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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

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

  • calcium ion binding Source: Ensembl
  • 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

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 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

Secreted

Pathology & Biotechi

Involvement in diseasei

Raine syndrome (RNS)1 Publication

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)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.

Polymorphism and mutation databases

BioMutaiFAM20C.
DMDMi327478506.

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

BgeeiQ8IXL6.
CleanExiHS_FAM20C.
GenevisibleiQ8IXL6. HS.

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.
GeneTreeiENSGT00390000007484.
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. 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 AAH40074.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence EAL23705.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

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:
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.3. human. [Q8IXL6-1]
uc011jvn.2. human. [Q8IXL6-2]

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

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiQ8IXL6.

Polymorphism and mutation databases

BioMutaiFAM20C.
DMDMi327478506.

Proteomic databases

MaxQBiQ8IXL6.
PaxDbiQ8IXL6.
PRIDEiQ8IXL6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi56975.
GeneCardsiGC07P000290.
H-InvDBHIX0019573.
HGNCiHGNC:22140. FAM20C.
HPAiHPA019823.
MIMi259775. phenotype.
611061. gene.
neXtProtiNX_Q8IXL6.
Orphaneti1832. Lethal osteosclerotic bone dysplasia.
PharmGKBiPA134898453.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG238678.
GeneTreeiENSGT00390000007484.
HOGENOMiHOG000231437.
HOVERGENiHBG051635.
InParanoidiQ8IXL6.
OMAiPDWPREG.
OrthoDBiEOG7JX33T.
PhylomeDBiQ8IXL6.
TreeFamiTF313276.

Miscellaneous databases

GeneWikiiFAM20C.
GenomeRNAii56975.
NextBioi62625.
PROiQ8IXL6.
SOURCEiSearch...

Gene expression databases

BgeeiQ8IXL6.
CleanExiHS_FAM20C.
GenevisibleiQ8IXL6. HS.

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. 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: June 24, 2015
This is version 102 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

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.