We have identified a new human gene coined sytdep ((sy) under bar napto (t) under bar agmin XIV-(de) under bar rived protein) in human neutrophils. Sytdep encodes a 188-amino acid sequence with a 21.435 kDa deduced molecular mass, showing 75% identity to human synaptotagmin (syt) XIV, Human neutrophils express sytdep, but not syt XIV Sytdep was upregulated during HL-60 neutrophil differentiation. Sytdep gene is located in human chromosome 4 and contains a unique exon, whereas syt XIV gene, located in chromosome 1, comprises 10 exons with 9 introns. Mouse genome did not contain sytdep. The N-terminal region of sytdep shows no homology with any known protein and, unlike synaptotagmin XIV isoforms, sytdep shows a unique C-terminal C2B domain. Polyclonal antibodies against the C2B domain of syt XIV recognized sytdep as a 27-kDa protein in human neutrophils. Genomic analyses suggest that human sytdep could derive from a retrotranslocation of a syt XIV transcript into chromosome 4. (c) 2005 Elsevier Inc. All rights reserved.