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Protein

Histidine ammonia-lyase

Gene

HAL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Caution

Catalytic activityi

L-histidine = urocanate + NH3.PROSITE-ProRule annotation

Pathwayi: L-histidine degradation into L-glutamate

This protein is involved in step 1 of the subpathway that synthesizes N-formimidoyl-L-glutamate from L-histidine.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Histidine ammonia-lyase (HAL)
  2. Urocanate hydratase (UROC1)
  3. Probable imidazolonepropionase (AMDHD1)
This subpathway is part of the pathway L-histidine degradation into L-glutamate, which is itself part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes N-formimidoyl-L-glutamate from L-histidine, the pathway L-histidine degradation into L-glutamate and in Amino-acid degradation.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLyase
Biological processHistidine metabolism

Enzyme and pathway databases

BioCyciMetaCyc:HS01466-MONOMER
ReactomeiR-HSA-70921 Histidine catabolism
UniPathwayiUPA00379; UER00549

Names & Taxonomyi

Protein namesi
Recommended name:
Histidine ammonia-lyase (EC:4.3.1.3)
Short name:
Histidase
Gene namesi
Name:HAL
Synonyms:HIS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000084110.10
HGNCiHGNC:4806 HAL
MIMi609457 gene
neXtProtiNX_P42357

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Histidinemia (HISTID)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive disease characterized by increased histidine and histamine as well as decreased urocanic acid in body fluids.
See also OMIM:235800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022915206R → T in HISTID. 1 PublicationCorresponds to variant dbSNP:rs121434327Ensembl.1
Natural variantiVAR_022916208R → L in HISTID. 1 PublicationCorresponds to variant dbSNP:rs121434328Ensembl.1
Natural variantiVAR_022917259P → L in HISTID. 1 PublicationCorresponds to variant dbSNP:rs121434329Ensembl.1
Natural variantiVAR_022918322R → P in HISTID. 1 PublicationCorresponds to variant dbSNP:rs121434330Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3034
MalaCardsiHAL
MIMi235800 phenotype
OpenTargetsiENSG00000084110
Orphaneti2157 Histidinemia
PharmGKBiPA29181

Chemistry databases

ChEMBLiCHEMBL4003
DrugBankiDB00117 L-Histidine

Polymorphism and mutation databases

BioMutaiHAL
DMDMi1170423

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001610581 – 657Histidine ammonia-lyaseAdd BLAST657

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki253 ↔ 2555-imidazolinone (Ala-Gly)By similarity
Modified residuei2542,3-didehydroalanine (Ser)PROSITE-ProRule annotation1
Modified residuei396PhosphothreonineBy similarity1
Modified residuei635PhosphoserineBy similarity1
Modified residuei637PhosphothreonineBy similarity1
Modified residuei648PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP42357
PaxDbiP42357
PeptideAtlasiP42357
PRIDEiP42357

PTM databases

iPTMnetiP42357
PhosphoSitePlusiP42357

Expressioni

Gene expression databases

BgeeiENSG00000084110
CleanExiHS_HAL
ExpressionAtlasiP42357 baseline and differential
GenevisibleiP42357 HS

Organism-specific databases

HPAiHPA038547
HPA038548

Interactioni

Protein-protein interaction databases

BioGridi10928444 interactors.
IntActiP42357 1 interactor.
STRINGi9606.ENSP00000261208

Structurei

3D structure databases

ProteinModelPortaliP42357
SMRiP42357
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the PAL/histidase family.Curated

Phylogenomic databases

eggNOGiKOG0222 Eukaryota
COG2986 LUCA
GeneTreeiENSGT00390000009047
HOGENOMiHOG000237619
HOVERGENiHBG004509
InParanoidiP42357
KOiK01745
OMAiCAPQVAG
OrthoDBiEOG091G036O
PhylomeDBiP42357
TreeFamiTF313824

Family and domain databases

CDDicd00332 PAL-HAL, 1 hit
Gene3Di1.10.275.101 hit
InterProiView protein in InterPro
IPR001106 Aromatic_Lyase
IPR024083 Fumarase/histidase_N
IPR005921 HutH
IPR008948 L-Aspartase-like
IPR021922 Par3/HAL_N
IPR022313 Phe/His_NH3-lyase_AS
PANTHERiPTHR10362 PTHR10362, 1 hit
PfamiView protein in Pfam
PF12053 DUF3534, 1 hit
PF00221 Lyase_aromatic, 1 hit
SUPFAMiSSF48557 SSF48557, 1 hit
TIGRFAMsiTIGR01225 hutH, 1 hit
PROSITEiView protein in PROSITE
PS00488 PAL_HISTIDASE, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P42357-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPRYTVHVRG EWLAVPCQDA QLTVGWLGRE AVRRYIKNKP DNGGFTSVDD
60 70 80 90 100
AHFLVRRCKG LGLLDNEDRL EVALENNEFV EVVIEGDAMS PDFIPSQPEG
110 120 130 140 150
VYLYSKYREP EKYIELDGDR LTTEDLVNLG KGRYKIKLTP TAEKRVQKSR
160 170 180 190 200
EVIDSIIKEK TVVYGITTGF GKFARTVIPI NKLQELQVNL VRSHSSGVGK
210 220 230 240 250
PLSPERCRML LALRINVLAK GYSGISLETL KQVIEMFNAS CLPYVPEKGT
260 270 280 290 300
VGASGDLAPL SHLALGLVGE GKMWSPKSGW ADAKYVLEAH GLKPVILKPK
310 320 330 340 350
EGLALINGTQ MITSLGCEAV ERASAIARQA DIVAALTLEV LKGTTKAFDT
360 370 380 390 400
DIHALRPHRG QIEVAFRFRS LLDSDHHPSE IAESHRFCDR VQDAYTLRCC
410 420 430 440 450
PQVHGVVNDT IAFVKNIITT ELNSATDNPM VFANRGETVS GGNFHGEYPA
460 470 480 490 500
KALDYLAIGI HELAAISERR IERLCNPSLS ELPAFLVAEG GLNSGFMIAH
510 520 530 540 550
CTAAALVSEN KALCHPSSVD SLSTSAATED HVSMGGWAAR KALRVIEHVE
560 570 580 590 600
QVLAIELLAA CQGIEFLRPL KTTTPLEKVY DLVRSVVRPW IKDRFMAPDI
610 620 630 640 650
EAAHRLLLEQ KVWEVAAPYI EKYRMEHIPE SRPLSPTAFS LQFLHKKSTK

IPESEDL
Length:657
Mass (Da):72,698
Last modified:November 1, 1995 - v1
Checksum:i6B9FF97C066FB8F1
GO
Isoform 2 (identifier: P42357-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     589-657: PWIKDRFMAPDIEAAHRLLLEQKVWEVAAPYIEKYRMEHIPESRPLSPTAFSLQFLHKKSTKIPESEDL → FGK

Note: No experimental confirmation available.
Show »
Length:591
Mass (Da):64,888
Checksum:iDEBBCF642F5BC7DB
GO
Isoform 3 (identifier: P42357-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-208: Missing.

Note: No experimental confirmation available.
Show »
Length:449
Mass (Da):49,123
Checksum:iDD7DB9B250E4AFDA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti549V → M in BAG64570 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022915206R → T in HISTID. 1 PublicationCorresponds to variant dbSNP:rs121434327Ensembl.1
Natural variantiVAR_022916208R → L in HISTID. 1 PublicationCorresponds to variant dbSNP:rs121434328Ensembl.1
Natural variantiVAR_022917259P → L in HISTID. 1 PublicationCorresponds to variant dbSNP:rs121434329Ensembl.1
Natural variantiVAR_022918322R → P in HISTID. 1 PublicationCorresponds to variant dbSNP:rs121434330Ensembl.1
Natural variantiVAR_006042439V → I4 PublicationsCorresponds to variant dbSNP:rs7297245Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0460031 – 208Missing in isoform 3. 1 PublicationAdd BLAST208
Alternative sequenceiVSP_044704589 – 657PWIKD…ESEDL → FGK in isoform 2. 1 PublicationAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS58264.1 [P42357-3]
CCDS58265.1 [P42357-2]
CCDS9058.1 [P42357-1]
PIRiS43415
RefSeqiNP_001245262.1, NM_001258333.1 [P42357-3]
NP_001245263.1, NM_001258334.1 [P42357-2]
NP_002099.1, NM_002108.3 [P42357-1]
UniGeneiHs.190783
Hs.742210

Genome annotation databases

EnsembliENST00000261208; ENSP00000261208; ENSG00000084110 [P42357-1]
ENST00000538703; ENSP00000440861; ENSG00000084110 [P42357-2]
ENST00000541929; ENSP00000446364; ENSG00000084110 [P42357-3]
GeneIDi3034
KEGGihsa:3034
UCSCiuc001tem.2 human [P42357-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHUTH_HUMAN
AccessioniPrimary (citable) accession number: P42357
Secondary accession number(s): B4DQC1
, B4E0V8, F5GXF2, F5H1U5, Q4VB92, Q4VB93
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: March 28, 2018
This is version 164 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome