MGP_HUMAN
ID MGP_HUMAN Reviewed; 103 AA.
AC P08493; A0M8W5; B2R519; J3KMX7; Q2TU41; Q567P9; Q6ICN5;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Matrix Gla protein;
DE Short=MGP;
DE AltName: Full=Cell growth-inhibiting gene 36 protein;
DE Flags: Precursor;
GN Name=MGP; Synonyms=MGLAP; ORFNames=GIG36;
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=2394711; DOI=10.1016/s0021-9258(18)77221-9;
RA Cancela M.L., Hsieh C.-L., Francke U., Price P.A.;
RT "Molecular structure, chromosome assignment, and promoter organization of
RT the human matrix Gla protein gene.";
RL J. Biol. Chem. 265:15040-15048(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-102.
RX PubMed=3387234; DOI=10.1093/nar/16.11.5213;
RA Kiefer M.C., Bauer D.M., Young D., Hermsen K.M., Masiarz F.K., Barr P.J.;
RT "The cDNA and derived amino acid sequences for human and bovine matrix Gla
RT protein.";
RL Nucleic Acids Res. 16:5213-5213(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-102.
RX PubMed=2216462;
RA Chen L., O'Bryan J.P., Smith H.S., Liu E.;
RT "Overexpression of matrix Gla protein mRNA in malignant human breast cells:
RT isolation by differential cDNA hybridization.";
RL Oncogene 5:1391-1395(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kim J.W.;
RT "Identification of a human cell growth inhibition gene.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-102.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-102.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-102.
RC TISSUE=Cervix;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-102.
RG SeattleSNPs variation discovery resource;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [10]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-102.
RC TISSUE=Brain;
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 [12]
RP PHOSPHORYLATION AT SER-22; SER-25 AND SER-28.
RX PubMed=8061611; DOI=10.1002/pro.5560030511;
RA Price P.A., Rice J.S., Williamson M.K.;
RT "Conserved phosphorylation of serines in the Ser-X-Glu/Ser(P) sequences of
RT the vitamin K-dependent matrix Gla protein from shark, lamb, rat, cow, and
RT human.";
RL Protein Sci. 3:822-830(1994).
RN [13]
RP PARTIAL PROTEIN SEQUENCE, AND PROTEOLYTIC PROCESSING OF C-TERMINAL.
RX PubMed=1939157; DOI=10.1016/s0021-9258(18)54832-8;
RA Hale J.E., Williamson M.K., Price P.A.;
RT "Carboxyl-terminal proteolytic processing of matrix Gla protein.";
RL J. Biol. Chem. 266:21145-21149(1991).
RN [14]
RP INVOLVEMENT IN KTLS.
RX PubMed=9916809; DOI=10.1038/5102;
RA Munroe P.B., Olgunturk R.O., Fryns J.-P., Van Maldergem L., Ziereisen F.,
RA Yuksel B., Gardiner R.M., Chung E.;
RT "Mutations in the gene encoding the human matrix Gla protein cause Keutel
RT syndrome.";
RL Nat. Genet. 21:142-144(1999).
CC -!- FUNCTION: Associates with the organic matrix of bone and cartilage.
CC Thought to act as an inhibitor of bone formation.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P08493-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08493-2; Sequence=VSP_046999;
CC -!- PTM: Requires vitamin K-dependent gamma-carboxylation for its function.
CC -!- DISEASE: Keutel syndrome (KTLS) [MIM:245150]: An autosomal recessive
CC disorder characterized by abnormal cartilage calcification, peripheral
CC pulmonary stenosis neural hearing loss and midfacial hypoplasia.
CC {ECO:0000269|PubMed:9916809}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the osteocalcin/matrix Gla protein family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/mgp/";
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DR EMBL; M58549; AAB53766.1; -; mRNA.
DR EMBL; M55270; AAB53765.1; -; Genomic_DNA.
DR EMBL; X07362; CAA30287.1; -; mRNA.
DR EMBL; X53331; CAA37418.1; -; mRNA.
DR EMBL; AY542304; AAT08173.1; -; mRNA.
DR EMBL; BT006733; AAP35379.1; -; mRNA.
DR EMBL; CR450358; CAG29354.1; -; mRNA.
DR EMBL; AK312029; BAG34966.1; -; mRNA.
DR EMBL; DQ004248; AAY16978.1; -; Genomic_DNA.
DR EMBL; AC007655; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471094; EAW96333.1; -; Genomic_DNA.
DR EMBL; BC005272; AAH05272.1; -; mRNA.
DR EMBL; BC070314; AAH70314.1; -; mRNA.
DR EMBL; BC093078; AAH93078.1; -; mRNA.
DR CCDS; CCDS53752.1; -. [P08493-2]
DR CCDS; CCDS8669.1; -. [P08493-1]
DR PIR; A35811; GEHUM.
DR RefSeq; NP_000891.2; NM_000900.4. [P08493-1]
DR RefSeq; NP_001177768.1; NM_001190839.2. [P08493-2]
DR AlphaFoldDB; P08493; -.
DR SMR; P08493; -.
DR BioGRID; 110412; 4.
DR IntAct; P08493; 1.
DR DrugBank; DB01373; Calcium.
DR iPTMnet; P08493; -.
DR PhosphoSitePlus; P08493; -.
DR BioMuta; MGP; -.
DR DMDM; 118572668; -.
DR CPTAC; non-CPTAC-1141; -.
DR jPOST; P08493; -.
DR MassIVE; P08493; -.
DR MaxQB; P08493; -.
DR PeptideAtlas; P08493; -.
DR PRIDE; P08493; -.
DR ProteomicsDB; 52112; -. [P08493-1]
DR Antibodypedia; 2842; 307 antibodies from 30 providers.
DR DNASU; 4256; -.
DR Ensembl; ENST00000228938.5; ENSP00000228938.5; ENSG00000111341.10. [P08493-2]
DR Ensembl; ENST00000539261.6; ENSP00000445907.1; ENSG00000111341.10. [P08493-1]
DR GeneID; 4256; -.
DR KEGG; hsa:4256; -.
DR MANE-Select; ENST00000539261.6; ENSP00000445907.1; NM_000900.5; NP_000891.2.
DR UCSC; uc001rcn.3; human. [P08493-1]
DR CTD; 4256; -.
DR DisGeNET; 4256; -.
DR GeneCards; MGP; -.
DR HGNC; HGNC:7060; MGP.
DR HPA; ENSG00000111341; Low tissue specificity.
DR MalaCards; MGP; -.
DR MIM; 154870; gene.
DR MIM; 245150; phenotype.
DR neXtProt; NX_P08493; -.
DR OpenTargets; ENSG00000111341; -.
DR Orphanet; 85202; Keutel syndrome.
DR PharmGKB; PA30790; -.
DR VEuPathDB; HostDB:ENSG00000111341; -.
DR GeneTree; ENSGT00390000003753; -.
DR HOGENOM; CLU_177119_1_0_1; -.
DR InParanoid; P08493; -.
DR OMA; MESYEIN; -.
DR OrthoDB; 1512503at2759; -.
DR PhylomeDB; P08493; -.
DR TreeFam; TF330920; -.
DR PathwayCommons; P08493; -.
DR SignaLink; P08493; -.
DR BioGRID-ORCS; 4256; 12 hits in 1073 CRISPR screens.
DR ChiTaRS; MGP; human.
DR GeneWiki; Matrix_gla_protein; -.
DR GenomeRNAi; 4256; -.
DR Pharos; P08493; Tbio.
DR PRO; PR:P08493; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P08493; protein.
DR Bgee; ENSG00000111341; Expressed in descending thoracic aorta and 187 other tissues.
DR ExpressionAtlas; P08493; baseline and differential.
DR Genevisible; P08493; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:ProtInc.
DR GO; GO:0008147; F:structural constituent of bone; TAS:ProtInc.
DR GO; GO:0001502; P:cartilage condensation; TAS:ProtInc.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0001503; P:ossification; TAS:ProtInc.
DR GO; GO:0030500; P:regulation of bone mineralization; IEA:InterPro.
DR InterPro; IPR035972; GLA-like_dom_SF.
DR InterPro; IPR000294; GLA_domain.
DR InterPro; IPR027118; MGP.
DR InterPro; IPR002384; Osteocalcin/MGP.
DR PANTHER; PTHR10109; PTHR10109; 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 Alternative splicing; Chondrogenesis; Deafness; Developmental protein;
KW Differentiation; Direct protein sequencing; Disulfide bond;
KW Gamma-carboxyglutamic acid; Osteogenesis; Phosphoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT CHAIN 20..96
FT /note="Matrix Gla protein"
FT /id="PRO_0000011109"
FT PROPEP 97..103
FT /note="Removed in mature form; probably by carboxypeptidase
FT N"
FT /id="PRO_0000011110"
FT DOMAIN 51..97
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 21
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07507,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:8061611"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:8061611"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:8061611"
FT MOD_RES 56
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07507,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 60
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07507,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 67
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07507,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 71
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07507,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT DISULFID 73..79
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT VAR_SEQ 20
FT /note="Y -> YGEWQKEENFGFDIVSVLSLNWHRAQ (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_046999"
FT VARIANT 53
FT /note="K -> E (in dbSNP:rs1801716)"
FT /id="VAR_016177"
FT VARIANT 102
FT /note="T -> A (in dbSNP:rs4236)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2216462,
FT ECO:0000269|PubMed:3387234, ECO:0000269|Ref.5,
FT ECO:0000269|Ref.6, ECO:0000269|Ref.8"
FT /id="VAR_016178"
FT CONFLICT 20
FT /note="Y -> C (in Ref. 11; AAH93078)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="R -> G (in Ref. 6; CAG29354)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 103 AA; 12353 MW; 243968D715D54549 CRC64;
MKSLILLAIL AALAVVTLCY ESHESMESYE LNPFINRRNA NTFISPQQRW RAKVQERIRE
RSKPVHELNR EACDDYRLCE RYAMVYGYNA AYNRYFRKRR GTK
