Difference between revisions of "Phosphatase Subfamily Synaptojanin"
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=== Domain === | === Domain === | ||
| − | Synaptojanin has two domains, a CC1-fold phosphatase domain and a 5-phosphatase domain. Both domains are active. | + | 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 <cite> Zucconi01 </cite>., 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 <cite>Cestra99, So00</cite>. |
=== Function === | === Function === | ||
| + | Human SYNJ1 is mainly expressed in brain <cite>McPherson94</cite>. | ||
| + | SYNJ1 binds to amphiphysin via SH3 domain of amphiphysin, which binds to dynamic directly via its SH3 domain. The three proteins form a stable complex in nerve terminals <cite>Micheva97</cite>. | ||
| + | |||
| + | SYNJ1 is stably associated with endophilin in the nerve termina via SH3 domain of endophilin <cite> Micheva97 </cite>. It is worthy pointing out that the SH3 domains of endophilin and amphiphysin bind to different sites of the proline-rich region of SYNJ1 <cite>Cestra99</cite>. | ||
| + | |||
| + | Human SYNJ1 also interacts with other proteins such as GRB2 <cite>McPherson94</cite>. SYNJ1 (p170 isoform) binds to Eps15, a clathrin coat-associated protein, via its proline-rich region <cite>Haffner97</cite>. SYNJ1 binds to sorting nexin 9 (SNX9), a binding partner for the non-receptor and Cdc42-associated kinase (ACK), via its proline-rich region <cite>Yeow-Fong05</cite>. | ||
| + | |||
| + | 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 <cite>Lee04</cite>. 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 <cite>Irie05</cite>. | ||
| + | |||
| + | SYNJ1 variants are associated with [http://en.wikipedia.org/wiki/Parkinsonism Parkinsonism] (a symptom complex that differs from Parkinson disease which is a progressive neurodegenerative illness) <cite>Krebs13, Quadri13, Picillo14, Olgiati14</cite> and bipolar disorder <cite>Saito01, Stopkova04</cite>. | ||
=== References === | === References === | ||
<biblio> | <biblio> | ||
| − | + | #Cestra99 pmid=10542231 | |
| + | #Haffner97 pmid=9428629 | ||
| + | #Irie05 pmid=15821731 | ||
| + | #Krebs13 pmid=23804563 | ||
| + | #Lee04 pmid=14704270 | ||
| + | #McPherson94 pmid=7982917 | ||
| + | #Micheva97 pmid=9341169 | ||
| + | #Olgiati14 pmid=24816432 | ||
| + | #Picillo14 pmid=24532203 | ||
| + | #Quadri13 pmid=23804577 | ||
| + | #Saito01 pmid=11443522 | ||
| + | #So00 pmid=10764144 | ||
| + | #Stopkova04 pmid=15261714 | ||
| + | #Yeow-Fong05 pmid=16137687 | ||
| + | #Zucconi01 pmid=11292345 | ||
</biblio> | </biblio> | ||
Revision as of 22:54, 16 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. The three proteins form a stable complex in nerve terminals [5].
SYNJ1 is stably associated with endophilin in the nerve termina via SH3 domain of endophilin [5]. 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]. SYNJ1 (p170 isoform) binds to Eps15, a clathrin coat-associated protein, via its proline-rich region [6]. SYNJ1 binds to sorting nexin 9 (SNX9), a binding partner for the non-receptor and Cdc42-associated kinase (ACK), via its proline-rich region [7].
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 [8]. 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 [9].
SYNJ1 variants are associated with Parkinsonism (a symptom complex that differs from Parkinson disease which is a progressive neurodegenerative illness) [10, 11, 12, 13] and bipolar disorder [14, 15].
References
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