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 02-OCT-2024, entry version 213. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 6. DR IntAct; P08493; 3. DR MINT; P08493; -. DR STRING; 9606.ENSP00000228938; -. 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 PeptideAtlas; P08493; -. DR ProteomicsDB; 52112; -. [P08493-1] DR Antibodypedia; 2842; 341 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 AGR; HGNC:7060; -. 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; NANTFMS; -. DR OrthoDB; 3885479at2759; -. DR PhylomeDB; P08493; -. DR TreeFam; TF330920; -. DR PathwayCommons; P08493; -. DR SignaLink; P08493; -. DR BioGRID-ORCS; 4256; 13 hits in 1151 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 189 other cell types or tissues. DR ExpressionAtlas; P08493; baseline and differential. 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; MATRIX GLA PROTEIN; 1. DR PANTHER; PTHR10109:SF0; MATRIX GLA PROTEIN; 1. DR PRINTS; PR00002; GLABONE. DR SMART; SM00069; GLA; 1. DR SUPFAM; SSF57630; GLA-domain; 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 Proteomics identification; 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 //