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Q8IXL6 (DMP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:FAM20C
Synonyms:DMP4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length584 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.10

Subcellular location

Secreted By similarity.

Tissue specificity

Widely expressed. Ref.8

Involvement in disease

Raine syndrome (RNS) [MIM:259775]: Autosomal recessive osteosclerotic bone dysplasia with neonatal lethal outcome. Clinical features include generalized osteosclerosis, craniofacial dysplasia and microcephaly.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Sequence similarities

Belongs to the FAM20 family.

Sequence caution

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.

Ontologies

Keywords
   Biological processBiomineralization
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainSignal
   LigandCalcium
Manganese
Metal-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdentinogenesis

Inferred from electronic annotation. Source: Ensembl

enamel mineralization

Inferred from electronic annotation. Source: Ensembl

odontoblast differentiation

Inferred from electronic annotation. Source: Ensembl

osteoclast maturation

Inferred from electronic annotation. Source: Ensembl

positive regulation of bone mineralization

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.10. Source: GOC

regulation of fibroblast growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of phosphorus metabolic process

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.10. Source: UniProt

extracellular space

Inferred from direct assay Ref.10. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708. Source: UniProt

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: Ensembl

protein serine/threonine kinase activity

Inferred from direct assay Ref.10. Source: UniProt

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IXL6-1)

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.
Isoform 2 (identifier: Q8IXL6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-332: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 584562Extracellular serine/threonine protein kinase FAM20C
PRO_0000008747

Regions

Region354 – 565212Kinase domain

Sites

Metal binding4631Manganese Probable
Metal binding4781Manganese Probable

Amino acid modifications

Glycosylation1011N-linked (GlcNAc...) Potential
Glycosylation3351N-linked (GlcNAc...) Potential
Glycosylation4701N-linked (GlcNAc...) Ref.9

Natural variations

Alternative sequence1 – 332332Missing in isoform 2.
VSP_040834
Natural variant3791G → E in RNS. Ref.11
VAR_037530
Natural variant3791G → R in RNS. Ref.11
VAR_037531
Natural variant3881L → R in RNS. Ref.11
VAR_037532
Natural variant5491R → W in RNS. Ref.11
VAR_037533

Experimental info

Mutagenesis4781D → A: Unable to bind manganese; abrogates kinase activity. Ref.10
Sequence conflict274 – 28815MTFQN…FKPMK → FLSDKPFLFLSCFLR in CAB99089. Ref.6
Sequence conflict5641N → D in AAH87853. Ref.5
Sequence conflict5641N → D in CAB99089. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 5, 2011. Version 2.
Checksum: ECD278B5EA681FEF

FASTA58466,234
        10         20         30         40         50         60 
MKMMLVRRFR VLILMVFLVA CALHIALDLL PRLERRGARP SGEPGCSCAQ PAAEVAAPGW 

        70         80         90        100        110        120 
AQVRGRPGEP PAASSAAGDA GWPNKHTLRI LQDFSSDPSS NLSSHSLEKL PPAAEPAERA 

       130        140        150        160        170        180 
LRGRDPGALR PHDPAHRPLL RDPGPRRSES PPGPGGDASL LARLFEHPLY RVAVPPLTEE 

       190        200        210        220        230        240 
DVLFNVNSDT RLSPKAAENP DWPHAGAEGA EFLSPGEAAV DSYPNWLKFH IGINRYELYS 

       250        260        270        280        290        300 
RHNPAIEALL HDLSSQRITS VAMKSGGTQL KLIMTFQNYG QALFKPMKQT REQETPPDFF 

       310        320        330        340        350        360 
YFSDYERHNA EIAAFHLDRI LDFRRVPPVA GRMVNMTKEI RDVTRDKKLW RTFFISPANN 

       370        380        390        400        410        420 
ICFYGECSYY CSTEHALCGK PDQIEGSLAA FLPDLSLAKR KTWRNPWRRS YHKRKKAEWE 

       430        440        450        460        470        480 
VDPDYCEEVK QTPPYDSSHR ILDVMDMTIF DFLMGNMDRH HYETFEKFGN ETFIIHLDNG 

       490        500        510        520        530        540 
RGFGKYSHDE LSILVPLQQC CRIRKSTYLR LQLLAKEEYK LSLLMAESLR GDQVAPVLYQ 

       550        560        570        580 
PHLEALDRRL RVVLKAVRDC VERNGLHSVV DDDLDTEHRA ASAR 

« Hide

Isoform 2 [UniParc].

Checksum: 7A3BDDE01D86D870
Show »

FASTA25229,597

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[7]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRT51872.
RefSeqNP_064608.2. NM_020223.3.
XP_005249871.1. XM_005249814.1.
UniGeneHs.134742.

3D structure databases

ProteinModelPortalQ8IXL6.
SMRQ8IXL6. Positions 171-578.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121294. 7 interactions.
IntActQ8IXL6. 8 interactions.
MINTMINT-6940404.
STRING9606.ENSP00000322323.

PTM databases

PhosphoSiteQ8IXL6.

Polymorphism databases

DMDM327478506.

Proteomic databases

PaxDbQ8IXL6.
PRIDEQ8IXL6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000313766; ENSP00000322323; ENSG00000177706. [Q8IXL6-1]
GeneID56975.
KEGGhsa:56975.
UCSCuc003sip.3. human. [Q8IXL6-1]
uc011jvn.2. human. [Q8IXL6-2]

Organism-specific databases

CTD56975.
GeneCardsGC07P000290.
H-InvDBHIX0019573.
HGNCHGNC:22140. FAM20C.
HPAHPA019823.
MIM259775. phenotype.
611061. gene.
neXtProtNX_Q8IXL6.
Orphanet1832. Lethal osteosclerotic bone dysplasia.
PharmGKBPA134898453.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238678.
HOGENOMHOG000231437.
HOVERGENHBG051635.
InParanoidQ8IXL6.
OMAPDWPREG.
OrthoDBEOG7JX33T.
PhylomeDBQ8IXL6.
TreeFamTF313276.

Gene expression databases

ArrayExpressQ8IXL6.
BgeeQ8IXL6.
CleanExHS_FAM20C.
GenevestigatorQ8IXL6.

Family and domain databases

InterProIPR009581. DUF1193.
IPR024869. FAM20.
[Graphical view]
PANTHERPTHR12450. PTHR12450. 1 hit.
PfamPF06702. DUF1193. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFAM20C.
GenomeRNAi56975.
NextBio62625.
PROQ8IXL6.
SOURCESearch...

Entry information

Entry nameDMP4_HUMAN
AccessionPrimary (citable) accession number: Q8IXL6
Secondary accession number(s): A4D2Q5 expand/collapse secondary AC list , L8B5W8, Q5I0W9, Q7Z4I0, Q9NPT2
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: April 5, 2011
Last modified: April 16, 2014
This is version 92 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM