SMCO3

Key takeaways

SMCO3 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect SMCO3 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of SMCO3 from memory before moving on to harder problems.

Reference excerpt

Single-pass membrane and coiled-coil domain-containing protein 3 is a protein that is encoded in humans by the SMCO3 gene.

Gene

Aliases SMCO3 has 2 aliases, C12orf69 and LOC440087.

Location SMCO3 is located on the negative strand of chromosome 12 (12p12.3) and spans 10,460 base pairs (chr12:14,803,723-14,814,182). It has 2 exons that flank a single intron.

Gene Neighborhood SMCO3 is flanked by WW domain binding protein 11 (WBP11) and Ecto-ADP-ribosyltransferase 4 (ART4) on the minus strand and overlaps with C12orf60 on the plus strand. There is only a single isoform of this gene.

Expression SMCO3 is expressed in very low levels in several different human tissues including cervix, connective tissue, eye, lung and prostate. This highest expression of SMCO3 is seen in the kidney, liver and spleen. SMCO3 is also expressed at higher levels in cancers, especially chondrosarcoma and clear-cell renal cell carcinoma. SMCO3 expression is only seen in the fetus and adult and not in the embryoid bodies, blastocysts, infants and juveniles stages of development. The expression of SMCO3 appears to depend upon the species, with the Mus musculus homolog of SMCO3 expressed at much higher levels in the eye compared to humans.

Promoter The promoter region of SMCO3 is 1,100 base pairs long and begins 961 base pairs upstream of the 5' UTR with the end of the promoter completely overlapping the first exon.

Variants There are 2,152 known nucleotide-level variants of which 27 are coding synonymous single nucleotide polymorphisms. The vast majority of single nucleotide polymorphisms (SNPs) occur within the intron with only a quarter occurring translated regions. No SMCO3 variants are known to be associated with any disorder.

mRNA

Splice Variants The mRNA transcript of SMCO3 is 2,104 base pair long. There are no mRNA variants of SMCO3.

Regulation The SMCO3 promoter has many transcription factors binding sites including for cartilage homeoprotein 1, cAMP-responsive element binding proteins, PAR/bZIP family and vertebrate TATA binding protein factor.

Protein

General Properties SMCO3 is 225 amino acid long with a predicted molecular weight of 24.9. It is a slightly basic protein with a predicted isoelectric point of 8.3.

Composition SMCO3 is comparably enriched in lysine and comparably poor in proline and phenylalanine compared to other human proteins. SMCO3 contains several long, uncharged segments but does not have any significantly charged segments. Despite being a transmembrane protein there are no significantly hydrophobic regions nor any significantly hydrophilic regions.

Domains and Motifs SMCO3 has a single domain, DUF4344 (aa15:221) which is currently uncharacterised. C12orf60 also contains this domain. It contains a single transmembrane region (aa155-175) and has two coiled-coil regions (aa62-92, aa183-207). The C-terminus of SMCO3 contains a KKXX-like motif suggesting endoplasmic reticulum localisation.

Structure The secondary structure of SMCO3 consists of several α-helices and a single β-pleated sheet interspersed with disordered coiled coil regions. in Orthologs of SMCO3 similarly show secondary structure dominated by alpha helices. There are no disulfide bridges predicted in the tertiary structure.

Biochemical Function The function of the SMCO3 protein is currently unknown.

Post-Translational Modifications The N-terminus of SMCO3 is cleaved, the first methionine residue removed and the N-terminus acetylated to improve stability. Additionally there are several sites that are likely phosphorylated and a single N-linked glycosylation site which is typical in ER integral membrane proteins. Unlike typical ER integral membrane proteins there is no amino-acid signal sequence.

Sub-Cellular Localisation SMCO3 contains a transmembrane domain (aa155-175). Additionally the KKXX-like motif highly suggest that it is an endoplasmic reticulum integral membrane protein.

Interacting Proteins Two-hybrid assays have identified that SMCO3 interacts with five proteins: FUS RNA Binding Protein (FUS), mitogen-activated protein kinase 9 (MAPK9), STN1 subunit of CST complex (OBFC1), protein phosphatase 2 catalytic subunit alpha (PPP2CA) and tripartite motif containing 39 (TRIM39). However, it is not known to take part in any pathway although the structure indicates that it takes part in protein-protein interactions. PP2CA, OBFC1, FUS1 and MAPK9 are all either implicated in cancer or have altered expression in cancer which suggests that SMCO3 may be useful as an eQTL for certain cancers.

Clinical Significance

Mutations Only 3.4% of SNPs were predicted to be deleterious, of which none had any clinical significance.

Disease Associations GWAS showed no significant associations of SMCO3 with any disease or traits. SMCO3 is not known to be implicated in any disease. SMCO3 is expressed at higher levels in certain cancers, especially chondrosarcoma and clear-cell renal cell carcinoma.

Evolution

Conservation

The amino acid sequence of SMCO3 is highly conserved compared to other human proteins. There is dramatically lower levels of sequence divergence than expected, even compared to proteins known to have low levels of sequence divergence with time.

Homology SMCO3 in largely conserved in amniotes. Orthologs have been identified in many mammals, reptiles and birds. The closest ortholog is found in Pan troglodytes and has a 99.7% sequence similarity. More distant homologs have also been identified in a select few bony fish but orthologs are not seen in cartilaginous fish, insects or other invertebrates. No paralogs of SMCO3 in humans have been identified.

References

Illustrations

Worked examples

Example 1 — a first encounter with SMCO3

Start with the simplest possible case. Write down what SMCO3 claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to SMCO3 before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about SMCO3 ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of SMCO3

In research: SMCO3 appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses SMCO3 in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: SMCO3 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 12, Proteins, so understanding it makes those chapters shorter.
In everyday life: Look for SMCO3 outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study SMCO3 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what SMCO3 means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain SMCO3 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is SMCO3 in simple terms?

Single-pass membrane and coiled-coil domain-containing protein 3 is a protein that is encoded in humans by the SMCO3 gene. Gene Aliases SMCO3 has 2 aliases, C12orf69 and LOC440087.

Why does SMCO3 matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study SMCO3?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on SMCO3.