SCRN3

SCRN3
Identifiers
Aliases	SCRN3, SES3, secernin 3
External IDs	OMIM: 614967 MGI: 1921866 HomoloGene: 11601 GeneCards: SCRN3
Gene location (Human) Chr. Chromosome 2 (human) Band 2q31.1 Start 174,395,730 bp End 174,429,575 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2|2 C3 Start 73,142,945 bp End 73,168,162 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence islet of Langerhans prefrontal cortex Achilles tendon jejunal mucosa rectum cavity of mouth monocyte gastrocnemius muscle amygdala Top expressed in facial motor nucleus triceps brachii muscle quadriceps femoris muscle intercostal muscle knee joint gastrocnemius muscle temporal muscle vastus lateralis muscle sternocleidomastoid muscle tibialis anterior muscle More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 79634 74616 Ensembl ENSG00000144306 ENSMUSG00000008226 UniProt Q0VDG4 Q0VDG5 Q3TMH2 RefSeq (mRNA) NM_001193528 NM_024583 NM_029022 NM_001355711 RefSeq (protein) NP_001180457 NP_078859 NP_078859.2 NP_083298 NP_001342640 Location (UCSC) Chr 2: 174.4 – 174.43 Mb Chr 2: 73.14 – 73.17 Mb PubMed search
Wikidata
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Secernin-3 (SCRN3) is a protein that is encoded by the human SCRN3 gene. SCRN3 belongs to the peptidase C69 family and the secernin subfamily. As a part of this family, the protein is predicted to enable cysteine-type exopeptidase activity and dipeptidase activity, as well as be involved in proteolysis. It is ubiquitously expressed in the brain, thyroid, and 25 other tissues. Additionally, SCRN3 is conserved in a variety of species, including mammals, birds, fish, amphibians, and invertebrates. SCRN3 is predicted to be an integral component of the cytoplasm.

Gene

SCRN3 is also commonly known as FLJ23142 and SES3.

Locus

Human SCRN3 Genetic Locus, found using NCBI Gene

Homo sapiens secernin-3 (SCRN3) is a protein-coding gene. It can be found on chromosome 2, with its specific location being 2q31.1, on the '+' strand. The gene is 33,846 base pairs long and contains 8 exons.

Transcript

The most common transcript of the SCRN3 protein-coding gene is transcript variant 1, which is 3052 base pairs long. SCRN3 is expressed at a high level, 2.4 times the average gene in this release.

Human SCRN3 Annotated Conceptual Translation. Translated NM_024583.5 mRNA sequence using Six-Frame Translation tool at Bioline.

Table of Human SCRN3 mRNA isoforms. Sequences and annotations found using isoforms listed in NCBI Gene.¹ Isoform name, accession number, and length of isoform transcript are listed on the left in units of nucleotides. Length of each exon is highlighted in yellow for each isoform variant. For Isoforms X1-X3, the BLAT Search Genome from UCSC was utilized in order to determine the locations of the exons within the sequence, in addition to NCBI Gene.

Human SCRN3 has 8 different isoforms.

Expression

The mRNA of SCRN3 was found to be moderate in humans. SCRN3 is expressed in most major tissues. The mRNA is expressed at slightly elevated levels in the brain, thyroid, heart, and prostate relative to other tissues, though the underlying trend was relatively consistent ubiquitous expression among various tissues.

In an analysis of SCRN3 in situ hybridization of both mouse brain and embryo, no specific areas of strong expression were located, instead showing a moderate expression throughout, confirming that SCRN3 likely has ubiquitous expression within most tissues. Immunohistochemistry data also indicated that human SCRN3 has low tissue, single cell, immune cell, and brain region specificity, once again adding to the evidence of ubiquitous expression.

Protein

Transcript variant 1 of the SCRN3 gene encodes the most common protein isoform, secernin-3 isoform 1, which is 424 amino acids long. The molecular weight of the unmodified SCRN3 protein is approximately 48.413 kDa and the theoretical isoelectric point (pI) of SCRN3 is 5.38. The theoretical isoelectric point, coupled with a predominance of acidic amino acids in the protein's composition, suggest that SCRN3 is a relatively acidic protein.

Additionally, the relative protein abundance of SCRN3 in humans was found to be moderately high compared to other human proteins, at 6.13 ppm.

Domains

SCRN3 has a single notable domain, identified as the Peptidase_C69 Domain, or PepD domain for short. This domain spans from amino acid position 5 to 226 of the protein. The sequences found within this domain are characteristic of the Peptidase C69 family, and more specifically the Secernin subfamily, known to be mainly dipeptidases. Within this family, comparative sequence and structural analysis revealed a cysteine as the catalytic nucleophile, a feature that can be found on Secernin-3.

Structure

Alphafold predicted tertiary structure for human SCRN3 protein

Within the predicted tertiary structure of SCRN3, the most highly conserved amino acids were found predominantly within the internal portion of the protein. This suggests that the most conserved amino acids, being on the inside, are important to providing the structure of the protein, as well as providing internal functionality.

Localization

Within the cell, SCRN3 is predicted to be primarily expressed in the cytoplasm. The cytoplasmic localization prediction was consistent among 5 additional orthologs (Mauremys reevesii, Gallus gallus, Microcaecilia unicolor, Danio rerio, & Anopheles gambiae), confirming the predicted cytoplasmic subcellular localization of human SCRN3.

Post-Translational Modifications

Human SCRN3 Predicted Protein Domain, Motif, and Post-Translational Modification diagram. P = Phosphorylation site, U = Ubiquitination site, S = Sumoylation site, L = Lysine-Acetylation site, O = O-beta-GlcNAc attachment site.

SCRN3 is subject to several predicted post-translational modifications, including phosphorylation, ubiquitylation, sumoylation, lysine acetylation, and O-beta-GlcNAc attachment sites, among others.

Additionally, Secernin-3 provided the first example of a predicted naturally occurring N-terminal glyoxylyl (Glox) electrophile through the use of reverse-polarity activity-based protein profiling (RP-ABPP). Using hydrazine probes, it was confirmed that the cysteine (Cys) residue was post-translationally converted to Glox. This identified an electrophilic n-terminal glyoxylyl group for the first time in secernin-3, though the functions of both the protein and Glox as a cofactor have not yet been experimentally validated.

Homology/Evolution

Paralogs

Multiple Sequence alignment of Human SCRN3 protein and its human paralogs, SCRN2 and SCRN1. Dark Shading indicates exact amino acid matches. Light shading indicates close matches. PepD region and exon boundaries determined from Homo sapiens SCRN3 sequence. Made using Clustal Omega

SCRN3 has two known paralogs, SCRN2 and SCRN1, which share a 67.4% and 63.8% similarity to the SCRN3 protein sequence, respectively. Both paralogs are moderately related to SCRN3. SCRN2 was found within the same species groups as SCRN3. SCRN1 was conserved in fewer species groups, including mammals, birds, reptiles, amphibians, and cartilaginous fish, but not in other fish or invertebrates.

Orthologs

Multiple Sequence Alignment of Human SCRN3 protein with identified invertebrate orthologs. Dark Shading indicates exact amino acid matches. Light shading indicates close matches. PepD region and exon boundaries determined from Homo sapiens SCRN3 sequence. Created using Clustal Omega

Over 100 orthologs exist for the human gene SCRN3. The known orthologs were found to exist in vertebrates and invertebrates, but not in plants, bacteria, or fungi. The divergence date of 20 orthologs found were compared relative to Homo sapiens. Invertebrates are the most distantly related orthologs to human SCRN3, with the furthest median date of divergence from this set of orthologs being 694 million years ago.

Evolution

Graph of Corrected Sequence Divergence vs. Median Date of Divergence. Blue indicates SCRN3. Red indicates SCRN2. Yellow indicates SCRN1. Green indicates Cytochrome C. Orange indicates Fibrinogen Alpha.

SCRN3 time-calibrated unrooted phylogenetic tree. Colored circles indicate taxonomic groupings. Created using Méthodes et Algorithmes pour la Bio-informatique LIRMM “One-Click” Phylogeny Tool

The relative rate of molecular evolution for SCRN3 was moderately high, being slightly lower than the evolution rate of Fibrinogen Alpha, and more rapid than the evolution rate of Cytochrome C. SCRN3 is estimated to have first appeared in invertebrates approximately 694 million years ago, evolving to eventually being found in humans.

Interacting Proteins

A search of PSCQUIC identified 5 proteins that interact with human SCRN3 protein.