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   23-MAY-2018, entry version 180.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX   PubMed=2394711;
RA   Cancela M.L., Hsieh C.-L., Francke U., Price P.A.;
RT   "Molecular structure, chromosome assignment, and promoter organization
RT   of 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.,
RA   Barr P.J.;
RT   "The cDNA and derived amino acid sequences for human and bovine matrix
RT   Gla 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
RT   cells: 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
RP   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
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP   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
RP   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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA   Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA   Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA   Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA   Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA   Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA   Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA   Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA   Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA   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.,
RA   Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA   Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA   Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA   Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA   Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA   Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA   Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA   Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA   Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA   Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA   Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA   Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA   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.,
RA   Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA   Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA   Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA   Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA   Kucherlapati R., Weinstock G., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RP   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
RT   project: 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)
RT   sequences of the vitamin K-dependent matrix Gla protein from shark,
RT   lamb, rat, cow, and human.";
RL   Protein Sci. 3:822-830(1994).
RN   [13]
RP   PARTIAL PROTEIN SEQUENCE, AND PROTEOLYTIC PROCESSING OF C-TERMINAL.
RX   PubMed=1939157;
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.,
RA   Ziereisen F., Yuksel B., Gardiner R.M., Chung E.;
RT   "Mutations in the gene encoding the human matrix Gla protein cause
RT   Keutel syndrome.";
RL   Nat. Genet. 21:142-144(1999).
CC   -!- FUNCTION: Associates with the organic matrix of bone and
CC       cartilage. 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         Note=Gene prediction based on EST data.;
CC   -!- PTM: Requires vitamin K-dependent gamma-carboxylation for its
CC       function.
CC   -!- DISEASE: Keutel syndrome (KTLS) [MIM:245150]: An autosomal
CC       recessive disorder characterized by abnormal cartilage
CC       calcification, peripheral pulmonary stenosis neural hearing loss
CC       and midfacial hypoplasia. {ECO:0000269|PubMed:9916809}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       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   UniGene; Hs.365706; -.
DR   ProteinModelPortal; P08493; -.
DR   BioGrid; 110412; 1.
DR   IntAct; P08493; 1.
DR   iPTMnet; P08493; -.
DR   PhosphoSitePlus; P08493; -.
DR   BioMuta; MGP; -.
DR   DMDM; 118572668; -.
DR   MaxQB; P08493; -.
DR   PeptideAtlas; P08493; -.
DR   PRIDE; P08493; -.
DR   DNASU; 4256; -.
DR   Ensembl; ENST00000228938; ENSP00000228938; ENSG00000111341. [P08493-2]
DR   Ensembl; ENST00000539261; ENSP00000445907; ENSG00000111341. [P08493-1]
DR   GeneID; 4256; -.
DR   KEGG; hsa:4256; -.
DR   UCSC; uc001rcn.3; human. [P08493-1]
DR   CTD; 4256; -.
DR   DisGeNET; 4256; -.
DR   EuPathDB; HostDB:ENSG00000111341.9; -.
DR   GeneCards; MGP; -.
DR   HGNC; HGNC:7060; MGP.
DR   HPA; HPA013949; -.
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   GeneTree; ENSGT00390000003753; -.
DR   HOGENOM; HOG000113581; -.
DR   HOVERGEN; HBG006353; -.
DR   InParanoid; P08493; -.
DR   KO; K19481; -.
DR   OMA; PFLNRRN; -.
DR   OrthoDB; EOG091G0XPC; -.
DR   PhylomeDB; P08493; -.
DR   TreeFam; TF330920; -.
DR   ChiTaRS; MGP; human.
DR   GeneWiki; Matrix_gla_protein; -.
DR   GenomeRNAi; 4256; -.
DR   PRO; PR:P08493; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000111341; -.
DR   CleanEx; HS_MGP; -.
DR   ExpressionAtlas; P08493; baseline and differential.
DR   Genevisible; P08493; HS.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0031012; C:extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0005578; C:proteinaceous extracellular matrix; TAS:ProtInc.
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; Complete proteome; Deafness;
KW   Developmental protein; Differentiation; Direct protein sequencing;
KW   Disulfide bond; Gamma-carboxyglutamic acid; Osteogenesis;
KW   Phosphoprotein; Polymorphism; Reference proteome; Secreted; Signal.
FT   SIGNAL        1     19
FT   CHAIN        20     96       Matrix Gla protein.
FT                                /FTId=PRO_0000011109.
FT   PROPEP       97    103       Removed in mature form; probably by
FT                                carboxypeptidase N.
FT                                /FTId=PRO_0000011110.
FT   DOMAIN       51     97       Gla. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463}.
FT   MOD_RES      21     21       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P07507,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      22     22       Phosphoserine.
FT                                {ECO:0000269|PubMed:8061611}.
FT   MOD_RES      25     25       Phosphoserine.
FT                                {ECO:0000269|PubMed:8061611}.
FT   MOD_RES      28     28       Phosphoserine.
FT                                {ECO:0000269|PubMed:8061611}.
FT   MOD_RES      56     56       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P07507,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      60     60       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P07507,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      67     67       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P07507,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      71     71       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P07507,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   DISULFID     73     79       {ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   VAR_SEQ      20     20       Y -> YGEWQKEENFGFDIVSVLSLNWHRAQ (in
FT                                isoform 2). {ECO:0000305}.
FT                                /FTId=VSP_046999.
FT   VARIANT      53     53       K -> E (in dbSNP:rs1801716).
FT                                /FTId=VAR_016177.
FT   VARIANT     102    102       T -> A (in dbSNP:rs4236).
FT                                {ECO:0000269|PubMed:14702039,
FT                                ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:2216462,
FT                                ECO:0000269|PubMed:3387234,
FT                                ECO:0000269|Ref.5, ECO:0000269|Ref.6,
FT                                ECO:0000269|Ref.8}.
FT                                /FTId=VAR_016178.
FT   CONFLICT     20     20       Y -> C (in Ref. 11; AAH93078).
FT                                {ECO:0000305}.
FT   CONFLICT     51     51       R -> G (in Ref. 6; CAG29354).
FT                                {ECO:0000305}.
SQ   SEQUENCE   103 AA;  12353 MW;  243968D715D54549 CRC64;
     MKSLILLAIL AALAVVTLCY ESHESMESYE LNPFINRRNA NTFISPQQRW RAKVQERIRE
     RSKPVHELNR EACDDYRLCE RYAMVYGYNA AYNRYFRKRR GTK
//