F
IPR052120

Fibronectin type III domain-containing protein 4/5

InterPro entry
Short nameFNDC_type_III_4/5

Description

This family of proteins includes fibronectin type III domain-containing protein 4 and 5 (FNDC4/5).

FDNC4 is involved in anti-inflammatory processes, particularly in the gastrointestinal tract. It interacts with macrophages to reduce the expression of pro-inflammatory genes and modulate macrophage functions such as phagocytosis, largely through STAT3 activation and signaling pathways
[3]
. These proteins play a role in controlling the immune response during inflammatory conditions like colitis.

FDNC5 is a type I membrane protein that is cleaved to produce irisin, a hormone-like molecule that is secreted from skeletal muscle into the extracellular milieu and circulation. Physical activity induces irisin production, and irisin mediates the beneficial effects of physical activity in adipose tissue, brain, and bone
[2]
. In mouse, it is implicated in the physiological changes associated with muscular exercise, including the induction of browning in white adipose tissue through the upregulation of UCP1 expression, potentially involving the nuclear receptor PPARA. However, the role of these proteins in exercise-induced benefits and adipose tissue browning may vary between species, as in humans may not be involved in the beneficial effects of muscular exercise, nor in the induction of browning of human white adipose tissue
[1, 4]
.

References

1.A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM. Nature 481, 463-8, (2012). View articlePMID: 22237023

2.Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors. Kim H, Wrann CD, Jedrychowski M, Vidoni S, Kitase Y, Nagano K, Zhou C, Chou J, Parkman VA, Novick SJ, Strutzenberg TS, Pascal BD, Le PT, Brooks DJ, Roche AM, Gerber KK, Mattheis L, Chen W, Tu H, Bouxsein ML, Griffin PR, Baron R, Rosen CJ, Bonewald LF, Spiegelman BM. Cell 175, 1756-1768.e17, (2018). View articlePMID: 30550785

3.FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice. Bosma M, Gerling M, Pasto J, Georgiadi A, Graham E, Shilkova O, Iwata Y, Almer S, Soderman J, Toftgard R, Wermeling F, Bostrom EA, Bostrom PA. Nat Commun 7, 11314, (2016). View articlePMID: 27066907

4.Evidence against a beneficial effect of irisin in humans. Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U, Brockmann B, Jung R, Wisloff U, Tjonna AE, Raastad T, Hallen J, Norheim F, Drevon CA, Romacho T, Eckardt K, Eckel J. PLoS One 8, e73680, (2013). View articlePMID: 24040023

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