Alpha-L-iduronidase

Details

Name
Alpha-L-iduronidase
Synonyms
  • 3.2.1.76
Gene Name
IDUA
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051582|Alpha-L-iduronidase
MRPLRPRAALLALLASLLAAPPVAPAEAPHLVHVDAARALWPLRRFWRSTGFCPPLPHSQ
ADQYVLSWDQQLNLAYVGAVPHRGIKQVRTHWLLELVTTRGSTGRGLSYNFTHLDGYLDL
LRENQLLPGFELMGSASGHFTDFEDKQQVFEWKDLVSSLARRYIGRYGLAHVSKWNFETW
NEPDHHDFDNVSMTMQGFLNYYDACSEGLRAASPALRLGGPGDSFHTPPRSPLSWGLLRH
CHDGTNFFTGEAGVRLDYISLHRKGARSSISILEQEKVVAQQIRQLFPKFADTPIYNDEA
DPLVGWSLPQPWRADVTYAAMVVKVIAQHQNLLLANTTSAFPYALLSNDNAFLSYHPHPF
AQRTLTARFQVNNTRPPHVQLLRKPVLTAMGLLALLDEEQLWAEVSQAGTVLDSNHTVGV
LASAHRPQGPADAWRAAVLIYASDDTRAHPNRSVAVTLRLRGVPPGPGLVYVTRYLDNGL
CSPDGEWRRLGRPVFPTAEQFRRMRAAEDPVAAAPRPLPAGGRLTLRPALRLPSLLLVHV
CARPEKPPGQVTRLRALPLTQGQLVLVWSDEHVGSKCLWTYEIQFSQDGKAYTPVSRKPS
TFNLFVFSPDTGAVSGSYRVRALDYWARPGPFSDPVPYLEVPVPRGPPSPGNP
Number of residues
653
Molecular Weight
72669.19
Theoretical pI
Not Available
GO Classification
Functions
L-iduronidase activity / receptor binding
Processes
chondroitin sulfate catabolic process / dermatan sulfate catabolic process / disaccharide metabolic process / glycosaminoglycan catabolic process
Components
coated vesicle / extracellular exosome / lysosomal lumen
General Function
Not Available
Specific Function
L-iduronidase activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Lysosome
Gene sequence
>lcl|BSEQ0051583|Alpha-L-iduronidase (IDUA)
ATGCGTCCCCTGCGCCCCCGCGCCGCGCTGCTGGCGCTCCTGGCCTCGCTCCTGGCCGCG
CCCCCGGTGGCCCCGGCCGAGGCCCCGCACCTGGTGCATGTGGACGCGGCCCGCGCGCTG
TGGCCCCTGCGGCGCTTCTGGAGGAGCACAGGCTTCTGCCCCCCGCTGCCACACAGCCAG
GCTGACCAGTACGTCCTCAGCTGGGACCAGCAGCTCAACCTCGCCTATGTGGGCGCCGTC
CCTCACCGCGGCATCAAGCAGGTCCGGACCCACTGGCTGCTGGAGCTTGTCACCACCAGG
GGGTCCACTGGACGGGGCCTGAGCTACAACTTCACCCACCTGGACGGGTACCTGGACCTT
CTCAGGGAGAACCAGCTCCTCCCAGGGTTTGAGCTGATGGGCAGCGCCTCGGGCCACTTC
ACTGACTTTGAGGACAAGCAGCAGGTGTTTGAGTGGAAGGACTTGGTCTCCAGCCTGGCC
AGGAGATACATCGGTAGGTACGGACTGGCGCATGTTTCCAAGTGGAACTTCGAGACGTGG
AATGAGCCAGACCACCACGACTTTGACAACGTCTCCATGACCATGCAAGGCTTCCTGAAC
TACTACGATGCCTGCTCGGAGGGTCTGCGCGCCGCCAGCCCCGCCCTGCGGCTGGGAGGC
CCCGGCGACTCCTTCCACACCCCACCGCGATCCCCGCTGAGCTGGGGCCTCCTGCGCCAC
TGCCACGACGGTACCAACTTCTTCACTGGGGAGGCGGGCGTGCGGCTGGACTACATCTCC
CTCCACAGGAAGGGTGCGCGCAGCTCCATCTCCATCCTGGAGCAGGAGAAGGTCGTCGCG
CAGCAGATCCGGCAGCTCTTCCCCAAGTTCGCGGACACCCCCATTTACAACGACGAGGCG
GACCCGCTGGTGGGCTGGTCCCTGCCACAGCCGTGGAGGGCGGACGTGACCTACGCGGCC
ATGGTGGTGAAGGTCATCGCGCAGCATCAGAACCTGCTACTGGCCAACACCACCTCCGCC
TTCCCCTACGCGCTCCTGAGCAACGACAATGCCTTCCTGAGCTACCACCCGCACCCCTTC
GCGCAGCGCACGCTCACCGCGCGCTTCCAGGTCAACAACACCCGCCCGCCGCACGTGCAG
CTGTTGCGCAAGCCGGTGCTCACGGCCATGGGGCTGCTGGCGCTGCTGGATGAGGAGCAG
CTCTGGGCCGAAGTGTCGCAGGCCGGGACCGTCCTGGACAGCAACCACACGGTGGGCGTC
CTGGCCAGCGCCCACCGCCCCCAGGGCCCGGCCGACGCCTGGCGCGCCGCGGTGCTGATC
TACGCGAGCGACGACACCCGCGCCCACCCCAACCGCAGCGTCGCGGTGACCCTGCGGCTG
CGCGGGGTGCCCCCCGGCCCGGGCCTGGTCTACGTCACGCGCTACCTGGACAACGGGCTC
TGCAGCCCCGACGGCGAGTGGCGGCGCCTGGGCCGGCCCGTCTTCCCCACGGCAGAGCAG
TTCCGGCGCATGCGCGCGGCTGAGGACCCGGTGGCCGCGGCGCCCCGCCCCTTACCCGCC
GGCGGCCGCCTGACCCTGCGCCCCGCGCTGCGGCTGCCGTCGCTTTTGCTGGTGCACGTG
TGTGCGCGCCCCGAGAAGCCGCCCGGGCAGGTCACGCGGCTCCGCGCCCTGCCCCTGACC
CAAGGGCAGCTGGTTCTGGTCTGGTCGGATGAACACGTGGGCTCCAAGTGCCTGTGGACA
TACGAGATCCAGTTCTCTCAGGACGGTAAGGCGTACACCCCGGTCAGCAGGAAGCCATCG
ACCTTCAACCTCTTTGTGTTCAGCCCAGACACAGGTGCTGTCTCTGGCTCCTACCGAGTT
CGAGCCCTGGACTACTGGGCCCGACCAGGCCCCTTCTCGGACCCTGTGCCGTACCTGGAG
GTCCCTGTGCCAAGAGGGCCCCCATCCCCGGGCAATCCATGA
Chromosome Location
4
Locus
4p16.3
External Identifiers
ResourceLink
UniProtKB IDP35475
UniProtKB Entry NameIDUA_HUMAN
HGNC IDHGNC:5391
General References
  1. Scott HS, Anson DS, Orsborn AM, Nelson PV, Clements PR, Morris CP, Hopwood JJ: Human alpha-L-iduronidase: cDNA isolation and expression. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9695-9. [PubMed:1946389]
  2. Scott HS, Guo XH, Hopwood JJ, Morris CP: Structure and sequence of the human alpha-L-iduronidase gene. Genomics. 1992 Aug;13(4):1311-3. [PubMed:1505961]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621]
  5. Scott HS, Bunge S, Gal A, Clarke LA, Morris CP, Hopwood JJ: Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications. Hum Mutat. 1995;6(4):288-302. doi: 10.1002/humu.1380060403. [PubMed:8680403]
  6. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218]
  7. Bie H, Yin J, He X, Kermode AR, Goddard-Borger ED, Withers SG, James MN: Insights into mucopolysaccharidosis I from the structure and action of alpha-L-iduronidase. Nat Chem Biol. 2013 Nov;9(11):739-45. doi: 10.1038/nchembio.1357. Epub 2013 Sep 11. [PubMed:24036510]
  8. Maita N, Tsukimura T, Taniguchi T, Saito S, Ohno K, Taniguchi H, Sakuraba H: Human alpha-L-iduronidase uses its own N-glycan as a substrate-binding and catalytic module. Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14628-33. doi: 10.1073/pnas.1306939110. Epub 2013 Aug 19. [PubMed:23959878]
  9. Clarke LA, Nelson PV, Warrington CL, Morris CP, Hopwood JJ, Scott HS: Mutation analysis of 19 North American mucopolysaccharidosis type I patients: identification of two additional frequent mutations. Hum Mutat. 1994;3(3):275-82. doi: 10.1002/humu.1380030316. [PubMed:8019563]
  10. Clarke LA, Scott HS: Two novel mutations causing mucopolysaccharidosis type I detected by single strand conformational analysis of the alpha-L-iduronidase gene. Hum Mol Genet. 1993 Aug;2(8):1311-2. [PubMed:8401515]
  11. Scott HS, Litjens T, Nelson PV, Thompson PR, Brooks DA, Hopwood JJ, Morris CP: Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes. Am J Hum Genet. 1993 Nov;53(5):973-86. [PubMed:8213840]
  12. Bach G, Moskowitz SM, Tieu PT, Matynia A, Neufeld EF: Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area. Am J Hum Genet. 1993 Aug;53(2):330-8. [PubMed:8328452]
  13. Scott HS, Litjens T, Nelson PV, Brooks DA, Hopwood JJ, Morris CP: alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype. Hum Mutat. 1992;1(4):333-9. doi: 10.1002/humu.1380010412. [PubMed:1301941]
  14. Bunge S, Kleijer WJ, Steglich C, Beck M, Zuther C, Morris CP, Schwinger E, Hopwood JJ, Scott HS, Gal A: Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients. Hum Mol Genet. 1994 Jun;3(6):861-6. [PubMed:7951228]
  15. Scott HS, Litjens T, Hopwood JJ, Morris CP: PCR detection of two RFLPs in exon I of the alpha-L-iduronidase (IDUA) gene. Hum Genet. 1992 Nov;90(3):327. [PubMed:1362562]
  16. Scott HS, Nelson PV, Litjens T, Hopwood JJ, Morris CP: Multiple polymorphisms within the alpha-L-iduronidase gene (IDUA): implications for a role in modification of MPS-I disease phenotype. Hum Mol Genet. 1993 Sep;2(9):1471-3. [PubMed:8242073]
  17. Tieu PT, Bach G, Matynia A, Hwang M, Neufeld EF: Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S). Hum Mutat. 1995;6(1):55-9. doi: 10.1002/humu.1380060111. [PubMed:7550232]
  18. Bunge S, Kleijer WJ, Steglich C, Beck M, Schwinger E, Gal A: Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene. Hum Mutat. 1995;6(1):91-4. doi: 10.1002/humu.1380060119. [PubMed:7550242]
  19. Aronovich EL, Pan D, Whitley CB: Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency. Am J Hum Genet. 1996 Jan;58(1):75-85. [PubMed:8554071]
  20. Lee-Chen GJ, Lin SP, Tang YF, Chin YW: Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity. Clin Genet. 1999 Jul;56(1):66-70. [PubMed:10466419]
  21. Teng YN, Wang TR, Hwu WL, Lin SP, Lee-Chen GJ: Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S. Clin Genet. 2000 Feb;57(2):131-6. [PubMed:10735634]
  22. Matte U, Yogalingam G, Brooks D, Leistner S, Schwartz I, Lima L, Norato DY, Brum JM, Beesley C, Winchester B, Giugliani R, Hopwood JJ: Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients. Mol Genet Metab. 2003 Jan;78(1):37-43. [PubMed:12559846]
  23. Yogalingam G, Guo XH, Muller VJ, Brooks DA, Clements PR, Kakkis ED, Hopwood JJ: Identification and molecular characterization of alpha-L-iduronidase mutations present in mucopolysaccharidosis type I patients undergoing enzyme replacement therapy. Hum Mutat. 2004 Sep;24(3):199-207. doi: 10.1002/humu.20081. [PubMed:15300847]
  24. Vazna A, Beesley C, Berna L, Stolnaja L, Myskova H, Bouckova M, Vlaskova H, Poupetova H, Zeman J, Magner M, Hlavata A, Winchester B, Hrebicek M, Dvorakova L: Mucopolysaccharidosis type I in 21 Czech and Slovak patients: mutation analysis suggests a functional importance of C-terminus of the IDUA protein. Am J Med Genet A. 2009 May;149A(5):965-74. doi: 10.1002/ajmg.a.32812. [PubMed:19396826]
  25. Bertola F, Filocamo M, Casati G, Mort M, Rosano C, Tylki-Szymanska A, Tuysuz B, Gabrielli O, Grossi S, Scarpa M, Parenti G, Antuzzi D, Dalmau J, Di Rocco M, Dionisi Vici C, Okur I, Rosell J, Rovelli A, Furlan F, Rigoldi M, Biondi A, Cooper DN, Parini R: IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel alpha-L-iduronidase (IDUA) alleles. Hum Mutat. 2011 Jun;32(6):E2189-210. doi: 10.1002/humu.21479. Epub 2011 Mar 10. [PubMed:21394825]
  26. Pasqualim G, Ribeiro MG, da Fonseca GG, Szlago M, Schenone A, Lemes A, Rojas MV, Matte U, Giugliani R: p.L18P: a novel IDUA mutation that causes a distinct attenuated phenotype in mucopolysaccharidosis type I patients. Clin Genet. 2015 Oct;88(4):376-80. doi: 10.1111/cge.12507. Epub 2014 Oct 21. [PubMed:25256405]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB09301Chondroitin sulfateapproved, investigational, nutraceuticalnosubstrateDetails