A Drosophila haemocyte-specific protein, hemolectin, similar to human von Willebrand factor

A. Goto, T. Kumagai, C. Kumagai, J. Hirose, H. Narita, H. Mori, T. Kadowaki, K. Beck, Y. Kitagawa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)

Abstract

We identified a novel Drosophila protein of ≈400 kDa, hemolectin (d-Hml), secreted from haemocyte-derived Kc167 cells. Its 11.7 kbp cDNA contains an open reading frame of 3843 amino acid residues, with conserved domains in von Willebrand factor (VWF), coagulation factor V/VIII and complement factors. The d-hml gene is located on the third chromosome (position 70C1-5) and consists of 26 exons. The major part of d-Hml consists of well-known motifs with the organization: CP1-EG1-CP2-EG2-CP3-VD1-VD2-VD′-VD3-VC1-VD″-VD‴-FC1-FC2- VC2-LA1-VD4-VD5-VC3-VB1-VB2-VC4-VC5-CK1 (CP, complement-control protein domain; EG, epidermal-growth-factor-like domain; VB, VC, VD, VWF type B-, C- and D-like domains; VD′, VD″, VD‴, truncated C-terminal VDs; FC, coagulation factor V/VIII type C domain; LA, low-density-lipoprotein-receptor class A domain; CK, cysteine knot domain). The organization of VD1-VD2-VD′-VD3, essential for VWF to be processed by furin, to bind to coagulation factor VIII and to form interchain disulphide linkages, is conserved. The 400 kDa form of d-Hml was sensitive to acidic cleavage near the boundary between VD2 and VD′, where the cleavage site of pro-VWF is located. Agarose-gel electrophoresis of metabolically radiolabelled d-Hml suggested that it is secreted from Kc167 cells mainly as dimers. Resembling VWF, 7.9% (305 residues) of cysteine residues on the d-Hml sequence had well-conserved positions in each motif. Coinciding with the development of phagocytic haemocytes, d-hml transcript was detected in late embryos and larvae. Its low-level expression in adult flies was induced by injury at any position on the body.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalBiochemical Journal
Volume359
Issue number1
DOIs
Publication statusPublished - 1 Oct 2001
Externally publishedYes

Keywords

  • Coagulation factor
  • Cysteine knot
  • Disulphide bond
  • Haemocytin
  • Haemostasis

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