C17orf58

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.

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 from 67,991,099 to 67,996,469, spanning 5,371 base pairs.

Expression

Gene

Gene expressed variably and ubiquitously at a moderate and high level across many tissues in humans. 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.

Clinical significance

C17orf58 is a prognostic marker in Kidney renal papillary cell carcinoma. 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.

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.

Transcript variant	Accession number	Length	Exons	Protein isoform	Protein Accession number	Length
variant 1		1,380 nt	1,2,3	isoform a		97
variant 2		1,523 nt	1,2,3	isoform b		75
variant 3		2,105 nt	1,2,3,4	isoform c		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.

Composition

C17orf58 protein is highly enriched of Arginine, Alanine and Proline and has lower amount of Threonine, Hydrophobic cluster and Aliphatic hydrophobic.

Domain

The protein has three domains: Netrin-like domain, PRK07764 and TIMP-like_OB-fold.

Protein interactions

Table 2. Interactants with C17orf58 protein.

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. 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,, and analyzed using .

Genus and species	Common name	Taxonomic group	Date of divergence from the human lineage	Accession number	sequence length	sequence identity to human protein	sequence similarity to human protein
Mammal	Human	Primates	0		339aa	100%	100%
Mammal	Chlorocebus sabaeus	Monkey	43		341aa	96%	96%
Mammal	Eschrichtius robustus	Whales	94		331aa	82%	86%
Birds	Rhea pennata	Birds	319		381aa	41%	52%
Reptiles	Lepidochelys kempii	Turtles	319		389aa	41%	49%
Amphibian	Ambystoma mexicanum	Salamanders	352		397aa	59%	77%
Amphibian	Xenopus laevis	Frogs	352		399 aa	56%	71%
Fish	Pangasianodon hypophthalmus	Ray-finned Fishes	429		384 aa	52%	69%
Fish	Engraulis encrasicolus	Ray-finned Fishes	429		393 aa	39%	54%