C3orf38

Chromosome 3 open reading frame 38 is a protein which in humans is encoded by the C3orf38 gene.

Gene

The C3orf38 gene is located on chromosome 3 on the forward strand. It spans 18,771 bases from chr3:88,149,959-88,168,729. It contains 3 exons. Common aliases for this gene are MGC26717, LOC285237, and FLJ54270. Some of the genes neighboring C3orf38 include ZNF654, CGGBP1, and LOC105377202.

Protein

The C3orf38 protein is 329 amino acids in length. A large domain of unknown function, DUF4518, encompasses majority of the C3orf38 protein. This domain is a part of the protein family pfam15008, which is thought to be involved in apoptosis regulation. This pfam15008 is the only member of the cl20886 superfamily. While the C3orf38 protein does not have any abnormal amino acid abundance as a whole, the DUF4518 has a high abundance of histidines and a low abundance of serines, according to compositional analysis. The predicted molecular weight of the entire C3orf38 protein is 37.0 kD and the isoelectric point is 6.01. The DUF4518 contained inside the C3orf38 protein has a predicted molecular weight of 31 kD and an isoelectric point of 6.49.

Regulation

Gene Level Regulation

There have been a number of potential promoters identified for the C3orf38 gene, which are described in the table below.

Promoter	Start	End	Length	Transcripts
GXP_203118	88148634	88150046	1413	GXT_23216585, GXT_22791246, GXT_2803824, GXT_26239186
GXP_9795962	88148768	88149807	1040	no transcript assigned; promoter based on comparative genomics
GXP_9795963	88148794	88150027	1234	no transcript assigned; promoter based on comparative genomics
GXP_3194836	88149604	88150643	1040	GXT_24485561

The C3orf38 gene exhibits ubiquitous expression in human tissues.

Protein Level Regulation

The C3orf38 protein is expected to be found with the highest confidence in the cytoplasm. This finding is supported by examination of an array of C3orf38 orthologs.
There are several well conserved post translation modification sites found amongst the human C3orf38 protein and its orthologs, which are depicted in the table below. Majority of these PTMs are PKC phosphorylation sites. Additionally, two confirmed active sites are located in the C3orf38 protein. The first is an aldehyde dehydrogenases glutamic acid active site located from amino acids 1-8. The second site is a eukaryotic thiol proteases histidine active site located from amino acids 227-237.

PTM	Protein Location
Myristyl site	235-240
PKC phosphorylation site	34-36
PKC phosphorylation site	86-88
PKC phosphorylation site	199-201
PKC phosphorylation site	265-267

Homology/evolution

Orthologs for the C3orf38 protein can be found in mammals, reptiles, birds, amphibians, fish, and invertebrates using BLAST searches. A selection of these orthologs can be found in the ortholog table below. There are no paralogs. Additionally, by comparing sequences of C3orf38 protein with cytochrome C and fibrinogen alpha proteins, a moderate rate of evolution was determined for the C3orf38 protein.

	Genus, species	Common name	Taxonomic group	Divergence Date	Accession number	Sequence length	Sequence identity	Sequence similarity
Mammals	Homo sapiens	Human	Primates	0	NP_776185.2	329	100	100
Mammals	Pan paniscus	Bonobo	Primates	6.7	XP_003831564.1	329	99.4	99.7
Mammals	Puma concolor	Puma	Carnivora	96	XP_025769652.1	348	79.8	86.6
Reptiles	Mauremys reevesii	Reeve's Turtle	Testudines	312	XP_039379932.1	315	55.7	70.5
Reptiles	Chelonoidis abingdonii	Abingdon Island Giant Tortoise	Testudines	312	XP_032650981.1	304	55.4	69.9
Birds	Strigops habroptila	Kākāpō	Psittaciformes	312	XP_030327387.1	309	52.1	66.3
Birds	Taeniopygia guttata	Zebra Finch	Passeriformes	312	XP_002190058.5	306	51	63.9
Birds	Gallus gallus	Chicken	Galliformes	312	XP_004938363.2	312	44.2	59.9
Amphibians	Rhinatrema bivittatum	Two-Lined Caecilian	Gymnophiona	351.8	XP_029434832.1	289	49.7	64.5
Amphibians	Bufo bufo	Common Toad	Anura	351.8	XP_040279187.1	289	43.9	62.1
Amphibians	Xenopus tropicalis	Tropical Clawed Frog	Anura	351.8	XP_017946806.1	261	38.6	54.8
Fish	Chelmon rostratus	Copperband Butterflyfish	Perciformes	435	XP_041807133.1	302	42.7	58.2
Fish	Coregonus clupeaformis	Lake Whitefish	Salmoniformes	435	XP_041700482.1	308	42.4	60.6
Fish	Carcharodon carcharias	Great White Shark	Lamniformes	473	XP_041066710.1	308	45	59.8
Fish	Amblyraja radiata	Thorny Skate	Rajiformes	473	XP_032888490.1	382	32.5	46.5
Invertebrates	Lytechinus variegatus	Sea Urchin	Temnopleuroida	684	XP_041465399.1	312	36.4	48.3
Invertebrates	Patiria miniata	Bat Star	Valvatida	684	XP_038067113.1	294	34.1	46.2
Invertebrates	Cryptotermes secundus	Termite	Blattodea	797	XP_023724689.1	296	30.1	48
Invertebrates	Crassostrea virginica	Eastern Oyster	Ostreidae	797	XP_022335568.1	340	29.6	46.5
Invertebrates	Diabrotica virgifera	Western Corn Rootworm	Coleoptera	797	XP_028133096.1	284	26.9	43.6
Invertebrates	Acropora millepora	Branching Stony Coral	Scleractinia	824	XP_029194133.1	288	32.6	50.9

Function

Although investigation into the function of the C3orf38 gene is ongoing, a couple studies have granted valuable insights into its role. One study has identified C3orf38 as a candidate proapoptotic gene. Another study identified C3orf38 as a top candidate tumor suppressor gene.

Interacting proteins

Of the various proteins C3orf38 protein interacts with, two are particularly interesting seeing as C3orf38 is a candidate proapoptotic and tumor suppressor gene. First, BAG family molecular chaperone regulator 4 is an anti-apoptotic protein that is known to interact with a number of apoptosis and growth-related proteins. Second, DnaJ Heat Shock Protein Family Member B4 is a member of the heat shock protein-40 family, a molecular chaperone, and a tumor suppressor.