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P42357 (HUTH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histidine ammonia-lyase

Short name=Histidase
EC=4.3.1.3
Gene names
Name:HAL
Synonyms:HIS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length657 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

L-histidine = urocanate + NH3.

Pathway

Amino-acid degradation; L-histidine degradation into L-glutamate; N-formimidoyl-L-glutamate from L-histidine: step 1/3.

Post-translational modification

Contains an active site 4-methylidene-imidazol-5-one (MIO), which is formed autocatalytically by cyclization and dehydration of residues Ala-Ser-Gly By similarity.

Involvement in disease

Histidinemia (HISTID) [MIM:235800]: Autosomal recessive disease characterized by increased histidine and histamine as well as decreased urocanic acid in body fluids.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the PAL/histidase family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P42357-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P42357-2)

The sequence of this isoform differs from the canonical sequence as follows:
     589-657: PWIKDRFMAPDIEAAHRLLLEQKVWEVAAPYIEKYRMEHIPESRPLSPTAFSLQFLHKKSTKIPESEDL → FGK
Note: No experimental confirmation available.
Isoform 3 (identifier: P42357-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-208: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 657657Histidine ammonia-lyase
PRO_0000161058

Amino acid modifications

Modified residue25412,3-didehydroalanine (Ser) By similarity
Modified residue3961Phosphothreonine By similarity
Modified residue6481Phosphoserine By similarity
Cross-link253 ↔ 2555-imidazolinone (Ala-Gly) By similarity

Natural variations

Alternative sequence1 – 208208Missing in isoform 3.
VSP_046003
Alternative sequence589 – 65769PWIKD…ESEDL → FGK in isoform 2.
VSP_044704
Natural variant2061R → T in HISTID. Ref.7
VAR_022915
Natural variant2081R → L in HISTID. Ref.7
VAR_022916
Natural variant2591P → L in HISTID. Ref.7
VAR_022917
Natural variant3221R → P in HISTID. Ref.7
VAR_022918
Natural variant4391V → I. Ref.2 Ref.3 Ref.5 Ref.6
Corresponds to variant rs7297245 [ dbSNP | Ensembl ].
VAR_006042

Experimental info

Sequence conflict5491V → M in BAG64570. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 6B9FF97C066FB8F1

FASTA65772,698
        10         20         30         40         50         60 
MPRYTVHVRG EWLAVPCQDA QLTVGWLGRE AVRRYIKNKP DNGGFTSVDD AHFLVRRCKG 

        70         80         90        100        110        120 
LGLLDNEDRL EVALENNEFV EVVIEGDAMS PDFIPSQPEG VYLYSKYREP EKYIELDGDR 

       130        140        150        160        170        180 
LTTEDLVNLG KGRYKIKLTP TAEKRVQKSR EVIDSIIKEK TVVYGITTGF GKFARTVIPI 

       190        200        210        220        230        240 
NKLQELQVNL VRSHSSGVGK PLSPERCRML LALRINVLAK GYSGISLETL KQVIEMFNAS 

       250        260        270        280        290        300 
CLPYVPEKGT VGASGDLAPL SHLALGLVGE GKMWSPKSGW ADAKYVLEAH GLKPVILKPK 

       310        320        330        340        350        360 
EGLALINGTQ MITSLGCEAV ERASAIARQA DIVAALTLEV LKGTTKAFDT DIHALRPHRG 

       370        380        390        400        410        420 
QIEVAFRFRS LLDSDHHPSE IAESHRFCDR VQDAYTLRCC PQVHGVVNDT IAFVKNIITT 

       430        440        450        460        470        480 
ELNSATDNPM VFANRGETVS GGNFHGEYPA KALDYLAIGI HELAAISERR IERLCNPSLS 

       490        500        510        520        530        540 
ELPAFLVAEG GLNSGFMIAH CTAAALVSEN KALCHPSSVD SLSTSAATED HVSMGGWAAR 

       550        560        570        580        590        600 
KALRVIEHVE QVLAIELLAA CQGIEFLRPL KTTTPLEKVY DLVRSVVRPW IKDRFMAPDI 

       610        620        630        640        650 
EAAHRLLLEQ KVWEVAAPYI EKYRMEHIPE SRPLSPTAFS LQFLHKKSTK IPESEDL 

« Hide

Isoform 2 [UniParc].

Checksum: DEBBCF642F5BC7DB
Show »

FASTA59164,888
Isoform 3 [UniParc].

Checksum: DD7DB9B250E4AFDA
Show »

FASTA44949,123

References

« Hide 'large scale' references
[1]"Molecular cloning of a cDNA encoding human histidase."
Suchi M., Harada N., Wada Y., Takagi Y.
Biochim. Biophys. Acta 1216:293-295(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[2]"Molecular cloning and structural characterization of the human histidase gene (HAL)."
Suchi M., Sano H., Mizuno H., Wada Y.
Genomics 29:98-104(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-439.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), VARIANT ILE-439.
Tissue: Thymus.
[4]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-439.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ILE-439.
[7]"Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene."
Kawai Y., Moriyama A., Asai K., Coleman-Campbell C.M., Sumi S., Morishita H., Suchi M.
Hum. Genet. 116:340-346(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HISTID THR-206; LEU-208; LEU-259 AND PRO-322.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D16626 mRNA. Translation: BAA04047.1.
AB042217 Genomic DNA. Translation: BAB61863.1.
AK298736 mRNA. Translation: BAG60883.1.
AK303544 mRNA. Translation: BAG64570.1.
AC007298 Genomic DNA. No translation available.
AC126174 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97556.1.
BC096097 mRNA. Translation: AAH96097.1.
BC096098 mRNA. Translation: AAH96098.1.
BC096099 mRNA. Translation: AAH96099.1.
CCDSCCDS58264.1. [P42357-3]
CCDS58265.1. [P42357-2]
CCDS9058.1. [P42357-1]
PIRS43415.
RefSeqNP_001245262.1. NM_001258333.1. [P42357-3]
NP_001245263.1. NM_001258334.1. [P42357-2]
NP_002099.1. NM_002108.3. [P42357-1]
UniGeneHs.190783.
Hs.742210.

3D structure databases

ProteinModelPortalP42357.
SMRP42357. Positions 114-648.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109284. 1 interaction.
STRING9606.ENSP00000261208.

Chemistry

ChEMBLCHEMBL4003.
DrugBankDB00117. L-Histidine.

PTM databases

PhosphoSiteP42357.

Polymorphism databases

DMDM1170423.

Proteomic databases

MaxQBP42357.
PaxDbP42357.
PRIDEP42357.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261208; ENSP00000261208; ENSG00000084110. [P42357-1]
ENST00000538703; ENSP00000440861; ENSG00000084110. [P42357-2]
ENST00000541929; ENSP00000446364; ENSG00000084110. [P42357-3]
GeneID3034.
KEGGhsa:3034.
UCSCuc001tem.2. human. [P42357-1]

Organism-specific databases

CTD3034.
GeneCardsGC12M096366.
HGNCHGNC:4806. HAL.
HPAHPA038547.
HPA038548.
MIM235800. phenotype.
609457. gene.
neXtProtNX_P42357.
Orphanet2157. Histidinemia.
PharmGKBPA29181.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2986.
HOGENOMHOG000237619.
HOVERGENHBG004509.
InParanoidP42357.
KOK01745.
OMAVHIRDEW.
OrthoDBEOG73RB9V.
PhylomeDBP42357.
TreeFamTF313824.

Enzyme and pathway databases

BioCycMetaCyc:HS01466-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00379; UER00549.

Gene expression databases

ArrayExpressP42357.
BgeeP42357.
CleanExHS_HAL.
GenevestigatorP42357.

Family and domain databases

Gene3D1.10.275.10. 1 hit.
InterProIPR001106. Aromatic_Lyase.
IPR024083. Fumarase/histidase_N.
IPR005921. HutH.
IPR008948. L-Aspartase-like.
IPR022313. Phe/His_NH3-lyase_AS.
[Graphical view]
PfamPF00221. Lyase_aromatic. 1 hit.
[Graphical view]
SUPFAMSSF48557. SSF48557. 1 hit.
TIGRFAMsTIGR01225. hutH. 1 hit.
PROSITEPS00488. PAL_HISTIDASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHistidine_ammonia-lyase.
GenomeRNAi3034.
NextBio12010.
PROP42357.
SOURCESearch...

Entry information

Entry nameHUTH_HUMAN
AccessionPrimary (citable) accession number: P42357
Secondary accession number(s): B4DQC1 expand/collapse secondary AC list , B4E0V8, F5GXF2, F5H1U5, Q4VB92, Q4VB93
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM