MINDY2

Key takeaways

MINDY2 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect MINDY2 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of MINDY2 from memory before moving on to harder problems.

Reference excerpt

Ubiquitin carboxyl-terminal hydrolase MINDY-2 is an enzyme which in humans is encoded by the gene MINDY2 (previously FAM63B). MINDY-2 functions to remove ubiquitin from proteins (specifically 'Lys-48'-linked conjugated ubiquitin), and may be involved in regulating the turnover of proteins in cells.

Gene

Locus FAM63B is located at 15q21.3-q22.1, spanning 90,707 base pairs on chromosome 15.

Alternative Names The full name of FAM63B is family with sequence similarity 63, member B. FAM63B is also listed by its alias, KIAA1164, in some publications.

mRNA

Isoforms The FAM63B gene encodes a primary transcript that can be alternatively spliced into 9 protein variants. FAM63B variant a is the most common isoform found in humans.

Protein

Structure

Primary Structure FAM63B is a member of the Pfam super family, and contains a domain of unknown function (DUF544) that is homologous within the protein family. FAM63B protein variant an also contains a bipartite tryptophan binding motif from W476 to W533. Variant a of the protein also contains a hydrophobic stretch of alanine from 567 to 574 and a mixed charge sequence from residue 598 to 617. FAM63B protein may contain a signal sequence specifying return to the endoplasmic reticulum (KDEL) from residue 607 to 621 in variant a.

Secondary Structure The secondary structure of FAM63B is a combination of coils, some α-helices, and few β-sheets. The Phyre 2 program predicts α-helices in 23% of the protein, β-strands in 9% of the protein, and the remaining 59% of the protein as disordered. The disordered regions coincide with the coiled regions predicted by other programs, and this results in the long stretch of coiled protein beginning at the N-terminus. According to the SOUSI program, there is a 16-amino acid-long span from residues 265 to 280 of FAM63B that could be a transmembrane sequence. However, transmembrane sequences generally need to be at least 20 amino acids long in order to be stable in the membrane, so a transmembrane sequence is unlikely. Therefore, FAM63B is not fixed in the membrane of any organelle and is free to move through the cell and between organelles.

Tertiary Structure Not much is known about the tertiary structure of FAM63B. A predicted folding is shown.

Post-translational Modifications Post-translational modifications of the FAM63B protein.

Subcellular Location FAM63B has predicted NES (nuclear export signals) at Val274 and Leu277. Also, a NLS (nuclear localization signal) is predicted for FAM63B at RKRK at residue 599. In agreement, Reinhardt's method for cytoplasmic/nuclear discrimination predicts FAM63B to be located in the nucleus with a reliability of 76.7%. The presence of both NLS and NES signals and O-GlcNAc post-translational modification of FAM63B supports the protein's location in both the nucleus and cytoplasm and the discovered protein function as a shuttle for vaccinia virus between the nucleus and the cell periphery.

Expression

Expression Level FAM63B has moderately-high to high expression and is constitutively expressed. FAM63B is likely ubiquitously expressed in humans.

Differential Expression Expression of FAM63B is high in the embryonic stem cells and differentiated tissues but low or off in embryoid bodies and other progenitor cells, such as the multipotent mesenchymal stem cells. It is likely that FAM63B is expressed during pluripotency and unipotency but is not important for differentiation, as is occurring in embryoid bodies, mesenchymal stem cells, and other progenitor cells.

Regulation of Expression

Transcriptional Regulation The promoter of FAM63B is GXP_5885, located on the positive strand of chromosome 15 from (58770692, 58771462) and is 711 base pairs long.

Interacting Proteins FAM63B is shown to interact with one protein, KLC-1. KLC-1, kinesin light chain 1, is a protein which recruits kinesin-1 via its cargo binding light chain and contains a bipartite tryptophan binding motif. This motif is present in a vaccinia virus integral membrane protein, A36, that is required for transport of the virus from the perinuclear space to the cell periphery. In the absence of A36, proteins with a bipartite tryptophan binding motif can interact with the kinesin light chain, recruit KLC-1, and promote virus transport from the nucleus to the cytoplasm.

Function The discovered function of FAM63B protein is a transporter of vaccinia virus in the human genome. FAM63B contains a bipartite tryptophan binding motif between W476 and W533. The motif also contains a Q residue at the +2 position, which was found to be a frequent occurrence in proteins that bind KLC-1 or KLC-2. FAM63B is among proteins studied that can rescue virus transport to the cell periphery when expressed in A36-deficient cells, successfully replacing the cytoplasmic domain A36 of vaccinia.

Clinical Significance

Pathology The specific pathology of FAM63B is unknown.

Disease Association FAM63B is part of four networks regulated by miRNA, three of which are linked to neuronal differentiation and dopaminergic gene expression. These findings indicate that FAM63B could be used as a biomarker for the detection and treatment of schizophrenia. Furthermore, aberrant methylation of FAM63B may play a role in the development of schizophrenia. FAM63B has also been ranked 13 of 25 on a list of associated genes relevant to arthritis.

Homology

Paralogs FAM63B has one paralog, FAM63A, which is a gene of unknown function. FAM63A gene encodes a protein that is 469 amino acids long and 76% similar to FAM63B.

Orthologs FAM63B has been found in all multicellular and unicellular eukaryotes, including plants but excluding protists and fungi. The gene has also been found in archaea but not bacteria.

Distant Homologs The most distant homolog of FAM63B is found in Thermoplasmatales archaeon, an archaea that diverged from the human gene 4.25 billion years ago.

Homologous Domains FAM63B is a member of the Pfam super family, and contains a domain of unknown function (DUF544) homologous within the protein family. This region of the protein is highly conserved through FAM63B homologs, as is the bipartite tryptophan binding motif of FAM63B and the C-terminus signal sequence.

Phylogeny The phylogenetic tree below shows a time calibration for the evolution of FAM63B.

References

Illustrations

Worked examples

Example 1 — a first encounter with MINDY2

Start with the simplest possible case. Write down what MINDY2 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 MINDY2 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 MINDY2 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 MINDY2

In research: MINDY2 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 MINDY2 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: MINDY2 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 15, Proteins, so understanding it makes those chapters shorter.
In everyday life: Look for MINDY2 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 MINDY2 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what MINDY2 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 MINDY2 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is MINDY2 in simple terms?

Ubiquitin carboxyl-terminal hydrolase MINDY-2 is an enzyme which in humans is encoded by the gene MINDY2 (previously FAM63B). MINDY-2 functions to remove ubiquitin from proteins (specifically 'Lys-48'-linked conjugated ubiquitin), and may be involved in regulating the turnover of proteins in cells.

Why does MINDY2 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 MINDY2?

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 MINDY2.