Difference between revisions of "Phosphatase Subfamily Synaptojanin"

Revision as of 20:09, 17 April 2015

Phosphatase Classification: Fold CC1: Superfamily CC1: Family Sac: Subfamily Synaptojanin

Evolution

Synaptojanin is found throughout eukaryotes except excavate and some chromalveolate. Human has two members (SYNJ1/INPP5G and SYNJ2/INPP5H) which originated from a duplication event in tetrapods (internal data of gOrtholog database).

Domain

Synaptojanin has two domains, a CC1-fold phosphatase domain and a 5-phosphatase domain. Both domains are active. Synaptojanin also has a proline-rich region at C-terminal tail [1]., which binds to SH3 or WW domains of other proteins (e.g. endophilin and amphiphysin, EEN and Abi-1). The SH3 domains of different proteins bind to different sites of the proline-rich region [2, 3].

Function

Human SYNJ1 is mainly expressed in brain [4].

SYNJ1 binds to amphiphysin via SH3 domain of amphiphysin, which binds to dynamic directly via its SH3 domain [5]. The three proteins form a stable complex in nerve terminals [6].

SYNJ1 is stably associated with endophilin in the nerve termina via SH3 domain of endophilin [6]. It is worthy pointing out that the SH3 domains of endophilin and amphiphysin bind to different sites of the proline-rich region of SYNJ1 [2].

Human SYNJ1 also interacts with other proteins such as GRB2 [4, 7]. SYNJ1 (p170 isoform) binds to Eps15, a clathrin coat-associated protein, via its proline-rich region [8]. SYNJ1 binds to sorting nexin 9 (SNX9), a binding partner for the non-receptor and Cdc42-associated kinase (ACK), via its proline-rich region [9].

SYNJ1 is regulated by its phosphorylation state in the proline-rich region at C terminal. CDK5 phosphorylates SYNJ1 at serine-1144 which is close to the endophilin-binding site, which results in inhibiting the association of SYNJ1 and endophilin [10]. EphB2 phosphorylates SYNJ1 at tyrosine residues in the proline-rich region and inhibits both the interaction with endophilin and the 5'-phosphatase activity of SYNJ1 [11].

SYNJ1 variants are associated with Parkinsonism (a symptom complex that differs from Parkinson disease which is a progressive neurodegenerative illness) [12, 13, 14, 15] and bipolar disorder [16, 17].

References

1. Error fetching PMID 11292345: [Zucconi01]
2. Error fetching PMID 10542231: [Cestra99]
3. Error fetching PMID 10764144: [So00]
4. Error fetching PMID 7982917: [McPherson94]
5. Error fetching PMID 8552192: [McPherson96]
6. Error fetching PMID 9341169: [Micheva97]
7. Error fetching PMID 8022809: [McPherson94b]
8. Error fetching PMID 9428629: [Haffner97]
9. Error fetching PMID 16137687: [Yeow-Fong05]
10. Error fetching PMID 14704270: [Lee04]
11. Error fetching PMID 15821731: [Irie05]
12. Error fetching PMID 23804563: [Krebs13]
13. Error fetching PMID 23804577: [Quadri13]
14. Error fetching PMID 24532203: [Picillo14]
15. Error fetching PMID 24816432: [Olgiati14]
16. Error fetching PMID 11443522: [Saito01]
17. Error fetching PMID 15261714: [Stopkova04]