SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2), also known as formin-binding protein 2 (FNBP2), is a

mammalian Mammals () are a group of vertebrate animals constituting the class (biology), class Mammalia (), characterized by the presence of mammary glands which in Female#Mammalian female, females produce milk for feeding (nursing) their young, a ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''SRGAP2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. It is involved in

neuronal migration The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The fiel ...

and differentiation and plays a critical role in synaptic development, brain mass and number of cortical neurons. Downregulation of srGAP2 inhibits cell–cell repulsion and enhances cell–cell contact duration. SRGAP2

dimerizes A dimer () ('' di-'', "two" + ''-mer'', "parts") is an oligomer consisting of two monomers joined by bonds that can be either strong or weak, covalent or intermolecular. Dimers also have significant implications in polymer chemistry, inorganic ch ...

through its F-BAR domain.

SRGAP2C SLIT-ROBO Rho GTPase activating protein 2C is a protein in humans that is encoded by the SRGAP2C gene. Cortical development gene Slit-Robo Rho GTPase-activating protein 2 (SRGAP2) has been highly conserved over mammalian evolution, and human is th ...

, a shortened version found in early

hominins The Hominini form a taxonomic tribe of the subfamily Homininae ("hominines"). Hominini includes the extant genera ''Homo'' (humans) and '' Pan'' (chimpanzees and bonobos) and in standard usage excludes the genus ''Gorilla'' (gorillas). The t ...

and humans that only has the F-BAR domain, antagonizes its action. It slows maturation of some neurons and increases neuronal spine density.

Evolution

''SRGAP2'' is one of 23 genes that are known to be duplicated in humans but not other

primates Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...

. ''SRGAP2'' has been duplicated three times in the

human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...

in the past 3.4 million years: one duplication 3.4 million years ago (mya) called SRGAP2B, followed by two that copied SRGAP2B 2.4 mya into

and ~1 mya into SRGAP2D. All three duplications are also present in

Denisovan The Denisovans or Denisova hominins ) are an extinct species or subspecies of archaic human that ranged across Asia during the Lower and Middle Paleolithic. Denisovans are known from few physical remains and consequently, most of what is known ...

s and

Neanderthal Neanderthals (, also ''Homo neanderthalensis'' and erroneously ''Homo sapiens neanderthalensis''), also written as Neandertals, are an extinct species or subspecies of archaic humans who lived in Eurasia until about 40,000 years ago. While th ...

s. They are shortened in the same manner, keeping the

F-box F-box proteins are proteins containing at least one F-box domain. The first identified F-box protein is one of three components of the SCF complex, which mediates ubiquitination of proteins targeted for degradation by the 26S proteasome. Core co ...

domain but ditching the

RhoGAP RhoGAP domain is an evolutionary conserved protein domain of GTPase activating proteins towards Rho/ Rac/ Cdc42-like small GTPases. Human proteins containing this domain ABR; ARHGAP1; ARHGAP10; ARHGAP11A; ARHGAP11B; ARHGAP12; AR ...

and SH3 domains. All humans possess SRGAP2C. * SRGAP2C inhibits the function of the ancestral copy, SRGAP2A, by heterodimerization and allows faster migration of neurons by interfering with

filopodia Filopodia (singular filopodium) are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. Within the lamellipodium, actin ribs are known as ''microspikes'', and when they extend beyond the lame ...

production as well as slowing the rate of synaptic maturation and increasing the density of synapses in the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...

. SRGAP2B is expressed at very low levels, and SRGAP2D is a

pseudogene Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by Reverse transcriptase, reverse transcription of an mRNA trans ...

. Not all humans have SRGAP2B or SRGAP2D.

References

External links

GeneCards
Developmental genes and proteins Genes on human chromosome 1 {{gene-1-stub