Q8IXL6 (DMP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	FAM20C
Synonyms:	DMP4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	584 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.8
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.8
Subcellular location	Secreted By similarity.
Tissue specificity	Widely expressed. Ref.6
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.9
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 process	Biomineralization
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Signal
Ligand	Calcium Manganese Metal-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	dentinogenesis Inferred from electronic annotation. Source: Compara enamel mineralization Inferred from electronic annotation. Source: Compara odontoblast differentiation Inferred from electronic annotation. Source: Compara osteoclast maturation Inferred from electronic annotation. Source: Compara positive regulation of bone mineralization Inferred from electronic annotation. Source: Compara positive regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara regulation of fibroblast growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara regulation of phosphorus metabolic process Inferred from electronic annotation. Source: Compara skeletal system development Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from electronic annotation. Source: Compara
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: Compara protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 584	562	Extracellular serine/threonine protein kinase FAM20C		PRO_0000008747
Regions
	Region	354 – 565	212	Kinase domain
Sites
	Metal binding	463	1	Manganese Probable
	Metal binding	478	1	Manganese Probable
Amino acid modifications
	Glycosylation	101	1	N-linked (GlcNAc...) Potential
	Glycosylation	335	1	N-linked (GlcNAc...) Potential
	Glycosylation	470	1	N-linked (GlcNAc...) Ref.7
Natural variations
	Alternative sequence	1 – 332	332	Missing in isoform 2.		VSP_040834
	Natural variant	379	1	G → E in RNS. Ref.9		VAR_037530
	Natural variant	379	1	G → R in RNS. Ref.9		VAR_037531
	Natural variant	388	1	L → R in RNS. Ref.9		VAR_037532
	Natural variant	549	1	R → W in RNS. Ref.9		VAR_037533
Experimental info
	Mutagenesis	478	1	D → A: Unable to bind manganese; abrogates kinase activity. Ref.8
	Sequence conflict	274 – 288	15	MTFQN…FKPMK → FLSDKPFLFLSCFLR in CAB99089. Ref.5
	Sequence conflict	564	1	N → D in AAH87853. Ref.4
	Sequence conflict	564	1	N → D in CAB99089. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 5, 2011. Version 2. Checksum: ECD278B5EA681FEF	FASTA	584	66,234
	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
	Isoform 2 [UniParc]. Checksum: 7A3BDDE01D86D870	FASTA	252	29,597
	10 20 30 40 50 60 MVNMTKEIRD VTRDKKLWRT FFISPANNIC FYGECSYYCS TEHALCGKPD QIEGSLAAFL 70 80 90 100 110 120 PDLSLAKRKT WRNPWRRSYH KRKKAEWEVD PDYCEEVKQT PPYDSSHRIL DVMDMTIFDF 130 140 150 160 170 180 LMGNMDRHHY ETFEKFGNET FIIHLDNGRG FGKYSHDELS ILVPLQQCCR IRKSTYLRLQ 190 200 210 220 230 240 LLAKEEYKLS LLMAESLRGD QVAPVLYQPH LEALDRRLRV VLKAVRDCVE RNGLHSVVDD 250 DLDTEHRAAS AR

References

	« Hide 'large scale' referencesShow '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]	"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].
[3]	"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].
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"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, MASS SPECTROMETRY. Tissue: Liver.
[8]	"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.
[9]	"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. CH236966 Genomic DNA. Translation: EAL23705.1. Different initiation. AC093627 Genomic DNA. No translation available. AC145676 Genomic DNA. No translation available. AC187652 Genomic DNA. No translation available. BC040074 mRNA. Translation: AAH40074.1. Different initiation. BC087853 mRNA. Translation: AAH87853.1. AL390147 mRNA. Translation: CAB99089.2.
IPI	IPI00470607. IPI01008847.
PIR	T51872.
RefSeq	NP_064608.2. NM_020223.3.
UniGene	Hs.134742.
3D structure databases
ProteinModelPortal	Q8IXL6.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000322323.
PTM databases
PhosphoSite	Q8IXL6.
Polymorphism databases
DMDM	34921806.
Proteomic databases
PaxDb	Q8IXL6.
PRIDE	Q8IXL6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000313766; ENSP00000322323; ENSG00000177706.
GeneID	56975.
KEGG	hsa:56975.
UCSC	uc003sip.3. human. uc011jvn.2. human.
Organism-specific databases
CTD	56975.
GeneCards	GC07P000290.
H-InvDB	HIX0019573.
HGNC	HGNC:22140. FAM20C.
HPA	HPA019823.
MIM	259775. phenotype. 611061. gene.
neXtProt	NX_Q8IXL6.
Orphanet	1832. Lethal osteosclerotic bone dysplasia.
PharmGKB	PA134898453.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG238678.
HOGENOM	HOG000231437.
HOVERGEN	HBG051635.
InParanoid	Q8IXL6.
OMA	ILDVMDM.
OrthoDB	EOG44F68Z.
Gene expression databases
Bgee	Q8IXL6.
CleanEx	HS_FAM20C.
Genevestigator	Q8IXL6.
Family and domain databases
InterPro	IPR009581. DUF1193. IPR024869. FAM20. [Graphical view]
PANTHER	PTHR12450. PTHR12450. 1 hit.
Pfam	PF06702. DUF1193. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	56975.
NextBio	62625.
SOURCE	Search...

Entry information

Entry name

DMP4_HUMAN

Accession

Primary (citable) accession number: Q8IXL6
Secondary accession number(s): A4D2Q5 , Q5I0W9, Q7Z4I0, Q9NPT2

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2003
Last sequence update:	April 5, 2011
Last modified:	May 1, 2013
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.