IDUA

Protein identityUniProt · HPA

UniProt accession

P35475

Gene

IDUA

Ensembl

ENSG00000127415

Chromosome

4

Canonical length

653 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Vesicles

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

653 residues, UniProt reviewed canonical sequence.

>P35475|IDUA
     1  MRPLRPRAAL LALLASLLAA PPVAPAEAPH LVHVDAARAL WPLRRFWRST GFCPPLPHSQ
    61  ADQYVLSWDQ QLNLAYVGAV PHRGIKQVRT HWLLELVTTR GSTGRGLSYN FTHLDGYLDL
   121  LRENQLLPGF ELMGSASGHF TDFEDKQQVF EWKDLVSSLA RRYIGRYGLA HVSKWNFETW
   181  NEPDHHDFDN VSMTMQGFLN YYDACSEGLR AASPALRLGG PGDSFHTPPR SPLSWGLLRH
   241  CHDGTNFFTG EAGVRLDYIS LHRKGARSSI SILEQEKVVA QQIRQLFPKF ADTPIYNDEA
   301  DPLVGWSLPQ PWRADVTYAA MVVKVIAQHQ NLLLANTTSA FPYALLSNDN AFLSYHPHPF
   361  AQRTLTARFQ VNNTRPPHVQ LLRKPVLTAM GLLALLDEEQ LWAEVSQAGT VLDSNHTVGV
   421  LASAHRPQGP ADAWRAAVLI YASDDTRAHP NRSVAVTLRL RGVPPGPGLV YVTRYLDNGL
   481  CSPDGEWRRL GRPVFPTAEQ FRRMRAAEDP VAAAPRPLPA GGRLTLRPAL RLPSLLLVHV
   541  CARPEKPPGQ VTRLRALPLT QGQLVLVWSD EHVGSKCLWT YEIQFSQDGK AYTPVSRKPS
   601  TFNLFVFSPD TGAVSGSYRV RALDYWARPG PFSDPVPYLE VPVPRGPPSP GNP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IDUA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

31 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IDUA.

Disease | AllUniProt

Conditions IDUA is implicated in, by any mechanism.

• Mucopolysaccharidosis 1H (MPS1H) MIM:607014
• Mucopolysaccharidosis 1H/S (MPS1H/S) MIM:607015
• Mucopolysaccharidosis 1S (MPS1S) MIM:607016

Disease | GeneticClinVar

418 pathogenic / likely-pathogenic of 1,932 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mucopolysaccharidosis type 1
• Hurler syndrome
• Mucopolysaccharidosis, MPS-I-H/S
• Mucopolysaccharidosis, MPS-I-S
• IDUA-related disorder

ReferencesPubMed · IEDB

Publications for IDUA from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.17

gnomAD pLI

0

gnomAD missense Z

-0.6

DepMap mean gene effect

0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• dermatan sulfate proteoglycan catabolic process
• glycosaminoglycan catabolic process
• heparan sulfate proteoglycan catabolic process
• disaccharide metabolic process
• heparin proteoglycan catabolic process

Molecular functions

• signaling receptor binding
• L-iduronidase activity

Cellular components

• extracellular exosome
• lysosomal lumen

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin-like fold
• Glycoside hydrolase superfamily
• Glycoside hydrolase, family 39
• Glycosyl hydrolases family 39, active site
• Glycosyl hydrolases family 39, N-terminal catalytic domain
• Alpha-L-iduronidase, C-terminal domain
• Glycosyl Hydrolase Family 39
• Glycosyl hydrolases family 39
• Alpha-L-iduronidase C-terminal domain

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Glycosidase
• Hydrolase
• Lysosome
• Mucopolysaccharidosis
• Signal

InteractionsUniProt · HPA

Protein binding partners of IDUA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FBXO6