HUTH_HUMAN
ID HUTH_HUMAN Reviewed; 657 AA.
AC P42357; B4DQC1; B4E0V8; F5GXF2; F5H1U5; Q4VB92; Q4VB93;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Histidine ammonia-lyase;
DE Short=Histidase;
DE EC=4.3.1.3;
GN Name=HAL; Synonyms=HIS;
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).
RC TISSUE=Liver;
RX PubMed=7916645; DOI=10.1016/0167-4781(93)90157-9;
RA Suchi M., Harada N., Wada Y., Takagi Y.;
RT "Molecular cloning of a cDNA encoding human histidase.";
RL Biochim. Biophys. Acta 1216:293-295(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-439.
RX PubMed=8530107; DOI=10.1006/geno.1995.1219;
RA Suchi M., Sano H., Mizuno H., Wada Y.;
RT "Molecular cloning and structural characterization of the human histidase
RT gene (HAL).";
RL Genomics 29:98-104(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT
RP ILE-439.
RC TISSUE=Thymus;
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=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-439.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-439.
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 [7]
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).
RN [8]
RP VARIANTS HISTID THR-206; LEU-208; LEU-259 AND PRO-322.
RX PubMed=15806399; DOI=10.1007/s00439-004-1232-5;
RA Kawai Y., Moriyama A., Asai K., Coleman-Campbell C.M., Sumi S.,
RA Morishita H., Suchi M.;
RT "Molecular characterization of histidinemia: identification of four
RT missense mutations in the histidase gene.";
RL Hum. Genet. 116:340-346(2005).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-histidine = NH4(+) + trans-urocanate; Xref=Rhea:RHEA:21232,
CC ChEBI:CHEBI:17771, ChEBI:CHEBI:28938, ChEBI:CHEBI:57595; EC=4.3.1.3;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10122};
CC -!- PATHWAY: Amino-acid degradation; L-histidine degradation into L-
CC glutamate; N-formimidoyl-L-glutamate from L-histidine: step 1/3.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P42357-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P42357-2; Sequence=VSP_044704;
CC Name=3;
CC IsoId=P42357-3; Sequence=VSP_046003;
CC -!- PTM: Contains an active site 4-methylidene-imidazol-5-one (MIO), which
CC is formed autocatalytically by cyclization and dehydration of residues
CC Ala-Ser-Gly. {ECO:0000250}.
CC -!- DISEASE: Histidinemia (HISTID) [MIM:235800]: Autosomal recessive
CC disease characterized by increased histidine and histamine as well as
CC decreased urocanic acid in body fluids. {ECO:0000269|PubMed:15806399}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the PAL/histidase family. {ECO:0000305}.
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DR EMBL; D16626; BAA04047.1; -; mRNA.
DR EMBL; AB042217; BAB61863.1; -; Genomic_DNA.
DR EMBL; AK298736; BAG60883.1; -; mRNA.
DR EMBL; AK303544; BAG64570.1; -; mRNA.
DR EMBL; AC007298; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC126174; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW97556.1; -; Genomic_DNA.
DR EMBL; BC096097; AAH96097.1; -; mRNA.
DR EMBL; BC096098; AAH96098.1; -; mRNA.
DR EMBL; BC096099; AAH96099.1; -; mRNA.
DR CCDS; CCDS58264.1; -. [P42357-3]
DR CCDS; CCDS58265.1; -. [P42357-2]
DR CCDS; CCDS9058.1; -. [P42357-1]
DR PIR; S43415; S43415.
DR RefSeq; NP_001245262.1; NM_001258333.1. [P42357-3]
DR RefSeq; NP_001245263.1; NM_001258334.1. [P42357-2]
DR RefSeq; NP_002099.1; NM_002108.3. [P42357-1]
DR AlphaFoldDB; P42357; -.
DR SMR; P42357; -.
DR BioGRID; 109284; 171.
DR IntAct; P42357; 48.
DR MINT; P42357; -.
DR STRING; 9606.ENSP00000261208; -.
DR ChEMBL; CHEMBL4003; -.
DR DrugBank; DB00117; Histidine.
DR GlyGen; P42357; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P42357; -.
DR PhosphoSitePlus; P42357; -.
DR BioMuta; HAL; -.
DR DMDM; 1170423; -.
DR MassIVE; P42357; -.
DR MaxQB; P42357; -.
DR PaxDb; P42357; -.
DR PeptideAtlas; P42357; -.
DR PRIDE; P42357; -.
DR ProteomicsDB; 24406; -.
DR ProteomicsDB; 25764; -.
DR ProteomicsDB; 55514; -. [P42357-1]
DR Antibodypedia; 30149; 156 antibodies from 26 providers.
DR DNASU; 3034; -.
DR Ensembl; ENST00000261208.8; ENSP00000261208.3; ENSG00000084110.11. [P42357-1]
DR Ensembl; ENST00000538703.5; ENSP00000440861.1; ENSG00000084110.11. [P42357-2]
DR Ensembl; ENST00000541929.5; ENSP00000446364.1; ENSG00000084110.11. [P42357-3]
DR GeneID; 3034; -.
DR KEGG; hsa:3034; -.
DR MANE-Select; ENST00000261208.8; ENSP00000261208.3; NM_002108.4; NP_002099.1.
DR UCSC; uc001tem.2; human. [P42357-1]
DR CTD; 3034; -.
DR DisGeNET; 3034; -.
DR GeneCards; HAL; -.
DR HGNC; HGNC:4806; HAL.
DR HPA; ENSG00000084110; Group enriched (liver, skin).
DR MalaCards; HAL; -.
DR MIM; 235800; phenotype.
DR MIM; 609457; gene.
DR neXtProt; NX_P42357; -.
DR OpenTargets; ENSG00000084110; -.
DR Orphanet; 2157; Histidinemia.
DR PharmGKB; PA29181; -.
DR VEuPathDB; HostDB:ENSG00000084110; -.
DR eggNOG; KOG0222; Eukaryota.
DR GeneTree; ENSGT00390000009047; -.
DR HOGENOM; CLU_014801_4_1_1; -.
DR InParanoid; P42357; -.
DR OMA; CAPQVAG; -.
DR OrthoDB; 923557at2759; -.
DR PhylomeDB; P42357; -.
DR TreeFam; TF313824; -.
DR BioCyc; MetaCyc:HS01466-MON; -.
DR BRENDA; 4.3.1.3; 2681.
DR PathwayCommons; P42357; -.
DR Reactome; R-HSA-70921; Histidine catabolism.
DR SignaLink; P42357; -.
DR UniPathway; UPA00379; UER00549.
DR BioGRID-ORCS; 3034; 12 hits in 1072 CRISPR screens.
DR GeneWiki; Histidine_ammonia-lyase; -.
DR GenomeRNAi; 3034; -.
DR Pharos; P42357; Tbio.
DR PRO; PR:P42357; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P42357; protein.
DR Bgee; ENSG00000084110; Expressed in right lobe of liver and 116 other tissues.
DR ExpressionAtlas; P42357; baseline and differential.
DR Genevisible; P42357; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016841; F:ammonia-lyase activity; IBA:GO_Central.
DR GO; GO:0004397; F:histidine ammonia-lyase activity; EXP:Reactome.
DR GO; GO:0006548; P:histidine catabolic process; IBA:GO_Central.
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 CDD; cd00332; PAL-HAL; 1.
DR Gene3D; 1.10.275.10; -; 1.
DR InterPro; IPR001106; Aromatic_Lyase.
DR InterPro; IPR024083; Fumarase/histidase_N.
DR InterPro; IPR005921; HutH.
DR InterPro; IPR008948; L-Aspartase-like.
DR InterPro; IPR022313; Phe/His_NH3-lyase_AS.
DR PANTHER; PTHR10362; PTHR10362; 1.
DR Pfam; PF00221; Lyase_aromatic; 1.
DR SUPFAM; SSF48557; SSF48557; 1.
DR TIGRFAMs; TIGR01225; hutH; 1.
DR PROSITE; PS00488; PAL_HISTIDASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Histidine metabolism; Lyase;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..657
FT /note="Histidine ammonia-lyase"
FT /id="PRO_0000161058"
FT MOD_RES 254
FT /note="2,3-didehydroalanine (Ser)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10122"
FT MOD_RES 396
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35492"
FT MOD_RES 635
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P21213"
FT MOD_RES 637
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35492"
FT MOD_RES 648
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35492"
FT CROSSLNK 253..255
FT /note="5-imidazolinone (Ala-Gly)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..208
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046003"
FT VAR_SEQ 589..657
FT /note="PWIKDRFMAPDIEAAHRLLLEQKVWEVAAPYIEKYRMEHIPESRPLSPTAFS
FT LQFLHKKSTKIPESEDL -> FGK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044704"
FT VARIANT 206
FT /note="R -> T (in HISTID; dbSNP:rs121434327)"
FT /evidence="ECO:0000269|PubMed:15806399"
FT /id="VAR_022915"
FT VARIANT 208
FT /note="R -> L (in HISTID; dbSNP:rs121434328)"
FT /evidence="ECO:0000269|PubMed:15806399"
FT /id="VAR_022916"
FT VARIANT 259
FT /note="P -> L (in HISTID; dbSNP:rs121434329)"
FT /evidence="ECO:0000269|PubMed:15806399"
FT /id="VAR_022917"
FT VARIANT 322
FT /note="R -> P (in HISTID; dbSNP:rs121434330)"
FT /evidence="ECO:0000269|PubMed:15806399"
FT /id="VAR_022918"
FT VARIANT 439
FT /note="V -> I (in dbSNP:rs7297245)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8530107,
FT ECO:0000269|Ref.5"
FT /id="VAR_006042"
FT CONFLICT 549
FT /note="V -> M (in Ref. 3; BAG64570)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 657 AA; 72698 MW; 6B9FF97C066FB8F1 CRC64;
MPRYTVHVRG EWLAVPCQDA QLTVGWLGRE AVRRYIKNKP DNGGFTSVDD AHFLVRRCKG
LGLLDNEDRL EVALENNEFV EVVIEGDAMS PDFIPSQPEG VYLYSKYREP EKYIELDGDR
LTTEDLVNLG KGRYKIKLTP TAEKRVQKSR EVIDSIIKEK TVVYGITTGF GKFARTVIPI
NKLQELQVNL VRSHSSGVGK PLSPERCRML LALRINVLAK GYSGISLETL KQVIEMFNAS
CLPYVPEKGT VGASGDLAPL SHLALGLVGE GKMWSPKSGW ADAKYVLEAH GLKPVILKPK
EGLALINGTQ MITSLGCEAV ERASAIARQA DIVAALTLEV LKGTTKAFDT DIHALRPHRG
QIEVAFRFRS LLDSDHHPSE IAESHRFCDR VQDAYTLRCC PQVHGVVNDT IAFVKNIITT
ELNSATDNPM VFANRGETVS GGNFHGEYPA KALDYLAIGI HELAAISERR IERLCNPSLS
ELPAFLVAEG GLNSGFMIAH CTAAALVSEN KALCHPSSVD SLSTSAATED HVSMGGWAAR
KALRVIEHVE QVLAIELLAA CQGIEFLRPL KTTTPLEKVY DLVRSVVRPW IKDRFMAPDI
EAAHRLLLEQ KVWEVAAPYI EKYRMEHIPE SRPLSPTAFS LQFLHKKSTK IPESEDL
