Logo of biochemjBJ Latest papers and much more!
Biochem J. 2001 Mar 1; 354(Pt 2): 249–257.
PMCID: PMC1221650

Characterization of KIAA1427 protein as an atypical synaptotagmin (Syt XIII).


Synaptotagmin (Syt) belongs to a family of type-I membrane proteins and is a protein that consists of a short extracellular N-terminus, a single transmembrane domain, two C2 domains and a short C-terminus. Here, we cloned and characterized a mouse orthologue of human KIAA1427 protein as an atypical Syt (named Syt XIII). Subcellular fractionation and antibody-uptake experiments indicate that Syt XIII is indeed a type-I membrane protein, but, unlike other Syt isoforms, lacks an N-terminal extracellular domain. Syt XIII C2 domains show relatively little similarity to Syt I (less than 35% identity at the amino acid level), and lack key amino acids responsible for Ca2+ binding. Because of these substitutions, the Syt XIII C2 domains did not show Ca2+-dependent phospholipid-binding activity, and Syt XIII is thus classified as a Ca2+ -independent isoform. By contrast, the Syt XIII C-terminal domain is highly homologous with other Syt isoforms and can function as a common receptor for neurexin Ialpha in vitro. Since Syt XIII is expressed in various tissues outside the brain, Syt XIII may be involved in constitutive vesicle transport.

Full Text

The Full Text of this article is available as a PDF (415K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Südhof TC, Rizo J. Synaptotagmins: C2-domain proteins that regulate membrane traffic. Neuron. 1996 Sep;17(3):379–388. [PubMed]
  • Nalefski EA, Falke JJ. The C2 domain calcium-binding motif: structural and functional diversity. Protein Sci. 1996 Dec;5(12):2375–2390. [PMC free article] [PubMed]
  • Fukuda M, Mikoshiba K. The function of inositol high polyphosphate binding proteins. Bioessays. 1997 Jul;19(7):593–603. [PubMed]
  • Schiavo G, Osborne SL, Sgouros JG. Synaptotagmins: more isoforms than functions? Biochem Biophys Res Commun. 1998 Jul 9;248(1):1–8. [PubMed]
  • Marquèze B, Berton F, Seagar M. Synaptotagmins in membrane traffic: which vesicles do the tagmins tag? Biochimie. 2000 May;82(5):409–420. [PubMed]
  • Shirataki H, Kaibuchi K, Sakoda T, Kishida S, Yamaguchi T, Wada K, Miyazaki M, Takai Y. Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-binding protein related to synaptotagmin. Mol Cell Biol. 1993 Apr;13(4):2061–2068. [PMC free article] [PubMed]
  • Orita S, Sasaki T, Naito A, Komuro R, Ohtsuka T, Maeda M, Suzuki H, Igarashi H, Takai Y. Doc2: a novel brain protein having two repeated C2-like domains. Biochem Biophys Res Commun. 1995 Jan 17;206(2):439–448. [PubMed]
  • Geppert M, Goda Y, Hammer RE, Li C, Rosahl TW, Stevens CF, Südhof TC. Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell. 1994 Nov 18;79(4):717–727. [PubMed]
  • Nonet ML, Grundahl K, Meyer BJ, Rand JB. Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin. Cell. 1993 Jul 2;73(7):1291–1305. [PubMed]
  • Littleton JT, Bellen HJ. Synaptotagmin controls and modulates synaptic-vesicle fusion in a Ca(2+)-dependent manner. Trends Neurosci. 1995 Apr;18(4):177–183. [PubMed]
  • Elferink LA, Peterson MR, Scheller RH. A role for synaptotagmin (p65) in regulated exocytosis. Cell. 1993 Jan 15;72(1):153–159. [PubMed]
  • Bommert K, Charlton MP, DeBello WM, Chin GJ, Betz H, Augustine GJ. Inhibition of neurotransmitter release by C2-domain peptides implicates synaptotagmin in exocytosis. Nature. 1993 May 13;363(6425):163–165. [PubMed]
  • Mikoshiba K, Fukuda M, Moreira JE, Lewis FM, Sugimori M, Niinobe M, Llinás R. Role of the C2A domain of synaptotagmin in transmitter release as determined by specific antibody injection into the squid giant synapse preterminal. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10703–10707. [PMC free article] [PubMed]
  • Fukuda M, Moreira JE, Lewis FM, Sugimori M, Niinobe M, Mikoshiba K, Llinás R. Role of the C2B domain of synaptotagmin in vesicular release and recycling as determined by specific antibody injection into the squid giant synapse preterminal. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10708–10712. [PMC free article] [PubMed]
  • Mochida S, Fukuda M, Niinobe M, Kobayashi H, Mikoshiba K. Roles of synaptotagmin C2 domains in neurotransmitter secretion and inositol high-polyphosphate binding at mammalian cholinergic synapses. Neuroscience. 1997 Apr;77(4):937–943. [PubMed]
  • Ohara-Imaizumi M, Fukuda M, Niinobe M, Misonou H, Ikeda K, Murakami T, Kawasaki M, Mikoshiba K, Kumakura K. Distinct roles of C2A and C2B domains of synaptotagmin in the regulation of exocytosis in adrenal chromaffin cells. Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):287–291. [PMC free article] [PubMed]
  • Lang J, Fukuda M, Zhang H, Mikoshiba K, Wollheim CB. The first C2 domain of synaptotagmin is required for exocytosis of insulin from pancreatic beta-cells: action of synaptotagmin at low micromolar calcium. EMBO J. 1997 Oct 1;16(19):5837–5846. [PMC free article] [PubMed]
  • Thomas DM, Elferink LA. Functional analysis of the C2A domain of synaptotagmin 1: implications for calcium-regulated secretion. J Neurosci. 1998 May 15;18(10):3511–3520. [PubMed]
  • Mochida S, Orita S, Sakaguchi G, Sasaki T, Takai Y. Role of the Doc2 alpha-Munc13-1 interaction in the neurotransmitter release process. Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11418–11422. [PMC free article] [PubMed]
  • Burns ME, Sasaki T, Takai Y, Augustine GJ. Rabphilin-3A: a multifunctional regulator of synaptic vesicle traffic. J Gen Physiol. 1998 Feb;111(2):243–255. [PMC free article] [PubMed]
  • Fukuda M, Mikoshiba K. Calcium-dependent and -independent hetero-oligomerization in the synaptotagmin family. J Biochem. 2000 Oct;128(4):637–645. [PubMed]
  • Fukuda M, Mikoshiba K. A novel alternatively spliced variant of synaptotagmin VI lacking a transmembrane domain. Implications for distinct functions of the two isoforms. J Biol Chem. 1999 Oct 29;274(44):31428–31434. [PubMed]
  • Craxton M, Goedert M. Alternative splicing of synaptotagmins involving transmembrane exon skipping. FEBS Lett. 1999 Nov 5;460(3):417–422. [PubMed]
  • Kabayama H, Takei K, Fukuda M, Ibata K, Mikoshiba K. Functional involvement of synaptotagmin I/II C2A domain in neurite outgrowth of chick dorsal root ganglion neuron. Neuroscience. 1999;88(4):999–1003. [PubMed]
  • Detrait E, Eddleman CS, Yoo S, Fukuda M, Nguyen MP, Bittner GD, Fishman HM. Axolemmal repair requires proteins that mediate synaptic vesicle fusion. J Neurobiol. 2000 Sep 15;44(4):382–391. [PubMed]
  • Detrait ER, Yoo S, Eddleman CS, Fukuda M, Bittner GD, Fishman HM. Plasmalemmal repair of severed neurites of PC12 cells requires Ca(2+) and synaptotagmin. J Neurosci Res. 2000 Nov 15;62(4):566–573. [PubMed]
  • Mizuta M, Kurose T, Miki T, Shoji-Kasai Y, Takahashi M, Seino S, Matsukura S. Localization and functional role of synaptotagmin III in insulin secretory vesicles in pancreatic beta-cells. Diabetes. 1997 Dec;46(12):2002–2006. [PubMed]
  • Gao Z, Reavey-Cantwell J, Young RA, Jegier P, Wolf BA. Synaptotagmin III/VII isoforms mediate Ca2+-induced insulin secretion in pancreatic islet beta -cells. J Biol Chem. 2000 Nov 17;275(46):36079–36085. [PubMed]
  • Brown H, Meister B, Deeney J, Corkey BE, Yang SN, Larsson O, Rhodes CJ, Seino S, Berggren PO, Fried G. Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis. Diabetes. 2000 Mar;49(3):383–391. [PubMed]
  • Martinez I, Chakrabarti S, Hellevik T, Morehead J, Fowler K, Andrews NW. Synaptotagmin VII regulates Ca(2+)-dependent exocytosis of lysosomes in fibroblasts. J Cell Biol. 2000 Mar 20;148(6):1141–1149. [PMC free article] [PubMed]
  • Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2000 Feb 28;7(1):65–73. [PubMed]
  • Fukuda M, Mikoshiba K. Doc2gamma, a third isoform of double C2 protein, lacking calcium-dependent phospholipid binding activity. Biochem Biophys Res Commun. 2000 Sep 24;276(2):626–632. [PubMed]
  • Fukuda M, Kanno E, Mikoshiba K. Conserved N-terminal cysteine motif is essential for homo- and heterodimer formation of synaptotagmins III, V, VI, and X. J Biol Chem. 1999 Oct 29;274(44):31421–31427. [PubMed]
  • Fukuda M, Aruga J, Niinobe M, Aimoto S, Mikoshiba K. Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II. J Biol Chem. 1994 Nov 18;269(46):29206–29211. [PubMed]
  • Smith DB, Johnson KS. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. [PubMed]
  • Ibata K, Fukuda M, Hamada T, Kabayama H, Mikoshiba K. Synaptotagmin IV is present at the Golgi and distal parts of neurites. J Neurochem. 2000 Feb;74(2):518–526. [PubMed]
  • Ushkaryov YA, Petrenko AG, Geppert M, Südhof TC. Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. Science. 1992 Jul 3;257(5066):50–56. [PubMed]
  • Fukuda M, Kojima T, Mikoshiba K. Phospholipid composition dependence of Ca2+-dependent phospholipid binding to the C2A domain of synaptotagmin IV. J Biol Chem. 1996 Apr 5;271(14):8430–8434. [PubMed]
  • Fukuda M, Kojima T, Mikoshiba K. Regulation by bivalent cations of phospholipid binding to the C2A domain of synaptotagmin III. Biochem J. 1997 Apr 15;323(Pt 2):421–425. [PMC free article] [PubMed]
  • Perin MS. Mirror image motifs mediate the interaction of the COOH terminus of multiple synaptotagmins with the neurexins and calmodulin. Biochemistry. 1996 Oct 29;35(43):13808–13816. [PubMed]
  • Veit M, Söllner TH, Rothman JE. Multiple palmitoylation of synaptotagmin and the t-SNARE SNAP-25. FEBS Lett. 1996 Apr 29;385(1-2):119–123. [PubMed]
  • Chapman ER, Blasi J, An S, Brose N, Johnston PA, Südhof TC, Jahn R. Fatty acylation of synaptotagmin in PC12 cells and synaptosomes. Biochem Biophys Res Commun. 1996 Aug 5;225(1):326–332. [PubMed]
  • Fukuda M, Mikoshiba K. Distinct self-oligomerization activities of synaptotagmin family. Unique calcium-dependent oligomerization properties of synaptotagmin VII. J Biol Chem. 2000 Sep 8;275(36):28180–28185. [PubMed]
  • Sugita S, Hata Y, Südhof TC. Distinct Ca(2+)-dependent properties of the first and second C2-domains of synaptotagmin I. J Biol Chem. 1996 Jan 19;271(3):1262–1265. [PubMed]
  • Chapman ER, An S, Edwardson JM, Jahn R. A novel function for the second C2 domain of synaptotagmin. Ca2+-triggered dimerization. J Biol Chem. 1996 Mar 8;271(10):5844–5849. [PubMed]
  • Damer CK, Creutz CE. Calcium-dependent self-association of synaptotagmin I. J Neurochem. 1996 Oct;67(4):1661–1668. [PubMed]
  • Chapman ER, Desai RC, Davis AF, Tornehl CK. Delineation of the oligomerization, AP-2 binding, and synprint binding region of the C2B domain of synaptotagmin. J Biol Chem. 1998 Dec 4;273(49):32966–32972. [PubMed]
  • Osborne SL, Herreros J, Bastiaens PI, Schiavo G. Calcium-dependent oligomerization of synaptotagmins I and II. Synaptotagmins I and II are localized on the same synaptic vesicle and heterodimerize in the presence of calcium. J Biol Chem. 1999 Jan 1;274(1):59–66. [PubMed]
  • Shao X, Davletov BA, Sutton RB, Südhof TC, Rizo J. Bipartite Ca2+-binding motif in C2 domains of synaptotagmin and protein kinase C. Science. 1996 Jul 12;273(5272):248–251. [PubMed]
  • Sutton RB, Davletov BA, Berghuis AM, Südhof TC, Sprang SR. Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold. Cell. 1995 Mar 24;80(6):929–938. [PubMed]
  • Fukuda M, Kojima T, Aruga J, Niinobe M, Mikoshiba K. Functional diversity of C2 domains of synaptotagmin family. Mutational analysis of inositol high polyphosphate binding domain. J Biol Chem. 1995 Nov 3;270(44):26523–26527. [PubMed]
  • Fukuda M, Moreira JE, Liu V, Sugimori M, Mikoshiba K, Llinás RR. Role of the conserved WHXL motif in the C terminus of synaptotagmin in synaptic vesicle docking. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14715–14719. [PMC free article] [PubMed]
  • Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. [PubMed]
  • Thompson CC. Thyroid hormone-responsive genes in developing cerebellum include a novel synaptotagmin and a hairless homolog. J Neurosci. 1996 Dec 15;16(24):7832–7840. [PubMed]
  • Ibata K, Fukuda M, Mikoshiba K. Inositol 1,3,4,5-tetrakisphosphate binding activities of neuronal and non-neuronal synaptotagmins. Identification of conserved amino acid substitutions that abolish inositol 1,3,4,5-tetrakisphosphate binding to synaptotagmins III, V, and X. J Biol Chem. 1998 May 15;273(20):12267–12273. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • Gene
    Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence and PMC links.
  • GEO Profiles
    GEO Profiles
    Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
  • HomoloGene
    HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
  • MedGen
    Related information in MedGen
  • Nucleotide
    Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • OMIM
    Genome Survey Sequence (GSS) nucleotide records reported in the current articles.
  • Pathways + GO
    Pathways + GO
    Pathways and biological systems (BioSystems) that cite the current articles. Citations are from the BioSystems source databases (KEGG and BioCyc).
  • Protein
    Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...