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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). Constitutes the main protein kinase for extracellular proteins, generating the majority of the extracellular phosphoproteome (By similarity). Mainly phosphorylates proteins within the Ser-x-Glu/pSer motif, but also displays a broader substrate specificity (By similarity). Phosphorylates casein as well as a number of proteins involved in biomineralization such as AMELX, AMTN, ENAM and SPP1 (PubMed:25789606). In addition to its role in biomineralization, also plays a role in lipid homeostasis, wound healing and cell migration and adhesion (By similarity).By similarity3 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

Manual assertion based on experiment ini

  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)DescriptionActionsGraphical viewLength
Binding sitei264ATP; via amide nitrogenBy similarity1
Binding sitei280ATPBy similarity1
Metal bindingi301ManganeseBy similarity1
Binding sitei301ATPBy similarity1
Active sitei453By similarity1
Binding sitei458ATPBy similarity1
Metal bindingi473ManganeseBy similarity1
Binding sitei473ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi384 – 387ATPBy similarity4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calcium ion binding Source: MGI
  • manganese ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • biomineral tissue development Source: UniProtKB
  • 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: UniProtKB
  • 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
Proteomesi
  • UP000000589 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: UniProtKB
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)DescriptionActionsGraphical viewLength
Mutagenesisi241I → N: Abrogates kinase activity. 1 Publication1
Mutagenesisi261G → R: Abrogates kinase activity. 1 Publication1
Mutagenesisi374G → E or R: Abrogates kinase activity. 1 Publication1
Mutagenesisi383L → R: Mislocalization of the protein from Golgi apparatus to endoplasmic reticulum. 1 Publication1
Mutagenesisi446D → N: Mislocalization of the protein from Golgi apparatus to endoplasmic reticulum. 1 Publication1
Mutagenesisi453D → G: Abrogates kinase activity without affecting subcellular location. 1 Publication1
Mutagenesisi473 – 474DN → GG: Abrogates kinase activity. 1 Publication2
Mutagenesisi544R → W: Mislocalization of the protein from Golgi apparatus to endoplasmic reticulum. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
PropeptideiPRO_000043388427 – 87By similarityAdd BLAST61
ChainiPRO_000029797888 – 579Extracellular serine/threonine protein kinase FAM20CAdd BLAST492

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi96N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi357 ↔ 373By similarity
Disulfide bondi362 ↔ 366By similarity
Disulfide bondi421 ↔ 495By similarity
Disulfide bondi496 ↔ 555By similarity

Post-translational modificationi

N-glycosylation is required for folding.By similarity
Autophosphorylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ5MJS3.
PaxDbiQ5MJS3.
PeptideAtlasiQ5MJS3.
PRIDEiQ5MJS3.

PTM databases

iPTMnetiQ5MJS3.
PhosphoSitePlusiQ5MJS3.

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

BgeeiENSMUSG00000025854.
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

IntActiQ5MJS3. 1 interactor.
STRINGi10090.ENSMUSP00000026972.

Structurei

3D structure databases

ProteinModelPortaliQ5MJS3.
SMRiQ5MJS3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni349 – 560Kinase domainBy similarityAdd BLAST212

Sequence similaritiesi

Belongs to the FAM20 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3829. Eukaryota.
ENOG410XQEJ. LUCA.
GeneTreeiENSGT00390000007484.
HOGENOMiHOG000231437.
HOVERGENiHBG051635.
InParanoidiQ5MJS3.
OMAiHRILDVM.
OrthoDBiEOG091G1BEO.
PhylomeDBiQ5MJS3.
TreeFamiTF313276.

Family and domain databases

InterProiIPR024869. FAM20.
IPR009581. FAM20_C.
[Graphical view]
PANTHERiPTHR12450. PTHR12450. 1 hit.
PfamiPF06702. Fam20C. 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 differs from that shown. Reason: Frameshift at position 294.Curated
The sequence AAH04044 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH25814 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH25826 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAD90211 differs from that shown. Reason: Frameshift at position 296.Curated
The sequence BAD90211 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti333K → N in CAJ18570 (Ref. 4) Curated1

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ5MJS3. 1 interactor.
STRINGi10090.ENSMUSP00000026972.

PTM databases

iPTMnetiQ5MJS3.
PhosphoSitePlusiQ5MJS3.

Proteomic databases

MaxQBiQ5MJS3.
PaxDbiQ5MJS3.
PeptideAtlasiQ5MJS3.
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

eggNOGiKOG3829. Eukaryota.
ENOG410XQEJ. LUCA.
GeneTreeiENSGT00390000007484.
HOGENOMiHOG000231437.
HOVERGENiHBG051635.
InParanoidiQ5MJS3.
OMAiHRILDVM.
OrthoDBiEOG091G1BEO.
PhylomeDBiQ5MJS3.
TreeFamiTF313276.

Miscellaneous databases

ChiTaRSiFam20c. mouse.
PROiQ5MJS3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025854.
ExpressionAtlasiQ5MJS3. baseline and differential.
GenevisibleiQ5MJS3. MM.

Family and domain databases

InterProiIPR024869. FAM20.
IPR009581. FAM20_C.
[Graphical view]
PANTHERiPTHR12450. PTHR12450. 1 hit.
PfamiPF06702. Fam20C. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 83 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

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 one 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.