HIS2_PICPA
ID HIS2_PICPA Reviewed; 842 AA.
AC P45353;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Histidine biosynthesis trifunctional protein;
DE Includes:
DE RecName: Full=Phosphoribosyl-AMP cyclohydrolase;
DE EC=3.5.4.19;
DE Includes:
DE RecName: Full=Phosphoribosyl-ATP pyrophosphohydrolase;
DE EC=3.6.1.31;
DE Includes:
DE RecName: Full=Histidinol dehydrogenase;
DE Short=HDH;
DE EC=1.1.1.23;
GN Name=HIS4;
OS Komagataella pastoris (Yeast) (Pichia pastoris).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Phaffomycetaceae; Komagataella.
OX NCBI_TaxID=4922;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7874737; DOI=10.1007/bf00309932;
RA Crane D.I., Gould S.J.;
RT "The Pichia pastoris HIS4 gene: nucleotide sequence, creation of a non-
RT reverting his4 deletion mutant, and development of HIS4-based replicating
RT and integrating plasmids.";
RL Curr. Genet. 26:443-450(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 76273 / CBS 7435 / CECT 11407 / NRRL Y-11430;
RA Koutz P.J., Davis G.R., Thill G.P.;
RL Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5-phospho-beta-D-ribosyl)-5'-AMP + H2O = 1-(5-phospho-beta-
CC D-ribosyl)-5-[(5-phospho-beta-D-
CC ribosylamino)methylideneamino]imidazole-4-carboxamide;
CC Xref=Rhea:RHEA:20049, ChEBI:CHEBI:15377, ChEBI:CHEBI:58435,
CC ChEBI:CHEBI:59457; EC=3.5.4.19;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5-phospho-beta-D-ribosyl)-ATP + H2O = 1-(5-phospho-beta-D-
CC ribosyl)-5'-AMP + diphosphate + H(+); Xref=Rhea:RHEA:22828,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:59457, ChEBI:CHEBI:73183; EC=3.6.1.31;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-histidinol + 2 NAD(+) = 3 H(+) + L-histidine + 2 NADH;
CC Xref=Rhea:RHEA:20641, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57595, ChEBI:CHEBI:57699,
CC ChEBI:CHEBI:57945; EC=1.1.1.23;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion. {ECO:0000250};
CC -!- PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine
CC from 5-phospho-alpha-D-ribose 1-diphosphate: step 2/9.
CC -!- PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine
CC from 5-phospho-alpha-D-ribose 1-diphosphate: step 3/9.
CC -!- PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine
CC from 5-phospho-alpha-D-ribose 1-diphosphate: step 9/9.
CC -!- SIMILARITY: In the C-terminal section; belongs to the histidinol
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; U14126; AAA67001.1; -; Genomic_DNA.
DR EMBL; X56180; CAA39641.1; -; Genomic_DNA.
DR PIR; S51513; S51513.
DR AlphaFoldDB; P45353; -.
DR SMR; P45353; -.
DR PRIDE; P45353; -.
DR UniPathway; UPA00031; UER00007.
DR UniPathway; UPA00031; UER00008.
DR UniPathway; UPA00031; UER00014.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004399; F:histidinol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0004635; F:phosphoribosyl-AMP cyclohydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0004636; F:phosphoribosyl-ATP diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0000105; P:histidine biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd06572; Histidinol_dh; 1.
DR Gene3D; 3.10.20.810; -; 1.
DR HAMAP; MF_01024; HisD; 1.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR008179; HisE.
DR InterPro; IPR016298; Histidine_synth_trifunct.
DR InterPro; IPR001692; Histidinol_DH_CS.
DR InterPro; IPR012131; Hstdl_DH.
DR InterPro; IPR021130; PRib-ATP_PPHydrolase-like.
DR InterPro; IPR002496; PRib_AMP_CycHydrolase_dom.
DR InterPro; IPR038019; PRib_AMP_CycHydrolase_sf.
DR PANTHER; PTHR21256; PTHR21256; 1.
DR Pfam; PF00815; Histidinol_dh; 1.
DR Pfam; PF01502; PRA-CH; 1.
DR Pfam; PF01503; PRA-PH; 1.
DR PIRSF; PIRSF001257; His_trifunctional; 1.
DR PRINTS; PR00083; HOLDHDRGNASE.
DR SUPFAM; SSF141734; SSF141734; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR TIGRFAMs; TIGR00069; hisD; 1.
DR TIGRFAMs; TIGR03188; histidine_hisI; 1.
DR PROSITE; PS00611; HISOL_DEHYDROGENASE; 1.
PE 3: Inferred from homology;
KW Amino-acid biosynthesis; ATP-binding; Histidine biosynthesis; Hydrolase;
KW Metal-binding; Multifunctional enzyme; NAD; Nucleotide-binding;
KW Oxidoreductase; Zinc.
FT CHAIN 1..842
FT /note="Histidine biosynthesis trifunctional protein"
FT /id="PRO_0000135912"
FT REGION 1..275
FT /note="Phosphoribosyl-AMP cyclohydrolase"
FT REGION 276..357
FT /note="Phosphoribosyl-ATP pyrophosphohydrolase"
FT REGION 358..842
FT /note="Histidinol dehydrogenase"
FT REGION 380..403
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 736
FT /evidence="ECO:0000250"
FT ACT_SITE 737
FT /evidence="ECO:0000250"
FT BINDING 667
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 670
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 769
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 828
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT CONFLICT 92
FT /note="R -> RM (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 507
FT /note="A -> T (in Ref. 2; CAA39641)"
FT /evidence="ECO:0000305"
FT CONFLICT 661
FT /note="V -> A (in Ref. 2; CAA39641)"
FT /evidence="ECO:0000305"
FT CONFLICT 746
FT /note="S -> SS (in Ref. 2; CAA39641)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 842 AA; 91942 MW; 67DA24E2266A4A3E CRC64;
MTFPLLPAYA SVAEFDNSLS LVGKAVFPYA ADQLHNLIKF TQSTELQVNV QVESSVTEDQ
FEELIDNLLK LYNNGINEVI LDLDLAERVV QRIPGARVIY RTLVDKVASL PANASIAVPF
SSPLGDLKSF TNGGSRTVYA FSETAKLVDV TSTVASGIIP IIDARQLTTE YELSEDVKKF
PVSEILLASL TTDRPDGLFT TLVADSSNYS LGLVYSSKKS IPEAIRTQTG VYQSRRHGLW
YKGATSGATQ KLLGIELDCD GDCLKFVVEQ TGVGFCHLER TSCFGQSKGL RAMEATLWDR
KSNAPEGSYT KRLFDDEVLL NAKIREEADE LAEAKSKEDI AWECADLFYF ALVRCAKYGV
TLDEVERNLD MKSLKVTRRK GDAKPGYTKE QPKEESKPKE VPSEGRIELC KIDVSKASSQ
EIEDALRRPI QKTEQIMELV KPIVDNVRQN GDKALLELTA KFDGVALKTP VLEAPFPEEL
MQLPDNVKRA IDLSIDNVRK FHEAQLAETL QVETCPGVVC SRFARPIEKV GLYIPGGTAI
LPSTSLMLGV PAKVAGCKEI VFASPPKKDG TLTPEVIYVA HKVGAKCIVL AGGAQAVAAM
AYGTETVPKC DKIFGPGNQF VTAAKMMVQN DTSALCSIDM PAGPSEVLVI ADKYADPDFV
VSDLLSQAEH GIDSQVILLA VDMTDKELAR IEDAVHNQAV QLPRVEIVRK CIAHSTTLSV
ATYEQALEMS NQYAPEHLIL QIENASYVDQ VQHAGSVFVG AYSPESCGDY SSGTNHTLPT
YGYARQYSGV NTATFQKFIT SQDVTPEGLK HIGQAVMDLA AVEGLDAHRN AVKVRMEKLG
LI
