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Review Article | Open Access

FAM20C: A key protein kinase in multiple diseases

Rui Zhanga,1Yanming Rena,1Yan JuaYuekang ZhangaYan Zhangb()Yuan Wanga()
Department of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China

1 These authors contributed equally to this work.

Peer review under responsibility of Chongqing Medical University.

Show Author Information

Abstract

Family with sequence similarity 20 C (FAM20C) is a Golgi protein kinase that phosphorylates the serine residue in the S-x-E/pS motif of target proteins. FAM20C phosphorylates most secreted proteins, which play important roles in multiple biological processes, including cancer progression, biomineralization, and lipid homeostasis. Numerous studies have documented the potential contribution of FAM20C to the growth, invasion, and metastasis of glioma, breast cancer, and other cancers, as well as to the mineralization process of teeth and bone. In addition, FAM20C has been found to be associated with the occurrence and development of certain cardiovascular diseases and endocrine metabolism disorders. It raises hopes that understanding the disease-specific mechanisms of FAM20C may hold the key to developing new strategies for these diseases. This review comprehensively covers the existing literature to provide a summary of the structure and biological functions of FAM20C, with a particular focus on its roles in the disease context.

References

1

Wu Y, Wang H, Liu C. From biomineralization to tumorogenesis-the expanding insight of the physiological and pathological roles of Fam20C. Biosci Rep. 2021;41(5):BSR20210040.

2

Fischer EH. Cellular regulation by protein phosphorylation. Biochem Biophys Res Commun. 2013;430(2):865-867.

3

Klement E, Medzihradszky KF. Extracellular protein phosphorylation, the neglected side of the modification. Mol Cell Proteomics. 2017;16(1):1-7.

4

Yalak G, Vogel V. Extracellular phosphorylation and phosphorylated proteins: not just curiosities but physiologically important. Sci Signal. 2012;5(255):re7.

5

Tagliabracci VS, Wiley SE, Guo X, et al. A single kinase generates the majority of the secreted phosphoproteome. Cell. 2015;161(7):1619-1632.

6

Worby CA, Mayfield JE, Pollak AJ, Dixon JE, Banerjee S. The ABCs of the atypical Fam20 secretory pathway kinases. J Biol Chem. 2021;296:100267.

7

Cozza G, Pinna LA. Casein kinases as potential therapeutic targets. Expert Opin Ther Targets. 2016;20(3):319-340.

8

Nalbant D, Youn H, Nalbant SI, et al. FAM20: an evolutionarily conserved family of secreted proteins expressed in hematopoietic cells. BMC Genom. 2005;6:11.

9

Bingham EW, Farrell Jr HM, Basch JJ. Phosphorylation of casein. Role of the Golgi apparatus. J Biol Chem. 1972;247(24):8193-8194.

10

Gerson-Gurwitz A, Worby CA, Lee KY, et al. Ancestral roles of the Fam20C family of secreted protein kinases revealed in C. elegans. J Cell Biol. 2019;218(11):3795-3811.

11

Simpson MA, Hsu R, Keir LS, et al. Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development. Am J Hum Genet. 2007;81(5):906-912.

12

Palma-Lara I, Pérez-Ramírez M, García Alonso-Themann P, et al. FAM20C overview: classic and novel targets, pathogenic variants and Raine syndrome phenotypes. Int J Mol Sci. 2021;22(15):8039.

13

Faundes V, Castillo-Taucher S, Gonzalez-Hormazabal P, Chandler K, Crosby A, Chioza B. Raine syndrome: an overview. Eur J Med Genet. 2014;57(9):536-542.

14

Tagliabracci VS, Engel JL, Wen J, et al. Secreted kinase phosphorylates extracellular proteins that regulate biomineralization. Science. 2012;336(6085):1150-1153.

15

Wang X, Wang S, Lu Y, et al. FAM20C plays an essential role in the formation of murine teeth. J Biol Chem. 2012;287(43):35934-35942.

16

Zhang J, Zhu Q, Wang XE, et al. Secretory kinase Fam20C tunes endoplasmic reticulum redox state via phosphorylation of Ero1α. EMBO J. 2018;37(14):e98699.

17

Hao J, Narayanan K, Muni T, Ramachandran A, George A. Dentin matrix protein 4, a novel secretory calcium-binding protein that modulates odontoblast differentiation. J Biol Chem. 2007;282(21):15357-15365.

18

Hung CY, Rodriguez M, Roberts A, Bauer M, Mihalek I, Bodamer O. A novel FAM20C mutation causes a rare form of neonatal lethal Raine syndrome. Am J Med Genet A. 2019;179(9):1866-1871.

19

Zhang H, Zhu Q, Cui J, et al. Structure and evolution of the Fam20 kinases. Nat Commun. 2018;9(1):1218.

20

Schytte GN, Christensen B, Bregenov I, et al. FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin. J Cell Biochem. 2020;121(12):4809-4818.

21

Xiao J, Tagliabracci VS, Wen J, Kim SA, Dixon JE. Crystal structure of the Golgi casein kinase. Proc Natl Acad Sci U S A. 2013;110(26):10574-10579.

22

Xu R, Tan H, Zhang J, Yuan Z, Xie Q, Zhang L. Fam20C in human diseases: emerging biological functions and therapeutic implications. Front Mol Biosci. 2021;8:790172.

23

Ishikawa HO, Xu A, Ogura E, Manning G, Irvine KD. The Raine syndrome protein FAM20C is a Golgi kinase that phosphorylates bio-mineralization proteins. PLoS One. 2012;7(8):e42988.

24

Brunati AM, Marin O, Bisinella A, Salviati A, Pinna LA. Novel consensus sequence for the Golgi apparatus casein kinase, revealed using proline-rich protein-1 (PRP1)-derived peptide substrates. Biochem J. 2000;351(Pt 3):765-768.

25

Ramos-Molina B, Lindberg I. Phosphorylation and alternative splicing of 7B2 reduce prohormone convertase 2 activation. Mol Endocrinol. 2015;29(5):756-764.

26

Cui J, Xiao J, Tagliabracci VS, Wen J, Rahdar M, Dixon JE. A secretory kinase complex regulates extracellular protein phosphorylation. Elife. 2015;4:e06120.

27

Cui J, Zhu Q, Zhang H, et al. Structure of Fam20A reveals a pseudokinase featuring a unique disulfide pattern and inverted ATP-binding. Elife. 2017;6:e23990.

28

Lasa M, Marin O, Pinna LA. Rat liver Golgi apparatus contains a protein kinase similar to the casein kinase of lactating mammary gland. Eur J Biochem. 1997;243(3):719-725.

29

Cozza G, Salvi M, Tagliabracci VS, Pinna LA. Fam20C is under the control of sphingolipid signaling in human cell lines. FEBS J. 2017;284(8):1246-1257.

30

Cozza G, Salvi M, Banerjee S, et al. A new role for sphingosine: up-regulation of Fam20C, the genuine casein kinase that phosphorylates secreted proteins. Biochim Biophys Acta. 2015;1854(10):1718-1726.

31

Chen X, Zhang J, Liu P, et al. Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization. Proc Natl Acad Sci U S A. 2021;118(32):e2100133118.

32

Yao J, Huang X, Ren J. In situ determination of secretory kinase Fam20C from living cells using fluorescence correlation spectroscopy. Talanta. 2021;232:122473.

33

Liu X, Zhan Y, Xu W, et al. Prognostic and immunological role of Fam20C in pan-cancer. Biosci Rep. 2021;41(1):BSR20201920.

34

Valiente M, Obenauf AC, Jin X, et al. Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell. 2014;156(5):1002-1016.

35

Zuo H, Yang D, Wan Y. Fam20C regulates bone resorption and breast cancer bone metastasis through osteopontin and BMP4. Cancer Res. 2021;81(20):5242-5254.

36

Kovářová M, Kalbacher H, Peter A, et al. Detection and characterization of phosphorylation, glycosylation, and fatty acid bound to fetuin A in human blood. J Clin Med. 2021;10(3):411.

37

Deng Y, Yang X, Hua H, Zhang C. IGFBP5 is upregulated and associated with poor prognosis in colorectal cancer. Int J Gen Med. 2022;15:6485-6497.

38

Lok ZSY, Lyle AN. Osteopontin in vascular disease. Arterioscler Thromb Vasc Biol. 2019;39(4):613-622.

39

Koguchi M, Nakahara Y, Ito H, et al. BMP4 induces asymmetric cell division in human glioma stem-like cells. Oncol Lett. 2020;19(2):1247-1254.

40

Gao W, Liu Y, Qin R, Liu D, Feng Q. Silence of fibronectin 1 increases cisplatin sensitivity of non-small cell lung cancer cell line. Biochem Biophys Res Commun. 2016;476(1):35-41.

41

Denecke B, Gräber S, Schäfer C, Heiss A, Wöltje M, Jahnen-Dechent W. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem J. 2003;376(pt 1):135-145.

42

Brown WM, Dziegielewska KM, Saunders NR, Møsllgård K. Fetuin - an old friend revisited. Bioessays. 1992;14(11):749-755.

43

Nangami GN, Sakwe AM, Izban MG, et al. Fetuin-A (alpha 2HS glycoprotein) modulates growth, motility, invasion, and senescence in high-grade astrocytomas. Cancer Med. 2016;5(12):3532-3543.

44

Ochieng J, Nangami G, Sakwe A, et al. Impact of fetuin-A (AHSG) on tumor progression and type 2 diabetes. Int J Mol Sci. 2018;19(8):E2211.

45

Dong C, Zhang J, Fang S, Liu F. IGFBP5 increases cell invasion and inhibits cell proliferation by EMT and Akt signaling pathway in Glioblastoma multiforme cells. Cell Div. 2020;15:4.

46

Wei J, Marisetty A, Schrand B, et al. Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target. J Clin Invest. 2019;129(1):137-149.

47

Hao C, Wang Z, Gu Y, Jiang WG, Cheng S. Prognostic value of osteopontin splice variant-c expression in breast cancers: a meta-analysis. BioMed Res Int. 2016;2016:7310694.

48

Burger AM, Leyland-Jones B, Banerjee K, Spyropoulos DD, Seth AK. Essential roles of IGFBP-3 and IGFBP-rP1 in breast cancer. Eur J Cancer. 2005;41(11):1515-1527.

49

Zhang XX, Luo JH, Wu LQ. FN1 overexpression is correlated with unfavorable prognosis and immune infiltrates in breast cancer. Front Genet. 2022;13:913659.

50

Nangami G, Koumangoye R, Shawn Goodwin J, et al. Fetuin A associates with histones intracellularly and shuttles them to exosomes to promote focal adhesion assembly resulting in rapid adhesion and spreading in breast carcinoma cells. Exp Cell Res. 2014;328(2):388-400.

51

Ohnami S, Maruyama K, Kai C, et al. BMP4 and PHLDA1 are plausible drug-targetable candidate genes for KRAS G12A-, G12D-, and G12V-driven colorectal cancer. Mol Cell Biochem. 2021;476(9):3469-3482.

52

Kundranda MN, Henderson M, Carter KJ, et al. The serum glycoprotein fetuin A promotes Lewis lung carcinoma tumorigenesis via adhesive-dependent and adhesive-independent mechanisms. Cancer Res. 2005;65(2):499-506.

53

Georges RB, Adwan H, Hamdi H, Hielscher T, Linnemann U, Berger MR. The insulin-like growth factor binding proteins 3 and 7 are associated with colorectal cancer and liver metastasis. Cancer Biol Ther. 2011;12(1):69-79.

54

Chen J, Wu W, Chen L, et al. Profiling the potential tumor markers of pancreatic ductal adenocarcinoma using 2D-DIGE and MALDI-TOF-MS: up-regulation of complement C3 and alpha-2-HS-glycoprotein. Pancreatology. 2013;13(3):290-297.

55

Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. 2019;29(3):212-226.

56

Zhang J, Cai H, Sun L, et al. LGR5, a novel functional glioma stem cell marker, promotes EMT by activating the Wnt/β-catenin pathway and predicts poor survival of glioma patients. J Exp Clin Cancer Res. 2018;37(1):225.

57

Karamanou K, Franchi M, Vynios D, Brézillon S. Epithelial-to-mesenchymal transition and invadopodia markers in breast cancer: lumican a key regulator. Semin Cancer Biol. 2020;62:125-133.

58

Deng G, Chen Y, Guo C, et al. BMP4 promotes the metastasis of gastric cancer by inducing epithelial-mesenchymal transition via ID1. J Cell Sci. 2020;133(11):jcs237222.

59

Zacharias M, Brcic L, Eidenhammer S, Popper H. Bulk tumour cell migration in lung carcinomas might be more common than epithelial-mesenchymal transition and be differently regulated. BMC Cancer. 2018;18(1):717.

60

Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011-2015. Neuro Oncol. 2018;20(suppl_4):iv1-iv86.

61

Feng J, Zhou J, Zhao L, et al. Fam20C overexpression predicts poor outcomes and is a diagnostic biomarker in lower-grade glioma. Front Genet. 2021;12:757014.

62

Pattwell SS, Arora S, Cimino PJ, et al. A kinase-deficient NTRK2 splice variant predominates in glioma and amplifies several oncogenic signaling pathways. Nat Commun. 2020;11(1):2977.

63

Gong B, Liang Y, Zhang Q, et al. Epigenetic and transcriptional activation of the secretory kinase FAM20C as an oncogene in glioma. J Genet Genomics. 2023;50(6):422-433.

64

Eckel-Passow JE, Drucker KL, Kollmeyer TM, et al. Adult diffuse glioma GWAS by molecular subtype identifies variants in D2HGDH and FAM20C. Neuro Oncol. 2020;22(11):1602-1613.

65

Eckel-Passow JE, Lachance DH, Decker PA, et al. Inherited genetics of adult diffuse glioma and polygenic risk scores - a review. Neurooncol Pract. 2022;9(4):259-270.

66

Sun LH, Yang FQ, Zhang CB, et al. Overexpression of paxillin correlates with tumor progression and predicts poor survival in glioblastoma. CNS Neurosci Ther. 2017;23(1):69-75.

67

Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709-722.

68

Linz U. Commentary on Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase Ⅲ study: 5-year analysis of the EORTC-NCIC trial (Lancet Oncol. 2009;10:459-466). Cancer. 2010;116(8):1844-1846.

69

Du S, Guan S, Zhu C, et al. Secretory pathway kinase FAM20C, a marker for glioma invasion and malignancy, predicts poor prognosis of glioma. OncoTargets Ther. 2020;13:11755-11768.

70

Arwert EN, Harney AS, Entenberg D, et al. A unidirectional transition from migratory to perivascular macrophage is required for tumor cell intravasation. Cell Rep. 2018;23(5):1239-1248.

71

Yang M, McKay D, Pollard JW, Lewis CE. Diverse functions of macrophages in different tumor microenvironments. Cancer Res. 2018;78(19):5492-5503.

72

MacKay A, Burford A, Carvalho D, et al. Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma. Cancer Cell. 2017;32(4):520-537.e5.

73

Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803-820.

74

Wu G, Broniscer A, McEachron TA, et al. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet. 2012;44(3):251-253.

75

Ren Y, Huang Z, Zhou L, et al. Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas. Nat Commun. 2023;14(1):1028.

76

Trendowski MR, Wheeler HE, El-Charif O, et al. Clinical and genome-wide analysis of multiple severe cisplatin-induced neurotoxicities in adult-onset cancer survivors. Clin Cancer Res. 2020;26(24):6550-6558.

77

Zhao R, Fu L, Yuan Z, et al. Discovery of a novel small-molecule inhibitor of Fam20C that induces apoptosis and inhibits migration in triple negative breast cancer. Eur J Med Chem. 2021;210:113088.

78

Qin Z, Wang P, Li X, et al. Systematic network-based discovery of a Fam20C inhibitor (FL-1607) with apoptosis modulation in triple-negative breast cancer. Mol Biosyst. 2016;12(7):2108-2118.

79

Li H, Tong L, Tao H, Liu Z. Genome-wide analysis of the hypoxia-related DNA methylation-driven genes in lung adenocarcinoma progression. Biosci Rep. 2020;40(2):BSR20194200.

80

Christensen B, Kazanecki CC, Petersen TE, Rittling SR, Denhardt DT, Sørensen ES. Cell type-specific post-translational modifications of mouse osteopontin are associated with different adhesive properties. J Biol Chem. 2007;282(27):19463-19472.

81

Fang ZH, Visker MHPW, Miranda G, Delacroix-Buchet A, Bovenhuis H, Martin P. The relationships among bovine αS-casein phosphorylation isoforms suggest different phosphorylation pathways. J Dairy Sci. 2016;99(10):8168-8177.

82

Yang X, Yan W, Tian Y, Ma P, Opperman LA, Wang X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone. Faseb J. 2016;30(1):121-128.

83

Wang X, Jung J, Liu Y, et al. The specific role of FAM20C in amelogenesis. J Dent Res. 2013;92(11):995-999.

84

Steitz SA, Speer MY, McKee MD, et al. Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification. Am J Pathol. 2002;161(6):2035-2046.

85

Narayanan K, Srinivas R, Ramachandran A, Hao J, Quinn B, George A. Differentiation of embryonic mesenchymal cells to odontoblast-like cells by overexpression of dentin matrix protein 1. Proc Natl Acad Sci U S A. 2001;98(8):4516-4521.

86

Ravindran S, George A. Dentin matrix proteins in bone tissue engineering. Adv Exp Med Biol. 2015;881:129-142.

87

Christensen B, Schytte GN, Scavenius C, Enghild JJ, McKee MD, Sørensen ES. FAM20C-mediated phosphorylation of MEPE and its acidic serine- and aspartate-rich motif. JBMR Plus. 2020;4(8):e10378.

88

Ho BB, Bergwitz C. FGF23 signalling and physiology. J Mol Endocrinol. 2021;66(2):R23-R32.

89

Wang X, Wang S, Li C, et al. Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice. PLoS Genet. 2012;8(5):e1002708.

90

Rafaelsen SH, Raeder H, Fagerheim AK, et al. Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23-related hypophosphatemia, dental anomalies, and ectopic calcification. J Bone Miner Res. 2013;28(6):1378-1385.

91

Zhang H, Li L, Kesterke MJ, Lu Y, Qin C. High-phosphate diet improved the skeletal development of Fam20c-deficient mice. Cells Tissues Organs. 2019;208(1-2):25-36.

92

Kinoshita Y, Hori M, Taguchi M, Fukumoto S. Functional analysis of mutant FAM20C in Raine syndrome with FGF23-related hypophosphatemia. Bone. 2014;67:145-151.

93

Seidahmed MZ, Alazami AM, Abdelbasit OB, et al. Report of a case of Raine syndrome and literature review. Am J Med Genet A. 2015;167A(10):2394-2398.

94

Tamai K, Tada K, Takeuchi A, et al. Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non-lethal form of Raine syndrome. Am J Med Genet A. 2018;176(3):682-686.

95

Rolvien T, Kornak U, Schinke T, Amling M, Oheim R. A novel FAM20C mutation causing hypophosphatemic osteomalacia with osteosclerosis (mild Raine syndrome) in an elderly man with spontaneous osteonecrosis of the knee. Osteoporos Int. 2019;30(3):685-689.

96

Eltan M, Alavanda C, Yavas Abali Z, et al. A rare cause of hypophosphatemia: raine syndrome changing clinical features with age. Calcif Tissue Int. 2020;107(1):96-103.

97

Mamedova E, Dimitrova D, Przhiyalkovskaya E, et al. Non-lethal raine syndrome in a middle-aged woman caused by a novel FAM20C mutation. Calcif Tissue Int. 2019;105(5):567-572.

98

Hernández-Zavala A, Cortés-Camacho F, Palma Lara I, et al. Two novel FAM20C variants in A family with raine syndrome. Genes (Basel). 2020;11(2):E222.

99

Ababneh FK, AlSwaid A, Youssef T, Al Azzawi M, Crosby A, AlBalwi MA. Hereditary deletion of the entire FAM20C gene in a patient with Raine syndrome. Am J Med Genet A. 2013;161A(12):3155-3160.

100

Gowen LC, Petersen DN, Mansolf AL, et al. Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. J Biol Chem. 2003;278(3):1998-2007.

101

Holm E, Gleberzon JS, Liao Y, et al. Osteopontin mediates mineralization and not osteogenic cell development in vitro. Biochem J. 2014;464(3):355-364.

102

Hayashibara T, Hiraga T, Sugita A, et al. Regulation of osteoclast differentiation and function by phosphate: potential role of osteoclasts in the skeletal abnormalities in hypophosphatemic conditions. J Bone Miner Res. 2007;22(11):1743-1751.

103

David V, Martin A, Hedge AM, Rowe PSN. Matrix extracellular phosphoglycoprotein (MEPE) is a new bone renal hormone and vascularization modulator. Endocrinology. 2009;150(9):4012-4023.

104

Bajaj S, Nabi F, Shah J, Sheth H. Recurrent variant c.1680C>A in FAM20C gene and genotype-phenotype correlation in a patient with Raine syndrome: a case report. BMC Pediatr. 2021;21(1):113.

105

Michałus I, Rusińska A. Rare, genetically conditioned forms of rickets: differential diagnosis and advances in diagnostics and treatment. Clin Genet. 2018;94(1):103-114.

106

Wang X, Hao J, Xie Y, et al. Expression of FAM20C in the osteogenesis and odontogenesis of mouse. J Histochem Cytochem. 2010;58(11):957-967.

107

Hirose K, Ishimoto T, Usami Y, et al. Overexpression of Fam20C in osteoblast in vivo leads to increased cortical bone formation and osteoclastic bone resorption. Bone. 2020;138:115414.

108

Liu C, Zhang H, Jani P, et al. FAM20C regulates osteoblast behaviors and intracellular signaling pathways in a cell-autonomous manner. J Cell Physiol. 2018;233(4):3476-3486.

109

Geng YW, Zhang Z, Jin H, et al. Mesenchymal-to-epithelial transition of osteoblasts induced by Fam20c knockout. Genes Genom. 2022;44(2):155-164.

110

Wang X, Wang J, Liu Y, et al. The specific role of FAM20C in dentinogenesis. J Dent Res. 2015;94(2):330-336.

111

Li Q, Yi B, Feng Z, Meng R, Tian C, Xu Q. FAM20C could be targeted by TET1 to promote odontoblastic differentiation potential of human dental pulp cells. Cell Prolif. 2018;51(2):e12426.

112

Liu C, Zhou N, Wang Y, et al. Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells. Exp Cell Res. 2018;363(2):188-195.

113

Liu P, Zhang H, Liu C, Wang X, Chen L, Qin C. Inactivation of Fam20C in cells expressing type I collagen causes periodontal disease in mice. PLoS One. 2014;9(12):e114396.

114

Nanci A, Bosshardt DD. Structure of periodontal tissues in health and disease. Periodontol 2000. 2006;40:11-28.

115

Tabata C, Hongo H, Sasaki M, et al. Altered distribution of extracellular matrix proteins in the periodontal ligament of periostin-deficient mice. Histol Histopathol. 2014;29(6):731-742.

116

Norris RA, Damon B, Mironov V, et al. Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues. J Cell Biochem. 2007;101(3):695-711.

117

Lin JH, Lin IP, Ohyama Y, et al. FAM20C directly binds to and phosphorylates Periostin. Sci Rep. 2020;10(1):17155.

118

O’Donnell CJ, Kavousi M, Smith AV, et al. Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. Circulation. 2011;124(25):2855-2864.

119

Goettsch C, Kjolby M, Aikawa E. Sortilin and its multiple roles in cardiovascular and metabolic diseases. Arterioscler Thromb Vasc Biol. 2018;38(1):19-25.

120

Goettsch C, Hutcheson JD, Aikawa M, et al. Sortilin mediates vascular calcification via its recruitment into extracellular vesicles. J Clin Invest. 2016;126(4):1323-1336.

121

Pollak AJ, Haghighi K, Kunduri S, et al. Phosphorylation of serine96 of histidine-rich calcium-binding protein by the Fam20C kinase functions to prevent cardiac arrhythmia. Proc Natl Acad Sci U S A. 2017;114(34):9098-9103.

122

Pollak AJ, Liu C, Gudlur A, et al. A secretory pathway kinase regulates sarcoplasmic reticulum Ca2+ homeostasis and protects against heart failure. Elife. 2018;7:e41378.

123

Park CS, Chen S, Lee H, et al. Targeted ablation of the histidine-rich Ca2+-binding protein (HRC) gene is associated with abnormal SR Ca2+-cycling and severe pathology under pressure-overload stress. Basic Res Cardiol. 2013;108(3):344.

124

Arvanitis DA, Sanoudou D, Kolokathis F, et al. The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy. Eur Heart J. 2008;29(20):2514-2525.

125

Arvanitis DA, Vafiadaki E, Johnson DM, Kranias EG, Sanoudou D. The histidine-rich calcium binding protein in regulation of cardiac rhythmicity. Front Physiol. 2018;9:1379.

126

Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298(17):2038-2047.

127

Ashraf Y, Duval S, Sachan V, et al. Proprotein convertase 7 (PCSK7) reduces apoA-V levels. FEBS J. 2020;287(16):3565-3578.

128

Ben Djoudi Ouadda A, Gauthier MS, Susan-Resiga D, et al. Ser-phosphorylation of PCSK9 (proprotein convertase subtilisin-kexin 9) by Fam20C (family with sequence similarity 20, member C) kinase enhances its ability to degrade the LDLR (low-density lipoprotein receptor). Arterioscler Thromb Vasc Biol. 2019;39(10):1996-2013.

129

Yu J, Li T, Liu Y, et al. Phosphorylation switches protein disulfide isomerase activity to maintain proteostasis and attenuate ER stress. EMBO J. 2020;39(10):e103841.

130

Kang T, Boland BB, Alarcon C, Grimsby JS, Rhodes CJ, Larsen MR. Proteomic analysis of restored insulin production and trafficking in obese diabetic mouse pancreatic islets following euglycemia. J Proteome Res. 2019;18(9):3245-3258.

131

Carrascal M, Gay M, Ovelleiro D, Casas V, Gelpí E, Abian J. Characterization of the human plasma phosphoproteome using linear ion trap mass spectrometry and multiple search engines. J Proteome Res. 2010;9(2):876-884.

132

Qiu Y, Poppleton E, Mekkat A, et al. Enzymatic phosphorylation of Ser in a type I collagen peptide. Biophys J. 2018;115(12):2327-2335.

133

Da Q, Han H, Valladolid C, et al. In vitro phosphorylation of von Willebrand factor by FAM20c enhances its ability to support platelet adhesion. J Thromb Haemostasis. 2019;17(6):866-877.

134

Hanna LS, Scheraga HA, Francis CW, Marder VJ. Comparison of structures of various human fibrinogens and a derivative thereof by a study of the kinetics of release of fibrinopeptides. Biochemistry. 1984;23(20):4681-4687.

135

Lietz CB, Toneff T, Mosier C, Podvin S, O’Donoghue AJ, Hook V. Phosphopeptidomics reveals differential phosphorylation states and novel SxE phosphosite motifs of neuropeptides in dense core secretory vesicles. J Am Soc Mass Spectrom. 2018;29(5):935-947.

136

Bright F, Katzeff JS, Hodges JR, et al. Glycoprotein pathways altered in frontotemporal dementia with autoimmune disease. Front Immunol. 2021;12:736260.

137

Tibaldi E, Brocca A, Sticca A, et al. Fam20C-mediated phosphorylation of osteopontin is critical for its secretion but dispensable for its action as a cytokine in the activation of hepatic stellate cells in liver fibrogenesis. Faseb J. 2020;34(1):1122-1135.

138

Miao N, Zhan Y, Xu Y, et al. Loss of Fam20c causes defects in the acinar and duct structure of salivary glands in mice. Int J Mol Med. 2019;43(5):2103-2117.

Genes & Diseases
Article number: 101179
Cite this article:
Zhang R, Ren Y, Ju Y, et al. FAM20C: A key protein kinase in multiple diseases. Genes & Diseases, 2025, 12(2): 101179. https://doi.org/10.1016/j.gendis.2023.101179
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