HUTU_HUMAN
ID HUTU_HUMAN Reviewed; 676 AA.
AC Q96N76; E9PE13; Q14C64; Q68CJ7;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Urocanate hydratase;
DE Short=Urocanase;
DE EC=4.2.1.49;
DE AltName: Full=Imidazolonepropionate hydrolase;
GN Name=UROC1;
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 2).
RX PubMed=15221005; DOI=10.1038/sj.onc.1207782;
RA Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S.,
RA Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S.,
RA Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A.;
RT "Expression profiling and differential screening between hepatoblastomas
RT and the corresponding normal livers: identification of high expression of
RT the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.";
RL Oncogene 23:5901-5911(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP CATALYTIC ACTIVITY, AND VARIANTS UROCD PRO-70 AND CYS-450.
RX PubMed=19304569; DOI=10.1136/jmg.2008.060632;
RA Espinos C., Pineda M., Martinez-Rubio D., Lupo V., Ormazabal A.,
RA Vilaseca M.A., Spaapen L.J.M., Palau F., Artuch R.;
RT "Mutations in the urocanase gene UROC1 are associated with urocanic
RT aciduria.";
RL J. Med. Genet. 46:407-411(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-imidazolone-5-propanoate = H2O + trans-urocanate;
CC Xref=Rhea:RHEA:13101, ChEBI:CHEBI:15377, ChEBI:CHEBI:17771,
CC ChEBI:CHEBI:77893; EC=4.2.1.49;
CC Evidence={ECO:0000269|PubMed:19304569};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540; Evidence={ECO:0000250};
CC -!- PATHWAY: Amino-acid degradation; L-histidine degradation into L-
CC glutamate; N-formimidoyl-L-glutamate from L-histidine: step 2/3.
CC -!- INTERACTION:
CC Q96N76; Q15699: ALX1; NbExp=3; IntAct=EBI-13073486, EBI-750671;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96N76-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96N76-2; Sequence=VSP_045422;
CC -!- DISEASE: Urocanase deficiency (UROCD) [MIM:276880]: An inborn error of
CC histidine metabolism resulting in urocanic aciduria and neurological
CC manifestations including intellectual disability, ataxia, episodic
CC aggressive behavior or exaggerated affection-seeking.
CC {ECO:0000269|PubMed:19304569}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the urocanase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD38651.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB075869; BAD38651.1; ALT_INIT; mRNA.
DR EMBL; AK055862; BAB71032.1; -; mRNA.
DR EMBL; AC024558; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC115405; AAI15406.1; -; mRNA.
DR EMBL; BC115406; AAI15407.1; -; mRNA.
DR CCDS; CCDS3038.1; -. [Q96N76-1]
DR CCDS; CCDS54636.1; -. [Q96N76-2]
DR RefSeq; NP_001159446.1; NM_001165974.1. [Q96N76-2]
DR RefSeq; NP_653240.1; NM_144639.2. [Q96N76-1]
DR AlphaFoldDB; Q96N76; -.
DR SMR; Q96N76; -.
DR BioGRID; 126291; 1.
DR IntAct; Q96N76; 1.
DR STRING; 9606.ENSP00000373073; -.
DR iPTMnet; Q96N76; -.
DR PhosphoSitePlus; Q96N76; -.
DR BioMuta; UROC1; -.
DR DMDM; 22256789; -.
DR MassIVE; Q96N76; -.
DR PaxDb; Q96N76; -.
DR PeptideAtlas; Q96N76; -.
DR PRIDE; Q96N76; -.
DR ProteomicsDB; 19788; -.
DR ProteomicsDB; 77480; -. [Q96N76-1]
DR Antibodypedia; 52455; 72 antibodies from 17 providers.
DR DNASU; 131669; -.
DR Ensembl; ENST00000290868.7; ENSP00000290868.2; ENSG00000159650.9. [Q96N76-1]
DR Ensembl; ENST00000383579.3; ENSP00000373073.3; ENSG00000159650.9. [Q96N76-2]
DR GeneID; 131669; -.
DR KEGG; hsa:131669; -.
DR MANE-Select; ENST00000290868.7; ENSP00000290868.2; NM_144639.3; NP_653240.1.
DR UCSC; uc003eiz.3; human. [Q96N76-1]
DR CTD; 131669; -.
DR DisGeNET; 131669; -.
DR GeneCards; UROC1; -.
DR HGNC; HGNC:26444; UROC1.
DR HPA; ENSG00000159650; Tissue enriched (liver).
DR MalaCards; UROC1; -.
DR MIM; 276880; phenotype.
DR MIM; 613012; gene.
DR neXtProt; NX_Q96N76; -.
DR OpenTargets; ENSG00000159650; -.
DR Orphanet; 210128; Urocanic aciduria.
DR PharmGKB; PA134879207; -.
DR VEuPathDB; HostDB:ENSG00000159650; -.
DR eggNOG; ENOG502QR75; Eukaryota.
DR GeneTree; ENSGT00390000015136; -.
DR HOGENOM; CLU_018868_3_0_1; -.
DR InParanoid; Q96N76; -.
DR OMA; LVGDWAN; -.
DR OrthoDB; 536177at2759; -.
DR PhylomeDB; Q96N76; -.
DR TreeFam; TF314306; -.
DR PathwayCommons; Q96N76; -.
DR Reactome; R-HSA-70921; Histidine catabolism.
DR SignaLink; Q96N76; -.
DR UniPathway; UPA00379; UER00550.
DR BioGRID-ORCS; 131669; 8 hits in 1063 CRISPR screens.
DR GenomeRNAi; 131669; -.
DR Pharos; Q96N76; Tbio.
DR PRO; PR:Q96N76; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q96N76; protein.
DR Bgee; ENSG00000159650; Expressed in right lobe of liver and 34 other tissues.
DR Genevisible; Q96N76; HS.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0016153; F:urocanate hydratase activity; IDA:BHF-UCL.
DR GO; GO:0006548; P:histidine catabolic process; IMP:BHF-UCL.
DR GO; GO:0019556; P:histidine catabolic process to glutamate and formamide; IEA:UniProtKB-UniPathway.
DR GO; GO:0019557; P:histidine catabolic process to glutamate and formate; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.10730; -; 1.
DR HAMAP; MF_00577; HutU; 1.
DR InterPro; IPR023637; Urocanase.
DR InterPro; IPR035401; Urocanase_C.
DR InterPro; IPR038364; Urocanase_central_sf.
DR InterPro; IPR023636; Urocanase_CS.
DR InterPro; IPR035400; Urocanase_N.
DR InterPro; IPR035085; Urocanase_Rossmann-like.
DR InterPro; IPR036190; Urocanase_sf.
DR PANTHER; PTHR12216; PTHR12216; 1.
DR Pfam; PF01175; Urocanase; 1.
DR Pfam; PF17392; Urocanase_C; 1.
DR Pfam; PF17391; Urocanase_N; 1.
DR PIRSF; PIRSF001423; Urocanate_hydrat; 1.
DR SUPFAM; SSF111326; SSF111326; 1.
DR PROSITE; PS01233; UROCANASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Histidine metabolism; Lyase; NAD;
KW Reference proteome.
FT CHAIN 1..676
FT /note="Urocanate hydratase"
FT /id="PRO_0000207374"
FT REGION 15..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 126..127
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P25503"
FT BINDING 204
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P25503"
FT BINDING 251..253
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P25503"
FT BINDING 271
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P25503"
FT BINDING 317..318
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P25503"
FT BINDING 343..347
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P25503"
FT BINDING 354..355
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P25503"
FT BINDING 403
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P25503"
FT BINDING 594
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P25503"
FT VAR_SEQ 300
FT /note="L -> LRVLQLGLQQALGWAGLPAALGLCVLSCFVNLAPLGEGRCLAPSGFS
FT RPLLGAPVLLLCPS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15221005"
FT /id="VSP_045422"
FT VARIANT 70
FT /note="L -> P (in UROCD; dbSNP:rs137852796)"
FT /evidence="ECO:0000269|PubMed:19304569"
FT /id="VAR_062649"
FT VARIANT 188
FT /note="R -> W (in dbSNP:rs34488036)"
FT /id="VAR_034000"
FT VARIANT 311
FT /note="S -> T (in dbSNP:rs35062810)"
FT /id="VAR_034001"
FT VARIANT 429
FT /note="R -> C (in dbSNP:rs9871671)"
FT /id="VAR_042732"
FT VARIANT 450
FT /note="R -> C (in UROCD; loss of activity;
FT dbSNP:rs137852795)"
FT /evidence="ECO:0000269|PubMed:19304569"
FT /id="VAR_060221"
SQ SEQUENCE 676 AA; 74831 MW; C940D3D068648D17 CRC64;
MSSLQALCSG LPLRPLPENR GRQAGVPHAP VRTPSLSPVE KQLALRNALR YFPPDVQELL
APEFAQELQL YGHIYMYRFC PDIEMRAYPI EQYPCQTKVA AAIMHMIMNN LDPAVAQFPQ
ELVTYGGNGQ VFSNWAQFWL TMFYLSKMTE EQTLVMYSGH PLGLFPSSRS APRLVITNGM
VIPNYSSRTE YEKLFALGVT MYGQMTAGSY CYIGPQGIVH GTVLTVLNAA RRYLGIEDLA
GKVFVTSGLG GMSGAQAKAA VIVGCIGVIA EVDKAALEKR HRQGWLMEVT DSLDRCIQRL
REARKKKEVL SLGYHGNVVA LWERLVHELD TTGECLVDLG SDQTSCHNPF NGGYYPVQLS
FTEAQSLMAS NPAVFKDLVQ ESLRRQVSAI NRLAEEKFFF WDYGNAFLLE AQRAGADVEK
KGAGRTEFRY PSYVQHIMGD IFSQGFGPFR WVCTSGDPQD LAVTDELATS VLEEAIADGV
KVSVKLQYMD NIRWIREAAR HRLVVGSQAR ILYSDQKGRV AIAVAINQAI ACRRIKAPVV
LSRDHHDVSG TDSPFRETSN IYDGSAFCAD MAVQNFVGDA CRGATWVALH NGGGVGWGEV
INGGFGLVLD GTPEAEGRAR LMLSWDVSNG VARRCWSGNQ KAYEIICQTM QENSTLVVTL
PHKVEDERVL QQALQL
