Protein Names (UNIPROT)

C-jun-amino-terminal kinase-interacting protein 4

Protein function and interaction

The protein encoded by SPAG9 gene belongs to the Jun N-terminal kinase (JNK) interacting protein (JIP) scaffold family. Scaffolding proteins assemble signaling proteins into specific multimeric functional complexes. Co-transfection and immunoprecipitation experiments demonstrated SPAG9 interaction with JNK1, JNK2 and JNK3 (Jagadish et al., 2005 PMID: 15693750).

“In vivo” pull-down assays have shown a role for JLP in bringing together Max and c-Myc along with JNK and p38MAPK,as well as their upstream kinases MKK4 (MAPK kinase 4) and MEKK3 (MAPK kinase kinase 3) (Lee et al, 2002 PMID: 12391307). JIP4 serves as an activator of the p38 mitogen-activated protein (MAP) kinase pathway by a mechanism that requires the MAP kinase kinases MKK3 and MKK6 (Kelkar et al., 2005 PMID: 15767678).

JLP mediates the formation of a ternary complex involving JLP, JNK, and the alpha-subunit of heterotrimeric G protein 13 (Galpha13) and this interaction enhances Galpha(13)-mediated JNK activation. (Kashef et al., 2005 PMID: 16245925).

Yeast two-hybrid screening identified kinesin light chain 1 (KLC1) as a binding partner for JLP (Nguyen et al, 2005 PMID: 15987681), and that Cdo (cell surface Ig) , JLP and p38alpha/beta form complexes in differentiating myoblasts (Takaesu et al., 2006 PMID: 17074887).

SPAG9 has been demonstrated to be a tyrosine phosphorylation target in T cells (Brill et al., 2004 PMID: 15144186) and after EGF stimulation in breast cancer cells (Chen et al., 2007 PMID: 17855441). SPAG9 may be phosphorilated by ATM and/or ATR in response to DNA damage (Matsuoka et al., 2007 PMID: 17525332).

In the germinative testicular cells, the testis specific isoform 5 of SPAG9 may have a role in spermatozoa adherence and/or in the subsequent fertilization process and may also be involved in transducing signals (Jagadish et al., 2005 PMID: 15693750).