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Enamelin

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242: 219: 1112:) proteolytically cleaves the secreted enamelin protein immediately upon release, into several smaller polypeptides; each having their own functions. However, the whole protein (~168 kDa) and its largest derivative fragment (~89 kDa) are undetectable in the secretory stage; these are existent only at the mineralisation front. Smaller polypeptide fragments remain embedded in the enamel, throughout the secretory stage enamel matrix. These strongly bind to the mineral and arrest seeded crystal growth. 116: 141: 248: 147: 1093:
Enamelin is thought to be the oldest member of the enamel matrix protein (EMP) family, with animal studies showing remarkable conservation of the gene phylogenetically. All other EMPs are derived from enamelin, such as amelogenin. EMPs belong to a larger family of proteins termed 'secretory
1085:, dentine sialophosphoprotein, and a variety of enzymes. Enamelin is the largest protein (~168kDa) in the enamel matrix of developing teeth and is the least abundant (encompasses approximately 1-5%) of total enamel matrix proteins. It is present predominantly at the growing enamel surface. 1671: 1120:
The primary function of the proteins acts at the mineralisation front; growth sites where it is the interface between the ameloblast plasma membrane and lengthening extremity of crystals. The key activities of enamelin can be summarised:
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It is speculated that this protein could interact with amelogenin or other enamel matrix proteins and be important in determining growth of the length of enamel crystallites. The mechanism of this proposed co-interaction is synergistic
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Hu CC, Hart TC, Dupont BR, Chen JJ, Sun X, Qian Q, Zhang CH, Jiang H, Mattern VL, Wright JT, Simmer JP (April 2000). "Cloning human enamelin cDNA, chromosomal localization, and analysis of expression during tooth development".
1105:) based on their distinctive Ser-x-Glu (S-x-E) motifs. The major secretory product of the ENAM gene has 1103 amino acids (post-secretion), and has an acidic isoelectric point ranging from 4.5–6.5 (depending on the fragment). 1073:(enamel development). The formation of enamel's intricate architecture is thought to be rigorously controlled in ameloblasts through interactions of various organic matrix protein molecules that include: enamelin, 2039:
Kida M, Ariga T, Shirakawa T, Oguchi H, Sakiyama Y (November 2002). "Autosomal-dominant hypoplastic form of amelogenesis imperfecta caused by an enamelin gene mutation at the exon-intron boundary".
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Similar to other enamel matrix proteins, enamelin undergoes extensive post-translational modifications (mainly phosphorylation), processing, and secretion by proteases. Enamelin has three putative
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Hart PS, Michalec MD, Seow WK, Hart TC, Wright JT (August 2003). "Identification of the enamelin (g.8344delG) mutation in a new kindred and presentation of a standardized ENAM nomenclature".
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Gutierrez SJ, Chaves M, Torres DM, Briceño I (May 2007). "Identification of a novel mutation in the enamalin gene in a family with autosomal-dominant amelogenesis imperfecta".
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Pavlic A, Petelin M, Battelino T (March 2007). "Phenotype and enamel ultrastructure characteristics in patients with ENAM gene mutations g.13185-13186insAG and 8344delG".
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Pavlic A, Petelin M, Battelino T (March 2007). "Phenotype and enamel ultrastructure characteristics in patients with ENAM gene mutations g.13185-13186insAG and 8344delG".
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Forsman K, Lind L, Bäckman B, Westermark E, Holmgren G (September 1994). "Localization of a gene for autosomal dominant amelogenesis imperfecta (ADAI) to chromosome 4q".
255: 154: 1144:"). With enamelin enhancing the rates of crystal nucleation via the creation of addition sites for EMPs, such as amelogenin, to template calcium phosphate nucleation. 1019: 1178:
expression leads to protrusive structures (often, horizontal grooves) on the surface of enamel, and with high transgene expression, the enamel layer is almost lost.
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Dong J, Gu TT, Simmons D, MacDougall M (October 2000). "Enamelin maps to human chromosome 4q21 within the autosomal dominant amelogenesis imperfecta locus".
1163:(AI), a heterogenous group of heritable conditions in which enamel in malformed. Point mutations can cause autosomal-dominant hypoplastic AI, and novel 687: 668: 77: 1827:
Kim JW, Seymen F, Lin BP, Kiziltan B, Gencay K, Simmer JP, Hu JC (March 2005). "ENAM mutations in autosomal-dominant amelogenesis imperfecta".
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gene mainly tend to lead to the autosomal-dominant AI. The phenotype of the mutations are generalised thin enamel and no defined enamel layer.
1672:"Control of Calcium Phosphate Nucleation and Transformation through Interactions of Enamelin and Amelogenin Exhibits the "Goldilocks Effect"" 1399:"The enamelin genes in lizard, crocodile, and frog and the pseudogene in the chicken provide new insights on enamelin evolution in tetrapods" 1281: 1263: 2283: 1147:
It is best thought to understand the overarching function of enamelin as the proteins responsible for correct enamel thickness formation.
241: 1373: 2249: 895: 1632: 902: 218: 1343: 1250: 1229: 1246: 1039: 140: 115: 2261: 1225: 2070:"Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta" 57: 1670:
Tao J, Fijneman A, Wan J, Prajapati S, Mukherjee K, Fernandez-Martinez A, Moradian-Oldak J, De Yoreo JJ (2018-12-05).
1301:"A nonsense mutation in the enamelin gene causes local hypoplastic autosomal dominant amelogenesis imperfecta (AIH2)" 254: 153: 2298: 1967:
Hart TC, Hart PS, Gorry MC, Michalec MD, Ryu OH, Uygur C, Ozdemir D, Firatli S, Aren G, Firatli E (December 2003).
1069:, which comprise 10% of the total enamel matrix proteins. It is one of the key proteins thought to be involved in 247: 146: 732: 65: 1969:"Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects" 1780:"Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects" 1027: 1202: 1160: 713: 1438:
Sire JY, Davit-Béal T, Delgado S, Gu X (2007). "The origin and evolution of enamel mineralization genes".
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Necessary for the adhesion of ameloblasts to the surface of the enamel in the secretory stage
1101:(Ser, Ser, and Ser in humans) phosphorylated by a Golgi-associated secretory pathway kinase ( 2222: 2185: 2155: 2124: 2116: 2081: 2048: 2019: 1988: 1980: 1945: 1912: 1883: 1836: 1799: 1791: 1752: 1691: 1683: 1592: 1551: 1543: 1502: 1494: 1447: 1410: 1312: 334: 265: 209: 164: 1006: 309: 85: 2159: 2303: 1993: 1968: 1804: 1779: 1778:
Hart TC, Hart PS, Gorry MC, Michalec MD, Ryu OH, Uygur C, et al. (December 2003).
1696: 1556: 1531: 1507: 1482: 2129: 2104: 2023: 1916: 1887: 1756: 602: 597: 592: 587: 582: 577: 572: 556: 551: 546: 530: 525: 2277: 1498: 1098: 512: 2205: 1532:"The importance of a potential phosphorylation site in enamelin on enamel formation" 1467: 980: 69: 1197: 1187: 1078: 1070: 1002: 327: 106: 1856: 1167:
mutations can cause autosomal-recessive hypoplastic AI. However, mutations in the
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Hu JC, Lertlam R, Richardson AS, Smith CE, McKee MD, Simmer JP (December 2011).
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National Center for Biotechnology Information, U.S. National Library of Medicine
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National Center for Biotechnology Information, U.S. National Library of Medicine
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Mårdh CK, Bäckman B, Holmgren G, Hu JC, Simmer JP, Forsman-Semb K (May 2002).
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Al-Hashimi N, Lafont AG, Delgado S, Kawasaki K, Sire JY (September 2010).
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Ballif BA, Villén J, Beausoleil SA, Schwartz D, Gygi SP (November 2004).
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Yan WJ, Ma P, Tian Y, Wang JY, Qin CL, Feng JQ, Wang XF (November 2017).
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Rajpar MH, Harley K, Laing C, Davies RM, Dixon MJ (August 2001).
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At the secretory stage, the enzyme matrix metalloproteinase-20 (
1062: 996: 975: 61: 1720:"ENAM enamelin [Homo sapiens (human)] - Gene - NCBI" 1128:
Binds to hydroxyapatite and promotes crystallite elongation
1934:"Phosphoproteomic analysis of the developing mouse brain" 1581:"Enamelin and autosomal-dominant amelogenesis imperfecta" 2105:"DNA cloning using in vitro site-specific recombination" 1483:"Cell proliferation and apoptosis in enamelin null mice" 317: 482: 1033: 1013: 995: 990: 974: 966: 961: 956: 871: 846: 820: 795: 2103:Hartley JL, Temple GF, Brasch MA (November 2000). 1242: 1240: 1238: 1221: 1219: 1217: 264: 163: 1247:GRCm38: Ensembl release 89: ENSMUSG00000029286 1625:Fundamentals of oral histology and physiology 1585:Critical Reviews in Oral Biology and Medicine 8: 598:positive regulation of enamel mineralization 1226:GRCh38: Ensembl release 89: ENSG00000132464 1655:: CS1 maint: location missing publisher ( 987: 628: 508: 305: 204: 101: 2128: 2085: 1992: 1949: 1803: 1695: 1596: 1555: 1506: 1414: 1316: 1094:calcium-binding phosphoproteins' (SCPP). 1058:(EMPs), that in humans is encoded by the 1338: 1336: 573:odontogenesis of dentin-containing tooth 379:Skeletal muscle tissue of biceps brachii 1213: 603:post-translational protein modification 16:Mammalian protein found in Homo sapiens 1648: 953: 526:structural constituent of tooth enamel 18: 1618: 1616: 1536:International Journal of Oral Science 269: 230: 225: 168: 127: 122: 7: 2160:10.1034/j.1600-0722.2000.108005353.x 1359: 1357: 1355: 1353: 1938:Molecular & Cellular Proteomics 1159:gene can cause certain subtypes of 868: 843: 817: 792: 768: 749: 723: 704: 678: 659: 487: 441:choroid plexus of fourth ventricle 405: 343: 322: 14: 2148:European Journal of Oral Sciences 1917:10.1016/j.archoralbio.2006.10.010 1888:10.1016/j.archoralbio.2006.09.014 1757:10.1016/j.archoralbio.2006.10.010 1487:European Journal of Oral Sciences 1623:Hand AR, Frank ME (2014-11-21). 1499:10.1111/j.1600-0722.2011.00860.x 1368:(8th ed.). Elsevier India. 588:regulation of cell morphogenesis 253: 246: 240: 217: 152: 145: 139: 114: 1403:Molecular Biology and Evolution 1174:A moderately higher than usual 471:More reference expression data 1: 2024:10.1016/S0003-9969(03)00114-6 1364:Nanci A, Ten Cate AR (2012). 991:Available protein structures: 578:biomineral tissue development 238: 137: 2190:10.1177/00220345000790040501 1344:"Entrez Gene: ENAM enamelin" 48:, AIH2, AI1C, ADAI, enamelin 2284:Genes on human chromosome 4 2254:human gene location in the 1973:Journal of Medical Genetics 1784:Journal of Medical Genetics 1676:Crystal Growth & Design 1579:Hu JC, Yamakoshi Y (2003). 552:endoplasmic reticulum lumen 2320: 2266:human gene details in the 2178:Journal of Dental Research 2053:10.1177/154405910208101103 2041:Journal of Dental Research 1951:10.1074/mcp.M400085-MCP200 1841:10.1177/154405910508400314 1829:Journal of Dental Research 1598:10.1177/154411130301400602 593:ameloblast differentiation 1366:Ten Cate's Oral Histology 1282:"Mouse PubMed Reference:" 1264:"Human PubMed Reference:" 986: 941: 936: 932: 925: 909: 890: 875: 850: 839: 824: 799: 788: 775: 771: 756: 752: 743: 730: 726: 711: 707: 698: 685: 681: 666: 662: 653: 638: 631: 627: 611: 511: 507: 495: 490: 481: 468: 417: 408: 355: 346: 316: 308: 304: 287: 274: 237: 216: 207: 203: 186: 173: 136: 113: 104: 100: 55: 52: 42: 35: 30: 26: 21: 2215:Human Molecular Genetics 2074:Human Molecular Genetics 2012:Archives of Oral Biology 1905:Archives of Oral Biology 1876:Archives of Oral Biology 1745:Archives of Oral Biology 1305:Human Molecular Genetics 1065:. It is part of the non- 1688:10.1021/acs.cgd.8b01066 1203:Amelogenesis imperfecta 1161:amelogenesis imperfecta 1131:Act as a modulator for 903:Chr 5: 88.64 – 88.65 Mb 896:Chr 4: 70.63 – 70.65 Mb 367:vastus lateralis muscle 2087:10.1093/hmg/10.16.1673 371:striated muscle tissue 1985:10.1136/jmg.40.12.900 1796:10.1136/jmg.40.12.900 1416:10.1093/molbev/msq098 1318:10.1093/hmg/11.9.1069 1151:Clinical significance 425:tracheobronchial tree 2227:10.1093/hmg/3.9.1621 1724:www.ncbi.nlm.nih.gov 1548:10.1038/ijos.2017.41 1440:Cells Tissues Organs 1054:is an enamel matrix 557:extracellular matrix 547:extracellular region 232:Chromosome 5 (mouse) 130:Chromosome 4 (human) 2268:UCSC Genome Browser 2256:UCSC Genome Browser 1493:(Suppl 1): 329–37. 457:superior colliculus 453:inferior colliculus 363:islet of Langerhans 733:ENSMUSG00000029286 566:Biological process 540:Cellular component 519:Molecular function 395:buccal mucosa cell 2299:Biomineralization 2121:10.1101/gr.143000 1682:(12): 7391–7400. 1452:10.1159/000102679 1155:Mutations in the 1142:Goldilocks effect 1135:mineral formation 1049: 1048: 1045: 1044: 1040:structure summary 952: 951: 948: 947: 921: 920: 886: 885: 865: 864: 835: 834: 814: 813: 784: 783: 765: 764: 739: 738: 720: 719: 694: 693: 675: 674: 623: 622: 503: 502: 499: 498: 477: 476: 464: 463: 449:lactiferous gland 437:perirhinal cortex 429:intestinal villus 402: 401: 391:corpus epididymis 300: 299: 199: 198: 2311: 2238: 2209: 2171: 2142: 2132: 2099: 2089: 2064: 2035: 2006: 1996: 1963: 1953: 1944:(11): 1093–101. 1928: 1899: 1861: 1860: 1824: 1818: 1817: 1807: 1775: 1769: 1768: 1740: 1734: 1733: 1731: 1730: 1716: 1710: 1709: 1699: 1667: 1661: 1660: 1654: 1646: 1620: 1611: 1610: 1600: 1576: 1570: 1569: 1559: 1527: 1521: 1520: 1510: 1478: 1472: 1471: 1435: 1429: 1428: 1418: 1394: 1388: 1387: 1361: 1348: 1347: 1340: 1331: 1330: 1320: 1296: 1290: 1289: 1278: 1272: 1271: 1260: 1254: 1244: 1233: 1223: 988: 954: 934: 933: 905: 898: 881: 869: 860: 844: 840:RefSeq (protein) 830: 818: 809: 793: 769: 750: 724: 705: 679: 660: 629: 509: 488: 473: 433:Ileal epithelium 413: 411:Top expressed in 406: 351: 349:Top expressed in 344: 323: 306: 296: 283: 272: 257: 250: 244: 233: 221: 205: 195: 182: 171: 156: 149: 143: 132: 118: 102: 96: 94:ENAM - orthologs 47: 40: 19: 2319: 2318: 2314: 2313: 2312: 2310: 2309: 2308: 2274: 2273: 2246: 2241: 2212: 2174: 2145: 2115:(11): 1788–95. 2109:Genome Research 2102: 2067: 2038: 2009: 1966: 1931: 1902: 1873: 1869: 1867:Further reading 1864: 1826: 1825: 1821: 1777: 1776: 1772: 1742: 1741: 1737: 1728: 1726: 1718: 1717: 1713: 1669: 1668: 1664: 1647: 1635: 1622: 1621: 1614: 1578: 1577: 1573: 1529: 1528: 1524: 1480: 1479: 1475: 1437: 1436: 1432: 1396: 1395: 1391: 1376: 1363: 1362: 1351: 1342: 1341: 1334: 1298: 1297: 1293: 1280: 1279: 1275: 1262: 1261: 1257: 1245: 1236: 1224: 1215: 1211: 1184: 1153: 1118: 1091: 943:View/Edit Mouse 938:View/Edit Human 901: 894: 891:Location (UCSC) 877: 856: 852: 826: 805: 801: 714:ENSG00000132464 607: 561: 535: 531:protein binding 469: 460: 455: 451: 447: 443: 439: 435: 431: 427: 423: 409: 398: 393: 389: 385: 381: 377: 373: 369: 365: 361: 347: 291: 278: 270: 260: 259: 258: 251: 231: 208:Gene location ( 190: 177: 169: 159: 158: 157: 150: 128: 105:Gene location ( 56: 43: 36: 17: 12: 11: 5: 2317: 2315: 2307: 2306: 2301: 2296: 2291: 2286: 2276: 2275: 2272: 2271: 2259: 2245: 2244:External links 2242: 2240: 2239: 2210: 2172: 2143: 2100: 2080:(16): 1673–7. 2065: 2047:(11): 738–42. 2036: 2007: 1964: 1929: 1900: 1870: 1868: 1865: 1863: 1862: 1819: 1770: 1735: 1711: 1662: 1633: 1627:. Ames, Iowa. 1612: 1571: 1522: 1473: 1430: 1409:(9): 2078–94. 1389: 1375:978-8131233436 1374: 1349: 1332: 1311:(9): 1069–74. 1291: 1273: 1255: 1234: 1212: 1210: 1207: 1206: 1205: 1200: 1195: 1190: 1183: 1180: 1152: 1149: 1137: 1136: 1129: 1126: 1117: 1114: 1099:phosphoserines 1090: 1087: 1047: 1046: 1043: 1042: 1037: 1031: 1030: 1017: 1011: 1010: 1000: 993: 992: 984: 983: 978: 972: 971: 968: 964: 963: 959: 958: 950: 949: 946: 945: 940: 930: 929: 923: 922: 919: 918: 916: 914: 907: 906: 899: 892: 888: 887: 884: 883: 873: 872: 866: 863: 862: 848: 847: 841: 837: 836: 833: 832: 822: 821: 815: 812: 811: 797: 796: 790: 786: 785: 782: 781: 773: 772: 766: 763: 762: 754: 753: 747: 741: 740: 737: 736: 728: 727: 721: 718: 717: 709: 708: 702: 696: 695: 692: 691: 683: 682: 676: 673: 672: 664: 663: 657: 651: 650: 645: 640: 636: 635: 625: 624: 621: 620: 609: 608: 606: 605: 600: 595: 590: 585: 580: 575: 569: 567: 563: 562: 560: 559: 554: 549: 543: 541: 537: 536: 534: 533: 528: 522: 520: 516: 515: 505: 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755: 751: 748: 746: 742: 735: 734: 729: 725: 722: 716: 715: 710: 706: 703: 701: 697: 690: 689: 684: 680: 677: 671: 670: 665: 661: 658: 656: 652: 649: 646: 644: 641: 637: 634: 630: 626: 619: 615: 610: 604: 601: 599: 596: 594: 591: 589: 586: 584: 581: 579: 576: 574: 571: 570: 568: 565: 564: 558: 555: 553: 550: 548: 545: 544: 542: 539: 538: 532: 529: 527: 524: 523: 521: 518: 517: 514: 513:Gene ontology 510: 506: 494: 489: 486: 484: 480: 472: 467: 456: 452: 448: 444: 440: 436: 432: 428: 424: 420: 419: 416: 412: 407: 404: 394: 390: 386: 382: 378: 374: 370: 366: 362: 358: 357: 354: 350: 345: 342: 341: 338: 336: 332: 330: 329: 325: 324: 321: 319: 315: 311: 307: 303: 295: 290: 286: 282: 277: 267: 263: 256: 249: 243: 236: 228: 224: 220: 215: 211: 206: 202: 194: 189: 185: 181: 176: 166: 162: 155: 148: 142: 135: 131: 125: 121: 117: 112: 108: 103: 99: 95: 91: 87: 83: 79: 75: 71: 67: 63: 59: 51: 46: 39: 34: 29: 25: 20: 2262: 2250: 2218: 2214: 2184:(4): 912–9. 2181: 2177: 2154:(5): 353–8. 2151: 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Index

Aliases
ENAM
OMIM
606585
MGI
1333772
HomoloGene
9698
GeneCards
ENAM
OMA
ENAM - orthologs
Human
Chromosome 4 (human)
Chr.
Chromosome 4 (human)
Chromosome 4 (human)
Genomic location for ENAM
Genomic location for ENAM
Band
bp
bp
Mouse
Chromosome 5 (mouse)
Chr.
Chromosome 5 (mouse)
Genomic location for ENAM
Genomic location for ENAM
Band
bp

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