The proteins that interact with CCDC200 highly are known as TRIM17, C6orf15, ADGRF4, CNTNAP5, LETM2, TMEM89, BPIFA, and OR1N2. Proteins such as VSTM2B, CATSPER2, and CCDC42 interact with CCDC200 less in comparison to the aforementioned proteins.

Sub-cellular Localization

the human CCDC200 protein is predicted to be localized in the nucleus (52.2%), mitochondria  (21.7%), cytoplasm (13%), cytoskeleton (8.7%), and in secretory vesicles (4.3%). There is a weak peripheral (30.6%), transmembrane (12.9%), and lipid anchor (11.8%) association, meaning that the protein is predicted to be localized primarily in the nucleus or cytoplasm.

Homology

Orthologs

Coiled-Coil Domain Containing protein 200 (CCDC200) is found in varying species of mammals such as primates, rodents, lagomorphs, and monotremes.Since orthologs of the human CCDC200 protein have been found in platypus, which diverged from humans around 180 million years ago, and have also been found in reptile species (such as the brown anole which diverged 319 mya), due to the presence of this gene, we can conclude that the CCDC200 gene is at least 319 million years old. Since this gene has been conserved across many different species for 320 million years, it suggests that it serves an important biological function.

The CCDC200 protein can be found in primata, rodentia, lagomorpha, carnivora, artiodactyla, monotremata, and reptilia, but was not found in aves or various fish clades. However, it is worth noting that some aquatic mammalian species do have the CCDC200 protein, notably Phocoena sinus, Orcinus orca, and Kogia breviceps.

Figure 6. Global sequence alignment comparing the CCDC200 protein in Homo sapiens and Mus musculus. There is a 39.9% sequence identity and 48.5% similarity between the human and mouse genes. Highly conserved areas are highlighted in blue (marked with -), while orange indicates similarity (marked with :).

Figure 7. This multiple sequence alignment was created using amino acid sequences of Homo sapiens, Ornithorhynchus anatinus, and Anolis sagrei. The first 13 amino acids are conserved across the three different species; however, the remaining amino acids vary more significantly. The N-terminal region of the CCDC200 protein is more conserved, further supporting the MSA of close orthologs, suggesting that there is an evolutionary benefit to preserving this region. (*) denotes areas of high conservation while (-) shows gaps (insertions/deletions).

Clades	Sequence #	Genus Species	Common Name	Family	Date of Divergence (MYA)	Accession Number	Sequence Length (AA)	Sequence Identity (%)	Sequence Similarity (%)
	1	Homo sapiens	Humans	Hominidae	0	A0A1B0GVQ3.1	168.00	100.00	100.00
	2	Pongo pygmaeus	Bornean Orangutan	Hominidae	15.2	XP_054313734.1	172.00	92.40	94.20
	3	Papio anubis	Olive Baboon	Cercopithecidae	28.8	XP_009189005.2	181.00	66.00	70.10
Primates	4	Cebus imitator	Panamanian White-Faced Capuchin	Cebidae	43	XP_037587582.1	168.00	74.90	80.70
	5	Nycticebus coucang	Sunda Slow Loris	Lorisidae	74	XP_053426744.1	154.00	56.00	63.40
Rodentia	6	Mus musculus	Mice	Muridae	87	XP_030102092.1	168.00	39.90	48.50
	7	Arvicanthis niloticus	African Grass Rat	Muridae	87	XP_034360446.1	215.00	86.96	86.03
Lagomorpha	8	Ochotona curzoniae	Pika	Ochotonidae	87	XP_040857462.1	155.00	47.40	56.10
	9	Suricata suricatta	Meercat	Herpestidae	94	XP_029782790.1	167.00	38.30	45.60
Carnivora	10	Panthera leo	Lion	Felidae	94	XP_042771316.1	182.00	44.60	52.90
	11	Lutra lutra	Eurasian River Otter	Mustelidae	94	XP_047561971.1	215.00	30.80	36.80
	12	Vicugna pacos	Alpaca	Camelidae	94	XP_072796168.1	168.00	44.10	51.00
	13	Camelus dromedarius	Arabian Camel	Camelidae	94	XP_031324555.1	160.00	48.10	56.90
Artiodactyla	14	Bos taurus	Cow	Bovidae	94	XP_024836665.1	151.00	52.70	58.60
	15	Budorcas taxicolor	Takin	Bovidae	94	XP_052514448.1	150.00	50.50	57.00
	17	Kogia breviceps	Pygymy Sperm Whale	Kogiidae	94	XP_066876845.1	160.00	47.90	56.30
	18	Phocoena sinus	Vaquita	Phocoenidae	94	XP_032471384.1	117.00	36.50	41.40
Monotremata	19	Ornithorhynchus anatinus	Platypus	Ornithorhynchidae	180.00	XP_028930563.1	114.00	25.00	32.70
Reptilia	20	Anolis sagrei	Brown Anole	Dactyloidae	319	XP_060639141.2	118.00	26.70	41.30

Table 2. Table of CCDC200 Orthologs

This figure shows 20 orthologs of the human CCDC200 protein. Orthologs in seven orders were analyzed: primata (56.00-94.4% sequence identity), rodentia (39.9-86.96%), lagomorphs (47.4%), carnivora (30.8-44.6%), artiodactyla (36.5-52.7%), monotremata (25.0%), and reptilia (26.7%). It is also important to note that , there were no orthologs present in avian or fish species.

The graph shows the molecular clock analysis for the CCDC200 protein which measures the mutation rate to determine rates of divergence. It plots fibrinogen alpha chain(FGA), cytochrome c, and CCDC200. FGA (blue) has the highest trendline of the three proteins, showing that it has a higher mutation rate. CCDC200 (yellow) has a more moderate trendline, suggesting that there is not much evolutionary pressure to have high conservation; however, cytochrome c (red) has the lowest, which shows that there is a higher need to have more conservation.

Paralogs

There are no human paralogs have been found yet for this protein.

Function

The CCDC family of proteins has been found to play a role in both physiological and pathological processes like hematopoiesis, embryogenesis, and have been implicated in the developments of some cancers. Researchers have also identified highly conserved motif sequences in CCDC200 found within humans, even though there was considerable differentiation in non-human primates, suggesting that environmental pressures have selected for different traits.

CCDC200 can be associated with immune function, cell communication, metabolic processes, and the nervous system due to its highly conserved motifs. The gene’s potential role in immune function can suggest that the CCDC200 protein could have co-evolved with environmental pathogens.

The knockout of CCDC200 was found to increase viral invasion and change host and pathogen interactions. Gene knockout suggests that CCDC200 may play a role in contributing to the immune defense system by regulating the life cycle of viruses.

References

This article "CCDC200" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:CCDC200. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.

---