FAM20C
entrez
56975
canonical
uniprot
Q8IXL6
canonical
ensembl
ENSG00000177706
resolver
ensembl
ENSG00000288499
resolver
ensp
ENSP00000322323
resolver
ensp
ENSP00000759653
resolver
genesymbol
FAM20C
resolver
genesymbol_syn
DMP4
resolver
hgnc
HGNC:22140
resolver
uniprot
A4D2Q5
resolver
uniprot
L8B5W8
resolver
uniprot
Q5I0W9
resolver
uniprot
Q7Z4I0
resolver
uniprot
Q9NPT2
resolver
uniprot_entry
FA20C_HUMAN
resolver
uniprot_sec
A4D2Q5
resolver
uniprot_sec
L8B5W8
resolver
uniprot_sec
Q5I0W9
resolver
uniprot_sec
Q7Z4I0
resolver
uniprot_sec
Q9NPT2
resolver
activity_regulation
ACTIVITY REGULATION: Serine/threonine protein kinase activity is increased upon interaction with FAM20A. {ECO:0000269|PubMed:25789606}.
uniprot
proteins
amino_acid_sequence
MKMMLVRRFRVLILMVFLVACALHIALDLLPRLERRGARPSGEPGCSCAQPAAEVAAPGWAQVRGRPGEPPAASSAAGDAGWPNKHTLRILQDFSSDPSSNLSSHSLEKLPPAAEPAERALRGRDPGALRPHDPAHRPLLRDPGPRRSESPPGPGGDASLLARLFEHPLYRVAVPPLTEEDVLFNVNSDTRLSPKAAENPDWPHAGAEGAEFLSPGEAAVDSYPNWLKFHIGINRYELYSRHNPAIEALLHDLSSQRITSVAMKSGGTQLKLIMTFQNYGQALFKPMKQTREQETPPDFFYFSDYERHNAEIAAFHLDRILDFRRVPPVAGRMVNMTKEIRDVTRDKKLWRTFFISPANNICFYGECSYYCSTEHALCGKPDQIEGSLAAFLPDLSLAKRKTWRNPWRRSYHKRKKAEWEVDPDYCEEVKQTPPYDSSHRILDVMDMTIFDFLMGNMDRHHYETFEKFGNETFIIHLDNGRGFGKYSHDELSILVPLQQCCRIRKSTYLRLQLLAKEEYKLSLLMAESLRGDQVAPVLYQPHLEALDRRLRVVLKAVRDCVERNGLHSVVDDDLDTEHRAASAR
uniprot
proteins
disease_involvement
DISEASE: Raine syndrome (RNS) [MIM:259775]: An autosomal recessive osteosclerotic bone dysplasia with neonatal lethal outcome, although some patients survive into childhood. Clinical features include generalized increase in the density of all bones and a marked increase in the ossification of the skull, craniofacial dysplasia and microcephaly. {ECO:0000269|PubMed:17924334, ECO:0000269|PubMed:22582013, ECO:0000269|PubMed:25789606}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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). {ECO:0000269|PubMed:22582013, ECO:0000269|PubMed:23754375, ECO:0000269|PubMed:25789606, ECO:0000269|PubMed:26091039, ECO:0000269|PubMed:29858230, ECO:0000269|PubMed:32149426, ECO:0000269|PubMed:34349020}.
uniprot
proteins
mass_dalton
66234
uniprot
proteins
mutagenesis
MUTAGEN 28..31; /note="DLLP->AAAA: Loss of membrane localization with more efficient secretion and loss of propeptide cleavage. Reduced oligomerization."; /evidence="ECO:0000269|PubMed:34349020"; MUTAGEN 46; /note="C->S: No effect on homodimer formation. Complete disruption of homodimer formation but no effect on secretion; when associated with S-48."; /evidence="ECO:0000269|PubMed:34349020"; MUTAGEN 48; /note="C->S: No effect on homodimer formation. Complete disruption of homodimer formation but no effect on secretion; when associated with S-46."; /evidence="ECO:0000269|PubMed:34349020"; MUTAGEN 89; /note="R->A: Impaired secretion. Loss of ability to promote osteoblast differentiation; when associated with A-92."; /evidence="ECO:0000269|PubMed:34349020"; MUTAGEN 90; /note="I->A: No effect on secretion."; /evidence="ECO:0000269|PubMed:34349020"; MUTAGEN 91..93; /note="LQD->AAA: No effect on secretion or activity."; /evidence="ECO:0000269|PubMed:26091039"; MUTAGEN 91; /note="L->S: Impaired secretion."; /evidence="ECO:0000269|PubMed:34349020"; MUTAGEN 92; /note="Q->A: Impaired secretion. Loss of ability to promote osteoblast differentiation; when associated with A-89."; /evidence="ECO:0000269|PubMed:34349020"; MUTAGEN 101; /note="N->A: Impaired secretion; when associated with A-335 and A-470."; /evidence="ECO:0000269|PubMed:26091039"; MUTAGEN 106; /note="S->A: Abolishes phosphorylation."; /evidence="ECO:0000269|PubMed:34349020"; MUTAGEN 271; /note="K->A: Reduced kinase activity."; /evidence="ECO:0000269|PubMed:23754375"; MUTAGEN 285; /note="K->A: Reduced kinase activity."; /evidence="ECO:0000269|PubMed:23754375"; MUTAGEN 306; /note="E->A,Q: Strongly reduced kinase activity."; /evidence="ECO:0000269|PubMed:23754375, ECO:0000269|PubMed:25789606"; MUTAGEN 311; /note="E->A: Reduced kinase activity."; /evidence="ECO:0000269|PubMed:23754375"; MUTAGEN 335; /note="N->A: Impaired secretion; when associated with A-101 and A-470."; /evidence="ECO:0000269|PubMed:26091039"; MUTAGEN 408; /note="R->A: Reduced kinase activity."; /evidence="ECO:0000269|PubMed:23754375"; MUTAGEN 458; /note="D->A: Abrogates kinase activity."; /evidence="ECO:0000269|PubMed:23754375"; MUTAGEN 470; /note="N->A: Impaired secretion; when associated with A-101 and A-335."; /evidence="ECO:0000269|PubMed:26091039"; MUTAGEN 478; /note="D->A: Unable to bind manganese. Abrogates kinase activity. Loss of ERO1A phosphorylation. Loss of autophosphorylation. Loss of ability to promote osteoblast differentiation."; /evidence="ECO:0000269|PubMed:22582013, ECO:0000269|PubMed:23754375, ECO:0000269|PubMed:25789606, ECO:0000269|PubMed:26091039, ECO:0000269|PubMed:29858230, ECO:0000269|PubMed:34349020
uniprot
proteins
post_translational_modification
PTM: N-glycosylation is required for folding. {ECO:0000305|PubMed:26091039}.; PTM: Autophosphorylated. {ECO:0000269|PubMed:26091039, ECO:0000269|PubMed:34349020}.; PTM: Propeptide cleavage by MBTPS1/S1P promotes FAM20C secretion and maximal kinase activity which is essential for efficient osteoblast differentiation and biomineralization. {ECO:0000269|PubMed:34349020}.
uniprot
proteins
protein_family
FAM20 family
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15676076
uniprot
proteins
pubmed
17924334
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
22582013
uniprot
proteins
pubmed
23754375
uniprot
proteins
pubmed
25789606
uniprot
proteins
pubmed
26091039
uniprot
proteins
pubmed
29858230
uniprot
proteins
pubmed
32149426
uniprot
proteins
pubmed
34349020
uniprot
proteins
sequence_length
584
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000269|PubMed:32149426, ECO:0000269|PubMed:34349020}; Single-pass type II membrane protein {ECO:0000269|PubMed:34349020}. Secreted {ECO:0000269|PubMed:26091039}. Endoplasmic reticulum {ECO:0000269|PubMed:32149426}. Note=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). {ECO:0000269|PubMed:32149426, ECO:0000269|PubMed:34349020}.
uniprot
proteins
transmembrane_region
TRANSMEM 11..31; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins