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MetaCyc Enzyme: synaptojanin 1

Gene: SYNJ1 Accession Number: HS08354 (MetaCyc)

Synonyms: INPP5G, KIAA0910, synaptic inositol-1,4,5-trisphosphate 5-phosphatase 1, inositol 5'-phosphatase, synaptojanin-1

Species: Homo sapiens

Summary:
General Background

The signalling activities of both D-myo-inositol (1,4,5)-trisphosphate and D-myo-inositol (1,3,4,5)-tetrakisphosphate are terminated by hydrolysis of their 5-phosphate groups. The inositol polyphosphate 5-phosphatases have been subdivided into four subgroups based on their size and substrate specificity [Jefferson97, Erneux98].

Type I enzymes hydrolyze only the water soluble D-myo-inositol (1,4,5)-trisphosphate and D-myo-inositol (1,3,4,5)-tetrakisphosphate [Verjans94, Laxminarayan94].

Type II enzymes also accept the insoluble phospholipids 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate and a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate as substrates [Jefferson95, Jackson95].

Type III enzymes hydrolyze only phosphoinositides and inositol polyphosphates that have a 3-position phosphate group, such as 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate [Jackson95].

Type IV enzymes hydrolyze 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate, 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate, and a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate D-myo-inositol (1,3,4,5)-tetrakisphosphate [Jefferson97]. They do not accept water soluble cyclitols [Kisseleva00].

About This Protein

Synaptojanin 1 was initially identified in nerve terminals and has been implicated in synaptic vesicle recycling [McPherson94, McPherson96]. It is composed of three domains: a central inositol 5-phosphatase domain, a N-terminal domain homologous to the yeast protein Sac I and a C-terminal proline-rich region that was shown to interact with the SH3 domain of amphiphysin [McPherson94a]. The protein was also shown to bind to the Epidermal growth factor receptor substrate 15 (Protein Eps15) [Haffner97].

A second isoform, synaptojanin 2, shares very little identity at the C-terminal domain [Nemoto97, Khvotchev98].

CHO cells transfected with synaptojanin 1 and 2 showed different subcellular localizations for the two isoforms: synaptojanin 2 was predominantly associated with the particulate fraction, while synaptojanin 1 was mainly in the soluble fraction of cell homogenates [Nemoto97].

The SYNJ1 gene has been located in chromosome 21q22.2 [Cremona00].

Map Position: [30,661,501 <- 30,760,665]

Molecular Weight of Polypeptide: 173.1 kD (from nucleotide sequence), 145.0 kD (experimental) [McPherson96 ]

Unification Links: ArrayExpress:O43426 , Entrez-Nucleotide:AF009039 , Mint:MINT-109209 , PhosphoSite:O43426 , Pride:O43426 , Protein Model Portal:O43426 , SMR:O43426 , String:9606.ENSP00000322234 , UniProt:O43426

Relationship Links: InterPro:IN-FAMILY:IPR000300 , InterPro:IN-FAMILY:IPR000504 , InterPro:IN-FAMILY:IPR002013 , InterPro:IN-FAMILY:IPR005135 , InterPro:IN-FAMILY:IPR012677 , InterPro:IN-FAMILY:IPR015047 , PDB:Structure:1W80 , PDB:Structure:2DNR , PDB:Structure:2VJ0 , Pfam:IN-FAMILY:PF02383 , Pfam:IN-FAMILY:PF03372 , Pfam:IN-FAMILY:PF08952 , Prosite:IN-FAMILY:PS50102 , Prosite:IN-FAMILY:PS50275 , Smart:IN-FAMILY:SM00128

Gene-Reaction Schematic: ?

Credits:
Created 19-Oct-2009 by Caspi R , SRI International


Enzymatic reaction of: inositol-1,4,5-trisphosphate 5-phosphatase (synaptojanin 1)

EC Number: 3.1.3.56

D-myo-inositol (1,4,5)-trisphosphate + H2O <=> D-myo-inositol (1,4)-bisphosphate + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of D-myo-inositol (1,4,5)-trisphosphate metabolism , D-myo-inositol (1,4,5)-trisphosphate degradation


Enzymatic reaction of: phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase (synaptojanin 1)

EC Number: 3.1.3.86

1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + H2O <=> a 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: 3-phosphoinositide degradation


Enzymatic reaction of: inositol-1,3,4,5-tetrakisphosphate 5-phosphatase (synaptojanin 1)

EC Number: 3.1.3.56

D-myo-inositol (1,3,4,5)-tetrakisphosphate + H2O <=> D-myo-inositol (1,3,4)-trisphosphate + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of D-myo-inositol (1,4,5)-trisphosphate metabolism , D-myo-inositol (1,3,4)-trisphosphate biosynthesis , 1D-myo-inositol hexakisphosphate biosynthesis II (mammalian)


Enzymatic reaction of: phosphatidylinositol-4,5-bisphosphate 5-phosphatase (synaptojanin 1)

EC Number: 3.1.3.36

a 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O <=> a 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: 3-phosphoinositide degradation


References

Cremona00: Cremona O, Nimmakayalu M, Haffner C, Bray-Ward P, Ward DC, De Camilli P (2000). "Assignment of SYNJ1 to human chromosome 21q22.2 and Synj12 to the murine homologous region on chromosome 16C3-4 by in situ hybridization." Cytogenet Cell Genet 88(1-2);89-90. PMID: 10773674

Erneux98: Erneux C, Govaerts C, Communi D, Pesesse X (1998). "The diversity and possible functions of the inositol polyphosphate 5-phosphatases." Biochim Biophys Acta 1436(1-2);185-99. PMID: 9838104

Haffner97: Haffner C, Takei K, Chen H, Ringstad N, Hudson A, Butler MH, Salcini AE, Di Fiore PP, De Camilli P (1997). "Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15." FEBS Lett 419(2-3);175-80. PMID: 9428629

Jackson95: Jackson SP, Schoenwaelder SM, Matzaris M, Brown S, Mitchell CA (1995). "Phosphatidylinositol 3,4,5-trisphosphate is a substrate for the 75 kDa inositol polyphosphate 5-phosphatase and a novel 5-phosphatase which forms a complex with the p85/p110 form of phosphoinositide 3-kinase." EMBO J 14(18);4490-500. PMID: 7556092

Jefferson95: Jefferson AB, Majerus PW (1995). "Properties of type II inositol polyphosphate 5-phosphatase." J Biol Chem 270(16);9370-7. PMID: 7721860

Jefferson97: Jefferson AB, Auethavekiat V, Pot DA, Williams LT, Majerus PW (1997). "Signaling inositol polyphosphate-5-phosphatase. Characterization of activity and effect of GRB2 association." J Biol Chem 272(9);5983-8. PMID: 9038219

Khvotchev98: Khvotchev M, Sudhof TC (1998). "Developmentally regulated alternative splicing in a novel synaptojanin." J Biol Chem 273(4);2306-11. PMID: 9442075

Kisseleva00: Kisseleva MV, Wilson MP, Majerus PW (2000). "The isolation and characterization of a cDNA encoding phospholipid-specific inositol polyphosphate 5-phosphatase." J Biol Chem 275(26);20110-6. PMID: 10764818

Laxminarayan94: Laxminarayan KM, Chan BK, Tetaz T, Bird PI, Mitchell CA (1994). "Characterization of a cDNA encoding the 43-kDa membrane-associated inositol-polyphosphate 5-phosphatase." J Biol Chem 269(25);17305-10. PMID: 8006039

Lecompte08: Lecompte O, Poch O, Laporte J (2008). "PtdIns5P regulation through evolution: roles in membrane trafficking?." Trends Biochem Sci 33(10);453-60. PMID: 18774718

McPherson94: McPherson PS, Takei K, Schmid SL, De Camilli P (1994). "p145, a major Grb2-binding protein in brain, is co-localized with dynamin in nerve terminals where it undergoes activity-dependent dephosphorylation." J Biol Chem 269(48);30132-9. PMID: 7982917

McPherson94a: McPherson PS, Czernik AJ, Chilcote TJ, Onofri F, Benfenati F, Greengard P, Schlessinger J, De Camilli P (1994). "Interaction of Grb2 via its Src homology 3 domains with synaptic proteins including synapsin I." Proc Natl Acad Sci U S A 91(14);6486-90. PMID: 8022809

McPherson96: McPherson PS, Garcia EP, Slepnev VI, David C, Zhang X, Grabs D, Sossin WS, Bauerfeind R, Nemoto Y, De Camilli P (1996). "A presynaptic inositol-5-phosphatase." Nature 379(6563);353-7. PMID: 8552192

Nemoto97: Nemoto Y, Arribas M, Haffner C, DeCamilli P (1997). "Synaptojanin 2, a novel synaptojanin isoform with a distinct targeting domain and expression pattern." J Biol Chem 272(49);30817-21. PMID: 9388224

Rohde02: Rohde G, Wenzel D, Haucke V (2002). "A phosphatidylinositol (4,5)-bisphosphate binding site within mu2-adaptin regulates clathrin-mediated endocytosis." J Cell Biol 158(2);209-14. PMID: 12119359

Verjans94: Verjans B, De Smedt F, Lecocq R, Vanweyenberg V, Moreau C, Erneux C (1994). "Cloning and expression in Escherichia coli of a dog thyroid cDNA encoding a novel inositol 1,4,5-trisphosphate 5-phosphatase." Biochem J 300 ( Pt 1);85-90. PMID: 8198557

Zhang07b: Zhang Y, Zolov SN, Chow CY, Slutsky SG, Richardson SC, Piper RC, Yang B, Nau JJ, Westrick RJ, Morrison SJ, Meisler MH, Weisman LS (2007). "Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice." Proc Natl Acad Sci U S A 104(44);17518-23. PMID: 17956977


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC13B.