Table 4 Short overview of SRGAP2 paralogs

SRGAP2A

protein sequence is highly constrained (no changes among non-human primates, and only a single amino-acid change between human and mouse orthologs)

22 exons;

N-terminal F-BAR domain – involved in membrane deformation;

central Rho-GAP domain – specifically stimulates GTPase activity of Rac1;

C-terminal tail with SH3 domain – interacts with

F-BAR domain = autoinhibition?

1q32.1

+

↑in the germinal layers and cortical plate

2

controls cortical neural migration

SRGPA2B

~3.4 million years

promoter and 1–9 exons of ancestral SRGAP2

3'-breakpoint located in intron 9 → truncated

F-BAR domain^b

1q21.1

-

↓

0-4

interacts with SRGAP2A

SRGAP2C

~2.4 million years

duplication of SRGAP2B to 1p11.2

3'-breakpoint located in intron 9 → truncated F-BAR domain^b

1p11.2

+

↑in the germinal layers (in culture longer maintains a high level of expression than SRGAP2A)

2

inhibits SRGAP2A - SRGAP2 knockdown

SRGAP2D

~1 million years

duplication of SRGAP2B and additional deletion of exons 2 and 3 → premature termination codon^b

1p21.1

+

↓

0-4

most likely no function – probably subjected to nonsense-mediated decay