Fibromodulin

Summary

Fibromodulin is a protein that in humans is encoded by the FMOD gene.[5][6]

FMOD
Identifiers
AliasesFMOD, FM, SLRR2E, fibromodulin
External IDsOMIM: 600245 MGI: 1328364 HomoloGene: 1530 GeneCards: FMOD
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002023

NM_021355

RefSeq (protein)

NP_002014

NP_067330

Location (UCSC)Chr 1: 203.34 – 203.35 MbChr 1: 133.96 – 133.98 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Fibromodulin is a 42kDa protein of a family of small interstitial leucine-rich repeat proteoglycans (SLRPs). It can have up to four N-linked keratan sulfate chains attached to the core protein within the leucine-rich region. It shares significant sequence homology with biglycan and decorin.[7]

Function edit

Fibromodulin participates in the assembly of the collagen fibers of the extracellular matrix. It binds to the same site on the collagen type I molecule as lumican.[8] It also inhibits fibrillogenesis of collagen type I and collagen type III in vitro.[9][10] It regulates TGF-beta activities by sequestering TGF-beta into the extracellular matrix.[6]

Clinical significance edit

There is an age-dependent decline in the synthesis of keratan sulfate chains, so non-glycated forms of fibromodulin can accumulate in tissues such as cartilage.[11]

Fibromodulin is found in the epidermis of human skin and is expressed by skin cells (keratinocytes) in culture. Mice with the gene for fibromodulin knocked out (Fmod-/-) have very fragile skin[12] and abnormal tail and Achilles tendons.[13] The collagen fiber bundles in these tendons are fewer and disorganised and there is less endotenon surrounding the tendon tissue. The levels of lumican, a SLRP with one of the same collagen binding sites as fibromodulin, is increased 4 fold in the tail tendons of Fmod-knockout mice.

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000122176 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041559 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Sztrolovics R, Chen XN, Grover J, Roughley PJ, Korenberg JR (Mar 1995). "Localization of the human fibromodulin gene (FMOD) to chromosome 1q32 and completion of the cDNA sequence". Genomics. 23 (3): 715–7. doi:10.1006/geno.1994.1567. PMID 7851907.
  6. ^ a b "Entrez Gene: FMOD fibromodulin".
  7. ^ Antonsson P, Heinegård D, Oldberg A (1993). "Structure and deduced amino acid sequence of the human fibromodulin gene". Biochim Biophys Acta. 1174 (2): 204–6. doi:10.1016/0167-4781(93)90117-V. PMID 8357838.
  8. ^ Halper J (2014). "Proteoglycans and Diseases of Soft Tissues". Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology. Vol. 802. pp. 49–58. doi:10.1007/978-94-007-7893-1_4. ISBN 978-94-007-7892-4. PMID 24443020.
  9. ^ Ezura Y, Chakravarti S, Oldberg A, Chervoneva I, Birk DE (2000). "Differential expression of lumican and fibromodulin regulate collagen fibrillogenesis in developing mouse tendons". J. Cell Biol. 151 (4): 779–88. doi:10.1083/jcb.151.4.779. PMC 2169450. PMID 11076963.
  10. ^ Kalamajski S, Oldberg A (2007). "Fibromodulin binds collagen type I via Glu-353 and Lys-355 in leucine-rich repeat 11". J Biol Chem. 282 (37): 26740–5. doi:10.1074/jbc.M704026200. PMID 17623650.
  11. ^ Roughley PJ, White RJ, Cs-Szabo G, Mort JS (1996). "Changes with age in the structure of fibromodulin in human articular cartilage". Osteoarthritis and Cartilage. 4 (3): 153–61. doi:10.1016/s1063-4584(96)80011-2. PMID 8895216.
  12. ^ Smith MM, Melrose J (2015). "Proteoglycans in normal and healing skin". Adv Wound Care. 4 (3): 152–73. doi:10.1089/wound.2013.0464. PMC 4352701. PMID 25785238.
  13. ^ Juneja SC, Veillette C (2013). "Defects in tendon, ligament, and enthesis in response to genetic alterations in key proteoglycans and glycoproteins: a review". Arthritis. 2013: 1–30. doi:10.1155/2013/154812. PMC 3842050. PMID 24324885.

Further reading edit

  • Roughley PJ, Lee ER (Aug 1994). "Cartilage proteoglycans: structure and potential functions". Microscopy Research and Technique. 28 (5): 385–97. doi:10.1002/jemt.1070280505. PMID 7919526. S2CID 43194492.
  • Hildebrand A, Romarís M, Rasmussen LM, Heinegård D, Twardzik DR, Border WA, Ruoslahti E (Sep 1994). "Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta". The Biochemical Journal. 302 (2): 527–34. doi:10.1042/bj3020527. PMC 1137259. PMID 8093006.
  • Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
  • Westergren-Thorsson G, Norman M, Björnsson S, Endrésen U, Stjernholm Y, Ekman G, Malmström A (Mar 1998). "Differential expressions of mRNA for proteoglycans, collagens and transforming growth factor-beta in the human cervix during pregnancy and involution". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1406 (2): 203–13. doi:10.1016/S0925-4439(98)00005-2. PMID 9573366.
  • Font B, Eichenberger D, Goldschmidt D, Boutillon MM, Hulmes DJ (Jun 1998). "Structural requirements for fibromodulin binding to collagen and the control of type I collagen fibrillogenesis--critical roles for disulphide bonding and the C-terminal region". European Journal of Biochemistry. 254 (3): 580–7. doi:10.1046/j.1432-1327.1998.2540580.x. PMID 9688269.
  • Schaefer L, Gröne HJ, Raslik I, Robenek H, Ugorcakova J, Budny S, Schaefer RM, Kresse H (Oct 2000). "Small proteoglycans of normal adult human kidney: distinct expression patterns of decorin, biglycan, fibromodulin, and lumican". Kidney International. 58 (4): 1557–68. doi:10.1046/j.1523-1755.2000.00317.x. PMID 11012890.
  • Gori F, Schipani E, Demay MB (2001). "Fibromodulin is expressed by both chondrocytes and osteoblasts during fetal bone development". Journal of Cellular Biochemistry. 82 (1): 46–57. doi:10.1002/jcb.1115. PMID 11400162. S2CID 41342892.
  • Mayr C, Bund D, Schlee M, Moosmann A, Kofler DM, Hallek M, Wendtner CM (Feb 2005). "Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes". Blood. 105 (4): 1566–73. doi:10.1182/blood-2004-04-1233. PMID 15471955.
  • Mikaelsson E, Danesh-Manesh AH, Lüppert A, Jeddi-Tehrani M, Rezvany MR, Sharifian RA, Safaie R, Roohi A, Osterborg A, Shokri F, Mellstedt H, Rabbani H (Jun 2005). "Fibromodulin, an extracellular matrix protein: characterization of its unique gene and protein expression in B-cell chronic lymphocytic leukemia and mantle cell lymphoma". Blood. 105 (12): 4828–35. doi:10.1182/blood-2004-10-3941. PMID 15741214.
  • Sjöberg A, Onnerfjord P, Mörgelin M, Heinegård D, Blom AM (Sep 2005). "The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q". The Journal of Biological Chemistry. 280 (37): 32301–8. doi:10.1074/jbc.M504828200. PMID 16046396.
  • Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
  • Sjöberg AP, Trouw LA, Clark SJ, Sjölander J, Heinegård D, Sim RB, Day AJ, Blom AM (Apr 2007). "The factor H variant associated with age-related macular degeneration (His-384) and the non-disease-associated form bind differentially to C-reactive protein, fibromodulin, DNA, and necrotic cells". The Journal of Biological Chemistry. 282 (15): 10894–900. doi:10.1074/jbc.M610256200. PMID 17293598.
  • Kalamajski S, Oldberg A (Sep 2007). "Fibromodulin binds collagen type I via Glu-353 and Lys-355 in leucine-rich repeat 11". The Journal of Biological Chemistry. 282 (37): 26740–5. doi:10.1074/jbc.M704026200. PMID 17623650.