C5orf46

C5orf46
Identifiers
Aliases	C5orf46, SSSP1, chromosome 5 open reading frame 46, AP-64
External IDs	MGI: 2684940; HomoloGene: 19192; GeneCards: C5orf46; OMA:C5orf46 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q32 Start 147,880,726 bp End 147,906,538 bp
Gene location (Mouse) Chr. Chromosome 18 (mouse) Band 18|18 B3 Start 43,910,261 bp End 43,925,943 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle skin of thigh human penis skin of abdomen ascending aorta skin of hip vulva parotid gland nipple Descending thoracic aorta Top expressed in esophagus lip skin of abdomen skin of external ear skin of back umbilical cord epidermis hair follicle stomach thymus More reference expression data BioGPS n/a
Gene ontology Molecular function molecular function Cellular component extracellular exosome extracellular region Biological process biological process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 389336 225443 Ensembl ENSG00000178776 ENSMUSG00000071858 UniProt Q6UWT4 Q3V2D2 RefSeq (mRNA) NM_206966 NM_001033280 RefSeq (protein) NP_996849 NP_001028452 Location (UCSC) Chr 5: 147.88 – 147.91 Mb Chr 18: 43.91 – 43.93 Mb PubMed search
Wikidata
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C5orf46 is a protein coding gene located on chromosome 5 in humans. It is also known as sssp1, or skin and saliva secreted protein 1. There are two known isoforms known in humans, with isoform 2 (analyzed throughout this page) being the longer of the two. The protein encoded is predicted to have one transmembrane domain, and has a predicted molecular weight of 9,692 Da, and a basal isoelectric point of 4.67.

Gene

Found on the minus strand of chromosome 5, the c5orf46 isoform X2 is 4679 nucleotides in length and has 4 exons.

Evolution and orthologs

C5orf46 orthologs are only found in Chordata, with the earliest instance being found in the Ornithorhynchus anatinus around 177 million years ago. Highly conserved regions include the signal peptide sequence found towards the N-terminus of the protein. There are no paralogs found in humans.

Table 1: C5orf46 Orthologs

Genus/Species	Organism Common Name	Order	Accession Number	Length (amino acids)	Sequence Identity with Human	Sequence Similarity with Human
Homo sapiens	Human	Primates	XP_005268503.2	102	100	100
Pan paniscus	Bonobo	Primates	XP_003829110.1	87	98	98
Octodon degus	Common degu	Rodentia	XP_004631400.1	73	68	82
Mus musculus	House mouse	Rodentia	NP_001028452.1	93	68	77
Urocitellus parryii	Arctic ground squirrel	Rodentia	XP_026240295.1	92	59	72
Leptonychotes weddelli	Weddell seal	Carnivora	XP_006732700.1	124	78	94
Acinonyx jubatus	Cheetah	Carnivora	XP_026897868.1	147	76	87
Zalophus califronianus	California sea lion	Carnivora	XP_027462230.1	84	75	86
Sorex araneus	Common shrew	Eulipotyphla	XP_004618219.1	73	74	79
Vicugna pacos	Alpaca	Artiodactyla	XP_006204536.1	88	73	81
Delphinapertus leucas	Beluga whale	Artiodactyla	XP_030618631.1	88	73	81
Camelus bactrianus	Bactrian camel	Artiodactyla	XP_010954370.1	83	73	79
Orcinus orca	Killer Whale	Artiodactyla	XP_004280428.1	88	71	83
Sus scrofa	Wild boar	Artiodactyla	XP_003354397.2	90	67	82
Manis javanica	Seunda pangolin	Pholidota	XP_017496222.1	155	62	79
Myotis davidii	Bat	Chiroptera	XP_015428095.1	104	41	50
Elephantulus edwardii	Cape elephant shrew	Macroscelidea	XP_006893786.1	76	78	80
Dasypus novemcinctus	Nine-banded armadillo	Cingulata	XP_004447160.1	88	72	82
Vombatus urinus	Common wombat	Diprotodontia	XP_027697780.1	78	45	62
Phascolarctos cinereus	Koala	Diprotodontia	XP_020854530.1	78	44	62
Ornithorhynchus anatinus	Platypus	Monotremata	XP_028912384.1	80	43	61

Promoters

A Genomatix ElDorado Archived 2021-12-02 at the Wayback Machine promoter database search predicted one promoter for c5orf46. This promoter has the ID number of GXP_123762 and transcript ID number GXT_22785522. The promoter is located on the minus strand of chromosome 5, and was predicted to range from nucleotides 147906451 to 147908007, making it 1557 nucleotides in length.

Transcription factors

A total of 428 transcription factor binding sites were predicted to be located within the predicted promoter sequence. The predictions included the following transcription factors:

• Sine oculis homeodomain factors (SIXF)
• p53 tumor suppressor (P53F)
• Vertebrate homologues of enhancer of split complex (HESF)
• Histone nuclear factor P (HNFP)
• NKX homeodomain factors (NKXH)
• C/EBP homologous protein (CHOP)
• X-box binding factors (XBBF)
• TALE homeodomain class recognizing TG motifs (TALE)
• Human and murine ETS1 factors (ETSF)
• SWI/SNF related nucleophosphoproteins with a RING finger DNA binding motif (RUSH)
• Fork head domain factors (FKHD)
• RNA Polymerase II transcription factor II B (TF2B)
• TGF-beta induced apoptosis proteins (TAIP)
• GATA binding factors (GATA)
• Ccaat/Enhancer binding protein (CEBP)
• cAMP-responsive element binding proteins (CREB)
• Vertebrate TATA binding protein factor (VTBP)

Expression

C5orf46 is largely expressed in salivary glands and skin tissue, though some expression in heart tissue, testis, and placenta is also observed.

C5orf46 expression microarray data comparisons between healthy and psoriasis patients.

Microarray data measuring c5orf46 expression in psoriasis patients revealed a trend of low expression in patients with lesional psoriasis. Samples from lesional psoriasis patients had significantly lower c5orf46 expression compared to non-lesional psoriasis patients and healthy control samples.

Protein

Primary structure

C5orf46 is 102 amino acids in length. The protein has a signal peptide sequence at its N-terminus. The signal peptide sequence is highly conserved in orthologs. The amino acid sequence includes a DDKPD sequence that is repeated, with an aspartate and lysine rich region.

Secondary structure

Through prediction software including the Chou and Fasman Secondary Structure Prediction server and Prabi GOR IV Prediction analysis, two alpha-helical segments were predicted.

Tertiary structure

Predictive models made by Phyre2 and SWISS-Model have shown two alpha-helical domains with a bend between them.

Protein regulation

C5orf46 has multiple predicted post-translation modification sites, and one modification identified through mass spectrometry. Mass spectrometry analysis of extracts from a NCI-H2228 lung cancer cell line have identified an acetylation site at K42. C5orf46 has predicted phosphorylation sites at T14, S52, S84, and S86. Predicted sumoylation sites are present at K41, K44, K48, K54, and K57. There are two predicted O-GlcNAcylation sites found at S100 and S101.

Localization

An analysis of the c5orf46 amino acid sequence revealed that the protein is likely to be secreted. Further sequence analyses have predicted that the protein has one transmembrane domain, with an intracellular N-terminal domain.

Interactions

C5orf46 has been predicted to interact with phosphopantothenoylcysteine synthetase (PPCS) and transmembrane BAX inhibitor motif containing 6 (TMBIM6) through affinity purification-mass spectrometry methods.

Clinical significance

C5orf46 has been shown to be a prognostic marker in renal and cervical cancer, with high expression being linked to unfavorable outcomes. These conclusions were based on Human Protein Pathology Atlas gene expression analyses and survival outcomes of 651 and 291 patients with renal and cervical cancer respectively. In these analyses, patients that were classified with high expression of c5orf46 were shown to have a 50% lower survival rate after 10 years than patients with low expression.