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Protein

Extracellular serine/threonine protein kinase FAM20C

Gene

FAM20C

Organism
Homo sapiens (Human)
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: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 casein as well as a number of proteins involved in biomineralization such as AMELX, AMTN, ENAM and SPP1 (PubMed:22582013, PubMed:25789606). In addition to its role in biomineralization, also plays a role in lipid homeostasis, wound healing and cell migration and adhesion (PubMed:26091039).4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.3 Publications

Cofactori

Mn2+1 Publication1 Publication

Enzyme regulationi

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

Kineticsi

  1. KM=0.8 µM for manganese/ATP1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei269ATP; via amide nitrogenBy similarity1
    Binding sitei285ATPBy similarity1
    Metal bindingi306ManganeseBy similarity1
    Binding sitei306ATPBy similarity1
    Active sitei4581 Publication1
    Binding sitei463ATPBy similarity1
    Metal bindingi478Manganese1 Publication1
    Binding sitei478ATPBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi389 – 392ATPBy similarity4

    GO - Molecular functioni

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

    GO - Biological processi

    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:2.7.11.13 Publications)
    Alternative name(s):
    Dentin matrix protein 4By similarity
    Short name:
    DMP-4By similarity
    Golgi casein kinase1 Publication
    Golgi-enriched fraction casein kinase1 Publication
    Short name:
    GEF-CK1 Publication
    Gene namesi
    Name:FAM20CImported
    Synonyms:DMP4By similarity
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:22140. FAM20C.

    Subcellular locationi

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Golgi apparatus, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Raine syndrome (RNS)3 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAutosomal recessive osteosclerotic bone dysplasia with neonatal lethal outcome. Clinical features include generalized osteosclerosis, craniofacial dysplasia and microcephaly.
    See also OMIM:259775
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_073660258I → N in RNS. 1 Publication1
    Natural variantiVAR_073661268T → M in RNS; mild non-lethal form; decreased protein kinase activity. 1 PublicationCorresponds to variant rs778899041dbSNPEnsembl.1
    Natural variantiVAR_073662280G → R in RNS. 1 PublicationCorresponds to variant rs779708323dbSNPEnsembl.1
    Natural variantiVAR_073663328P → S in RNS; mild non-lethal form; decreased protein kinase activity; FAM20A is still able to increase remaining protein kinase activity. 2 Publications1
    Natural variantiVAR_037530379G → E in RNS. 2 PublicationsCorresponds to variant rs796051852dbSNPEnsembl.1
    Natural variantiVAR_037531379G → R in RNS. 2 Publications1
    Natural variantiVAR_037532388L → R in RNS. 2 PublicationsCorresponds to variant rs796051849dbSNPEnsembl.1
    Natural variantiVAR_073664451D → N in RNS; mild non-lethal form; decreased protein kinase activity. 1 Publication1
    Natural variantiVAR_037533549R → W in RNS. 2 PublicationsCorresponds to variant rs796051850dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi91 – 93LQD → AAA: Does not affect secretion or activity. 1 Publication3
    Mutagenesisi101N → A: Impaired secretion; when associated with A-335 and A-470. 1 Publication1
    Mutagenesisi271K → A: Reduced kinase activity. 1 Publication1
    Mutagenesisi285K → A: Reduced kinase activity. 1 Publication1
    Mutagenesisi306E → A or Q: Strongly reduced kinase activity. 2 Publications1
    Mutagenesisi311E → A: Reduced kinase activity. 1 Publication1
    Mutagenesisi335N → A: Impaired secretion; when associated with A-101 and A-470. 1 Publication1
    Mutagenesisi408R → A: Reduced kinase activity. 1 Publication1
    Mutagenesisi458D → A: Abrogates kinase activity. 1 Publication1
    Mutagenesisi470N → A: Impaired secretion; when associated with A-101 and A-335. 1 Publication1
    Mutagenesisi478D → A: Unable to bind manganese; abrogates kinase activity. 4 Publications1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi56975.
    MalaCardsiFAM20C.
    MIMi259775. phenotype.
    OpenTargetsiENSG00000177706.
    Orphaneti1832. Lethal osteosclerotic bone dysplasia.
    PharmGKBiPA134898453.

    Polymorphism and mutation databases

    BioMutaiFAM20C.
    DMDMi327478506.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 22Sequence analysisAdd BLAST22
    PropeptideiPRO_000043388323 – 921 PublicationAdd BLAST70
    ChainiPRO_000000874793 – 584Extracellular serine/threonine protein kinase FAM20CAdd BLAST492

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi101N-linked (GlcNAc...)1 Publication1
    Glycosylationi335N-linked (GlcNAc...)1 Publication1
    Disulfide bondi362 ↔ 378By similarity
    Disulfide bondi367 ↔ 371By similarity
    Disulfide bondi426 ↔ 500By similarity
    Glycosylationi470N-linked (GlcNAc...)2 Publications1
    Disulfide bondi501 ↔ 560By similarity

    Post-translational modificationi

    N-glycosylation is required for folding.1 Publication
    Autophosphorylated.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    EPDiQ8IXL6.
    MaxQBiQ8IXL6.
    PaxDbiQ8IXL6.
    PeptideAtlasiQ8IXL6.
    PRIDEiQ8IXL6.

    PTM databases

    iPTMnetiQ8IXL6.
    PhosphoSitePlusiQ8IXL6.

    Expressioni

    Tissue specificityi

    Widely expressed.1 Publication

    Gene expression databases

    BgeeiENSG00000177706.
    CleanExiHS_FAM20C.
    GenevisibleiQ8IXL6. HS.

    Organism-specific databases

    HPAiHPA019823.

    Interactioni

    Subunit structurei

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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AMBNQ9NP702EBI-7147442,EBI-11893530
    AMTNQ6UX392EBI-7147442,EBI-11892684
    ENAMQ9NRM12EBI-7147442,EBI-11892601
    FAM20AQ96MK33EBI-7147442,EBI-11892970

    Protein-protein interaction databases

    BioGridi121294. 7 interactors.
    IntActiQ8IXL6. 15 interactors.
    MINTiMINT-6940404.
    STRINGi9606.ENSP00000322323.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8IXL6.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni354 – 565Kinase domain1 PublicationAdd BLAST212

    Sequence similaritiesi

    Belongs to the FAM20 family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG3829. Eukaryota.
    ENOG410XQEJ. LUCA.
    GeneTreeiENSGT00390000007484.
    HOGENOMiHOG000231437.
    HOVERGENiHBG051635.
    InParanoidiQ8IXL6.
    OMAiHRILDVM.
    OrthoDBiEOG091G1BEO.
    PhylomeDBiQ8IXL6.
    TreeFamiTF313276.

    Family and domain databases

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

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q8IXL6-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MKMMLVRRFR VLILMVFLVA CALHIALDLL PRLERRGARP SGEPGCSCAQ
    60 70 80 90 100
    PAAEVAAPGW AQVRGRPGEP PAASSAAGDA GWPNKHTLRI LQDFSSDPSS
    110 120 130 140 150
    NLSSHSLEKL PPAAEPAERA LRGRDPGALR PHDPAHRPLL RDPGPRRSES
    160 170 180 190 200
    PPGPGGDASL LARLFEHPLY RVAVPPLTEE DVLFNVNSDT RLSPKAAENP
    210 220 230 240 250
    DWPHAGAEGA EFLSPGEAAV DSYPNWLKFH IGINRYELYS RHNPAIEALL
    260 270 280 290 300
    HDLSSQRITS VAMKSGGTQL KLIMTFQNYG QALFKPMKQT REQETPPDFF
    310 320 330 340 350
    YFSDYERHNA EIAAFHLDRI LDFRRVPPVA GRMVNMTKEI RDVTRDKKLW
    360 370 380 390 400
    RTFFISPANN ICFYGECSYY CSTEHALCGK PDQIEGSLAA FLPDLSLAKR
    410 420 430 440 450
    KTWRNPWRRS YHKRKKAEWE VDPDYCEEVK QTPPYDSSHR ILDVMDMTIF
    460 470 480 490 500
    DFLMGNMDRH HYETFEKFGN ETFIIHLDNG RGFGKYSHDE LSILVPLQQC
    510 520 530 540 550
    CRIRKSTYLR LQLLAKEEYK LSLLMAESLR GDQVAPVLYQ PHLEALDRRL
    560 570 580
    RVVLKAVRDC VERNGLHSVV DDDLDTEHRA ASAR
    Length:584
    Mass (Da):66,234
    Last modified:April 5, 2011 - v2
    Checksum:iECD278B5EA681FEF
    GO
    Isoform 2 (identifier: Q8IXL6-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-332: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:252
    Mass (Da):29,597
    Checksum:i7A3BDDE01D86D870
    GO

    Sequence cautioni

    The sequence AAH40074 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence EAL23705 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti274 – 288MTFQN…FKPMK → FLSDKPFLFLSCFLR in CAB99089 (PubMed:17974005).CuratedAdd BLAST15
    Sequence conflicti564N → D in AAH87853 (PubMed:15489334).Curated1
    Sequence conflicti564N → D in CAB99089 (PubMed:17974005).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_073660258I → N in RNS. 1 Publication1
    Natural variantiVAR_073661268T → M in RNS; mild non-lethal form; decreased protein kinase activity. 1 PublicationCorresponds to variant rs778899041dbSNPEnsembl.1
    Natural variantiVAR_073662280G → R in RNS. 1 PublicationCorresponds to variant rs779708323dbSNPEnsembl.1
    Natural variantiVAR_073663328P → S in RNS; mild non-lethal form; decreased protein kinase activity; FAM20A is still able to increase remaining protein kinase activity. 2 Publications1
    Natural variantiVAR_037530379G → E in RNS. 2 PublicationsCorresponds to variant rs796051852dbSNPEnsembl.1
    Natural variantiVAR_037531379G → R in RNS. 2 Publications1
    Natural variantiVAR_037532388L → R in RNS. 2 PublicationsCorresponds to variant rs796051849dbSNPEnsembl.1
    Natural variantiVAR_073664451D → N in RNS; mild non-lethal form; decreased protein kinase activity. 1 Publication1
    Natural variantiVAR_037533549R → W in RNS. 2 PublicationsCorresponds to variant rs796051850dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0408341 – 332Missing in isoform 2. 1 PublicationAdd BLAST332

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF533706 mRNA. Translation: AAQ09019.1.
    AB545605 mRNA. Translation: BAM78534.1.
    AC093627 Genomic DNA. No translation available.
    AC145676 Genomic DNA. No translation available.
    AC187652 Genomic DNA. No translation available.
    CH236966 Genomic DNA. Translation: EAL23705.1. Different initiation.
    CH471144 Genomic DNA. Translation: EAW87149.1.
    BC040074 mRNA. Translation: AAH40074.1. Different initiation.
    BC087853 mRNA. Translation: AAH87853.1.
    AL390147 mRNA. Translation: CAB99089.2.
    CCDSiCCDS47522.1. [Q8IXL6-1]
    PIRiT51872.
    RefSeqiNP_064608.2. NM_020223.3. [Q8IXL6-1]
    UniGeneiHs.134742.
    Hs.733582.

    Genome annotation databases

    EnsembliENST00000313766; ENSP00000322323; ENSG00000177706. [Q8IXL6-1]
    GeneIDi56975.
    KEGGihsa:56975.
    UCSCiuc003sip.4. human. [Q8IXL6-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF533706 mRNA. Translation: AAQ09019.1.
    AB545605 mRNA. Translation: BAM78534.1.
    AC093627 Genomic DNA. No translation available.
    AC145676 Genomic DNA. No translation available.
    AC187652 Genomic DNA. No translation available.
    CH236966 Genomic DNA. Translation: EAL23705.1. Different initiation.
    CH471144 Genomic DNA. Translation: EAW87149.1.
    BC040074 mRNA. Translation: AAH40074.1. Different initiation.
    BC087853 mRNA. Translation: AAH87853.1.
    AL390147 mRNA. Translation: CAB99089.2.
    CCDSiCCDS47522.1. [Q8IXL6-1]
    PIRiT51872.
    RefSeqiNP_064608.2. NM_020223.3. [Q8IXL6-1]
    UniGeneiHs.134742.
    Hs.733582.

    3D structure databases

    ProteinModelPortaliQ8IXL6.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi121294. 7 interactors.
    IntActiQ8IXL6. 15 interactors.
    MINTiMINT-6940404.
    STRINGi9606.ENSP00000322323.

    PTM databases

    iPTMnetiQ8IXL6.
    PhosphoSitePlusiQ8IXL6.

    Polymorphism and mutation databases

    BioMutaiFAM20C.
    DMDMi327478506.

    Proteomic databases

    EPDiQ8IXL6.
    MaxQBiQ8IXL6.
    PaxDbiQ8IXL6.
    PeptideAtlasiQ8IXL6.
    PRIDEiQ8IXL6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000313766; ENSP00000322323; ENSG00000177706. [Q8IXL6-1]
    GeneIDi56975.
    KEGGihsa:56975.
    UCSCiuc003sip.4. human. [Q8IXL6-1]

    Organism-specific databases

    CTDi56975.
    DisGeNETi56975.
    GeneCardsiFAM20C.
    H-InvDBHIX0019573.
    HGNCiHGNC:22140. FAM20C.
    HPAiHPA019823.
    MalaCardsiFAM20C.
    MIMi259775. phenotype.
    611061. gene.
    neXtProtiNX_Q8IXL6.
    OpenTargetsiENSG00000177706.
    Orphaneti1832. Lethal osteosclerotic bone dysplasia.
    PharmGKBiPA134898453.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3829. Eukaryota.
    ENOG410XQEJ. LUCA.
    GeneTreeiENSGT00390000007484.
    HOGENOMiHOG000231437.
    HOVERGENiHBG051635.
    InParanoidiQ8IXL6.
    OMAiHRILDVM.
    OrthoDBiEOG091G1BEO.
    PhylomeDBiQ8IXL6.
    TreeFamiTF313276.

    Miscellaneous databases

    GeneWikiiFAM20C.
    GenomeRNAii56975.
    PROiQ8IXL6.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000177706.
    CleanExiHS_FAM20C.
    GenevisibleiQ8IXL6. HS.

    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_HUMAN
    AccessioniPrimary (citable) accession number: Q8IXL6
    Secondary accession number(s): A4D2Q5
    , L8B5W8, Q5I0W9, Q7Z4I0, Q9NPT2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 19, 2003
    Last sequence update: April 5, 2011
    Last modified: November 30, 2016
    This is version 115 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. 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.