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P35475

- IDUA_HUMAN

UniProt

P35475 - IDUA_HUMAN

Protein

Alpha-L-iduronidase

Gene

IDUA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 2 (04 Apr 2006)
      Previous versions | rss
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    Functioni

    Catalytic activityi

    Hydrolysis of unsulfated alpha-L-iduronosidic linkages in dermatan sulfate.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei91 – 911Substrate
    Binding sitei181 – 1811Substrate
    Active sitei182 – 1821Proton donor1 PublicationPROSITE-ProRule annotation
    Binding sitei264 – 2641Substrate
    Active sitei299 – 2991Nucleophile1 Publication
    Binding sitei349 – 3491Substrate
    Binding sitei363 – 3631Substrate

    GO - Molecular functioni

    1. L-iduronidase activity Source: UniProtKB

    GO - Biological processi

    1. carbohydrate metabolic process Source: Reactome
    2. cell morphogenesis Source: Ensembl
    3. chemical homeostasis Source: Ensembl
    4. chondroitin sulfate catabolic process Source: Reactome
    5. chondroitin sulfate metabolic process Source: Reactome
    6. dermatan sulfate catabolic process Source: UniProtKB
    7. disaccharide metabolic process Source: ProtInc
    8. glycosaminoglycan catabolic process Source: Reactome
    9. glycosaminoglycan metabolic process Source: Reactome
    10. limb morphogenesis Source: Ensembl
    11. lysosome organization Source: Ensembl
    12. skeletal system morphogenesis Source: Ensembl
    13. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Glycosidase, Hydrolase

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05096-MONOMER.
    BRENDAi3.2.1.76. 2681.
    ReactomeiREACT_120752. HS-GAG degradation.
    REACT_120888. CS/DS degradation.
    SABIO-RKP35475.

    Protein family/group databases

    CAZyiGH39. Glycoside Hydrolase Family 39.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Alpha-L-iduronidase (EC:3.2.1.76)
    Gene namesi
    Name:IDUA
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:5391. IDUA.

    Subcellular locationi

    GO - Cellular componenti

    1. coated vesicle Source: Ensembl
    2. extracellular vesicular exosome Source: UniProt
    3. lysosomal lumen Source: Reactome

    Keywords - Cellular componenti

    Lysosome

    Pathology & Biotechi

    Involvement in diseasei

    Mucopolysaccharidosis 1H (MPS1H) [MIM:607014]: A severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe mental retardation. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age.13 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti16 – 194Missing in MPS1H.
    VAR_003349
    Natural varianti51 – 511G → D in MPS1H. 2 Publications
    VAR_003351
    Natural varianti75 – 751A → T in MPS1H. 2 Publications
    VAR_003352
    Natural varianti79 – 791A → V in MPS1H/S; reduction of activity and protein levels. 1 Publication
    VAR_020975
    Natural varianti82 – 821H → P in MPS1H/S. 1 Publication
    VAR_003353
    Natural varianti84 – 841G → R in MPS1H/S. 1 Publication
    VAR_066216
    Natural varianti103 – 1031T → P in MPS1H; uncertain pathological role. 1 Publication
    VAR_066217
    Natural varianti133 – 1331M → I in MPS1H. 1 Publication
    VAR_020977
    Natural varianti178 – 1781E → K in MPS1H/S. 1 Publication
    VAR_066218
    Natural varianti182 – 1821E → K in MPS1H. 1 Publication
    VAR_020978
    Natural varianti188 – 1881F → L in MPS1H/S; associated with R-423. 1 Publication
    VAR_066219
    Natural varianti208 – 2081G → D in MPS1H. 1 Publication
    VAR_020979
    Natural varianti218 – 2181L → P in MPS1H. 1 Publication
    VAR_003358
    Natural varianti238 – 2381L → Q in MPS1H/S. 1 Publication
    VAR_020980
    Natural varianti260 – 2601S → F in MPS1H/S. 1 Publication
    VAR_020981
    Natural varianti265 – 2651G → R in MPS1H/S. 1 Publication
    VAR_066221
    Natural varianti276 – 2761E → K in MPS1H/S and MPS1S. 1 Publication
    VAR_066222
    Natural varianti327 – 3271A → P in MPS1H and MPS1H/S. 4 Publications
    VAR_003361
    Natural varianti346 – 3461L → R in MPS1H/S; 0.4% of normal activity. 1 Publication
    VAR_017436
    Natural varianti349 – 3502Missing in MPS1H. 1 Publication
    VAR_003363
    Natural varianti349 – 3491D → N in MPS1H.
    VAR_003362
    Natural varianti349 – 3491D → Y in MPS1H. 1 Publication
    VAR_020982
    Natural varianti363 – 3631R → C in MPS1H/S; loss of activity. 1 Publication
    VAR_020984
    Natural varianti366 – 3661T → P in MPS1H. 1 Publication
    VAR_003365
    Natural varianti380 – 3801Q → R in MPS1H/S. 2 Publications
    VAR_003366
    Natural varianti385 – 3851P → R in MPS1H. 1 Publication
    VAR_066225
    Natural varianti388 – 3881T → R in MPS1H. 1 Publication
    VAR_003368
    Natural varianti396 – 3961L → LALL in MPS1H.
    VAR_003369
    Natural varianti409 – 4091G → R in MPS1H. 1 Publication
    Corresponds to variant rs11934801 [ dbSNP | Ensembl ].
    VAR_003370
    Natural varianti423 – 4231S → R in MPS1S and MPS1H/S; associated with L-188 in a patient with MPS1H/S; significant reduction of activity and protein levels. 2 Publications
    VAR_020985
    Natural varianti436 – 4361A → P in MPS1H/S. 1 Publication
    VAR_066227
    Natural varianti489 – 4891R → P in MPS1H. 1 Publication
    Corresponds to variant rs4690226 [ dbSNP | Ensembl ].
    VAR_003373
    Natural varianti490 – 4901L → P in MPS1H/S and MPS1S. 2 Publications
    VAR_003374
    Natural varianti496 – 4961P → L in MPS1H/S. 1 Publication
    VAR_003376
    Natural varianti496 – 4961P → R in MPS1H/S. 1 Publication
    VAR_066229
    Natural varianti504 – 5041M → T in MPS1H/S. 1 Publication
    VAR_003377
    Natural varianti533 – 5331P → R in MPS1H and MPS1H/S; in 3% of the MPS1H patients; reduces catalytic activity and protein stability. 4 Publications
    VAR_003378
    Natural varianti535 – 5351L → F in MPS1H/S. 1 Publication
    VAR_066230
    Natural varianti602 – 6021F → I in MPS1H/S; reduction of activity and protein levels. 1 Publication
    VAR_020986
    Natural varianti619 – 6191R → G in MPS1H/S; 1.5% of normal activity. 1 Publication
    VAR_017437
    Natural varianti626 – 6261W → R in MPS1H/S. 1 Publication
    VAR_003379
    Natural varianti628 – 6281R → P in MPS1H/S. 1 Publication
    VAR_020987
    Mucopolysaccharidosis 1H/S (MPS1H/S) [MIM:607015]: A form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti79 – 791A → V in MPS1H/S; reduction of activity and protein levels. 1 Publication
    VAR_020975
    Natural varianti82 – 821H → P in MPS1H/S. 1 Publication
    VAR_003353
    Natural varianti84 – 841G → R in MPS1H/S. 1 Publication
    VAR_066216
    Natural varianti178 – 1781E → K in MPS1H/S. 1 Publication
    VAR_066218
    Natural varianti188 – 1881F → L in MPS1H/S; associated with R-423. 1 Publication
    VAR_066219
    Natural varianti238 – 2381L → Q in MPS1H/S. 1 Publication
    VAR_020980
    Natural varianti260 – 2601S → F in MPS1H/S. 1 Publication
    VAR_020981
    Natural varianti265 – 2651G → R in MPS1H/S. 1 Publication
    VAR_066221
    Natural varianti276 – 2761E → K in MPS1H/S and MPS1S. 1 Publication
    VAR_066222
    Natural varianti327 – 3271A → P in MPS1H and MPS1H/S. 4 Publications
    VAR_003361
    Natural varianti346 – 3461L → R in MPS1H/S; 0.4% of normal activity. 1 Publication
    VAR_017436
    Natural varianti363 – 3631R → C in MPS1H/S; loss of activity. 1 Publication
    VAR_020984
    Natural varianti380 – 3801Q → R in MPS1H/S. 2 Publications
    VAR_003366
    Natural varianti423 – 4231S → R in MPS1S and MPS1H/S; associated with L-188 in a patient with MPS1H/S; significant reduction of activity and protein levels. 2 Publications
    VAR_020985
    Natural varianti436 – 4361A → P in MPS1H/S. 1 Publication
    VAR_066227
    Natural varianti490 – 4901L → P in MPS1H/S and MPS1S. 2 Publications
    VAR_003374
    Natural varianti496 – 4961P → L in MPS1H/S. 1 Publication
    VAR_003376
    Natural varianti496 – 4961P → R in MPS1H/S. 1 Publication
    VAR_066229
    Natural varianti504 – 5041M → T in MPS1H/S. 1 Publication
    VAR_003377
    Natural varianti533 – 5331P → R in MPS1H and MPS1H/S; in 3% of the MPS1H patients; reduces catalytic activity and protein stability. 4 Publications
    VAR_003378
    Natural varianti535 – 5351L → F in MPS1H/S. 1 Publication
    VAR_066230
    Natural varianti602 – 6021F → I in MPS1H/S; reduction of activity and protein levels. 1 Publication
    VAR_020986
    Natural varianti619 – 6191R → G in MPS1H/S; 1.5% of normal activity. 1 Publication
    VAR_017437
    Natural varianti626 – 6261W → R in MPS1H/S. 1 Publication
    VAR_003379
    Natural varianti628 – 6281R → P in MPS1H/S. 1 Publication
    VAR_020987
    Mucopolysaccharidosis 1S (MPS1S) [MIM:607016]: A mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding.6 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti76 – 761Y → C in MPS1S. 1 Publication
    VAR_066215
    Natural varianti89 – 891R → Q in MPS1S; in Japanese 21% of alleles. 2 Publications
    VAR_003354
    Natural varianti89 – 891R → W in MPS1S. 2 Publications
    VAR_003355
    Natural varianti219 – 2191G → E in MPS1S. 1 Publication
    VAR_066220
    Natural varianti276 – 2761E → K in MPS1H/S and MPS1S. 1 Publication
    VAR_066222
    Natural varianti306 – 3061W → L in MPS1S. 1 Publication
    VAR_066223
    Natural varianti348 – 3481N → K in MPS1S. 1 Publication
    VAR_066224
    Natural varianti350 – 3501N → I in MPS1S. 1 Publication
    VAR_020983
    Natural varianti383 – 3831R → H in MPS1S; 2-3% of normal activity. 2 Publications
    VAR_003367
    Natural varianti423 – 4231S → R in MPS1S and MPS1H/S; associated with L-188 in a patient with MPS1H/S; significant reduction of activity and protein levels. 2 Publications
    VAR_020985
    Natural varianti445 – 4451Missing in MPS1S. 1 Publication
    VAR_003371
    Natural varianti490 – 4901L → P in MPS1H/S and MPS1S. 2 Publications
    VAR_003374
    Natural varianti492 – 4921R → P in MPS1S. 2 Publications
    VAR_003375

    Keywords - Diseasei

    Disease mutation, Mucopolysaccharidosis

    Organism-specific databases

    MIMi607014. phenotype.
    607015. phenotype.
    607016. phenotype.
    Orphaneti93473. Hurler syndrome.
    93476. Hurler-Scheie syndrome.
    93474. Scheie syndrome.
    PharmGKBiPA29638.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2727Sequence AnalysisAdd
    BLAST
    Chaini28 – 653626Alpha-L-iduronidasePRO_0000012200Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi110 – 1101N-linked (GlcNAc...)3 Publications
    Glycosylationi190 – 1901N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi336 – 3361N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi372 – 3721N-linked (GlcNAc...)2 Publications
    Glycosylationi415 – 4151N-linked (GlcNAc...)2 Publications
    Glycosylationi451 – 4511N-linked (GlcNAc...)1 Publication
    Disulfide bondi541 ↔ 5772 Publications

    Post-translational modificationi

    N-glycosylation at Asn-372 contributes to substrate binding and is required for full enzymatic activity.3 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiP35475.
    PaxDbiP35475.
    PRIDEiP35475.

    Expressioni

    Tissue specificityi

    Ubiquitous.

    Gene expression databases

    ArrayExpressiP35475.
    BgeeiP35475.
    CleanExiHS_IDUA.
    GenevestigatoriP35475.

    Organism-specific databases

    HPAiCAB025901.

    Interactioni

    Subunit structurei

    Monomer.2 Publications

    Protein-protein interaction databases

    IntActiP35475. 1 interaction.
    MINTiMINT-1397491.
    STRINGi9606.ENSP00000247933.

    Structurei

    Secondary structure

    1
    653
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi30 – 4213
    Beta strandi49 – 524
    Helixi58 – 603
    Helixi64 – 663
    Helixi68 – 7811
    Helixi81 – 833
    Beta strandi87 – 904
    Helixi93 – 953
    Beta strandi98 – 1003
    Turni103 – 1053
    Beta strandi108 – 1103
    Helixi112 – 12312
    Beta strandi127 – 1315
    Turni136 – 1394
    Beta strandi142 – 1443
    Helixi146 – 16722
    Helixi169 – 1724
    Beta strandi176 – 1783
    Helixi183 – 1853
    Helixi195 – 21218
    Beta strandi217 – 2237
    Helixi232 – 24312
    Turni247 – 2493
    Beta strandi257 – 2615
    Helixi269 – 28618
    Helixi288 – 2903
    Beta strandi295 – 2984
    Beta strandi302 – 3043
    Beta strandi306 – 3083
    Helixi311 – 3144
    Helixi316 – 33217
    Beta strandi334 – 3363
    Beta strandi343 – 3464
    Turni359 – 3613
    Beta strandi362 – 37110
    Beta strandi374 – 3763
    Beta strandi378 – 3836
    Helixi385 – 3939
    Beta strandi398 – 40710
    Beta strandi410 – 4123
    Beta strandi414 – 42512
    Beta strandi429 – 4313
    Beta strandi435 – 4428
    Beta strandi449 – 46113
    Beta strandi470 – 4778
    Turni478 – 4803
    Helixi483 – 4897
    Helixi498 – 5058
    Beta strandi511 – 5177
    Turni520 – 5223
    Beta strandi524 – 5263
    Beta strandi529 – 54113
    Beta strandi552 – 5609
    Beta strandi563 – 5697
    Turni571 – 5733
    Beta strandi578 – 5869
    Beta strandi602 – 6076
    Beta strandi616 – 6249
    Beta strandi636 – 6383

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1Y24model-A36-522[»]
    3W81X-ray2.30A/B27-653[»]
    3W82X-ray2.76A/B27-653[»]
    4KGJX-ray2.99A/B27-653[»]
    4KGLX-ray2.70A/B27-653[»]
    4KH2X-ray2.36A/B27-653[»]
    4MJ2X-ray2.10A/B1-653[»]
    4MJ4X-ray2.17A1-653[»]
    ProteinModelPortaliP35475.
    SMRiP35475. Positions 27-642.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni305 – 3062Substrate binding

    Sequence similaritiesi

    Belongs to the glycosyl hydrolase 39 family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiCOG3664.
    HOGENOMiHOG000007042.
    HOVERGENiHBG006121.
    InParanoidiP35475.
    KOiK01217.
    OrthoDBiEOG70088F.
    PhylomeDBiP35475.
    TreeFamiTF323228.

    Family and domain databases

    Gene3Di3.20.20.80. 1 hit.
    InterProiIPR000514. Glyco_hydro_39.
    IPR013781. Glyco_hydro_catalytic_dom.
    IPR017853. Glycoside_hydrolase_SF.
    [Graphical view]
    PfamiPF01229. Glyco_hydro_39. 1 hit.
    [Graphical view]
    PRINTSiPR00745. GLHYDRLASE39.
    SUPFAMiSSF51445. SSF51445. 1 hit.
    PROSITEiPS01027. GLYCOSYL_HYDROL_F39. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P35475-1 [UniParc]FASTAAdd to Basket

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    MRPLRPRAAL LALLASLLAA PPVAPAEAPH LVHVDAARAL WPLRRFWRST    50
    GFCPPLPHSQ ADQYVLSWDQ QLNLAYVGAV PHRGIKQVRT HWLLELVTTR 100
    GSTGRGLSYN FTHLDGYLDL LRENQLLPGF ELMGSASGHF TDFEDKQQVF 150
    EWKDLVSSLA RRYIGRYGLA HVSKWNFETW NEPDHHDFDN VSMTMQGFLN 200
    YYDACSEGLR AASPALRLGG PGDSFHTPPR SPLSWGLLRH CHDGTNFFTG 250
    EAGVRLDYIS LHRKGARSSI SILEQEKVVA QQIRQLFPKF ADTPIYNDEA 300
    DPLVGWSLPQ PWRADVTYAA MVVKVIAQHQ NLLLANTTSA FPYALLSNDN 350
    AFLSYHPHPF AQRTLTARFQ VNNTRPPHVQ LLRKPVLTAM GLLALLDEEQ 400
    LWAEVSQAGT VLDSNHTVGV LASAHRPQGP ADAWRAAVLI YASDDTRAHP 450
    NRSVAVTLRL RGVPPGPGLV YVTRYLDNGL CSPDGEWRRL GRPVFPTAEQ 500
    FRRMRAAEDP VAAAPRPLPA GGRLTLRPAL RLPSLLLVHV CARPEKPPGQ 550
    VTRLRALPLT QGQLVLVWSD EHVGSKCLWT YEIQFSQDGK AYTPVSRKPS 600
    TFNLFVFSPD TGAVSGSYRV RALDYWARPG PFSDPVPYLE VPVPRGPPSP 650
    GNP 653
    Length:653
    Mass (Da):72,670
    Last modified:April 4, 2006 - v2
    Checksum:i9D2399B22FD172BD
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti622 – 6221A → T in AAA51698. (PubMed:1505961)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti16 – 194Missing in MPS1H.
    VAR_003349
    Natural varianti33 – 331H → Q.4 Publications
    Corresponds to variant rs10794537 [ dbSNP | Ensembl ].
    VAR_003350
    Natural varianti51 – 511G → D in MPS1H. 2 Publications
    VAR_003351
    Natural varianti75 – 751A → T in MPS1H. 2 Publications
    VAR_003352
    Natural varianti76 – 761Y → C in MPS1S. 1 Publication
    VAR_066215
    Natural varianti79 – 791A → V in MPS1H/S; reduction of activity and protein levels. 1 Publication
    VAR_020975
    Natural varianti82 – 821H → P in MPS1H/S. 1 Publication
    VAR_003353
    Natural varianti82 – 821H → Q Reduction of protein levels. 1 Publication
    Corresponds to variant rs148775298 [ dbSNP | Ensembl ].
    VAR_020976
    Natural varianti84 – 841G → R in MPS1H/S. 1 Publication
    VAR_066216
    Natural varianti89 – 891R → Q in MPS1S; in Japanese 21% of alleles. 2 Publications
    VAR_003354
    Natural varianti89 – 891R → W in MPS1S. 2 Publications
    VAR_003355
    Natural varianti103 – 1031T → P in MPS1H; uncertain pathological role. 1 Publication
    VAR_066217
    Natural varianti105 – 1051R → Q.2 Publications
    Corresponds to variant rs3755955 [ dbSNP | Ensembl ].
    VAR_003356
    Natural varianti116 – 1161G → R.
    Corresponds to variant rs148946496 [ dbSNP | Ensembl ].
    VAR_003357
    Natural varianti133 – 1331M → I in MPS1H. 1 Publication
    VAR_020977
    Natural varianti178 – 1781E → K in MPS1H/S. 1 Publication
    VAR_066218
    Natural varianti182 – 1821E → K in MPS1H. 1 Publication
    VAR_020978
    Natural varianti188 – 1881F → L in MPS1H/S; associated with R-423. 1 Publication
    VAR_066219
    Natural varianti208 – 2081G → D in MPS1H. 1 Publication
    VAR_020979
    Natural varianti218 – 2181L → P in MPS1H. 1 Publication
    VAR_003358
    Natural varianti219 – 2191G → E in MPS1S. 1 Publication
    VAR_066220
    Natural varianti238 – 2381L → Q in MPS1H/S. 1 Publication
    VAR_020980
    Natural varianti260 – 2601S → F in MPS1H/S. 1 Publication
    VAR_020981
    Natural varianti265 – 2651G → R in MPS1H/S. 1 Publication
    VAR_066221
    Natural varianti276 – 2761E → K in MPS1H/S and MPS1S. 1 Publication
    VAR_066222
    Natural varianti279 – 2791V → A.
    VAR_003359
    Natural varianti300 – 3001A → T in IDUA pseudodeficiency. 1 Publication
    VAR_017435
    Natural varianti306 – 3061W → L in MPS1S. 1 Publication
    VAR_066223
    Natural varianti315 – 3151D → Y in MPS1.
    VAR_003360
    Natural varianti327 – 3271A → P in MPS1H and MPS1H/S. 4 Publications
    VAR_003361
    Natural varianti346 – 3461L → R in MPS1H/S; 0.4% of normal activity. 1 Publication
    VAR_017436
    Natural varianti348 – 3481N → K in MPS1S. 1 Publication
    VAR_066224
    Natural varianti349 – 3502Missing in MPS1H. 1 Publication
    VAR_003363
    Natural varianti349 – 3491D → N in MPS1H.
    VAR_003362
    Natural varianti349 – 3491D → Y in MPS1H. 1 Publication
    VAR_020982
    Natural varianti350 – 3501N → I in MPS1S. 1 Publication
    VAR_020983
    Natural varianti361 – 3611A → T.3 Publications
    Corresponds to variant rs6831280 [ dbSNP | Ensembl ].
    VAR_003364
    Natural varianti363 – 3631R → C in MPS1H/S; loss of activity. 1 Publication
    VAR_020984
    Natural varianti366 – 3661T → P in MPS1H. 1 Publication
    VAR_003365
    Natural varianti380 – 3801Q → R in MPS1H/S. 2 Publications
    VAR_003366
    Natural varianti383 – 3831R → H in MPS1S; 2-3% of normal activity. 2 Publications
    VAR_003367
    Natural varianti385 – 3851P → R in MPS1H. 1 Publication
    VAR_066225
    Natural varianti388 – 3881T → R in MPS1H. 1 Publication
    VAR_003368
    Natural varianti396 – 3961L → LALL in MPS1H.
    VAR_003369
    Natural varianti396 – 3961L → P in MPS1. 1 Publication
    VAR_066226
    Natural varianti409 – 4091G → R in MPS1H. 1 Publication
    Corresponds to variant rs11934801 [ dbSNP | Ensembl ].
    VAR_003370
    Natural varianti423 – 4231S → R in MPS1S and MPS1H/S; associated with L-188 in a patient with MPS1H/S; significant reduction of activity and protein levels. 2 Publications
    VAR_020985
    Natural varianti436 – 4361A → P in MPS1H/S. 1 Publication
    VAR_066227
    Natural varianti445 – 4451Missing in MPS1S. 1 Publication
    VAR_003371
    Natural varianti449 – 4491H → N.1 Publication
    VAR_066228
    Natural varianti454 – 4541V → I.2 Publications
    Corresponds to variant rs73066479 [ dbSNP | Ensembl ].
    VAR_003372
    Natural varianti489 – 4891R → P in MPS1H. 1 Publication
    Corresponds to variant rs4690226 [ dbSNP | Ensembl ].
    VAR_003373
    Natural varianti490 – 4901L → P in MPS1H/S and MPS1S. 2 Publications
    VAR_003374
    Natural varianti492 – 4921R → P in MPS1S. 2 Publications
    VAR_003375
    Natural varianti496 – 4961P → L in MPS1H/S. 1 Publication
    VAR_003376
    Natural varianti496 – 4961P → R in MPS1H/S. 1 Publication
    VAR_066229
    Natural varianti504 – 5041M → T in MPS1H/S. 1 Publication
    VAR_003377
    Natural varianti533 – 5331P → R in MPS1H and MPS1H/S; in 3% of the MPS1H patients; reduces catalytic activity and protein stability. 4 Publications
    VAR_003378
    Natural varianti535 – 5351L → F in MPS1H/S. 1 Publication
    VAR_066230
    Natural varianti591 – 5911A → T.1 Publication
    VAR_066231
    Natural varianti602 – 6021F → I in MPS1H/S; reduction of activity and protein levels. 1 Publication
    VAR_020986
    Natural varianti619 – 6191R → G in MPS1H/S; 1.5% of normal activity. 1 Publication
    VAR_017437
    Natural varianti626 – 6261W → R in MPS1H/S. 1 Publication
    VAR_003379
    Natural varianti628 – 6281R → P in MPS1H/S. 1 Publication
    VAR_020987

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M74715 mRNA. Translation: AAA81589.1.
    M95740, M95739 Genomic DNA. Translation: AAA51698.1.
    CCDSiCCDS3343.1.
    PIRiS53645.
    RefSeqiNP_000194.2. NM_000203.4.
    UniGeneiHs.89560.

    Genome annotation databases

    EnsembliENST00000247933; ENSP00000247933; ENSG00000127415.
    GeneIDi3425.
    KEGGihsa:3425.
    UCSCiuc003gby.3. human.

    Polymorphism databases

    DMDMi92090608.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M74715 mRNA. Translation: AAA81589.1 .
    M95740 , M95739 Genomic DNA. Translation: AAA51698.1 .
    CCDSi CCDS3343.1.
    PIRi S53645.
    RefSeqi NP_000194.2. NM_000203.4.
    UniGenei Hs.89560.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1Y24 model - A 36-522 [» ]
    3W81 X-ray 2.30 A/B 27-653 [» ]
    3W82 X-ray 2.76 A/B 27-653 [» ]
    4KGJ X-ray 2.99 A/B 27-653 [» ]
    4KGL X-ray 2.70 A/B 27-653 [» ]
    4KH2 X-ray 2.36 A/B 27-653 [» ]
    4MJ2 X-ray 2.10 A/B 1-653 [» ]
    4MJ4 X-ray 2.17 A 1-653 [» ]
    ProteinModelPortali P35475.
    SMRi P35475. Positions 27-642.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P35475. 1 interaction.
    MINTi MINT-1397491.
    STRINGi 9606.ENSP00000247933.

    Chemistry

    DrugBanki DB00090. Laronidase.

    Protein family/group databases

    CAZyi GH39. Glycoside Hydrolase Family 39.

    Polymorphism databases

    DMDMi 92090608.

    Proteomic databases

    MaxQBi P35475.
    PaxDbi P35475.
    PRIDEi P35475.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000247933 ; ENSP00000247933 ; ENSG00000127415 .
    GeneIDi 3425.
    KEGGi hsa:3425.
    UCSCi uc003gby.3. human.

    Organism-specific databases

    CTDi 3425.
    GeneCardsi GC04P000970.
    GeneReviewsi IDUA.
    H-InvDB HIX0200643.
    HGNCi HGNC:5391. IDUA.
    HPAi CAB025901.
    MIMi 252800. gene.
    607014. phenotype.
    607015. phenotype.
    607016. phenotype.
    neXtProti NX_P35475.
    Orphaneti 93473. Hurler syndrome.
    93476. Hurler-Scheie syndrome.
    93474. Scheie syndrome.
    PharmGKBi PA29638.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG3664.
    HOGENOMi HOG000007042.
    HOVERGENi HBG006121.
    InParanoidi P35475.
    KOi K01217.
    OrthoDBi EOG70088F.
    PhylomeDBi P35475.
    TreeFami TF323228.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS05096-MONOMER.
    BRENDAi 3.2.1.76. 2681.
    Reactomei REACT_120752. HS-GAG degradation.
    REACT_120888. CS/DS degradation.
    SABIO-RK P35475.

    Miscellaneous databases

    GenomeRNAii 3425.
    NextBioi 13508.
    PROi P35475.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P35475.
    Bgeei P35475.
    CleanExi HS_IDUA.
    Genevestigatori P35475.

    Family and domain databases

    Gene3Di 3.20.20.80. 1 hit.
    InterProi IPR000514. Glyco_hydro_39.
    IPR013781. Glyco_hydro_catalytic_dom.
    IPR017853. Glycoside_hydrolase_SF.
    [Graphical view ]
    Pfami PF01229. Glyco_hydro_39. 1 hit.
    [Graphical view ]
    PRINTSi PR00745. GLHYDRLASE39.
    SUPFAMi SSF51445. SSF51445. 1 hit.
    PROSITEi PS01027. GLYCOSYL_HYDROL_F39. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-33.
      Tissue: Liver.
    2. "Structure and sequence of the human alpha-L-iduronidase gene."
      Scott H.S., Guo X.H., Hopwood J.J., Morris C.P.
      Genomics 13:1311-1313(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-33.
    3. "Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications."
      Scott H.S., Bunge S., Gal A., Clarke L.A., Morris C.P., Hopwood J.J.
      Hum. Mutat. 6:288-302(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON VARIANTS.
    4. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-110.
      Tissue: Liver.
    5. "Insights into mucopolysaccharidosis I from the structure and action of alpha-L-iduronidase."
      Bie H., Yin J., He X., Kermode A.R., Goddard-Borger E.D., Withers S.G., James M.N.
      Nat. Chem. Biol. 9:739-745(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 27-653 IN COMPLEX WITH IDURONATE ANALOGS, CATALYTIC ACTIVITY, ACTIVE SITE, CHARACTERIZATION OF VARIANT MPS1H ARG-533, DISULFIDE BOND, GLYCOSYLATION AT ASN-110; ASN-372 AND ASN-415.
    6. "Human alpha-L-iduronidase uses its own N-glycan as a substrate-binding and catalytic module."
      Maita N., Tsukimura T., Taniguchi T., Saito S., Ohno K., Taniguchi H., Sakuraba H.
      Proc. Natl. Acad. Sci. U.S.A. 110:14628-14633(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 27-653 IN COMPLEX WITH IDURONATE, CATALYTIC ACTIVITY, DISULFIDE BOND, SUBUNIT, GLYCOSYLATION AT ASN-110; ASN-372; ASN-415 AND ASN-451, IDENTIFICATION BY MASS SPECTROMETRY.
    7. "Mutation analysis of 19 North American mucopolysaccharidosis type I patients: identification of two additional frequent mutations."
      Clarke L.A., Nelson P.V., Warrington C.L., Morris C.P., Hopwood J.J., Scott H.S.
      Hum. Mutat. 3:275-282(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MPS1H THR-75.
    8. "Two novel mutations causing mucopolysaccharidosis type I detected by single strand conformational analysis of the alpha-L-iduronidase gene."
      Clark L.A., Scott H.S.
      Hum. Mol. Genet. 2:1311-1312(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MPS1H/S PRO-82.
    9. "Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes."
      Scott H.S., Litjens T., Nelson P.V., Thompson P.R., Brooks D.A., Hopwood J.J., Morris C.P.
      Am. J. Hum. Genet. 53:973-986(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MPS1S GLN-89.
    10. "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."
      Bach G., Moskowitz S.M., Tieu P.T., Matynia A., Neufeld E.F.
      Am. J. Hum. Genet. 53:330-338(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MPS1H PRO-366 AND ARG-409.
    11. "Alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype."
      Scott H.S., Litjens T., Nelson P.V., Brooks D.A., Hopwood J.J., Morris C.P.
      Hum. Mutat. 1:333-339(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MPS1H ARG-533.
    12. "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."
      Bunge S., Kleijer W.J., Steglich C., Beck M., Zuther C., Morris C.P., Schwinger E., Hopwood J.J., Scott H.S., Gal A.
      Hum. Mol. Genet. 3:861-866(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MPS1H ASP-51; THR-75; PRO-218; PRO-327; PRO-489 AND 16-SER--ALA-19 DEL.
    13. "PCR detection of two RFLPs in exon I of the alpha-L-iduronidase (IDUA) gene."
      Scott H.S., Litjens T., Hopwood J.J., Morris C.P.
      Hum. Genet. 90:327-327(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT GLN-33.
    14. "Multiple polymorphisms within the alpha-L-iduronidase gene (IDUA): implications for a role in modification of MPS-I disease phenotype."
      Scott H.S., Nelson P.V., Litjens T., Hopwood J.J., Morris C.P.
      Hum. Mol. Genet. 2:1471-1473(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT THR-361.
    15. "Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S)."
      Tieu P.T., Bach G., Matynia A., Hwang M., Neufeld E.F.
      Hum. Mutat. 6:55-59(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MPS1H/S PRO-490 AND LEU-496, VARIANT MPS1S PRO-492.
    16. "Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene."
      Bunge S., Kleijer W.J., Steglich C., Beck M., Schwinger E., Gal A.
      Hum. Mutat. 6:91-94(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MPS1S TRP-89 AND HIS-383, VARIANT MPS1H 349-ASP-ASN-350 DEL, VARIANTS MPS1H/S THR-504 AND ARG-626.
    17. "Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency."
      Aronovich E.L., Pan D., Whitley C.B.
      Am. J. Hum. Genet. 58:75-85(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT IDUA PSEUDODEFICIENCY THR-300.
    18. "A novel missense mutation in the human IDUA gene associated with a severe Hurler's phenotype."
      Bartholomew D.W., McClellan J.M.
      Hum. Mutat. 12:291-291(1998)
      Cited for: VARIANT MPS1H ARG-388.
    19. "Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity."
      Lee-Chen G.J., Lin S.P., Tang Y.F., Chin Y.W.
      Clin. Genet. 56:66-70(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MPS1H/S GLY-619.
    20. "Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S."
      Teng Y.N., Wang T.R., Hwu W.L., Lin S.P., Lee-Chen G.J.
      Clin. Genet. 57:131-136(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MPS1H/S ARG-346.
    21. "Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients."
      Matte U., Yogalingam G., Brooks D., Leistner S., Schwartz I., Lima L., Norato D.Y., Brum J.M., Beesley C., Winchester B., Giugliani R., Hopwood J.J.
      Mol. Genet. Metab. 78:37-43(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MPS1H ILE-133; LYS-182; ASP-208; TYR-349 AND ARG-533, VARIANTS MPS1H/S PHE-260; PRO-327; ARG-380 AND PRO-628, VARIANTS MPS1S GLN-89; ILE-350; HIS-383 AND ASP-445 DEL.
    22. "Identification and molecular characterization of alpha-L-iduronidase mutations present in mucopolysaccharidosis type I patients undergoing enzyme replacement therapy."
      Yogalingam G., Guo X.H., Muller V.J., Brooks D.A., Clements P.R., Kakkis E.D., Hopwood J.J.
      Hum. Mutat. 24:199-207(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MPS1H/S VAL-79; GLN-238; PRO-327; CYS-363; ARG-380; ARG-533 AND ILE-602, VARIANT MPS1S ARG-423, VARIANTS GLN-82; GLN-105; THR-361 AND ILE-454, CHARACTERIZATION OF VARIANTS MPS1H/S VAL-79; GLN-238; CYS-363 AND ILE-602, CHARACTERIZATION OF VARIANT MPS1S ARG-423, CHARACTERIZATION OF VARIANT GLN-82.
    23. "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."
      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., Vici C.D., Okur I., Rosell J., Rovelli A.
      , Furlan F., Rigoldi M., Biondi A., Cooper D.N., Parini R.
      Hum. Mutat. 32:E2189-E2210(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MPS1H/S ARG-84; LYS-178; LEU-188; ARG-265; LYS-276; ARG-423; PRO-436; ARG-496; ARG-533 AND PHE-535, VARIANTS MPS1H ASP-51; PRO-103; PRO-327 AND ARG-385, VARIANTS MPS1S CYS-76; TRP-89; GLU-219; LYS-276; LEU-306; LYS-348; PRO-490 AND PRO-492, VARIANT MPS1 PRO-396, VARIANTS GLN-33; GLN-105; THR-361; ASN-449; ILE-454 AND THR-591.

    Entry informationi

    Entry nameiIDUA_HUMAN
    AccessioniPrimary (citable) accession number: P35475
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: April 4, 2006
    Last modified: October 1, 2014
    This is version 137 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Glycosyl hydrolases
      Classification of glycosyl hydrolase families and list of entries
    2. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3