IDUA_HUMAN
ID IDUA_HUMAN Reviewed; 653 AA.
AC P35475; B3KWK6;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Alpha-L-iduronidase;
DE EC=3.2.1.76;
DE Flags: Precursor;
GN Name=IDUA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-33.
RC TISSUE=Liver;
RX PubMed=1946389; DOI=10.1073/pnas.88.21.9695;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-33.
RX PubMed=1505961; DOI=10.1016/0888-7543(92)90053-u;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP REVIEW ON VARIANTS.
RX PubMed=8680403; DOI=10.1002/humu.1380060403;
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, clinical,
RT and biological implications.";
RL Hum. Mutat. 6:288-302(1995).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-110.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 27-653 IN COMPLEX WITH IDURONATE
RP ANALOGS, CATALYTIC ACTIVITY, ACTIVE SITE, CHARACTERIZATION OF VARIANT MPS1H
RP ARG-533, DISULFIDE BOND, AND GLYCOSYLATION AT ASN-110; ASN-372 AND ASN-415.
RX PubMed=24036510; DOI=10.1038/nchembio.1357;
RA Bie H., Yin J., He X., Kermode A.R., Goddard-Borger E.D., Withers S.G.,
RA James M.N.;
RT "Insights into mucopolysaccharidosis I from the structure and action of
RT alpha-L-iduronidase.";
RL Nat. Chem. Biol. 9:739-745(2013).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 27-653 IN COMPLEX WITH IDURONATE,
RP CATALYTIC ACTIVITY, DISULFIDE BOND, SUBUNIT, GLYCOSYLATION AT ASN-110;
RP ASN-372; ASN-415 AND ASN-451, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23959878; DOI=10.1073/pnas.1306939110;
RA Maita N., Tsukimura T., Taniguchi T., Saito S., Ohno K., Taniguchi H.,
RA Sakuraba H.;
RT "Human alpha-L-iduronidase uses its own N-glycan as a substrate-binding and
RT catalytic module.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:14628-14633(2013).
RN [9]
RP VARIANT MPS1H THR-75.
RX PubMed=8019563; DOI=10.1002/humu.1380030316;
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 [10]
RP VARIANT MPS1H/S PRO-82.
RX PubMed=8401515; DOI=10.1093/hmg/2.8.1311;
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 gene.";
RL Hum. Mol. Genet. 2:1311-1312(1993).
RN [11]
RP VARIANT MPS1S GLN-89.
RX 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) that
RT cause Hurler and Scheie syndromes.";
RL Am. J. Hum. Genet. 53:973-986(1993).
RN [12]
RP VARIANTS MPS1H PRO-366 AND ARG-409.
RX 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 patients in
RT Israel: multiple allelic mutations of the IDUA gene in a small geographic
RT area.";
RL Am. J. Hum. Genet. 53:330-338(1993).
RN [13]
RP VARIANT MPS1H ARG-533.
RX PubMed=1301941; DOI=10.1002/humu.1380010412;
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 severe
RT Hurler phenotype.";
RL Hum. Mutat. 1:333-339(1992).
RN [14]
RP VARIANTS MPS1H ASP-51; THR-75; PRO-218; PRO-327; PRO-489 AND 16-SER--ALA-19
RP DEL.
RX PubMed=7951228; DOI=10.1093/hmg/3.6.861;
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 and
RT determination of the frequency of the two common alpha-L-iduronidase
RT mutations (W402X and Q70X) among European patients.";
RL Hum. Mol. Genet. 3:861-866(1994).
RN [15]
RP VARIANT GLN-33.
RX PubMed=1362562; DOI=10.1007/bf00220095;
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 (IDUA)
RT gene.";
RL Hum. Genet. 90:327-327(1992).
RN [16]
RP VARIANT THR-361.
RX PubMed=8242073; DOI=10.1093/hmg/2.9.1471;
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 [17]
RP VARIANTS MPS1H/S PRO-490 AND LEU-496, AND VARIANT MPS1S PRO-492.
RX PubMed=7550232; DOI=10.1002/humu.1380060111;
RA Tieu P.T., Bach G., Matynia A., Hwang M., Neufeld E.F.;
RT "Four novel mutations underlying mild or intermediate forms of alpha-L-
RT iduronidase deficiency (MPS IS and MPS IH/S).";
RL Hum. Mutat. 6:55-59(1995).
RN [18]
RP VARIANTS MPS1S TRP-89 AND HIS-383, VARIANT MPS1H 349-ASP-ASN-350 DEL, AND
RP VARIANTS MPS1H/S THR-504 AND ARG-626.
RX PubMed=7550242; DOI=10.1002/humu.1380060119;
RA Bunge S., Kleijer W.J., Steglich C., Beck M., Schwinger E., Gal A.;
RT "Mucopolysaccharidosis type I: identification of 13 novel mutations of the
RT alpha-L-iduronidase gene.";
RL Hum. Mutat. 6:91-94(1995).
RN [19]
RP VARIANT IDUA PSEUDODEFICIENCY THR-300.
RX PubMed=8554071;
RA Aronovich E.L., Pan D., Whitley C.B.;
RT "Molecular genetic defect underlying alpha-L-iduronidase
RT pseudodeficiency.";
RL Am. J. Hum. Genet. 58:75-85(1996).
RN [20]
RP VARIANT MPS1H ARG-388.
RA Bartholomew D.W., McClellan J.M.;
RT "A novel missense mutation in the human IDUA gene associated with a severe
RT Hurler's phenotype.";
RL Hum. Mutat. 12:291-291(1998).
RN [21]
RP VARIANT MPS1H/S GLY-619.
RX PubMed=10466419; DOI=10.1034/j.1399-0004.1999.560109.x;
RA Lee-Chen G.J., Lin S.P., Tang Y.F., Chin Y.W.;
RT "Mucopolysaccharidosis type I: characterization of novel mutations
RT affecting alpha-L-iduronidase activity.";
RL Clin. Genet. 56:66-70(1999).
RN [22]
RP VARIANT MPS1H/S ARG-346.
RX PubMed=10735634; DOI=10.1034/j.1399-0004.2000.570207.x;
RA Teng Y.N., Wang T.R., Hwu W.L., Lin S.P., Lee-Chen G.J.;
RT "Identification and characterization of -3c-g acceptor splice site mutation
RT in human alpha-L-iduronidase associated with mucopolysaccharidosis type
RT IH/S.";
RL Clin. Genet. 57:131-136(2000).
RN [23]
RP VARIANTS MPS1H ILE-133; LYS-182; ASP-208; TYR-349 AND ARG-533, VARIANTS
RP MPS1H/S PHE-260; PRO-327; ARG-380 AND PRO-628, AND VARIANTS MPS1S GLN-89;
RP ILE-350; HIS-383 AND ASP-445 DEL.
RX PubMed=12559846; DOI=10.1016/s1096-7192(02)00200-7;
RA Matte U., Yogalingam G., Brooks D., Leistner S., Schwartz I., Lima L.,
RA Norato D.Y., Brum J.M., Beesley C., Winchester B., Giugliani R.,
RA Hopwood J.J.;
RT "Identification and characterization of 13 new mutations in
RT mucopolysaccharidosis type I patients.";
RL Mol. Genet. Metab. 78:37-43(2003).
RN [24]
RP VARIANTS MPS1H/S VAL-79; GLN-238; PRO-327; CYS-363; ARG-380; ARG-533 AND
RP ILE-602, VARIANT MPS1S ARG-423, VARIANTS GLN-82; GLN-105; THR-361 AND
RP ILE-454, CHARACTERIZATION OF VARIANTS MPS1H/S VAL-79; GLN-238; CYS-363 AND
RP ILE-602, CHARACTERIZATION OF VARIANT MPS1S ARG-423, AND CHARACTERIZATION OF
RP VARIANT GLN-82.
RX PubMed=15300847; DOI=10.1002/humu.20081;
RA Yogalingam G., Guo X.H., Muller V.J., Brooks D.A., Clements P.R.,
RA Kakkis E.D., Hopwood J.J.;
RT "Identification and molecular characterization of alpha-L-iduronidase
RT mutations present in mucopolysaccharidosis type I patients undergoing
RT enzyme replacement therapy.";
RL Hum. Mutat. 24:199-207(2004).
RN [25]
RP VARIANTS MPS1H TYR-315; PRO-327 AND PHE-620, CHARACTERIZATION OF VARIANTS
RP MPS1H TYR-315 AND PHE-620, VARIANT MPS1S ARG-380, AND VARIANTS GLN-33;
RP GLN-105; THR-361 AND ILE-454.
RX PubMed=19396826; DOI=10.1002/ajmg.a.32812;
RA Vazna A., Beesley C., Berna L., Stolnaja L., Myskova H., Bouckova M.,
RA Vlaskova H., Poupetova H., Zeman J., Magner M., Hlavata A., Winchester B.,
RA Hrebicek M., Dvorakova L.;
RT "Mucopolysaccharidosis type I in 21 Czech and Slovak patients: mutation
RT analysis suggests a functional importance of C-terminus of the IDUA
RT protein.";
RL Am. J. Med. Genet. A 149A:965-974(2009).
RN [26]
RP VARIANTS MPS1H/S ARG-84; LYS-178; LEU-188; ARG-265; LYS-276; PRO-396;
RP ARG-423; PRO-436; ARG-496; ARG-533 AND PHE-535, VARIANTS MPS1H ASP-51;
RP PRO-103; PRO-327 AND ARG-385, VARIANTS MPS1S CYS-76; TRP-89; GLU-219;
RP LYS-276; LEU-306; LYS-348; PRO-490 AND PRO-492, AND VARIANTS GLN-33;
RP GLN-105; THR-361; ASN-449; ILE-454 AND THR-591.
RX PubMed=21394825; DOI=10.1002/humu.21479;
RA Bertola F., Filocamo M., Casati G., Mort M., Rosano C., Tylki-Szymanska A.,
RA Tuysuz B., Gabrielli O., Grossi S., Scarpa M., Parenti G., Antuzzi D.,
RA Dalmau J., Di Rocco M., Vici C.D., Okur I., Rosell J., Rovelli A.,
RA Furlan F., Rigoldi M., Biondi A., Cooper D.N., Parini R.;
RT "IDUA mutational profiling of a cohort of 102 European patients with
RT mucopolysaccharidosis type I: identification and characterization of 35
RT novel alpha-L-iduronidase (IDUA) alleles.";
RL Hum. Mutat. 32:E2189-E2210(2011).
RN [27]
RP VARIANT MPS1S PRO-18.
RX PubMed=25256405; DOI=10.1111/cge.12507;
RA Pasqualim G., Ribeiro M.G., da Fonseca G.G., Szlago M., Schenone A.,
RA Lemes A., Rojas M.V., Matte U., Giugliani R.;
RT "p.L18P: a novel IDUA mutation that causes a distinct attenuated phenotype
RT in mucopolysaccharidosis type I patients.";
RL Clin. Genet. 88:376-380(2015).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of unsulfated alpha-L-iduronosidic linkages in
CC dermatan sulfate.; EC=3.2.1.76;
CC Evidence={ECO:0000269|PubMed:23959878, ECO:0000269|PubMed:24036510};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23959878,
CC ECO:0000269|PubMed:24036510}.
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P35475-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35475-2; Sequence=VSP_057029, VSP_057030;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: N-glycosylation at Asn-372 contributes to substrate binding and is
CC required for full enzymatic activity. {ECO:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:23959878, ECO:0000269|PubMed:24036510}.
CC -!- DISEASE: Mucopolysaccharidosis 1H (MPS1H) [MIM:607014]: A severe form
CC of mucopolysaccharidosis type 1, a rare lysosomal storage disease
CC characterized by progressive physical deterioration with urinary
CC excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H
CC usually present, within the first year of life, a combination of
CC hepatosplenomegaly, skeletal deformities, corneal clouding and severe
CC intellectual disability. Obstructive airways disease, respiratory
CC infection and cardiac complications usually result in death before 10
CC years of age. {ECO:0000269|PubMed:10466419,
CC ECO:0000269|PubMed:10735634, ECO:0000269|PubMed:12559846,
CC ECO:0000269|PubMed:1301941, ECO:0000269|PubMed:15300847,
CC ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825,
CC ECO:0000269|PubMed:24036510, ECO:0000269|PubMed:7550232,
CC ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:7951228,
CC ECO:0000269|PubMed:8019563, ECO:0000269|PubMed:8328452,
CC ECO:0000269|PubMed:8401515, ECO:0000269|Ref.20}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Mucopolysaccharidosis 1H/S (MPS1H/S) [MIM:607015]: A form of
CC mucopolysaccharidosis type 1, a rare lysosomal storage disease
CC characterized by progressive physical deterioration with urinary
CC excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents
CC an intermediate phenotype of the MPS1 clinical spectrum. It is
CC characterized by relatively little neurological involvement, but most
CC of the somatic symptoms described for severe MPS1 develop in the early
CC to mid-teens, causing considerable loss of mobility.
CC {ECO:0000269|PubMed:10466419, ECO:0000269|PubMed:10735634,
CC ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:15300847,
CC ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:7550232,
CC ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:8401515}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Mucopolysaccharidosis 1S (MPS1S) [MIM:607016]: A mild form of
CC mucopolysaccharidosis type 1, a rare lysosomal storage disease
CC characterized by progressive physical deterioration with urinary
CC excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S
CC may have little or no neurological involvement, normal stature and life
CC span, but present development of joints stiffness, mild
CC hepatosplenomegaly, aortic valve disease and corneal clouding.
CC {ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:15300847,
CC ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825,
CC ECO:0000269|PubMed:25256405, ECO:0000269|PubMed:7550232,
CC ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:8213840}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 39 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; M74715; AAA81589.1; -; mRNA.
DR EMBL; M95740; AAA51698.1; -; Genomic_DNA.
DR EMBL; M95739; AAA51698.1; JOINED; Genomic_DNA.
DR EMBL; AK125223; BAG54168.1; -; mRNA.
DR EMBL; AC019103; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS3343.1; -. [P35475-1]
DR PIR; S53645; S53645.
DR RefSeq; NP_000194.2; NM_000203.4. [P35475-1]
DR PDB; 3W81; X-ray; 2.30 A; A/B=27-653.
DR PDB; 3W82; X-ray; 2.76 A; A/B=27-653.
DR PDB; 4KGJ; X-ray; 2.99 A; A/B=27-653.
DR PDB; 4KGL; X-ray; 2.70 A; A/B=27-653.
DR PDB; 4KH2; X-ray; 2.36 A; A/B=27-653.
DR PDB; 4MJ2; X-ray; 2.10 A; A/B=1-653.
DR PDB; 4MJ4; X-ray; 2.17 A; A=1-653.
DR PDB; 4OBR; X-ray; 2.46 A; A/B=27-653.
DR PDB; 4OBS; X-ray; 2.26 A; A=27-653.
DR PDB; 6I6R; X-ray; 2.02 A; A/B=27-653.
DR PDB; 6I6X; X-ray; 2.39 A; A/B=27-653.
DR PDBsum; 3W81; -.
DR PDBsum; 3W82; -.
DR PDBsum; 4KGJ; -.
DR PDBsum; 4KGL; -.
DR PDBsum; 4KH2; -.
DR PDBsum; 4MJ2; -.
DR PDBsum; 4MJ4; -.
DR PDBsum; 4OBR; -.
DR PDBsum; 4OBS; -.
DR PDBsum; 6I6R; -.
DR PDBsum; 6I6X; -.
DR AlphaFoldDB; P35475; -.
DR SMR; P35475; -.
DR BioGRID; 109651; 88.
DR IntAct; P35475; 2.
DR STRING; 9606.ENSP00000247933; -.
DR DrugBank; DB09301; Chondroitin sulfate.
DR CAZy; GH39; Glycoside Hydrolase Family 39.
DR GlyConnect; 1006; 5 N-Linked glycans (2 sites).
DR GlyGen; P35475; 6 sites, 4 N-linked glycans (2 sites).
DR iPTMnet; P35475; -.
DR PhosphoSitePlus; P35475; -.
DR BioMuta; IDUA; -.
DR DMDM; 92090608; -.
DR EPD; P35475; -.
DR jPOST; P35475; -.
DR MassIVE; P35475; -.
DR MaxQB; P35475; -.
DR PaxDb; P35475; -.
DR PeptideAtlas; P35475; -.
DR PRIDE; P35475; -.
DR ProteomicsDB; 3793; -.
DR ProteomicsDB; 55068; -. [P35475-1]
DR Antibodypedia; 43016; 222 antibodies from 26 providers.
DR DNASU; 3425; -.
DR Ensembl; ENST00000247933.9; ENSP00000247933.4; ENSG00000127415.13. [P35475-1]
DR Ensembl; ENST00000514224.2; ENSP00000425081.2; ENSG00000127415.13. [P35475-1]
DR GeneID; 3425; -.
DR KEGG; hsa:3425; -.
DR MANE-Select; ENST00000514224.2; ENSP00000425081.2; NM_000203.5; NP_000194.2.
DR UCSC; uc003gby.5; human. [P35475-1]
DR CTD; 3425; -.
DR DisGeNET; 3425; -.
DR GeneCards; IDUA; -.
DR GeneReviews; IDUA; -.
DR HGNC; HGNC:5391; IDUA.
DR HPA; ENSG00000127415; Low tissue specificity.
DR MalaCards; IDUA; -.
DR MIM; 252800; gene.
DR MIM; 607014; phenotype.
DR MIM; 607015; phenotype.
DR MIM; 607016; phenotype.
DR neXtProt; NX_P35475; -.
DR OpenTargets; ENSG00000127415; -.
DR Orphanet; 93473; Hurler syndrome.
DR Orphanet; 93476; Hurler-Scheie syndrome.
DR Orphanet; 93474; Scheie syndrome.
DR PharmGKB; PA29638; -.
DR VEuPathDB; HostDB:ENSG00000127415; -.
DR eggNOG; ENOG502QRES; Eukaryota.
DR GeneTree; ENSGT00390000015494; -.
DR InParanoid; P35475; -.
DR OMA; AHYTSGD; -.
DR PhylomeDB; P35475; -.
DR TreeFam; TF323228; -.
DR BioCyc; MetaCyc:HS05096-MON; -.
DR BRENDA; 3.2.1.76; 2681.
DR PathwayCommons; P35475; -.
DR Reactome; R-HSA-2024096; HS-GAG degradation.
DR Reactome; R-HSA-2024101; CS/DS degradation.
DR Reactome; R-HSA-2206302; MPS I - Hurler syndrome.
DR SABIO-RK; P35475; -.
DR SignaLink; P35475; -.
DR BioGRID-ORCS; 3425; 11 hits in 1076 CRISPR screens.
DR ChiTaRS; IDUA; human.
DR GenomeRNAi; 3425; -.
DR Pharos; P35475; Tbio.
DR PRO; PR:P35475; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P35475; protein.
DR Bgee; ENSG00000127415; Expressed in right hemisphere of cerebellum and 129 other tissues.
DR ExpressionAtlas; P35475; baseline and differential.
DR Genevisible; P35475; HS.
DR GO; GO:0030135; C:coated vesicle; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0004553; F:hydrolase activity, hydrolyzing O-glycosyl compounds; IBA:GO_Central.
DR GO; GO:0003940; F:L-iduronidase activity; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl.
DR GO; GO:0030207; P:chondroitin sulfate catabolic process; TAS:Reactome.
DR GO; GO:0030209; P:dermatan sulfate catabolic process; IDA:UniProtKB.
DR GO; GO:0005984; P:disaccharide metabolic process; TAS:ProtInc.
DR GO; GO:0006027; P:glycosaminoglycan catabolic process; TAS:Reactome.
DR GO; GO:0030211; P:heparin catabolic process; IMP:MGI.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR000514; Glyco_hydro_39.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF01229; Glyco_hydro_39; 1.
DR PRINTS; PR00745; GLHYDRLASE39.
DR SUPFAM; SSF51445; SSF51445; 1.
DR PROSITE; PS01027; GLYCOSYL_HYDROL_F39; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant; Disulfide bond;
KW Glycoprotein; Glycosidase; Hydrolase; Lysosome; Mucopolysaccharidosis;
KW Reference proteome; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..653
FT /note="Alpha-L-iduronidase"
FT /id="PRO_0000012200"
FT ACT_SITE 182
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10068,
FT ECO:0000269|PubMed:24036510"
FT ACT_SITE 299
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:24036510"
FT BINDING 91
FT /ligand="substrate"
FT BINDING 181
FT /ligand="substrate"
FT BINDING 264
FT /ligand="substrate"
FT BINDING 305..306
FT /ligand="substrate"
FT BINDING 349
FT /ligand="substrate"
FT BINDING 363
FT /ligand="substrate"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:23959878, ECO:0000269|PubMed:24036510"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23959878,
FT ECO:0000269|PubMed:24036510"
FT CARBOHYD 415
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23959878,
FT ECO:0000269|PubMed:24036510"
FT CARBOHYD 451
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23959878"
FT DISULFID 541..577
FT /evidence="ECO:0000269|PubMed:23959878,
FT ECO:0000269|PubMed:24036510"
FT VAR_SEQ 53..100
FT /note="CPPLPHSQADQYVLSWDQQLNLAYVGAVPHRGIKQVRTHWLLELVTTR ->
FT W (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057029"
FT VAR_SEQ 265..324
FT /note="GARSSISILEQEKVVAQQIRQLFPKFADTPIYNDEADPLVGWSLPQPWRADV
FT TYAAMVVK -> VRPAPPSAPVFCALSRCAPGRADPGGAEAAPPAGCAQLHLHPGAGEG
FT RRAADPAALPQVRGHPHLQRRGGPAGGLVPATAVEGGRDLRGHGGEGGPAQRPARPPAT
FT FLPRRDRRAVAAPPGPSCPGHPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057030"
FT VARIANT 16..19
FT /note="Missing (in MPS1H)"
FT /evidence="ECO:0000269|PubMed:7951228"
FT /id="VAR_003349"
FT VARIANT 18
FT /note="L -> P (in MPS1S; dbSNP:rs794726878)"
FT /evidence="ECO:0000269|PubMed:25256405"
FT /id="VAR_072367"
FT VARIANT 33
FT /note="H -> Q (in dbSNP:rs10794537)"
FT /evidence="ECO:0000269|PubMed:1362562,
FT ECO:0000269|PubMed:1505961, ECO:0000269|PubMed:19396826,
FT ECO:0000269|PubMed:1946389, ECO:0000269|PubMed:21394825"
FT /id="VAR_003350"
FT VARIANT 51
FT /note="G -> D (in MPS1H; dbSNP:rs794726877)"
FT /evidence="ECO:0000269|PubMed:21394825,
FT ECO:0000269|PubMed:7951228"
FT /id="VAR_003351"
FT VARIANT 75
FT /note="A -> T (in MPS1H; dbSNP:rs758452450)"
FT /evidence="ECO:0000269|PubMed:7951228,
FT ECO:0000269|PubMed:8019563"
FT /id="VAR_003352"
FT VARIANT 76
FT /note="Y -> C (in MPS1S; dbSNP:rs780165694)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066215"
FT VARIANT 79
FT /note="A -> V (in MPS1H/S; reduction of activity and
FT protein levels; dbSNP:rs747981483)"
FT /evidence="ECO:0000269|PubMed:15300847"
FT /id="VAR_020975"
FT VARIANT 82
FT /note="H -> P (in MPS1H/S; dbSNP:rs794727239)"
FT /evidence="ECO:0000269|PubMed:8401515"
FT /id="VAR_003353"
FT VARIANT 82
FT /note="H -> Q (reduction of protein levels;
FT dbSNP:rs148775298)"
FT /evidence="ECO:0000269|PubMed:15300847"
FT /id="VAR_020976"
FT VARIANT 84
FT /note="G -> R (in MPS1H/S)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066216"
FT VARIANT 89
FT /note="R -> Q (in MPS1S; dbSNP:rs121965029)"
FT /evidence="ECO:0000269|PubMed:12559846,
FT ECO:0000269|PubMed:8213840"
FT /id="VAR_003354"
FT VARIANT 89
FT /note="R -> W (in MPS1S; dbSNP:rs754966840)"
FT /evidence="ECO:0000269|PubMed:21394825,
FT ECO:0000269|PubMed:7550242"
FT /id="VAR_003355"
FT VARIANT 103
FT /note="T -> P (in MPS1H; uncertain pathological role)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066217"
FT VARIANT 105
FT /note="R -> Q (in dbSNP:rs3755955)"
FT /evidence="ECO:0000269|PubMed:15300847,
FT ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825"
FT /id="VAR_003356"
FT VARIANT 116
FT /note="G -> R (in dbSNP:rs148946496)"
FT /id="VAR_003357"
FT VARIANT 133
FT /note="M -> I (in MPS1H; dbSNP:rs558683362)"
FT /evidence="ECO:0000269|PubMed:12559846"
FT /id="VAR_020977"
FT VARIANT 178
FT /note="E -> K (in MPS1H/S; dbSNP:rs992336192)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066218"
FT VARIANT 182
FT /note="E -> K (in MPS1H; dbSNP:rs754154200)"
FT /evidence="ECO:0000269|PubMed:12559846"
FT /id="VAR_020978"
FT VARIANT 188
FT /note="F -> L (in MPS1H/S; associated with R-423)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066219"
FT VARIANT 208
FT /note="G -> D (in MPS1H; dbSNP:rs1430681871)"
FT /evidence="ECO:0000269|PubMed:12559846"
FT /id="VAR_020979"
FT VARIANT 218
FT /note="L -> P (in MPS1H; dbSNP:rs869025584)"
FT /evidence="ECO:0000269|PubMed:7951228"
FT /id="VAR_003358"
FT VARIANT 219
FT /note="G -> E (in MPS1S; dbSNP:rs1230234600)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066220"
FT VARIANT 238
FT /note="L -> Q (in MPS1H/S; dbSNP:rs148789453)"
FT /evidence="ECO:0000269|PubMed:15300847"
FT /id="VAR_020980"
FT VARIANT 260
FT /note="S -> F (in MPS1H/S)"
FT /evidence="ECO:0000269|PubMed:12559846"
FT /id="VAR_020981"
FT VARIANT 265
FT /note="G -> R (in MPS1H/S; dbSNP:rs369090960)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066221"
FT VARIANT 276
FT /note="E -> K (in MPS1H/S and MPS1S)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066222"
FT VARIANT 279
FT /note="V -> A"
FT /id="VAR_003359"
FT VARIANT 300
FT /note="A -> T (in IDUA pseudodeficiency;
FT dbSNP:rs121965030)"
FT /evidence="ECO:0000269|PubMed:8554071"
FT /id="VAR_017435"
FT VARIANT 306
FT /note="W -> L (in MPS1S)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066223"
FT VARIANT 315
FT /note="D -> Y (in MPS1H; loss of function; undetectable
FT enzyme activity)"
FT /evidence="ECO:0000269|PubMed:19396826"
FT /id="VAR_003360"
FT VARIANT 327
FT /note="A -> P (in MPS1H; MPS1H/S; dbSNP:rs199801029)"
FT /evidence="ECO:0000269|PubMed:12559846,
FT ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:19396826,
FT ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:7951228"
FT /id="VAR_003361"
FT VARIANT 346
FT /note="L -> R (in MPS1H/S; 0.4% of normal activity;
FT dbSNP:rs121965033)"
FT /evidence="ECO:0000269|PubMed:10735634"
FT /id="VAR_017436"
FT VARIANT 348
FT /note="N -> K (in MPS1S; dbSNP:rs746766617)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066224"
FT VARIANT 349..350
FT /note="Missing (in MPS1H)"
FT /evidence="ECO:0000269|PubMed:7550242"
FT /id="VAR_003363"
FT VARIANT 349
FT /note="D -> N (in MPS1H; dbSNP:rs368454909)"
FT /id="VAR_003362"
FT VARIANT 349
FT /note="D -> Y (in MPS1H)"
FT /evidence="ECO:0000269|PubMed:12559846"
FT /id="VAR_020982"
FT VARIANT 350
FT /note="N -> I (in MPS1S)"
FT /evidence="ECO:0000269|PubMed:12559846"
FT /id="VAR_020983"
FT VARIANT 361
FT /note="A -> T (in dbSNP:rs6831280)"
FT /evidence="ECO:0000269|PubMed:15300847,
FT ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825,
FT ECO:0000269|PubMed:8242073"
FT /id="VAR_003364"
FT VARIANT 363
FT /note="R -> C (in MPS1H/S; loss of activity;
FT dbSNP:rs750496798)"
FT /evidence="ECO:0000269|PubMed:15300847"
FT /id="VAR_020984"
FT VARIANT 366
FT /note="T -> P (in MPS1H; dbSNP:rs121965024)"
FT /evidence="ECO:0000269|PubMed:8328452"
FT /id="VAR_003365"
FT VARIANT 380
FT /note="Q -> R (in MPS1H/S and MPS1S; dbSNP:rs762903007)"
FT /evidence="ECO:0000269|PubMed:12559846,
FT ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:19396826"
FT /id="VAR_003366"
FT VARIANT 383
FT /note="R -> H (in MPS1S; 2-3% of normal activity;
FT dbSNP:rs754949360)"
FT /evidence="ECO:0000269|PubMed:12559846,
FT ECO:0000269|PubMed:7550242"
FT /id="VAR_003367"
FT VARIANT 385
FT /note="P -> R (in MPS1H; dbSNP:rs1553917309)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066225"
FT VARIANT 388
FT /note="T -> R (in MPS1H; dbSNP:rs794727896)"
FT /evidence="ECO:0000269|Ref.20"
FT /id="VAR_003368"
FT VARIANT 396
FT /note="L -> LALL (in MPS1H)"
FT /id="VAR_003369"
FT VARIANT 396
FT /note="L -> P (in MPS1H/S)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066226"
FT VARIANT 409
FT /note="G -> R (in MPS1H; dbSNP:rs11934801)"
FT /evidence="ECO:0000269|PubMed:8328452"
FT /id="VAR_003370"
FT VARIANT 423
FT /note="S -> R (in MPS1S and MPS1H/S; associated with L-188
FT in a patient with MPS1H/S; significant reduction of
FT activity and protein levels; dbSNP:rs931627770)"
FT /evidence="ECO:0000269|PubMed:15300847,
FT ECO:0000269|PubMed:21394825"
FT /id="VAR_020985"
FT VARIANT 436
FT /note="A -> P (in MPS1H/S)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066227"
FT VARIANT 445
FT /note="Missing (in MPS1S)"
FT /evidence="ECO:0000269|PubMed:12559846"
FT /id="VAR_003371"
FT VARIANT 449
FT /note="H -> N (in dbSNP:rs532731688)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066228"
FT VARIANT 454
FT /note="V -> I (in dbSNP:rs73066479)"
FT /evidence="ECO:0000269|PubMed:15300847,
FT ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825"
FT /id="VAR_003372"
FT VARIANT 489
FT /note="R -> P (in MPS1H)"
FT /evidence="ECO:0000269|PubMed:7951228"
FT /id="VAR_003373"
FT VARIANT 490
FT /note="L -> P (in MPS1H/S and MPS1S; dbSNP:rs121965027)"
FT /evidence="ECO:0000269|PubMed:21394825,
FT ECO:0000269|PubMed:7550232"
FT /id="VAR_003374"
FT VARIANT 492
FT /note="R -> P (in MPS1S; dbSNP:rs121965026)"
FT /evidence="ECO:0000269|PubMed:21394825,
FT ECO:0000269|PubMed:7550232"
FT /id="VAR_003375"
FT VARIANT 496
FT /note="P -> L (in MPS1H/S; dbSNP:rs772416503)"
FT /evidence="ECO:0000269|PubMed:7550232"
FT /id="VAR_003376"
FT VARIANT 496
FT /note="P -> R (in MPS1H/S; dbSNP:rs772416503)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066229"
FT VARIANT 504
FT /note="M -> T (in MPS1H/S)"
FT /evidence="ECO:0000269|PubMed:7550242"
FT /id="VAR_003377"
FT VARIANT 533
FT /note="P -> R (in MPS1H and MPS1H/S; in 3% of the MPS1H
FT patients; reduces catalytic activity and protein stability;
FT dbSNP:rs121965021)"
FT /evidence="ECO:0000269|PubMed:12559846,
FT ECO:0000269|PubMed:1301941, ECO:0000269|PubMed:15300847,
FT ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:24036510"
FT /id="VAR_003378"
FT VARIANT 535
FT /note="L -> F (in MPS1H/S)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066230"
FT VARIANT 591
FT /note="A -> T (in dbSNP:rs398123257)"
FT /evidence="ECO:0000269|PubMed:21394825"
FT /id="VAR_066231"
FT VARIANT 602
FT /note="F -> I (in MPS1H/S; reduction of activity and
FT protein levels)"
FT /evidence="ECO:0000269|PubMed:15300847"
FT /id="VAR_020986"
FT VARIANT 619
FT /note="R -> G (in MPS1H/S; 1.5% of normal activity;
FT dbSNP:rs121965031)"
FT /evidence="ECO:0000269|PubMed:10466419"
FT /id="VAR_017437"
FT VARIANT 620
FT /note="V -> F (in MPS1H; loss of function; undetectable
FT enzyme activity)"
FT /evidence="ECO:0000269|PubMed:19396826"
FT /id="VAR_072368"
FT VARIANT 626
FT /note="W -> R (in MPS1H/S; dbSNP:rs1281475543)"
FT /evidence="ECO:0000269|PubMed:7550242"
FT /id="VAR_003379"
FT VARIANT 628
FT /note="R -> P (in MPS1H/S; dbSNP:rs200448421)"
FT /evidence="ECO:0000269|PubMed:12559846"
FT /id="VAR_020987"
FT CONFLICT 622
FT /note="A -> T (in Ref. 2; AAA51698)"
FT /evidence="ECO:0000305"
FT STRAND 30..42
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:3W81"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:4MJ4"
FT HELIX 68..78
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:6I6R"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:3W81"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 112..123
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 127..131
FT /evidence="ECO:0007829|PDB:6I6R"
FT TURN 136..139
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:4KGJ"
FT HELIX 146..167
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:4MJ2"
FT HELIX 195..212
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 232..243
FT /evidence="ECO:0007829|PDB:6I6R"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 269..286
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 295..298
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:4KGL"
FT HELIX 311..314
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 316..332
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:4KGJ"
FT STRAND 343..346
FT /evidence="ECO:0007829|PDB:6I6R"
FT TURN 359..361
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 362..371
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 374..376
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 378..383
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 385..393
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 398..407
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 410..412
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 414..425
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:4KGL"
FT STRAND 435..442
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 453..461
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 470..477
FT /evidence="ECO:0007829|PDB:6I6R"
FT TURN 478..480
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 483..489
FT /evidence="ECO:0007829|PDB:6I6R"
FT HELIX 498..505
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 511..517
FT /evidence="ECO:0007829|PDB:6I6R"
FT TURN 520..522
FT /evidence="ECO:0007829|PDB:4MJ2"
FT STRAND 524..526
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 529..541
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 552..560
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 563..569
FT /evidence="ECO:0007829|PDB:6I6R"
FT TURN 571..573
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 578..586
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 602..607
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 616..624
FT /evidence="ECO:0007829|PDB:6I6R"
FT STRAND 636..641
FT /evidence="ECO:0007829|PDB:6I6R"
SQ SEQUENCE 653 AA; 72670 MW; 9D2399B22FD172BD CRC64;
MRPLRPRAAL LALLASLLAA PPVAPAEAPH LVHVDAARAL 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
