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Q8IXL6

- DMP4_HUMAN

UniProt

Q8IXL6 - DMP4_HUMAN

Protein

Extracellular serine/threonine protein kinase FAM20C

Gene

FAM20C

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 96 (01 Oct 2014)
      Sequence version 2 (05 Apr 2011)
      Previous versions | rss
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    Functioni

    Calcium-binding kinase that phosphorylates the caseins and several secreted proteins implicated in biomineralization, including the secretory calcium binding phosphoproteins (SCPP). Preferencially phosphorylates its targets within the S-x-E/pS motif.1 Publication

    Catalytic activityi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi463 – 4631ManganeseCurated
    Metal bindingi478 – 4781ManganeseCurated

    GO - Molecular functioni

    1. calcium ion binding Source: Ensembl
    2. protein serine/threonine kinase activity Source: UniProt

    GO - Biological processi

    1. dentinogenesis Source: Ensembl
    2. enamel mineralization Source: Ensembl
    3. odontoblast differentiation Source: Ensembl
    4. osteoclast maturation Source: Ensembl
    5. positive regulation of bone mineralization Source: Ensembl
    6. positive regulation of osteoblast differentiation Source: Ensembl
    7. protein phosphorylation Source: GOC
    8. regulation of fibroblast growth factor receptor signaling pathway Source: Ensembl
    9. regulation of phosphorus metabolic process Source: Ensembl
    10. skeletal system development Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Biomineralization

    Keywords - Ligandi

    Calcium, Manganese, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Extracellular serine/threonine protein kinase FAM20C (EC:2.7.11.1)
    Alternative name(s):
    Dentin matrix protein 4
    Short name:
    DMP-4
    Golgi-enriched fraction casein kinase
    Short name:
    GEF-CK
    Protein FAM20C
    Gene namesi
    Name:FAM20C
    Synonyms:DMP4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:22140. FAM20C.

    Subcellular locationi

    Secreted By similarity

    GO - Cellular componenti

    1. extracellular space Source: UniProt
    2. extracellular vesicular exosome Source: UniProt
    3. Golgi apparatus Source: UniProt

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Raine syndrome (RNS) [MIM:259775]: Autosomal recessive osteosclerotic bone dysplasia with neonatal lethal outcome. Clinical features include generalized osteosclerosis, craniofacial dysplasia and microcephaly.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti379 – 3791G → E in RNS. 1 Publication
    VAR_037530
    Natural varianti379 – 3791G → R in RNS. 1 Publication
    VAR_037531
    Natural varianti388 – 3881L → R in RNS. 1 Publication
    VAR_037532
    Natural varianti549 – 5491R → W in RNS. 1 Publication
    VAR_037533

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi478 – 4781D → A: Unable to bind manganese; abrogates kinase activity. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi259775. phenotype.
    Orphaneti1832. Lethal osteosclerotic bone dysplasia.
    PharmGKBiPA134898453.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222Sequence AnalysisAdd
    BLAST
    Chaini23 – 584562Extracellular serine/threonine protein kinase FAM20CPRO_0000008747Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi101 – 1011N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi335 – 3351N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi470 – 4701N-linked (GlcNAc...)1 Publication

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiQ8IXL6.
    PaxDbiQ8IXL6.
    PRIDEiQ8IXL6.

    PTM databases

    PhosphoSiteiQ8IXL6.

    Expressioni

    Tissue specificityi

    Widely expressed.1 Publication

    Gene expression databases

    ArrayExpressiQ8IXL6.
    BgeeiQ8IXL6.
    CleanExiHS_FAM20C.
    GenevestigatoriQ8IXL6.

    Organism-specific databases

    HPAiHPA019823.

    Interactioni

    Protein-protein interaction databases

    BioGridi121294. 7 interactions.
    IntActiQ8IXL6. 8 interactions.
    MINTiMINT-6940404.
    STRINGi9606.ENSP00000322323.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8IXL6.
    SMRiQ8IXL6. Positions 225-570.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni354 – 565212Kinase domainAdd
    BLAST

    Sequence similaritiesi

    Belongs to the FAM20 family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG238678.
    HOGENOMiHOG000231437.
    HOVERGENiHBG051635.
    InParanoidiQ8IXL6.
    OMAiPDWPREG.
    OrthoDBiEOG7JX33T.
    PhylomeDBiQ8IXL6.
    TreeFamiTF313276.

    Family and domain databases

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

    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

    MKMMLVRRFR VLILMVFLVA CALHIALDLL PRLERRGARP SGEPGCSCAQ    50
    PAAEVAAPGW AQVRGRPGEP PAASSAAGDA GWPNKHTLRI LQDFSSDPSS 100
    NLSSHSLEKL PPAAEPAERA LRGRDPGALR PHDPAHRPLL RDPGPRRSES 150
    PPGPGGDASL LARLFEHPLY RVAVPPLTEE DVLFNVNSDT RLSPKAAENP 200
    DWPHAGAEGA EFLSPGEAAV DSYPNWLKFH IGINRYELYS RHNPAIEALL 250
    HDLSSQRITS VAMKSGGTQL KLIMTFQNYG QALFKPMKQT REQETPPDFF 300
    YFSDYERHNA EIAAFHLDRI LDFRRVPPVA GRMVNMTKEI RDVTRDKKLW 350
    RTFFISPANN ICFYGECSYY CSTEHALCGK PDQIEGSLAA FLPDLSLAKR 400
    KTWRNPWRRS YHKRKKAEWE VDPDYCEEVK QTPPYDSSHR ILDVMDMTIF 450
    DFLMGNMDRH HYETFEKFGN ETFIIHLDNG RGFGKYSHDE LSILVPLQQC 500
    CRIRKSTYLR LQLLAKEEYK LSLLMAESLR GDQVAPVLYQ PHLEALDRRL 550
    RVVLKAVRDC VERNGLHSVV DDDLDTEHRA ASAR 584
    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 AAH40074.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
    The sequence EAL23705.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti274 – 28815MTFQN…FKPMK → FLSDKPFLFLSCFLR in CAB99089. (PubMed:17974005)CuratedAdd
    BLAST
    Sequence conflicti564 – 5641N → D in AAH87853. (PubMed:15489334)Curated
    Sequence conflicti564 – 5641N → D in CAB99089. (PubMed:17974005)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti379 – 3791G → E in RNS. 1 Publication
    VAR_037530
    Natural varianti379 – 3791G → R in RNS. 1 Publication
    VAR_037531
    Natural varianti388 – 3881L → R in RNS. 1 Publication
    VAR_037532
    Natural varianti549 – 5491R → W in RNS. 1 Publication
    VAR_037533

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 332332Missing in isoform 2. 1 PublicationVSP_040834Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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]
    XP_005249871.1. XM_005249814.1. [Q8IXL6-2]
    UniGeneiHs.134742.
    Hs.733582.

    Genome annotation databases

    EnsembliENST00000313766; ENSP00000322323; ENSG00000177706. [Q8IXL6-1]
    GeneIDi56975.
    KEGGihsa:56975.
    UCSCiuc003sip.3. human. [Q8IXL6-1]
    uc011jvn.2. human. [Q8IXL6-2]

    Polymorphism databases

    DMDMi327478506.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS47522.1. [Q8IXL6-1 ]
    PIRi T51872.
    RefSeqi NP_064608.2. NM_020223.3. [Q8IXL6-1 ]
    XP_005249871.1. XM_005249814.1. [Q8IXL6-2 ]
    UniGenei Hs.134742.
    Hs.733582.

    3D structure databases

    ProteinModelPortali Q8IXL6.
    SMRi Q8IXL6. Positions 225-570.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121294. 7 interactions.
    IntActi Q8IXL6. 8 interactions.
    MINTi MINT-6940404.
    STRINGi 9606.ENSP00000322323.

    PTM databases

    PhosphoSitei Q8IXL6.

    Polymorphism databases

    DMDMi 327478506.

    Proteomic databases

    MaxQBi Q8IXL6.
    PaxDbi Q8IXL6.
    PRIDEi Q8IXL6.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000313766 ; ENSP00000322323 ; ENSG00000177706 . [Q8IXL6-1 ]
    GeneIDi 56975.
    KEGGi hsa:56975.
    UCSCi uc003sip.3. human. [Q8IXL6-1 ]
    uc011jvn.2. human. [Q8IXL6-2 ]

    Organism-specific databases

    CTDi 56975.
    GeneCardsi GC07P000290.
    H-InvDB HIX0019573.
    HGNCi HGNC:22140. FAM20C.
    HPAi HPA019823.
    MIMi 259775. phenotype.
    611061. gene.
    neXtProti NX_Q8IXL6.
    Orphaneti 1832. Lethal osteosclerotic bone dysplasia.
    PharmGKBi PA134898453.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG238678.
    HOGENOMi HOG000231437.
    HOVERGENi HBG051635.
    InParanoidi Q8IXL6.
    OMAi PDWPREG.
    OrthoDBi EOG7JX33T.
    PhylomeDBi Q8IXL6.
    TreeFami TF313276.

    Miscellaneous databases

    GeneWikii FAM20C.
    GenomeRNAii 56975.
    NextBioi 62625.
    PROi Q8IXL6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8IXL6.
    Bgeei Q8IXL6.
    CleanExi HS_FAM20C.
    Genevestigatori Q8IXL6.

    Family and domain databases

    InterProi IPR009581. DUF1193.
    IPR024869. FAM20.
    [Graphical view ]
    PANTHERi PTHR12450. PTHR12450. 1 hit.
    Pfami PF06702. DUF1193. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Wu C., Ding P., Han W., Rui M., Wang Y., Song Q., Ma D.
      Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Brain.
    2. "Molecular cloning and characterization of a novel xylosylkinase."
      Kitagawa H., Izumikawa T., Koike T.
      Submitted (FEB-2010) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "The DNA sequence of human chromosome 7."
      Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
      , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
      Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "Human chromosome 7: DNA sequence and biology."
      Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
      , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
      Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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] (ISOFORM 1).
      Tissue: Brain.
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Brain.
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "FAM20: an evolutionarily conserved family of secreted proteins expressed in hematopoietic cells."
      Nalbant D., Youn H., Nalbant S.I., Sharma S., Cobos E., Beale E.G., Du Y., Williams S.C.
      BMC Genomics 6:11-11(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    9. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-470.
      Tissue: Liver.
    10. "Secreted kinase phosphorylates extracellular proteins that regulate biomineralization."
      Tagliabracci V.S., Engel J.L., Wen J., Wiley S.E., Worby C.A., Kinch L.N., Xiao J., Grishin N.V., Dixon J.E.
      Science 336:1150-1153(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, MANGANESE-BINDING, MUTAGENESIS OF ASP-478.
    11. "Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development."
      Simpson M.A., Hsu R., Keir L.S., Hao J., Sivapalan G., Ernst L.M., Zackai E.H., Al-Gazali L.I., Hulskamp G., Kingston H.M., Prescott T.E., Ion A., Patton M.A., Murday V., George A., Crosby A.H.
      Am. J. Hum. Genet. 81:906-912(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS RNS ARG-379; GLU-379; ARG-388 AND TRP-549.

    Entry informationi

    Entry nameiDMP4_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: October 1, 2014
    This is version 96 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, 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

    External Data

    Dasty 3