Jan Hofsteenge

Jan Hofsteenge

Molecular and functional aspects of co- and posttranslational protein modifications

Modulation of protein function by covalent modification is of increasing importance as a factor in disease and as a therapeutic target. The discovery of new protein modifications and their function remains a challenge. Using protein/peptide purification and mass spectrometry as well as molecular and cell biology techniques, we focus on two unique forms of glycosylation in secreted proteins, C-mannosylation of tryptophan and O-fucosylation of serine or threonine residues. About 50 examples of the former modification are known, in organisms ranging from C. elegans to man. We are studying enzymes involved in the process and analysing specific proteins lacking the modification. Of the two kinds of O-fucose-linked polysaccharides known, O-linked tetrasaccharide appears to function in intercellular signalling. We have found the first protein containing the product of the second pathway, i.e. Glc-Fuc-O-Ser/Thr and are seeking its function.

Gonzalez de Peredo A, Klein D, Macek B, Hess D, Peter-Katalinic J, Hofsteenge (2002) C-Mannosylation and O-fucosylation of thrombospondin type 1 repeats

Cell Proteomics 1:11-18

Hofsteenge J, Müller DR, de Beer T, Löffler A, Richter WJ, Vliegenthart JFG (1994) New type of linkage between a carbohydrate and a protein: C- glycosylation of a specific tryptophan residue in human RNase Us

Biochemistry 33:13524-13530

Krieg J, Hartmann S, Vicentini A, Gläsner W, Hess D, Hofsteenge J (1998) The recognition signal for C-mannosylation of Trp-7 in RNase 2 consists of the sequence Trp-x-x-Trp

Mol Biol Cell 9:301-309

Furmanek A, Hess D, Rogniaux H, Hofsteenge J (2003) The WSAWS motif is C-hexosylated in a soluble form of the erythropoietin receptor

Biochemistry 42:8452-8458

Zanetta JP, Pons A, Richet C, Huet G, Timmerman P, Leroy Y, Bohin A, Bohin JP, Trinel PA, Poulain D, Hofsteenge J (2004) Quantitative gas chromatography/mass spectrometry determination of C-mannosylation of tryptophan residues in glycoproteins

Anal Biochem 329:199-206

Doucey MA, Hess D, Cacan R, Hofsteenge J (1998) Protein C-mannosylation is enzyme-catalysed and uses dolichyl-phosphate-mannose as a precursor

Mol Biol Cell 9:291-300

Hartmann S, Hofsteenge J (2000) Properdin, the positive regulator of complement, is highly C-mannosylated

J Biol Chem 275:28569-28574

Kozma K, Keusch JJ, Hegemann B, Lutter KB, Klein D, Hess D, Haltiwanger RS, Hofsteenge J (2006) Identification and characterization of a beta 1,3-glucosyltransferase that synthesizes the Glc-beta 1,3-Fuc disaccharide on thrombospondin type 1 repeats

J Biol Chem 281:36742-36751

Hess D, Keusch JJ, Lesnik Oberstein SA, Hennekam RC, Hofsteenge J (2008) Peters plus syndrome is a new congenital disorder of glycosylation and involves defective O-glycosylation of thrombospondin type 1 repeats

J Biol Chem. 2008 Mar 21;283(12):7354-60

Macek B, Hofsteenge J, Peter-Katalinic J (2001) Direct determination of glycosylation sites in O-fucosylated glycopeptides using nano-electrospray quadrupole time-of-flight mass spectrometry

Rapid Commun Mass Spectrom 15:771-777

PhD students

Chun-I Chen (2007-2008)
Constanze Heinrich (2005-2008)
Matthias Scharenberg (2008)
Krisztina Keusch (2003-2008)
Carsten Krantz (2003-2008)
Florence Roux (2002-2006)
Aleksandra Furmanek (1998-2003)
Neelaabh Shankar (2000-2001)
Steffen Hartmann (1996-2000)
Marie-Agnes Doucey (1996-1999)
Montserrat Blazquez-Domingo (1992-1997)
Ottilie Zelenko (1991-1994)
Andreas Betz (1989-1993)
Denise Rennex (1985-1989)

Postdoctoral fellows

Stefano Canevascini (2006-2009)
Jeremy Keusch (2002-2007)
Guillaume De Sampaio (2002-2005)
Tim Smilda (1999-2002)
Stefan Irmler (2000-2002)
Anne Gonzalez de Peredo (2000-2001)
Hans-Joachim Krieg (1995-1999)
Wolfgang Glasner (1995-1998)
Olga Miroshynichenko (1996-1998)
Andreas Loffler (1994-1996)
Zsofia Jarai-Kote (1993-1994)
Ulf Neumann (1991-1994)
Jesus Fominaya Gutierrez (1989-1993)
Martin P. Jackman (1989-1992)
Stanley Dennis (1987-1990)
Brigitte Kieffer (1987-1990)
Catherine Servis (1989-1990)
Andrew D. Wallace (1987-1990)
Paul J. Braun (1985-1987)
Gudrun Noe (1985-1986)
Hayao Taguchi (1984-1985)

Technical/Research associates

Jeremy Keusch (2007-2009)
Dominique Klein (1998-2009)
Marianne Grob (2000-2005)
Anna M. Buxton-Vicentini (1989-1998)
Carolyn Pearson(Adams-) (1987-1990)
Monique Pedrocca (1984-1988)
Roland J. Goepfert (1984-1985)
Pia Wittlin (1985)


Claudia Keller (2007-2008)
Ivana Trogrlic (2006-2007)
Jasmin Althaus (2004-2005)
Nominerdene Battsengel (2004-2005)
Alexandra Bezler (2004-2005)
Pascal Hermann (2003-2004)
Bjoern Hegemann (2003)
Anne Ulvestad (1999-2000)
Sigrun Lindhom (1997-1998)
Roland Degen (1995-1996)
Carina Moldow (1993-1994)
Ekkehard Kustermann (1991-1992)
Marina A.A. Parry (1990-1992)
Martin Lenter (1989-1990)

Visiting scientists

Boris Macek (2002)


PhD, State University Groningen, Gronigen
BSc, State University Groningen, Gronigen, The Netherlands

Positions held

Senior Group Leader, Friedrich Miescher Institute for Biomedical Research, Basel
Junior Group Leader and Head of the Protein Chemistry Facility, Friedrich Miescher Institute for Biomedical Research, Basel
Research Associate, The Rockefeller University, New York, USA


Privatdozent, University of Basel, Basel