ID IDUA_HUMAN STANDARD; PRT; 653 AA. AC P35475; DT 01-JUN-1994 (Rel. 29, Created) DT 01-JUN-1994 (Rel. 29, Last sequence update) DT 20-AUG-2001 (Rel. 40, Last annotation update) DE ALPHA-L-IDURONIDASE PRECURSOR (EC 3.2.1.76). GN IDUA. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Liver; RX MEDLINE=92052158; PubMed=1946389; RA Scott H.S., Anson D.S., Orsborn A.M., Nelson P.V., Clements P.R., RA Morris C.P., Hopwood J.J.; RT "Human alpha-L-iduronidase: cDNA isolation and expression."; RL Proc. Natl. Acad. Sci. U.S.A. 88:9695-9699(1991). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=92372031; PubMed=1505961; RA Scott H.S., Guo X.H., Hopwood J.J., Morris C.P.; RT "Structure and sequence of the human alpha-L-iduronidase gene."; RL Genomics 13:1311-1313(1992). RN [3] RP REVIEW ON VARIANTS. RX MEDLINE=96287378; PubMed=8680403; RA Scott H.S., Bunge S., Gal A., Clarke L.A., Morris C.P., Hopwood J.J.; RT "Molecular genetics of mucopolysaccharidosis type I: diagnostic, RT clinical, and biological implications."; RL Hum. Mutat. 6:288-302(1995). RN [4] RP VARIANT MPS-I THR-75. RX MEDLINE=94290500; PubMed=8019563; RA Clarke L.A., Nelson P.V., Warrington C.L., Morris C.P., Hopwood J.J., RA Scott H.S.; RT "Mutation analysis of 19 North American mucopolysaccharidosis type I RT patients: identification of two additional frequent mutations."; RL Hum. Mutat. 3:275-282(1994). RN [5] RP VARIANT MPS-I PRO-82. RX MEDLINE=94004880; PubMed=8401515; RA Clark L.A., Scott H.S.; RT "Two novel mutations causing mucopolysaccharidosis type I detected by RT single strand conformational analysis of the alpha-L-iduronidase RT gene."; RL Hum. Mol. Genet. 2:1311-1312(1993). RN [6] RP VARIANT MPS-I GLN-89. RX MEDLINE=94027086; PubMed=8213840; RA Scott H.S., Litjens T., Nelson P.V., Thompson P.R., Brooks D.A., RA Hopwood J.J., Morris C.P.; RT "Identification of mutations in the alpha-L-iduronidase gene (IDUA) RT that cause Hurler and Scheie syndromes."; RL Am. J. Hum. Genet. 53:973-986(1993). RN [7] RP VARIANTS MPS-I PRO-366 AND ARG-409. RX MEDLINE=93318833; PubMed=8328452; RA Bach G., Moskowitz S.M., Tieu P.T., Matynia A., Neufeld E.F.; RT "Molecular analysis of Hurler syndrome in Druze and Muslim Arab RT patients in Israel: multiple allelic mutations of the IDUA gene in a RT small geographic area."; RL Am. J. Hum. Genet. 53:330-338(1993). RN [8] RP VARIANT MPS-I ARG-533. RX MEDLINE=93250829; PubMed=1301941; RA Scott H.S., Litjens T., Nelson P.V., Brooks D.A., Hopwood J.J., RA Morris C.P.; RT "Alpha-L-iduronidase mutations (Q70X and P533R) associate with a RT severe Hurler phenotype."; RL Hum. Mutat. 1:333-339(1992). RN [9] RP VARIANTS MPS-I D-51; T-75; P-218; P-327; P-489 AND S-16--A-19 DEL. RX MEDLINE=95038736; PubMed=7951228; RA Bunge S., Kleijer W.J., Steglich C., Beck M., Zuther C., Morris C.P., RA Schwinger E., Hopwood J.J., Scott H.S., Gal A.; RT "Mucopolysaccharidosis type I: identification of 8 novel mutations RT and determination of the frequency of the two common RT alpha-L-iduronidase mutations (W402X and Q70X) among European RT patients."; RL Hum. Mol. Genet. 3:861-866(1994). RN [10] RP VARIANT HIS-33. RX MEDLINE=93138632; PubMed=1362562; RA Scott H.S., Litjens T., Hopwood J.J., Morris C.P.; RT "PCR detection of two RFLPs in exon I of the alpha-L-iduronidase RT (IDUA) gene."; RL Hum. Genet. 90:327-327(1992). RN [11] RP VARIANT THR-361. RX MEDLINE=94061048; PubMed=8242073; RA Scott H.S., Nelson P.V., Litjens T., Hopwood J.J., Morris C.P.; RT "Multiple polymorphisms within the alpha-L-iduronidase gene (IDUA): RT implications for a role in modification of MPS-I disease phenotype."; RL Hum. Mol. Genet. 2:1471-1473(1993). RN [12] RP VARIANTS MPS-I PRO-490; PRO-492; LEU-496. RX MEDLINE=96055518; PubMed=7550232; RA Tieu P.T., Bach G., Matynia A., Hwang M., Neufeld E.F.; RT "Four novel mutations underlying mild or intermediate forms of RT alpha-L-iduronidase deficiency (MPS IS and MPS IH/S)."; RL Hum. Mutat. 6:55-59(1995). RN [13] RP VARIANTS MPS-I W-89; D-349--N-350 DEL; H-383; T-504 AND R-626. RX MEDLINE=96055526; PubMed=7550242; RA Bunge S., Kleijer W.J., Steglich C., Beck M., Schwinger E., Gal A.; RT "Mucopolysaccharidosis type I: identification of 13 novel mutations RT of the alpha-L-iduronidase gene."; RL Hum. Mutat. 6:91-94(1995). RN [14] RP VARIANT MPS-I ARG-388. RA Bartholomew D.W., McClellan J.M.; RT "A novel missense mutation in the human IDUA gene associated with a RT severe Hurler's phenotype."; RL Hum. Mutat. 12:291-291(1998). CC -!- CATALYTIC ACTIVITY: HYDROLYSIS OF ALPHA-L-IDURONOSIDIC LINKAGES IN CC DESULFATED DERMATAN. CC -!- SUBUNIT: MONOMER (PROBABLE). CC -!- SUBCELLULAR LOCATION: LYSOSOMAL. CC -!- TISSUE SPECIFICITY: FOUND UBIQUITOUSLY. CC -!- DISEASE: DEFECTS IN IDUA ARE THE CAUSE OF MUCOPOLYSACCHARIDOSIS CC TYPE I (MPS-I), A DISEASE CHARACTERIZED BY THE ACCUMULATION OF THE CC GLYCOSAMINOGLYCANS HEPARAN SULFATE AND DERMATAN SULFATE. PATIENTS CC WITH SEVERE MPS-I (HURLER SYNDROME) USUALLY PRESENT WITHIN THE CC FIRST YEAR OF LIFE A COMBINATION OF HEPATOSPLENOMEGALY, SKELETAL CC DEFORMITIES, CORNEAL CLOUDING AND SEVERE MENTAL RETARDATION. CC OBSTRUCTIVE AIRWAYS DISEASE, RESPIRATORY INFECTION AND CARDIAC CC COMPLICATIONS USUALLY RESULTS IN DEATH BEFORE 10 YEARS OF AGE. CC PATIENTS WITH MILD MPS-I (SCHEIE SYNDROME) MAY HAVE LITTLE OR NO CC NEUROLOGICAL INVOLVEMENT, NORMAL STATURE AND LIFE SPAN, BUT ARE CC CHARACTERIZED BY THE DEVELOPMENT OF JOINTS STIFFNESS, MILD CC HEPATOSPLENOMEGALY, AORTIC VALVE DISEASE AND CORNEAL CLOUDING. THE CC INTERMEDIATE FORM (HURLER/SCHEIE) MAY BE CHARACTERIZED BY CC RELATIVELY LITTLE NEUROLOGICAL INVOLVEMENT, BUT MOST OF THE CC SOMATIC SYMPTOMS DESCRIBED FOR SEVERE MPS-I DEVELOP IN THE EARLY CC TO MID-TEENS, CAUSING CONSIDERABLE LOSS OF MOBILITY. CC -!- SIMILARITY: BELONGS TO FAMILY 39 OF GLYCOSYL HYDROLASES. 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; M74715; AAA81589.1; -. DR EMBL; M95740; AAA51698.1; -. DR EMBL; M95739; AAA51698.1; JOINED. DR MIM; 252800; -. DR InterPro; IPR000514; Glyco_hydro_39. DR Pfam; PF01229; Glyco_hydro_39; 1. DR PRINTS; PR00745; GLHYDRLASE39. DR PROSITE; PS01027; GLYCOSYL_HYDROL_F39; 1. KW Hydrolase; Glycosidase; Lysosome; Signal; Disease mutation; KW Polymorphism; Mucopolysaccharidosis. FT SIGNAL 1 27 POTENTIAL. FT CHAIN 28 653 ALPHA-L-IDURONIDASE. FT ACT_SITE 182 182 PROTON DONOR (POTENTIAL). FT ACT_SITE 299 299 NUCLEOPHILE (POTENTIAL). FT CARBOHYD 110 110 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 190 190 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 336 336 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 372 372 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 415 415 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 451 451 N-LINKED (GLCNAC...) (POTENTIAL). FT VARIANT 16 19 MISSING (IN MPS-I; HURLER). FT /FTId=VAR_003349. FT VARIANT 33 33 Q -> H. FT /FTId=VAR_003350. FT VARIANT 51 51 G -> D (IN MPS-I; HURLER). FT /FTId=VAR_003351. FT VARIANT 75 75 A -> T (IN MPS-I; HURLER). FT /FTId=VAR_003352. FT VARIANT 82 82 H -> P (IN MPS-I; HURLER/SCHEIE). FT /FTId=VAR_003353. FT VARIANT 89 89 R -> Q (IN MPS-I; SCHEIE; IN JAPANESE FT 21% OF ALLELES). FT /FTId=VAR_003354. FT VARIANT 89 89 R -> W (IN MPS-I; SCHEIE). FT /FTId=VAR_003355. FT VARIANT 105 105 R -> Q. FT /FTId=VAR_003356. FT VARIANT 116 116 G -> R. FT /FTId=VAR_003357. FT VARIANT 218 218 L -> P (IN MPS-I; HURLER). FT /FTId=VAR_003358. FT VARIANT 279 279 V -> A. FT /FTId=VAR_003359. FT VARIANT 315 315 D -> Y (IN MPS-I). FT /FTId=VAR_003360. FT VARIANT 327 327 A -> P (IN MPS-I; HURLER). FT /FTId=VAR_003361. FT VARIANT 349 349 D -> N (IN MPS-I; HURLER). FT /FTId=VAR_003362. FT VARIANT 349 350 MISSING (IN MPS-I; HURLER). FT /FTId=VAR_003363. FT VARIANT 361 361 A -> T. FT /FTId=VAR_003364. FT VARIANT 366 366 T -> P (IN MPS-I; HURLER). FT /FTId=VAR_003365. FT VARIANT 380 380 Q -> R (IN MPS-I; HURLER/SCHEIE). FT /FTId=VAR_003366. FT VARIANT 383 383 R -> H (IN MPS-I; SCHEIE; 2-3% OF FT ACTIVITY). FT /FTId=VAR_003367. FT VARIANT 388 388 T -> R (IN MPS-I; HURLER). FT /FTId=VAR_003368. FT VARIANT 396 396 L -> LALL (IN MPS-I; HURLER). FT /FTId=VAR_003369. FT VARIANT 409 409 G -> R (IN MPS-I; HURLER). FT /FTId=VAR_003370. FT VARIANT 445 445 MISSING (IN MPS-I; SCHEIE). FT /FTId=VAR_003371. FT VARIANT 454 454 V -> I. FT /FTId=VAR_003372. FT VARIANT 489 489 R -> P (IN MPS-I; HURLER). FT /FTId=VAR_003373. FT VARIANT 490 490 L -> P (IN MPS-I; HURLER/SCHEIE). FT /FTId=VAR_003374. FT VARIANT 492 492 R -> P (IN MPS-I; SCHEIE). FT /FTId=VAR_003375. FT VARIANT 496 496 P -> L (IN MPS-I; HURLER/SCHEIE). FT /FTId=VAR_003376. FT VARIANT 504 504 M -> T (IN MPS-I; HURLER/SCHEIE). FT /FTId=VAR_003377. FT VARIANT 533 533 P -> R (IN MPS-I; HURLER; IN 3% OF THE FT MPS-I PATIENTS). FT /FTId=VAR_003378. FT VARIANT 626 626 W -> R (IN MPS-I; HURLER/SCHEIE). FT /FTId=VAR_003379. FT CONFLICT 622 622 A -> T (IN REF. 2). SQ SEQUENCE 653 AA; 72660 MW; 4BF8F3003E095212 CRC64; MRPLRPRAAL LALLASLLAA PPVAPAEAPH LVQVDAARAL WPLRRFWRST GFCPPLPHSQ ADQYVLSWDQ QLNLAYVGAV PHRGIKQVRT HWLLELVTTR GSTGRGLSYN FTHLDGYLDL LRENQLLPGF ELMGSASGHF TDFEDKQQVF EWKDLVSSLA RRYIGRYGLA HVSKWNFETW NEPDHHDFDN VSMTMQGFLN YYDACSEGLR AASPALRLGG PGDSFHTPPR SPLSWGLLRH CHDGTNFFTG EAGVRLDYIS LHRKGARSSI SILEQEKVVA QQIRQLFPKF ADTPIYNDEA DPLVGWSLPQ PWRADVTYAA MVVKVIAQHQ NLLLANTTSA FPYALLSNDN AFLSYHPHPF AQRTLTARFQ VNNTRPPHVQ LLRKPVLTAM GLLALLDEEQ LWAEVSQAGT VLDSNHTVGV LASAHRPQGP ADAWRAAVLI YASDDTRAHP NRSVAVTLRL RGVPPGPGLV YVTRYLDNGL CSPDGEWRRL GRPVFPTAEQ FRRMRAAEDP VAAAPRPLPA GGRLTLRPAL RLPSLLLVHV CARPEKPPGQ VTRLRALPLT QGQLVLVWSD EHVGSKCLWT YEIQFSQDGK AYTPVSRKPS TFNLFVFSPD TGAVSGSYRV RALDYWARPG PFSDPVPYLE VPVPRGPPSP GNP //