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 27-MAR-2024, entry version 197. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 186. DR IntAct; P42357; 51. 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; 9606-ENSP00000261208; -. DR PeptideAtlas; P42357; -. DR PRIDE; P42357; -. DR ProteomicsDB; 24406; -. DR ProteomicsDB; 25764; -. DR ProteomicsDB; 55514; -. [P42357-1] DR Pumba; P42357; -. DR Antibodypedia; 30149; 174 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 AGR; HGNC:4806; -. 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; YSLRCMP; -. DR OrthoDB; 1030318at2759; -. DR PhylomeDB; P42357; -. DR TreeFam; TF313824; -. DR BioCyc; MetaCyc:HS01466-MONOMER; -. 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 1152 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 cell types or tissues. DR ExpressionAtlas; P42357; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. 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; 1.20.200.10; Fumarase/aspartase (Central domain); 1. DR Gene3D; 1.10.275.10; Fumarase/aspartase (N-terminal domain); 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 NCBIfam; TIGR01225; hutH; 1. DR PANTHER; PTHR10362; HISTIDINE AMMONIA-LYASE; 1. DR PANTHER; PTHR10362:SF7; HISTIDINE AMMONIA-LYASE; 1. DR Pfam; PF00221; Lyase_aromatic; 1. DR SUPFAM; SSF48557; L-aspartase-like; 1. DR PROSITE; PS00488; PAL_HISTIDASE; 1. DR Genevisible; P42357; HS. 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 //