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

C3orf38
Identifiers
AliasesC3orf38, chromosome 3 open reading frame 38
External IDsMGI: 1914859; HomoloGene: 27867; GeneCards: C3orf38; OMA:C3orf38 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_173824

NM_026273

RefSeq (protein)

NP_776185

NP_080549

Location (UCSC)Chr 3: 88.15 – 88.17 MbChr 16: 64.57 – 64.59 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

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Figure depicting human chromosome 3 and the 3p11.1 location at which the C3orf38 gene is found. Image derived from GeneCards.[5]

The C3orf38 gene is located on chromosome 3 (3p11.1) on the forward strand.[5] It spans 18,771 bases from chr3:88,149,959-88,168,729.[5] It contains 3 exons.[6] Common aliases for this gene are MGC26717, LOC285237, and FLJ54270.[7] Some of the genes neighboring C3orf38 include ZNF654, CGGBP1, and LOC105377202.[8]

Transcripts

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C3orf38 Transcripts
Protein Name Gene ID Transcript Accession Length (nt) Length (aa)
uncharacterized protein C3orf38 285237 NM_173824.4 2414 329
uncharacterized protein C3orf38 isoform X1 285237 XM_005264745.5 2356 328

Protein

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Multiple sequence alignment of C3orf38 protein in humans and various orthologs showing DUF conservation. MSA created using BoxShade tools.

The C3orf38 protein is 329 amino acids in length.[9] A large domain of unknown function, DUF4518, encompasses majority of the C3orf38 protein.[9] This domain is a part of the protein family pfam15008, which is thought to be involved in apoptosis regulation.[10] This pfam15008 is the only member of the cl20886 superfamily.[10] 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.[11] The predicted molecular weight of the entire C3orf38 protein is 37.0 kD and the isoelectric point is 6.01.[12] The DUF4518 contained inside the C3orf38 protein has a predicted molecular weight of 31 kD and an isoelectric point of 6.49.[12]

Regulation

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Gene Level Regulation

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There have been a number of potential promoters identified for the C3orf38 gene, which are described in the table below.[13]

Potential Promoters for the C3orf38 Gene[13]
Promoter Start End Length (bp) 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.[14]

 
Normal human tissue expression profiling (HG-U95E) for the C3orf38 gene. Data pictured is captured from the NCBI GEO database.[14]

Protein Level Regulation

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The C3orf38 protein is expected to be found with the highest confidence in the cytoplasm.[15] This finding is supported by examination of an array of C3orf38 orthologs.[15]

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.[16] Majority of these PTMs are PKC phosphorylation sites.[16] 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.[16] The second site is a eukaryotic thiol (cysteine) proteases histidine active site located from amino acids 227-237.[16]

 
Predicted cellular localization of C3orf38 in humans and several orthologs. Localization predictions gathered from PSORT II Prediction tool.[15]
Conserved Post Translational Modification Sites
PTM Protein Location (aa)
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

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Orthologs for the C3orf38 protein can be found in mammals, reptiles, birds, amphibians, fish, and invertebrates using BLAST searches.[17] A selection of these orthologs can be found in the ortholog table below. There are no paralogs.[17] 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 Table[17][18][19]
Genus, species Common Name Taxonomic Group Divergence Date (MYA) Accession Number Sequence Length (aa) Sequence Identity (%) Sequence Similarity (%)
Mammals Homo sapiens Human Primates 0 NP_776185.2 329 100 100
Pan paniscus Bonobo Primates 6.7 XP_003831564.1 329 99.4 99.7
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
Chelonoidis abingdonii Abingdon Island Giant Tortoise Testudines 312 XP_032650981.1 304 55.4 69.9
Birds Strigops habroptila Kakapo Psittaciformes 312 XP_030327387.1 309 52.1 66.3
Taeniopygia guttata Zebra Finch Passeriformes 312 XP_002190058.5 306 51 63.9
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
Bufo bufo Common Toad Anura 351.8 XP_040279187.1 289 43.9 62.1
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
Coregonus clupeaformis Lake Whitefish Salmoniformes 435 XP_041700482.1 308 42.4 60.6
Carcharodon carcharias Great White Shark Lamniformes 473 XP_041066710.1 308 45 59.8
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
Patiria miniata Bat Star Valvatida 684 XP_038067113.1 294 34.1 46.2
Cryptotermes secundus Termite Blattodea 797 XP_023724689.1 296 30.1 48
Crassostrea virginica Eastern Oyster Ostreidae 797 XP_022335568.1 340 29.6 46.5
Diabrotica virgifera Western Corn Rootworm Coleoptera 797 XP_028133096.1 284 26.9 43.6
Acropora millepora Branching Stony Coral Scleractinia 824 XP_029194133.1 288 32.6 50.9
 
Figure showing an evolution rate graph comparing the C3orf38, cytochrome C, and fibrinogen alpha proteins. Noting the cytochrome C to be a relatively slow-evolving protein and the fibrinogen alpha to be a relatively fast-evolving protein, it is clear that C3orf38 protein evolves at a comparatively moderate rate.

Function

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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.[20] Another study identified C3orf38 as a top candidate tumor suppressor gene (TSG).[21]

Interacting proteins

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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.[22] 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).[23]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000179021Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000059920Ensembl, 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. ^ a b c "C3orf38". www.genecards.org. Archived from the original on 2011-11-29. Retrieved 2021-09-30.
  6. ^ "Homo sapiens chromosome 3 open reading frame 38 (C3orf38), mRNA". 2021-04-16. {{cite journal}}: Cite journal requires |journal= (help)
  7. ^ "AceView: Gene:C3orf38, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2021-09-30.
  8. ^ "C3orf38 chromosome 3 open reading frame 38 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-17.
  9. ^ a b "uncharacterized protein C3orf38 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-09-30.
  10. ^ a b "CDD Conserved Protein Domain Family: DUF4518". www.ncbi.nlm.nih.gov. Retrieved 2021-12-17.
  11. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2021-12-17.
  12. ^ a b "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2021-12-17.
  13. ^ a b "Genomatix Software Suite". Archived from the original on 2012-01-14.
  14. ^ a b "2928464 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-18.
  15. ^ a b c "PSORT II Prediction". psort.hgc.jp. Retrieved 2021-12-18.
  16. ^ a b c d "Motif Scan". myhits.sib.swiss. Retrieved 2021-12-18.
  17. ^ a b c "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2021-12-17.
  18. ^ "EMBOSS Needle < Pairwise Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2021-12-17.
  19. ^ "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2021-12-17.
  20. ^ Park, Kyung Mi; Kang, Eunju; Jeon, Yeo-Jin; Kim, Nayoung; Kim, Nam-Soon; Yoo, Hyang-Sook; Yeom, Young Il; Kim, Soo Jung (2007-04-30). "Identification of novel regulators of apoptosis using a high-throughput cell-based screen". Molecules and Cells. 23 (2): 170–174. doi:10.1016/S1016-8478(23)07370-3. ISSN 1016-8478. PMID 17464193.
  21. ^ Cody, Neal A. L.; Shen, Zhen; Ripeau, Jean-Sebastien; Provencher, Diane M.; Mes-Masson, Anne-Marie; Chevrette, Mario; Tonin, Patricia N. (2009). "Characterization of the 3p12.3-pcen region associated with tumor suppression in a novel ovarian cancer cell line model genetically modified by chromosome 3 fragment transfer". Molecular Carcinogenesis. 48 (12): 1077–1092. doi:10.1002/mc.20535. ISSN 1098-2744. PMID 19347865. S2CID 10259832.
  22. ^ "BAG4". www.genecards.org. Archived from the original on 2011-11-27. Retrieved 2021-12-18.
  23. ^ "DNAJB4". www.genecards.org. Archived from the original on 2021-12-18. Retrieved 2021-12-18.