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MetaCyc Enzyme: synaptojanin 2

Gene: SYNJ2 Accession Number: HS01279 (MetaCyc)

Synonyms: INPP5H, KIAA0348, inositol-1,4,5-trisphosphate 5-phosphatase 2, inositol phosphate 5'-phosphatase 2 (synaptojanin 2)

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 2 is an isoform of synaptojanin 1, a protein found in nerve terminals, which has a broader tissue distribution. The carboxyl-terminal proline-rich regions of the two isoforms bear little homology. Expression of synaptojanin 2 in COS7 cells produced a 140-kDa protein with inositol 5'-phosphatase actvity [Nemoto97].

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].

Synaptojanin 2 directly and specifically interacts with Rac1 in a GTP-dependent manner [Malecz00]. The protein has several alternatively spliced forms [Seet98]. Both amphiphysin and endophilin, two partners synaptojanin 1, bind synaptojanin 2B2, whereas only amphiphysin binds synaptojanin 2B1. synaptojanin 2B1 is localized at nerve terminals in brain and at the spermatid manchette in testis [Nemoto01].

Map Position: [158,276,475 -> 158,393,768]

Molecular Weight of Polypeptide: 165.54 kD (from nucleotide sequence), 140.0 kD (experimental) [Nemoto97 ]

Unification Links: ArrayExpress:O15056 , Entrez-Nucleotide:AF318616 , Entrez-Nucleotide:AY152396 , Mint:MINT-3976061 , PhosphoSite:O15056 , PhylomeDB:O15056 , Pride:O15056 , Protein Model Portal:O15056 , SMR:O15056 , String:9606.ENSP00000347792 , UniProt:O15056

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:1UFW , 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 2)

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 2)

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 2)

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 2)

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

Exons/Introns:


References

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

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

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

Malecz00: Malecz N, McCabe PC, Spaargaren C, Qiu R, Chuang Y, Symons M (2000). "Synaptojanin 2, a novel Rac1 effector that regulates clathrin-mediated endocytosis." Curr Biol 10(21);1383-6. PMID: 11084340

Nemoto01: Nemoto Y, Wenk MR, Watanabe M, Daniell L, Murakami T, Ringstad N, Yamada H, Takei K, De Camilli P (2001). "Identification and characterization of a synaptojanin 2 splice isoform predominantly expressed in nerve terminals." J Biol Chem 276(44);41133-42. PMID: 11498538

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

Seet98: Seet LF, Cho S, Hessel A, Dumont DJ (1998). "Molecular cloning of multiple isoforms of synaptojanin 2 and assignment of the gene to mouse chromosome 17A2-3.1." Biochem Biophys Res Commun 247(1);116-22. PMID: 9636665

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 Fri Dec 19, 2014, biocyc14.