FA20A_MOUSE
ID FA20A_MOUSE Reviewed; 541 AA.
AC Q8CID3;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Pseudokinase FAM20A {ECO:0000305};
DE Flags: Precursor;
GN Name=Fam20a {ECO:0000312|MGI:MGI:2388266};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP SUBCELLULAR LOCATION, GLYCOSYLATION, DEVELOPMENTAL STAGE, INDUCTION, AND
RP MUTAGENESIS OF 14-LEU-LEU-15.
RX PubMed=15676076; DOI=10.1186/1471-2164-6-11;
RA Nalbant D., Youn H., Nalbant S.I., Sharma S., Cobos E., Beale E.G., Du Y.,
RA Williams S.C.;
RT "FAM20: an evolutionarily conserved family of secreted proteins expressed
RT in hematopoietic cells.";
RL BMC Genomics 6:11-11(2005).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=21549343; DOI=10.1016/j.ajhg.2011.04.005;
RA O'Sullivan J., Bitu C.C., Daly S.B., Urquhart J.E., Barron M.J.,
RA Bhaskar S.S., Martelli-Junior H., dos Santos Neto P.E., Mansilla M.A.,
RA Murray J.C., Coletta R.D., Black G.C., Dixon M.J.;
RT "Whole-exome sequencing identifies FAM20A mutations as a cause of
RT amelogenesis imperfecta and gingival hyperplasia syndrome.";
RL Am. J. Hum. Genet. 88:616-620(2011).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=22900076; DOI=10.1371/journal.pone.0042988;
RA Ishikawa H.O., Xu A., Ogura E., Manning G., Irvine K.D.;
RT "The Raine syndrome protein FAM20C is a Golgi kinase that phosphorylates
RT bio-mineralization proteins.";
RL PLoS ONE 7:E42988-E42988(2012).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22732358; DOI=10.1177/0300985812453177;
RA Vogel P., Hansen G.M., Read R.W., Vance R.B., Thiel M., Liu J.,
RA Wronski T.J., Smith D.D., Jeter-Jones S., Brommage R.;
RT "Amelogenesis imperfecta and other biomineralization defects in Fam20a and
RT Fam20c null mice.";
RL Vet. Pathol. 49:998-1017(2012).
RN [6]
RP FUNCTION, AND INTERACTION WITH FAM20C.
RX PubMed=25789606; DOI=10.7554/elife.06120;
RA Cui J., Xiao J., Tagliabracci V.S., Wen J., Rahdar M., Dixon J.E.;
RT "A secretory kinase complex regulates extracellular protein
RT phosphorylation.";
RL Elife 4:0-0(2015).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=29858230; DOI=10.15252/embj.201798699;
RA Zhang J., Zhu Q., Wang X., Yu J., Chen X., Wang J., Wang X., Xiao J.,
RA Wang C.C., Wang L.;
RT "Secretory kinase Fam20C tunes endoplasmic reticulum redox state via
RT phosphorylation of Ero1alpha.";
RL EMBO J. 37:0-0(2018).
CC -!- FUNCTION: Pseudokinase that acts as an allosteric activator of the
CC Golgi serine/threonine protein kinase FAM20C and is involved in
CC biomineralization of teeth. Forms a complex with FAM20C and increases
CC the ability of FAM20C to phosphorylate the proteins that form the
CC 'matrix' that guides the deposition of the enamel minerals.
CC {ECO:0000269|PubMed:25789606}.
CC -!- SUBUNIT: Interacts with FAM20C; probably forming a heterotetramer of 2
CC subunits of FAM20A and 2 subunits of FAM20C.
CC {ECO:0000269|PubMed:25789606}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15676076}. Golgi
CC apparatus {ECO:0000269|PubMed:22900076}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:22900076}.
CC -!- TISSUE SPECIFICITY: In the mammary gland, expressed at higher levels in
CC lactating mice than in virgin mice (PubMed:29858230). Observed
CC throughout the tissues of the mandibular incisor, including the
CC secretory and maturation stage ameloblasts, the suprabasal layers of
CC the gingival epithelium and the odontoblasts. Weak expression in the
CC enamel matrix. {ECO:0000269|PubMed:21549343,
CC ECO:0000269|PubMed:22732358, ECO:0000269|PubMed:29858230}.
CC -!- DEVELOPMENTAL STAGE: In EML and MPRO cell lines, low levels in
CC undifferentiated cells. Induced during maturation to promyelocyte stage
CC of neutrophil differentiation. Decreased during neutrophil terminal
CC differentiation. {ECO:0000269|PubMed:15676076}.
CC -!- INDUCTION: By all-trans retinoic acid (atRA) and IL3 in EML cell line.
CC {ECO:0000269|PubMed:15676076}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15676076}.
CC -!- DISRUPTION PHENOTYPE: Mice survive to adulthood and show
CC biomineralization defects such as severe amelogenesis imperfecta (AI).
CC In addition, mice develop disseminated calcifications of muscular
CC arteries and intrapulmonary calcifications, similar to those of fetuin-
CC A (Ahsg) deficient mice, although they are normocalcemic and
CC normophosphatemic, with normal dentin and bone.
CC {ECO:0000269|PubMed:22732358}.
CC -!- SIMILARITY: Belongs to the FAM20 family. {ECO:0000305}.
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DR EMBL; BC029169; AAH29169.1; -; mRNA.
DR CCDS; CCDS25584.1; -.
DR RefSeq; NP_722477.1; NM_153782.1.
DR AlphaFoldDB; Q8CID3; -.
DR SMR; Q8CID3; -.
DR IntAct; Q8CID3; 1.
DR STRING; 10090.ENSMUSP00000020938; -.
DR GlyGen; Q8CID3; 5 sites.
DR iPTMnet; Q8CID3; -.
DR PhosphoSitePlus; Q8CID3; -.
DR EPD; Q8CID3; -.
DR MaxQB; Q8CID3; -.
DR PaxDb; Q8CID3; -.
DR PeptideAtlas; Q8CID3; -.
DR PRIDE; Q8CID3; -.
DR ProteomicsDB; 275833; -.
DR Antibodypedia; 31793; 120 antibodies from 23 providers.
DR DNASU; 208659; -.
DR Ensembl; ENSMUST00000020938; ENSMUSP00000020938; ENSMUSG00000020614.
DR Ensembl; ENSMUST00000155559; ENSMUSP00000116687; ENSMUSG00000020614.
DR GeneID; 208659; -.
DR KEGG; mmu:208659; -.
DR UCSC; uc007mcw.1; mouse.
DR CTD; 54757; -.
DR MGI; MGI:2388266; Fam20a.
DR VEuPathDB; HostDB:ENSMUSG00000020614; -.
DR eggNOG; KOG3829; Eukaryota.
DR GeneTree; ENSGT00950000182951; -.
DR HOGENOM; CLU_028926_2_0_1; -.
DR InParanoid; Q8CID3; -.
DR OMA; HDMRHLP; -.
DR OrthoDB; 484324at2759; -.
DR PhylomeDB; Q8CID3; -.
DR TreeFam; TF313276; -.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 208659; 7 hits in 72 CRISPR screens.
DR ChiTaRS; Fam20a; mouse.
DR PRO; PR:Q8CID3; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8CID3; protein.
DR Bgee; ENSMUSG00000020614; Expressed in molar tooth and 111 other tissues.
DR Genevisible; Q8CID3; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISS:UniProtKB.
DR GO; GO:0031214; P:biomineral tissue development; ISS:UniProtKB.
DR GO; GO:0055074; P:calcium ion homeostasis; ISO:MGI.
DR GO; GO:0070166; P:enamel mineralization; IMP:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0044691; P:tooth eruption; ISO:MGI.
DR InterPro; IPR024869; FAM20.
DR InterPro; IPR009581; FAM20_C.
DR PANTHER; PTHR12450; PTHR12450; 1.
DR Pfam; PF06702; Fam20C; 1.
PE 1: Evidence at protein level;
KW Biomineralization; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Golgi apparatus; Reference proteome; Secreted; Signal.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..541
FT /note="Pseudokinase FAM20A"
FT /id="PRO_0000008744"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 538
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 314..330
FT /evidence="ECO:0000250|UniProtKB:Q9XTW2"
FT DISULFID 319..323
FT /evidence="ECO:0000250|UniProtKB:Q9XTW2"
FT DISULFID 378..452
FT /evidence="ECO:0000250|UniProtKB:Q9XTW2"
FT DISULFID 453..512
FT /evidence="ECO:0000250|UniProtKB:Q9XTW2"
FT MUTAGEN 14..15
FT /note="LL->DE: Not secreted; nuclear localization."
FT /evidence="ECO:0000269|PubMed:15676076"
SQ SEQUENCE 541 AA; 61526 MW; 2F6B2DCF9A447CDA CRC64;
MPGLRRDRLL ALLLLGALFS ADLYFHLWPQ VQRQLRPGER PAACPCSGRA PSASLHSAAA
SRDLGTASHN FSGALPRVEH PSRGHPAPRS KLQALFAHSL YQVLEDPPLL GPEDWLLASQ
EALRYYRRKV ARWNRRHKIY KEQFNLTSLD PPLQFRPEAS WVQFHLGINS HGLYSRSSLA
ISKLLHDMRH FPTISADYSQ DEKALLGACD CSQIVKPSGV HLKLVLRFSD FGKAMFKPMR
QQREEETPED FFYFIDFQRH NAEIAAFHLD RILDFRRVPP TVGRLVNVTK EILEVTKNEI
LQSVFFVSPA NNVCFFAKCP YMCKTEYAVC GNPHLLEGSL SAFLPSLNLA PRLSVPNPWI
RSYSLSGKEE WELNPLYCDT VKQIYPYNSS NRLLGIIDMA VFDFLIGNMD RHHYEMFTKF
GDDGYLIHLD NARGFGRHSQ DEISILAPLA QCCMIKRKTL LHLQLLAQAD YRLSDVMRES
LLEDQLSPVL TEPHLLALDR RLQIILKTVE DCIEAHGERR VIAEGSAQRS APDSGQANLT
S
