GRB2-associated-binding protein (GAB) gene family includes four homologous (paralogous) namely GAB1, GAB2, GAB3 and GAB4. Collectively, proteins encoded by GAB family genes are associated with variety of functions, of these some important are: development of heart and epidermis, regulation of innate immune response (GAB1), cell proliferation and tyrosine kinase signalling (GAB2), macrophage differentiation (GAB3) and integrin mediated signalling (GAB4) Expansion of Gene Family XKR3 GPM6BPGPM6BP MTND1PMTND1P IGKV2PIGKV2P IGKV1PIGKV1P IL9RP CCECR7ECR7 RPL32RPL32P62P62 UC CECR1 at the Root of Greater Ch#22Ch#22 GAB4GAB4 Apes By Gene Duplication UC HSFY1PHSFY1P ZF4ZF402P02P IGKV2PIGKV2P IGKV3PIGKV3P VN1R9PVN1R9P IL17RAIL17RA CECR6 CECR5 RPL32P5RPL32R P5 AAMDAAMDCC INTS4 THRTHRSPSP ALALG8G8 USP35U ZF75CPZF75CP UC TENM4 MIR708MIR708 ORCPORCP Ch#11Ch#11 GAB2GAB2 RRPS20P27PS20P27 RRPL21P95PL21P95 KKCTD14CTD14 NADNADUFC2UFC2 KKCTD21CTD21 UC NARS2NARS2 UC MIR5579MIR5579 UC Expansion of ZF330ZF330 UC LSM3P4LSM3P4 INPP4B USP38USP38 MIR3139MIR3139 RPSAP36RPSAP36 GUSBP5GUSBP5 EK1PEK1P SSFWWPFWWP Gene Family at the CCh#4h#4# GAB1GAB1 Root of RNF150RNF150 UC IL15 UC LysMPLysMP RPS2P20RPS2P20 SMARCA5SMARCA5 FREM3 GGYPEYPE UC Vertebrates By Genome G6PD CTAG1ACTAG1A ATF4P1ATF4P1 IKBKGP1IKBKGP1 OR3B1POR3B1P DKC1 MIR664bMIR664b MPP1 SMIM9 H2AFB Duplication CCh#Xh#X# GAB3GAB3 FAM3A ATF4P2 CTAG1BCTAG1B FAM223BFAM223B CTAG2CTAG2 SNORA36ASNORA36A SNORA56SNORA56 HMGN1PHMGN1P CF8CF8 MIR1184-1MIR1184-1 CComparisonomparison ooff genomicgenomic Expansion of Gene Protein codincodingg ggenesenes ((nonnon GGAB)AB) Extensive ggeneene deadeathth sysynteniesntenies ooff human GABGAB Family at the Root of PseudogenesPseudogenes rereflectingflecting ggeneene death GeneGene duplication event Vertebrates By Gene genegene ffamilyamily paraloparaloguesgues Duplication RNARNA codincodingg ggenesenes Nucleotide changes/site GenomeGenome duplication event hhighlightsighlights differentdifferent reflect rate of UncharacterizedUncharacterized genesgenes IntraIntra chromosomalchromosomal mmodesodes ooff ggeneene birth and evolution ssegmentalegmental duplication event deadeathth Protein Domains Gene Partner Proteins Expression Interactions GAB4 (574) GAB2 (676) Structure of GAB1 (694) PH domain GAB3 (586) Lineal ancestry PH domains are present in between 3/4 vertebrate several evolutionary GAB genes and single unrelated proteins (GAB, invertebrate GAB gene BTK, OSBP, ARF etc) Pleckstrin Homology (PH) domain Proline rich domain SH3 binding sites implicating the possibility of origin of genes by domain Invertebrates have only one homologue of GAB gene The differences in gene expression, partner protein interactions acquisition (sequentially similar to GAB) suggesting expansion of and protein domain architecture suggest the sub-neo- GAB genes with the origin of vertebrates functionalization after expansion in the GAB gene family .