Synaptojanin-1 (SYNJ1)
The protein contains 1573 amino acids for an estimated molecular weight of 173103 Da.
Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:27435091). Has a role in clathrin-mediated endocytosis (By similarity). Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2 (By similarity). (updated: Oct. 25, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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Biological Process
Brain development
Inositol phosphate dephosphorylation
Inositol phosphate metabolic process
Learning
Membrane organization
Neurotransmitter transport
Phosphate-containing compound metabolic process
Phosphatidylinositol biosynthetic process
Phosphatidylinositol dephosphorylation
Phosphatidylinositol metabolic process
Phospholipid metabolic process
Positive regulation of endosome organization
Positive regulation of gliogenesis
Positive regulation of receptor-mediated endocytosis
Positive regulation of synaptic vesicle uncoating
Postsynaptic neurotransmitter receptor internalization
Regulation of synaptic vesicle membrane organization
Response to cytokine
Response to retinoic acid
Small molecule metabolic process
Synaptic vesicle endocytosis
Synaptic vesicle priming
Synaptic vesicle transport
Synaptic vesicle uncoating
Cellular Component
Clathrin coat of coated pit
Cytosol
Membrane coat
Neuron projection
Obsolete cell
Perinuclear region of cytoplasm
Postsynapse
Presynapse
Synaptic membrane
Terminal bouton
Vesicle membrane
Molecular Function
Inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity
Inositol-1,4,5-trisphosphate 5-phosphatase activity
Inositol-polyphosphate 5-phosphatase activity
Nucleotide binding
Phosphatidylinositol phosphate 4-phosphatase activity
Phosphatidylinositol phosphate 5-phosphatase activity
Phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity
Phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity
Phosphatidylinositol-3-phosphatase activity
Phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity
Phosphatidylinositol-4-phosphate phosphatase activity
RNA binding
SH3 domain binding
The reference OMIM entry for this protein is 604297
Synaptojanin 1; synj1
DESCRIPTION
Synaptojanin-1 is a polyphosphoinositide phosphatase that has a role in clathrin-coated pit dynamics (Perera et al., 2006).CLONING
Haffner et al. (1997) used rat synaptojanin probes to isolate from a human cerebellum cDNA library 2 overlapping clones encompassing the complete coding region of the human SYNJ1 gene, which encodes a major presynaptic protein concentrated at clathrin-coated endocytic intermediates in nerve terminals. The authors found that synaptojanin-170, an alternatively spliced isoform of SYNJ1, binds EPS15 (600051), a clathrin coat-associated protein. Binding was mediated by the C-terminal region of synaptojanin-170, which contains 3 asparagine-proline-phenylalanine (NPF) repeats. This motif had been found to be the core of the binding site for the EH domains of EPS15. These findings suggested that SYNJ1 can be recruited to clathrin-coated pits via a multiplicity of interactions. In the rat, McPherson et al. (1996) found that synaptojanin is a nerve terminal protein that appears to participate with dynamin (see 602377) in synaptic vesicle recycling It has a molecular mass of 145 kD and is a member of the inositol-5-phosphatase family, which includes the product of the gene that is defective in the oculocerebrorenal syndrome of Lowe (OCRL; 300535). Synaptojanin has 5-phosphatase activity, and its N-terminal domain is homologous with yeast Sac1 (SACM1L; 606569), which is genetically implicated in phospholipid metabolism and in the function of the actin cytoskeleton. The C terminus, which is of different lengths in adult and developing neurons due to the alternative use of 2 termination sites, is proline-rich, consistent with the reported interaction of synaptojanin with the SH3 domains of GRB2 (108355). Synaptojanin also bound the SH3 domain of amphiphysin (AMPH; 600418), a presynaptic protein with a putative function in endocytosis. These data suggested a link between phosphoinositide metabolism and synaptic vesicle recycling. Perera et al. (2006) stated that both the 145-kD and 170-kD synaptojanin isoforms contain an N-terminal SAC1-like domain, followed by a 5-prime phosphatase domain and a proline-rich domain. Only the 170-kD isoform has an NPF domain and a C-terminal region containing binding sites for the ear domains of AP2 (see AP2A1; 601026) and clathrin.GENE FUNCTION
Cremona et al. (1999) generated mice with targeted disruption of the Synj1 gene. These Synj1-deficient mice exhibited neurologic defects and died shortly after birth. In neurons of mutant animals, phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) levels were increased, and clathrin-coated vesicles accumulated in the cytomatrix-rich area surrounding the synaptic vesicle cluster in nerve endings. In cell-free assays, reduced phosphoinositide phosphatase activity correlated with increased association of clathrin coats with liposomes. Intracellular recording in hippocampal slices revealed enhanced synaptic depression during prolonged high-frequency stimulation, followed by delayed recovery. These results provided genetic evidence for a crucial role of phosphoinositide metabolism in synaptic vesicle recycling. Using multicolor total internal reflection fluorescence microscopy, Perera et al. (2006) found that the 2 major SYNJ1 isoforms were differentially recruited to clathrin-coated pits in transiently transfected COS-7 cells. The ubiquitously expressed 170-kD isoform was present at all stages of clathrin- ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604297 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed