Chromosome 3 open reading frame 38 (C3orf38) is a protein which in humans is encoded by the C3orf38 gene.
Gene The C3orf38 gene is located on chromosome 3 (3p11.1) 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.
Transcripts +C3orf38 TranscriptsProtein NameGene IDTranscript AccessionLength (nt)Length (aa)uncharacterized protein C3orf38285237NM_173824.42414329uncharacterized protein C3orf38 isoform X1285237XM_005264745.52356328
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. +Potential Promoters for the C3orf38 GenePromoterStartEndLength (bp)TranscriptsGXP_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 1234no 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 (cysteine) proteases histidine active site located from amino acids 227-237. +Conserved Post Translational Modification SitesPTMProtein Location (aa)Myristyl site235-240PKC phosphorylation site34-36PKC phosphorylation site86-88PKC phosphorylation site199-201PKC phosphorylation site265-267
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. +C3orf38 Ortholog TableGenus, speciesCommon nameTaxonomic groupDivergence Date (MYA)Accession numberSequence length (aa)Sequence identity (%)Sequence similarity (%)MammalsHomo sapiensHumanPrimates0NP_776185.2 329100100Pan paniscusBonoboPrimates6.7XP_003831564.1 32999.499.7Puma concolorPumaCarnivora96XP_025769652.1 34879.886.6ReptilesMauremys reevesiiReeve's TurtleTestudines312XP_039379932.1 31555.770.5Chelonoidis abingdoniiAbingdon Island Giant TortoiseTestudines312XP_032650981.1 30455.469.9BirdsStrigops habroptilaKākāpōPsittaciformes312XP_030327387.1 30952.166.3Taeniopygia guttataZebra FinchPasseriformes312XP_002190058.5 3065163.9Gallus gallusChickenGalliformes312XP_004938363.2 31244.259.9AmphibiansRhinatrema bivittatumTwo-Lined CaecilianGymnophiona351.8XP_029434832.1 28949.764.5Bufo bufoCommon ToadAnura351.8XP_040279187.1 28943.962.1Xenopus tropicalisTropical Clawed FrogAnura351.8XP_017946806.1 26138.654.8FishChelmon rostratusCopperband ButterflyfishPerciformes435XP_041807133.1 30242.758.2Coregonus clupeaformisLake WhitefishSalmoniformes435XP_041700482.1 30842.460.6Carcharodon carchariasGreat White SharkLamniformes473XP_041066710.1 3084559.8Amblyraja radiataThorny SkateRajiformes473XP_032888490.1 38232.546.5InvertebratesLytechinus variegatusSea UrchinTemnopleuroida684XP_041465399.1 31236.448.3Patiria miniataBat StarValvatida684XP_038067113.1 29434.146.2Cryptotermes secundusTermiteBlattodea797XP_023724689.1 29630.148Crassostrea virginicaEastern OysterOstreidae797XP_022335568.1 34029.646.5Diabrotica virgiferaWestern Corn RootwormColeoptera797XP_028133096.1 28426.943.6Acropora milleporaBranching Stony CoralScleractinia824XP_029194133.1 28832.650.9
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 (TSG).
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 (BAG4) 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 (DNAJB4) is a member of the heat shock protein-40 family (Hsp40), a molecular chaperone, and a tumor suppressor (specifically for colorectal carcinoma).
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