OSTCN_HUMAN
ID OSTCN_HUMAN Reviewed; 100 AA.
AC P02818; Q5TCK6;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Osteocalcin;
DE AltName: Full=Bone Gla protein;
DE Short=BGP;
DE AltName: Full=Gamma-carboxyglutamic acid-containing protein;
DE Flags: Precursor;
GN Name=BGLAP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2336375; DOI=10.1093/nar/18.7.1909;
RA Kiefer M.C., Saphire A.C.S., Bauer D.M., Barr P.J.;
RT "The cDNA and derived amino acid sequences of human and bovine bone Gla
RT protein.";
RL Nucleic Acids Res. 18:1909-1909(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3019668; DOI=10.1002/j.1460-2075.1986.tb04440.x;
RA Celeste A.J., Buecker J.L., Kriz R., Wang E.A., Wozney J.M.;
RT "Isolation of the human gene for bone gla protein utilizing mouse and rat
RT cDNA clones.";
RL EMBO J. 5:1885-1890(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-94.
RG SeattleSNPs variation discovery resource;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 52-100, GAMMA-CARBOXYGLUTAMATION AT GLU-68; GLU-72 AND
RP GLU-75, AND LACK OF HYDROXYLATION AT PRO-60.
RX PubMed=6967872; DOI=10.1016/s0021-9258(18)43554-5;
RA Poser J.W., Esch F.S., Ling N.C., Price P.A.;
RT "Isolation and sequence of the vitamin K-dependent protein from human bone.
RT Undercarboxylation of the first glutamic acid residue.";
RL J. Biol. Chem. 255:8685-8691(1980).
CC -!- FUNCTION: Constitutes 1-2% of the total bone protein. It binds strongly
CC to apatite and calcium.
CC -!- INTERACTION:
CC P02818; Q12797-6: ASPH; NbExp=3; IntAct=EBI-12927282, EBI-12092171;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: Gamma-carboxyglutamate residues are formed by vitamin K dependent
CC carboxylation. These residues are essential for the binding of calcium.
CC {ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:6967872}.
CC -!- SIMILARITY: Belongs to the osteocalcin/matrix Gla protein family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Osteocalcin entry;
CC URL="https://en.wikipedia.org/wiki/Osteocalcin";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/bglap/";
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DR EMBL; X53698; CAA37736.1; -; mRNA.
DR EMBL; X51699; CAA35996.1; -; mRNA.
DR EMBL; X04143; CAA27763.1; -; Genomic_DNA.
DR EMBL; DQ007079; AAY16981.1; -; Genomic_DNA.
DR EMBL; AL135927; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52986.1; -; Genomic_DNA.
DR EMBL; BC113432; AAI13433.1; -; mRNA.
DR EMBL; BC113434; AAI13435.1; -; mRNA.
DR CCDS; CCDS1134.1; -.
DR PIR; S12652; GEHU.
DR RefSeq; NP_954642.1; NM_199173.5.
DR AlphaFoldDB; P02818; -.
DR SMR; P02818; -.
DR BioGRID; 107101; 14.
DR IntAct; P02818; 1.
DR STRING; 9606.ENSP00000357255; -.
DR DrugBank; DB05260; Gallium nitrate.
DR DrugBank; DB03847; gamma-carboxy-L-glutamic acid.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB01022; Phylloquinone.
DR BioMuta; BGLAP; -.
DR DMDM; 129253; -.
DR MassIVE; P02818; -.
DR PaxDb; P02818; -.
DR PeptideAtlas; P02818; -.
DR PRIDE; P02818; -.
DR ProteomicsDB; 51606; -.
DR ABCD; P02818; 5 sequenced antibodies.
DR Antibodypedia; 34848; 991 antibodies from 40 providers.
DR DNASU; 632; -.
DR Ensembl; ENST00000368272.5; ENSP00000357255.4; ENSG00000242252.2.
DR GeneID; 632; -.
DR KEGG; hsa:632; -.
DR MANE-Select; ENST00000368272.5; ENSP00000357255.4; NM_199173.6; NP_954642.1.
DR UCSC; uc001fnt.4; human.
DR CTD; 632; -.
DR DisGeNET; 632; -.
DR GeneCards; BGLAP; -.
DR HGNC; HGNC:1043; BGLAP.
DR HPA; ENSG00000242252; Group enriched (brain, choroid plexus, intestine).
DR MIM; 112260; gene.
DR neXtProt; NX_P02818; -.
DR OpenTargets; ENSG00000242252; -.
DR PharmGKB; PA25345; -.
DR VEuPathDB; HostDB:ENSG00000242252; -.
DR eggNOG; ENOG502S85I; Eukaryota.
DR GeneTree; ENSGT00410000026290; -.
DR HOGENOM; CLU_160110_0_0_1; -.
DR InParanoid; P02818; -.
DR OMA; PQREVCE; -.
DR OrthoDB; 1520921at2759; -.
DR PhylomeDB; P02818; -.
DR TreeFam; TF330920; -.
DR PathwayCommons; P02818; -.
DR Reactome; R-HSA-159740; Gamma-carboxylation of protein precursors.
DR Reactome; R-HSA-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
DR Reactome; R-HSA-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins.
DR Reactome; R-HSA-8940973; RUNX2 regulates osteoblast differentiation.
DR SignaLink; P02818; -.
DR SIGNOR; P02818; -.
DR BioGRID-ORCS; 632; 19 hits in 1071 CRISPR screens.
DR GeneWiki; Osteocalcin; -.
DR GenomeRNAi; 632; -.
DR Pharos; P02818; Tbio.
DR PRO; PR:P02818; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P02818; protein.
DR Bgee; ENSG00000242252; Expressed in right hemisphere of cerebellum and 92 other tissues.
DR Genevisible; P02818; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0031982; C:vesicle; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0046848; F:hydroxyapatite binding; IBA:GO_Central.
DR GO; GO:0008147; F:structural constituent of bone; IBA:GO_Central.
DR GO; GO:0005198; F:structural molecule activity; NAS:ProtInc.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0060348; P:bone development; IBA:GO_Central.
DR GO; GO:0030282; P:bone mineralization; NAS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; NAS:UniProtKB.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl.
DR GO; GO:0042476; P:odontogenesis; IEA:Ensembl.
DR GO; GO:0002076; P:osteoblast development; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:BHF-UCL.
DR GO; GO:0030500; P:regulation of bone mineralization; IEA:InterPro.
DR GO; GO:0045124; P:regulation of bone resorption; NAS:UniProtKB.
DR GO; GO:1900076; P:regulation of cellular response to insulin stimulus; IEA:InterPro.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; NAS:UniProtKB.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0009629; P:response to gravity; IEA:Ensembl.
DR GO; GO:0033594; P:response to hydroxyisoflavone; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:0033280; P:response to vitamin D; IEP:BHF-UCL.
DR GO; GO:0032571; P:response to vitamin K; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR InterPro; IPR035972; GLA-like_dom_SF.
DR InterPro; IPR000294; GLA_domain.
DR InterPro; IPR039176; Osteocalcin.
DR InterPro; IPR002384; Osteocalcin/MGP.
DR PANTHER; PTHR14235; PTHR14235; 1.
DR PRINTS; PR00002; GLABONE.
DR SMART; SM00069; GLA; 1.
DR SUPFAM; SSF57630; SSF57630; 1.
DR PROSITE; PS00011; GLA_1; 1.
DR PROSITE; PS50998; GLA_2; 1.
PE 1: Evidence at protein level;
KW Biomineralization; Calcium; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Gamma-carboxyglutamic acid;
KW Metal-binding; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000305"
FT PROPEP 24..51
FT /evidence="ECO:0000305|PubMed:6967872"
FT /id="PRO_0000011086"
FT CHAIN 52..100
FT /note="Osteocalcin"
FT /id="PRO_0000011087"
FT DOMAIN 52..98
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 75
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 75
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 81
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT SITE 60
FT /note="Not hydroxylated"
FT /evidence="ECO:0000269|PubMed:6967872"
FT MOD_RES 68
FT /note="4-carboxyglutamate; partial"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6967872"
FT MOD_RES 72
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6967872"
FT MOD_RES 75
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6967872"
FT DISULFID 74..80
FT VARIANT 94
FT /note="R -> Q (in dbSNP:rs34702397)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_038743"
FT CONFLICT 33..34
FT /note="Missing (in Ref. 2; CAA27763)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 100 AA; 10963 MW; 4DF2A0A80849CB71 CRC64;
MRALTLLALL ALAALCIAGQ AGAKPSGAES SKGAAFVSKQ EGSEVVKRPR RYLYQWLGAP
VPYPDPLEPR REVCELNPDC DELADHIGFQ EAYRRFYGPV
