UniProt:Q8IXL6 FAM20C

chain
  • propeptide:1-92
  • chain:93-584
checksum ECD278B5EA681FEF
comment
  • FUNCTION Golgi serine/threonine protein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs and plays a key role in biomineralization of bones and teeth (PubMed:22582013, PubMed:23754375, PubMed:25789606). Constitutes the main protein kinase for extracellular proteins, generating the majority of the extracellular phosphoproteome (PubMed:26091039). Mainly phosphorylates proteins within the Ser-x-Glu/pSer motif, but also displays a broader substrate specificity (PubMed:26091039). Phosphorylates ERO1A, enhancing its activity which is required to maintain endoplasmic reticulum redox homeostasis and for oxidative protein folding (PubMed:29858230, PubMed:34349020). During endoplasmic reticulum stress, phosphorylates P4HB/PDIA1 which induces a functional switch, causing P4HB to change from an oxidoreductase to a molecular chaperone (PubMed:32149426). This is critical to maintain ER proteostasis and reduce cell death under ER stress (PubMed:32149426). Phosphorylation of P4HB also promotes its interaction with ERN1, leading to reduced activity of ERN1, a key sensor for the endoplasmic reticulum unfolded protein response (PubMed:32149426). Required for osteoblast differentiation and mineralization (PubMed:34349020). Phosphorylates casein as well as a number of proteins involved in biomineralization such as AMELX, AMTN, ENAM and SPP1/OPN (PubMed:22582013, PubMed:25789606, PubMed:34349020). In addition to its role in biomineralization, also plays a role in lipid homeostasis, wound healing and cell migration and adhesion (PubMed:26091039).CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR Serine/threonine protein kinase activity is increased upon interaction with FAM20A.BIOPHYSICOCHEMICAL PROPERTIES Homodimer; disulfide-linked (PubMed:34349020). Interacts with FAM20A; probably forming a heterotetramer of 2 subunits of FAM20A and 2 subunits of FAM20C (PubMed:25789606). Interacts with protease MBTPS1/S1P; the interaction results in FAM20C cleavage and secretion (PubMed:34349020). Interacts with COPII components SEC23A and SEC24A; transport of FAM20C from the endoplasmic reticulum to the Golgi is likely to be mediated by COPII vesicles (PubMed:34349020).INTERACTION Resides in the Golgi apparatus membrane and is secreted following propeptide cleavage (PubMed:34349020). Retained in the endoplasmic reticulum (ER) in response to ER stress where it phosphorylates P4HB (PubMed:32149426).ALTERNATIVE PRODUCTS Widely expressed.PTM N-glycosylation is required for folding.PTM Autophosphorylated.PTM Propeptide cleavage by MBTPS1/S1P promotes FAM20C secretion and maximal kinase activity which is essential for efficient osteoblast differentiation and biomineralization.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the FAM20 family.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Truncated N-terminus.
crossReference
databaseName UniProt
dbId 90174
description
  • recommendedName: fullName evidence="17"Extracellular serine/threonine protein kinase FAM20C ecNumber evidence="8 9 10 12 13 14"2.7.11.1 alternativeName: fullName evidence="1"Dentin matrix protein 4 shortName evidence="1"DMP-4 alternativeName: fullName evidence="16"Golgi casein kinase alternativeName: fullName evidence="16"Golgi-enriched fraction casein kinase shortName evidence="16"GEF-CK
displayName UniProt:Q8IXL6 FAM20C
geneName
  • FAM20C
  • DMP4
identifier Q8IXL6
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • ATP-binding
  • Biomineralization
  • Calcium
  • Direct protein sequencing
  • Disease variant
  • Disulfide bond
  • Endoplasmic reticulum
  • Glycoprotein
  • Golgi apparatus
  • Kinase
  • Manganese
  • Membrane
  • Metal-binding
  • Nucleotide-binding
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Secreted
  • Serine/threonine-protein kinase
  • Signal-anchor
  • Transferase
  • Transmembrane
  • Transmembrane helix
modified [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType Protein
name
  • FAM20C
otherIdentifier
  • 11731678_s_at
  • 11731679_x_at
  • 17042681
  • 226722_PM_at
  • 226722_at
  • 234466_PM_at
  • 234466_at
  • 2986723
  • 2986724
  • 2986728
  • 2986729
  • 2986730
  • 2986731
  • 2986732
  • 2986733
  • 2986739
  • 2986740
  • 56975
  • 72964_at
  • 8130993
  • 90257_at
  • A_14_P200939
  • A_23_P250122
  • A_33_P3346635
  • A_33_P3390823
  • GE86504
  • GO:0000139
  • GO:0000166
  • GO:0001501
  • GO:0002020
  • GO:0003824
  • GO:0004672
  • GO:0004674
  • GO:0005509
  • GO:0005515
  • GO:0005524
  • GO:0005576
  • GO:0005615
  • GO:0005654
  • GO:0005737
  • GO:0005783
  • GO:0005788
  • GO:0005794
  • GO:0006468
  • GO:0016020
  • GO:0016301
  • GO:0016740
  • GO:0030145
  • GO:0030154
  • GO:0030501
  • GO:0031214
  • GO:0036179
  • GO:0040036
  • GO:0043687
  • GO:0045669
  • GO:0046872
  • GO:0048856
  • GO:0051174
  • GO:0070062
  • GO:0070166
  • GO:0071895
  • GO:0097187
  • GO:0106310
  • GO:0140096
  • HMNXSV003025013
  • HMNXSV003051065
  • Hs.134742.0.S1_3p_at
  • Hs.283861.0.S1_3p_at
  • ILMN_1683165
  • ILMN_1703009
  • ILMN_1705982
  • ILMN_1712684
  • ILMN_1757634
  • PH_hs_0027843
  • PH_hs_0039836
  • TC07000004.hg
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • FA20C_HUMAN
  • A4D2Q5
  • L8B5W8
  • Q5I0W9
  • Q7Z4I0
  • Q9NPT2
sequenceLength 584
species [Species:48887] Homo sapiens
stId uniprot:Q8IXL6
url http://purl.uniprot.org/uniprot/Q8IXL6
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