Chromosome 17 open reading frame 58 or C17orf58 is a protein coding human gene that located in collagen-containing extracellular matrix and encodes protein C17orf58 isoform c precursor.[1]
Gene
C17orf58 is a protein which in humans is the longest isoform encoded by the C17orf58 gene. C17orf58, also known as chromosome 17 open reading frame 58, is located on the negative strand of chromosome 17 (17q24.2) from 67,991,099 to 67,996,469, spanning 5,371 base pairs.[2]
Expression
- Gene
Gene expressed variably and ubiquitously at a moderate and high level across many tissues in humans.[3] The gene has high tissue specificity with enhanced expression in the placenta. The gene has low cell type specificity and immune cell specificity, but enriched in fibroblasts and cardiomyocytes. Expression clusters are associated with ECM organization in tissues and fibroblasts, and with innate immunity in immune cells.[4]
Clinical significance
C17orf58 is a prognostic marker in Kidney renal papillary cell carcinoma.[5] Recent research has observed overexpression of C17orf58 in T-cell lymphomas and leukemias. Since the RNA expression is relatively low in most normal cell, and C17ORF58 knockdown in T-cell lines results in the upregulation of numerous pro-apoptotic genes, it suggests that increased expression of c17orf58 might linked with the proliferation of malignant T cells.[6]
mRNA
C17orf58 contains four exons. There are 3 different transcript variants in humans through alternative splicing: transcript variant 1, transcript variant 2, transcript variant 3(see Table 1).
| Transcript variant | Accession number | Length(nt) | Exons | Protein isoform | Protein Accession number | Length(aa) |
|---|---|---|---|---|---|---|
| variant 1 | NM_181655.4 | 1,380 nt | 1,2,3 | isoform a | NP_858041.2 | 97 |
| variant 2 | NM_181656.5 | 1,523 nt | 1,2,3 | isoform b | NP_858042.2 | 75 |
| variant 3 | NM_001382359.1 | 2,105 nt | 1,2,3,4 | isoform c | NP_001369288.1 | 339 |
Protein
UPF0450 protein C17orf58 isoform c precursor is the longest isoform of c17orf58 protein. It consists of 339 amino acids. It has a molecular mass of 37~kDa and its PI is approximately 10. The protein is expressed in the nucleus in most tissues and localized to the plasma membrane and in the cytosol.[4]
Composition
C17orf58 protein is highly enriched of Arginine (R), Alanine (A) and Proline (P) and has lower amount of Threonine (T), Hydrophobic cluster (FIKMNY) and Aliphatic hydrophobic (LVIFM).[7]
Domain
The protein has three domains: Netrin-like domain, PRK07764 (DNA polymerase III subunits gamma and tau) and TIMP-like_OB-fold.[8][9]
Protein interactions
Table 2. Interactants with C17orf58 protein.[10]
| Protein symbol | Protein name | Description |
| MYSM1 | Myb like, SWIRM and MPN domains 1 | a specific tag for epigenetic transcriptional repression, acting as a coactivator. |
| SMARCB1 | SWI/SNF related BAF chromatin remodeling complex subunit B1 | An ATP- dependent chromatin-remodeling complex plays roles in cell proliferation and differentiation. |
| BPTF | bromodomain PHD finger transcription factor | a complex which catalyzes ATP-dependent nucleosome sliding and facilitates transcription of chromatin. |
| PBRM1 | polybromo 1 | Acts as a negative regulator of cell proliferation. |
| ANKFN1 | Ankyrin repeat and fibronectin type III domain containing 1. | Predicted to be involved in establishment of mitotic spindle orientation. |
| SMARCE1 | SWI/SNF related BAF chromatin remodeling complex subunit E1 | Involved in transcriptional activation. |
| SLC35G1 | solute carrier family 35 member G1 | negative regulator of plasma membrane calcium-transporting ATPases preventing calcium efflux from the cell |
| C1QTNF4 | C1q and TNF related 4 | May be involved in the regulation of the inflammatory network. |
| OR7D2 | olfactory receptor family 7 subfamily D member 2 | G-protein-coupled receptors. Located in the nose. |
Evolution
C17orf58 orthologs are found in mammals, birds/reptiles, amphibians and fish but not in any invertebrates( See Table 3). C17orf58 first appeared approximately 429 millions years ago in fish. C17orf58 does not belong to a multi-gene family. While the gene in humans has evolved alternative splicing to produce multiple isoforms, there are no known alternate splice isoforms of the c17orf58 protein found within the most distantly related Engraulis encrasicolus.
Table 3. c17orf58 orthologs and related properties. It shows 8 orthologs of the c17orf58 in mammals, birds & reptiles, amphibians and fishes. Collected data are from NCBI, Time-Tree, and analyzed using EMBOSS NEEDLE.
| Genus and species | Common name | Taxonomic group | Date of divergence from the human lineage(MYA) | Accession number | sequence length (aa) | sequence identity to human protein | sequence similarity to human protein |
| Mammal | Human | Primates | 0 | NP_001369288.1 | 339aa | 100% | 100% |
| Mammal | Chlorocebus sabaeus | Monkey | 43 | XP_072861199.1 | 341aa | 96% | 96% |
| Mammal | Eschrichtius robustus | Whales | 94 | XP_068386886.1 | 331aa | 82% | 86% |
| Birds | Rhea pennata | Birds | 319 | XP_062447700.1 | 381aa | 41% | 52% |
| Reptiles | Lepidochelys kempii | Turtles | 319 | XP_073166835.1 | 389aa | 41% | 49% |
| Amphibian | Ambystoma mexicanum | Salamanders | 352 | XP_069511122.1 | 397aa | 59% | 77% |
| Amphibian | Xenopus laevis | Frogs | 352 | XP_018089386.1 | 399 aa | 56% | 71% |
| Fish | Pangasianodon hypophthalmus | Ray-finned Fishes | 429 | XP_026788945.1 | 384 aa | 52% | 69% |
| Fish | Engraulis encrasicolus | Ray-finned Fishes | 429 | XP_063050989.1 | 393 aa | 39% | 54% |
Reference
- ^ "C17orf58 chromosome 17 open reading frame 58 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-09-21.
- ^ "C17orf58 chromosome 17 open reading frame 58 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-10-19.
- ^ "C17orf58 Gene Expression - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-04.
- ^ "C17orf58 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2025-10-19.
- ^ "C17orf58 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2025-09-21.
- ^ Tobon J, Nowialis P, Lopusna K, Chen D, Badar A, Abdelghany R, Noel E, Fingeret J, Pozas G, Opavska J, Fujiwara H (November 2023). "C17ORF58 Is Upregulated in Peripheral T-Cell Lymphomas and Encodes a Protein Critical for Survival of PTCL Cells.". Blood. 142: 4145. doi:10.1182/blood-2023-186873
- ^ EMBL-EBI & European Bioinformatics Institute. "Job Dispatcher homepage | EMBL-EBI". www.ebi.ac.uk. Retrieved 2025-12-04.
- ^ "GeneCards.C17orf58"
- ^ "UPF0450 protein C17orf58 isoform c precursor [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-12.
- ^ "STRING: functional protein association networks". string-db.org. Retrieved 2025-12-04.