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Protein

Extracellular serine/threonine protein kinase FAM20C

Gene

Fam20c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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:22900076, PubMed:22732358, PubMed:25789606). Phosphorylates casein as well as a number of proteins involved in biomineralization such as AMELX, AMTN, ENAM and SPP1 (PubMed:25789606).3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mn2+By similarity

Enzyme regulationi

Serine/threonine protein kinase activity is increased upon interaction with FAM20A.1 Publication

Kineticsi

kcat is 52 min(-1).1 Publication

  1. KM=1.5 µM for casein1 Publication
  2. KM=78 µM for ATP1 Publication
  1. Vmax=0.7 µmol/min/mg enzyme1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei264 – 2641ATP; via amide nitrogenBy similarity
Binding sitei280 – 2801ATPBy similarity
Metal bindingi301 – 3011ManganeseBy similarity
Binding sitei301 – 3011ATPBy similarity
Active sitei453 – 4531By similarity
Binding sitei458 – 4581ATPBy similarity
Metal bindingi473 – 4731ManganeseBy similarity
Binding sitei473 – 4731ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi384 – 3874ATPBy similarity

GO - Molecular functioni

  • calcium ion binding Source: MGI
  • protein serine/threonine kinase activity Source: MGI

GO - Biological processi

  • dentinogenesis Source: MGI
  • enamel mineralization Source: MGI
  • odontoblast differentiation Source: MGI
  • osteoclast maturation Source: MGI
  • positive regulation of bone mineralization Source: MGI
  • positive regulation of osteoblast differentiation Source: MGI
  • protein phosphorylation Source: MGI
  • regulation of fibroblast growth factor receptor signaling pathway Source: MGI
  • regulation of phosphorus metabolic process Source: MGI
  • skeletal system development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Biomineralization

Keywords - Ligandi

ATP-binding, Calcium, Manganese, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Extracellular serine/threonine protein kinase FAM20CCurated (EC:2.7.11.11 Publication)
Alternative name(s):
Dentin matrix protein 41 Publication
Short name:
DMP-41 Publication
Golgi-enriched fraction casein kinaseBy similarity
Short name:
GEF-CKBy similarity
Gene namesi
Name:Fam20cImported
Synonyms:Dmp41 Publication, Kiaa40811 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:2136853. Fam20c.

Subcellular locationi

  • Secreted 1 Publication
  • Golgi apparatus 1 Publication

GO - Cellular componenti

  • extracellular exosome Source: MGI
  • extracellular space Source: MGI
  • Golgi apparatus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Secreted

Pathology & Biotechi

Disruption phenotypei

Mice survive to adulthood and show biomineralization defects, suc as severe amelogenesis imperfecta (AI). In addition, mice are severely hypophosphatemic and develop notable lesions in both dentin and bone.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi241 – 2411I → N: Abrogates kinase activity. 1 Publication
Mutagenesisi261 – 2611G → R: Abrogates kinase activity. 1 Publication
Mutagenesisi374 – 3741G → E or R: Abrogates kinase activity. 1 Publication
Mutagenesisi383 – 3831L → R: Mislocalization of the protein from Golgi apparatus to endoplasmic reticulum. 1 Publication
Mutagenesisi446 – 4461D → N: Mislocalization of the protein from Golgi apparatus to endoplasmic reticulum. 1 Publication
Mutagenesisi453 – 4531D → G: Abrogates kinase activity without affecting subcellular location. 1 Publication
Mutagenesisi473 – 4742DN → GG: Abrogates kinase activity. 1 Publication
Mutagenesisi544 – 5441R → W: Mislocalization of the protein from Golgi apparatus to endoplasmic reticulum. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626Sequence AnalysisAdd
BLAST
Chaini27 – 579553Extracellular serine/threonine protein kinase FAM20CPRO_0000297978Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi96 – 961N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi357 ↔ 373By similarity
Disulfide bondi362 ↔ 366By similarity
Disulfide bondi421 ↔ 495By similarity
Disulfide bondi496 ↔ 555By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ5MJS3.
PaxDbiQ5MJS3.
PRIDEiQ5MJS3.

PTM databases

PhosphoSiteiQ5MJS3.

Expressioni

Tissue specificityi

Highly expressed in the tooth. No expression in the dental pulp. At the secretory stage of amelogenesis, it is detected in the matrix of the enamel, in the ameloblasts, and within the cells adjoining the stratum intermedium (a tissue layer analogous to the stellate reticulum seen in the developing molar). Strong expression is observed in maturation stage ameloblasts and throughout the non-cornified layers of the gingival epithelium. Expressed at moderate levels in bone and at low levels in kidney, liver, brain and lung. Very low expression, if any, in spleen and skeletal muscle.2 Publications

Developmental stagei

In the developing tooth, initial expression observed in odontoblasts at all stages of development. At later stages, restricted expression pattern in ameloblasts. Also observed in osteoblats in the alveolar bone.1 Publication

Gene expression databases

BgeeiQ5MJS3.
ExpressionAtlasiQ5MJS3. baseline and differential.
GenevisibleiQ5MJS3. MM.

Interactioni

Subunit structurei

Interacts with FAM20A; probably forming a heterotetramer of 2 subunits of FAM20A and 2 subunits of FAM20C.1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000026972.

Structurei

3D structure databases

ProteinModelPortaliQ5MJS3.
SMRiQ5MJS3. Positions 220-565.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni349 – 560212Kinase domainBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the FAM20 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG238678.
GeneTreeiENSGT00390000007484.
HOGENOMiHOG000231437.
HOVERGENiHBG051635.
InParanoidiQ5MJS3.
OMAiHRILDVM.
OrthoDBiEOG7JX33T.
PhylomeDBiQ5MJS3.
TreeFamiTF313276.

Family and domain databases

InterProiIPR009581. DUF1193.
IPR024869. FAM20.
[Graphical view]
PANTHERiPTHR12450. PTHR12450. 1 hit.
PfamiPF06702. DUF1193. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q5MJS3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKMILVRRFR VLILVVFLLA CALHIAVDLL PKLDRRATRS SGEPGCSCAQ
60 70 80 90 100
PAAEAAGPGW AQARSRPGES AGGDAGWPNK HTLRILQDFS SDPASNLTSH
110 120 130 140 150
SLEKLPSAAE PVDHAPRGQE PRSPPPRDPA HRPLLRDPGP RPRVPPPGPS
160 170 180 190 200
GDGSLLAKLF EHPLYQGAVP PLTEDDVLFN VNSDIRFNPK AAENPDWPHE
210 220 230 240 250
GAEGAEFLPT GEAAVNLYPN WLKFHIGINR YELYSRHNPA IDALLRDLGS
260 270 280 290 300
QKITSVAMKS GGTQLKLIMT FQNYGQALFK PMKQTREQET PPDFFYFSDY
310 320 330 340 350
ERHNAEIAAF HLDRILDFRR VPPVAGRMIN MTKEIRDVTR DKKLWRTFFV
360 370 380 390 400
SPANNICFYG ECSYYCSTEH ALCGRPDQIE GSLAAFLPDL SLAKRKTWRN
410 420 430 440 450
PWRRSYHKRK KAEWEVDPDY CEEVKQTPPY DSGHRILDIM DMTVFDFLMG
460 470 480 490 500
NMDRHHYETF EKFGNETFII HLDNGRGFGK YSHDELSILA PLHQCCRIRR
510 520 530 540 550
STYLRLQLLA KEEHKLSLLM AESLQHDKVA PVLYQLHLEA LDRRLRIVLQ
560 570
AVRDCVEKDG LSSVVEDDLA TEHRASTER
Length:579
Mass (Da):65,766
Last modified:February 1, 2005 - v1
Checksum:i9DE5F5496AC117FE
GO

Sequence cautioni

The sequence AAH04044.3 differs from that shown. Reason: Frameshift at position 294. Curated
The sequence AAH04044.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH25814.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAH25826.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAD90211.1 differs from that shown. Reason: Frameshift at position 296. Curated
The sequence BAD90211.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti333 – 3331K → N in CAJ18570 (Ref. 4) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY778962 mRNA. Translation: AAV91326.1.
AK220286 mRNA. Translation: BAD90211.1. Sequence problems.
BC004044 mRNA. Translation: AAH04044.3. Sequence problems.
BC025814 mRNA. Translation: AAH25814.1. Different initiation.
BC025826 mRNA. Translation: AAH25826.1. Different initiation.
CT010363 mRNA. Translation: CAJ18570.1.
CCDSiCCDS51681.1.
RefSeqiNP_085042.2. NM_030565.6.
UniGeneiMm.320355.

Genome annotation databases

EnsembliENSMUST00000026972; ENSMUSP00000026972; ENSMUSG00000025854.
GeneIDi80752.
KEGGimmu:80752.
UCSCiuc009afv.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY778962 mRNA. Translation: AAV91326.1.
AK220286 mRNA. Translation: BAD90211.1. Sequence problems.
BC004044 mRNA. Translation: AAH04044.3. Sequence problems.
BC025814 mRNA. Translation: AAH25814.1. Different initiation.
BC025826 mRNA. Translation: AAH25826.1. Different initiation.
CT010363 mRNA. Translation: CAJ18570.1.
CCDSiCCDS51681.1.
RefSeqiNP_085042.2. NM_030565.6.
UniGeneiMm.320355.

3D structure databases

ProteinModelPortaliQ5MJS3.
SMRiQ5MJS3. Positions 220-565.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000026972.

PTM databases

PhosphoSiteiQ5MJS3.

Proteomic databases

MaxQBiQ5MJS3.
PaxDbiQ5MJS3.
PRIDEiQ5MJS3.

Protocols and materials databases

DNASUi80752.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026972; ENSMUSP00000026972; ENSMUSG00000025854.
GeneIDi80752.
KEGGimmu:80752.
UCSCiuc009afv.2. mouse.

Organism-specific databases

CTDi56975.
MGIiMGI:2136853. Fam20c.
RougeiSearch...

Phylogenomic databases

eggNOGiNOG238678.
GeneTreeiENSGT00390000007484.
HOGENOMiHOG000231437.
HOVERGENiHBG051635.
InParanoidiQ5MJS3.
OMAiHRILDVM.
OrthoDBiEOG7JX33T.
PhylomeDBiQ5MJS3.
TreeFamiTF313276.

Miscellaneous databases

ChiTaRSiFam20c. mouse.
NextBioi350121.
PROiQ5MJS3.
SOURCEiSearch...

Gene expression databases

BgeeiQ5MJS3.
ExpressionAtlasiQ5MJS3. baseline and differential.
GenevisibleiQ5MJS3. MM.

Family and domain databases

InterProiIPR009581. DUF1193.
IPR024869. FAM20.
[Graphical view]
PANTHERiPTHR12450. PTHR12450. 1 hit.
PfamiPF06702. DUF1193. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Dentin matrix protein 4, a novel secretory calcium-binding protein that modulates odontoblast differentiation."
    Hao J., Narayanan K., Muni T., Ramachandran A., George A.
    J. Biol. Chem. 282:15357-15365(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  2. "Prediction of the coding sequences of mouse homologues of KIAA gene. The complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Seino S., Nishimura M., Nagase T., Ohara O., Koga H.
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Pancreatic islet.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Liver and Mammary tumor.
  4. "Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)."
    Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 331-579.
  5. "Whole-exome sequencing identifies FAM20A mutations as a cause of amelogenesis imperfecta and gingival hyperplasia syndrome."
    O'Sullivan J., Bitu C.C., Daly S.B., Urquhart J.E., Barron M.J., Bhaskar S.S., Martelli-Junior H., dos Santos Neto P.E., Mansilla M.A., Murray J.C., Coletta R.D., Black G.C., Dixon M.J.
    Am. J. Hum. Genet. 88:616-620(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  6. "The Raine syndrome protein FAM20C is a Golgi kinase that phosphorylates bio-mineralization proteins."
    Ishikawa H.O., Xu A., Ogura E., Manning G., Irvine K.D.
    PLoS ONE 7:E42988-E42988(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, MUTAGENESIS OF ILE-241; GLY-261; GLY-374; LEU-383; ASP-446; ASP-453; 473-ASP-ASN-474 AND ARG-544.
  7. "Amelogenesis imperfecta and other biomineralization defects in Fam20a and Fam20c null mice."
    Vogel P., Hansen G.M., Read R.W., Vance R.B., Thiel M., Liu J., Wronski T.J., Smith D.D., Jeter-Jones S., Brommage R.
    Vet. Pathol. 49:998-1017(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  8. "A secretory kinase complex regulates extracellular protein phosphorylation."
    Cui J., Xiao J., Tagliabracci V.S., Wen J., Rahdar M., Dixon J.E.
    Elife 4:0-0(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH FAM20A, ENZYME REGULATION.

Entry informationi

Entry nameiFA20C_MOUSE
AccessioniPrimary (citable) accession number: Q5MJS3
Secondary accession number(s): Q4FJP0
, Q571A3, Q6PKA8, Q8JZP7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 21, 2007
Last sequence update: February 1, 2005
Last modified: July 22, 2015
This is version 74 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.