P02818 (OSTCN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Osteocalcin

Alternative name(s):
Bone Gla protein
Short name=BGP
Gamma-carboxyglutamic acid-containing protein

Gene names

Name:

BGLAP

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	100 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	Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium.
Subcellular location	Secreted.
Post-translational modification	Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.
Sequence similarities	Belongs to the osteocalcin/matrix Gla protein family. Contains 1 Gla (gamma-carboxy-glutamate) domain.

Ontologies

Keywords
Biological process	Biomineralization
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Calcium Metal-binding
PTM	Cleavage on pair of basic residues Disulfide bond Gamma-carboxyglutamic acid
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	bone development Inferred from electronic annotation. Source: Ensembl bone mineralization Non-traceable author statement PubMed 10486212. Source: UniProtKB cell adhesion Non-traceable author statement PubMed 12202187. Source: UniProtKB cell aging Inferred from electronic annotation. Source: Ensembl cellular response to growth factor stimulus Inferred from electronic annotation. Source: Ensembl cellular response to vitamin D Inferred from electronic annotation. Source: Ensembl odontogenesis Non-traceable author statement PubMed 11856645. Source: UniProtKB osteoblast development Inferred from electronic annotation. Source: Ensembl osteoblast differentiation Inferred from expression pattern PubMed 17023519. Source: BHF-UCL regulation of bone mineralization Inferred from electronic annotation. Source: InterPro regulation of bone resorption Non-traceable author statement PubMed 10486212. Source: UniProtKB regulation of osteoclast differentiation Non-traceable author statement PubMed 10486212. Source: UniProtKB response to activity Inferred from electronic annotation. Source: Ensembl response to drug Inferred from electronic annotation. Source: Ensembl response to estrogen stimulus Inferred from electronic annotation. Source: Ensembl response to ethanol Inferred from electronic annotation. Source: Ensembl response to glucocorticoid stimulus Inferred from electronic annotation. Source: Ensembl response to gravity Inferred from electronic annotation. Source: Ensembl response to hydroxyisoflavone Inferred from electronic annotation. Source: Ensembl response to mechanical stimulus Inferred from electronic annotation. Source: Ensembl response to testosterone stimulus Inferred from electronic annotation. Source: Ensembl response to vitamin D Inferred from expression pattern PubMed 17023519. Source: BHF-UCL response to vitamin K Inferred from electronic annotation. Source: Ensembl response to zinc ion Inferred from electronic annotation. Source: Ensembl skeletal system development Traceable author statement PubMed 10865224. Source: ProtInc
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Ensembl dendrite Inferred from electronic annotation. Source: Ensembl extracellular region Non-traceable author statement PubMed 11856645. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: Ensembl membrane-bounded vesicle Inferred from electronic annotation. Source: Ensembl perikaryon Inferred from electronic annotation. Source: Ensembl rough endoplasmic reticulum Inferred from electronic annotation. Source: Ensembl
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro hydroxyapatite binding Non-traceable author statement PubMed 10486212. Source: UniProtKB structural constituent of bone Non-traceable author statement PubMed 12467198. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Probable
	Propeptide	24 – 51	28	Probable		PRO_0000011086
	Chain	52 – 100	49	Osteocalcin		PRO_0000011087
Regions
	Domain	52 – 98	47	Gla
Sites
	Metal binding	68	1	Calcium 3 By similarity
	Metal binding	72	1	Calcium 2 By similarity
	Metal binding	75	1	Calcium 1 By similarity
	Metal binding	75	1	Calcium 2 By similarity
	Metal binding	81	1	Calcium 1 By similarity
	Site	60	1	Not hydroxylated
Amino acid modifications
	Modified residue	68	1	4-carboxyglutamate; partial Ref.7
	Modified residue	72	1	4-carboxyglutamate Ref.7
	Modified residue	75	1	4-carboxyglutamate Ref.7
	Disulfide bond	74 ↔ 80
Natural variations
	Natural variant	94	1	R → Q. Ref.3 Corresponds to variant rs34702397 [ dbSNP | Ensembl ].		VAR_038743
Experimental info
	Sequence conflict	33 – 34	2	Missing in CAA27763. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P02818 [UniParc]. Last modified August 1, 1990. Version 2. Checksum: 4DF2A0A80849CB71	FASTA	100	10,963
	10 20 30 40 50 60 MRALTLLALL ALAALCIAGQ AGAKPSGAES SKGAAFVSKQ EGSEVVKRPR RYLYQWLGAP 70 80 90 100 VPYPDPLEPR REVCELNPDC DELADHIGFQ EAYRRFYGPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The cDNA and derived amino acid sequences of human and bovine bone Gla protein." Kiefer M.C., Saphire A.C.S., Bauer D.M., Barr P.J. Nucleic Acids Res. 18:1909-1909(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Isolation of the human gene for bone gla protein utilizing mouse and rat cDNA clones." Celeste A.J., Buecker J.L., Kriz R., Wang E.A., Wozney J.M. EMBO J. 5:1885-1890(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	SeattleSNPs variation discovery resource Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-94.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.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. , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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].
[7]	"Isolation and sequence of the vitamin K-dependent protein from human bone. Undercarboxylation of the first glutamic acid residue." Poser J.W., Esch F.S., Ling N.C., Price P.A. J. Biol. Chem. 255:8685-8691(1980) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 52-100, GAMMA-CARBOXYGLUTAMATION AT GLU-68; GLU-72 AND GLU-75, ABSENCE OF HYDROXYLATION AT PRO-60.
+	Additional computationally mapped references.

Web resources

Wikipedia

Osteocalcin entry

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	X53698 mRNA. Translation: CAA37736.1. X51699 mRNA. Translation: CAA35996.1. X04143 Genomic DNA. Translation: CAA27763.1. DQ007079 Genomic DNA. Translation: AAY16981.1. AL135927 Genomic DNA. Translation: CAI15541.1. CH471121 Genomic DNA. Translation: EAW52986.1. BC113432 mRNA. Translation: AAI13433.1. BC113434 mRNA. Translation: AAI13435.1.
IPI	IPI00023015.
PIR	GEHU. S12652.
RefSeq	NP_954642.1. NM_199173.4.
UniGene	Hs.654541.
3D structure databases
ProteinModelPortal	P02818.
SMR	P02818. Positions 64-98.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000357255.
Polymorphism databases
DMDM	129253.
Proteomic databases
PaxDb	P02818.
PeptideAtlas	P02818.
PRIDE	P02818.
Protocols and materials databases
DNASU	632.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368272; ENSP00000357255; ENSG00000242252.
GeneID	632.
KEGG	hsa:632.
UCSC	uc001fnt.3. human.
Organism-specific databases
CTD	632.
GeneCards	GC01P156211.
HGNC	HGNC:1043. BGLAP.
MIM	112260. gene.
neXtProt	NX_P02818.
PharmGKB	PA25345.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG72046.
HOGENOM	HOG000115820.
OMA	PKREVCE.
OrthoDB	EOG7VDXRQ.
Gene expression databases
Bgee	P02818.
CleanEx	HS_BGLAP.
Genevestigator	P02818.
Family and domain databases
InterPro	IPR000294. GLA_domain. IPR002384. Osteocalcin/MGP. [Graphical view]
Pfam	PF00594. Gla. 1 hit. [Graphical view]
PRINTS	PR00002. GLABONE.
SMART	SM00069. GLA. 1 hit. [Graphical view]
SUPFAM	SSF57630. SSF57630. 1 hit.
PROSITE	PS00011. GLA_1. 1 hit. PS50998. GLA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB01022. Phytonadione.
GeneWiki	Osteocalcin.
GenomeRNAi	632.
NextBio	2554.
PMAP-CutDB	P02818.
PRO	P02818.
SOURCE	Search...

Entry information

Entry name

OSTCN_HUMAN

Accession

Primary (citable) accession number: P02818
Secondary accession number(s): Q5TCK6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	August 1, 1990
Last modified:	November 13, 2013
This is version 131 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.