HETR_NOSS1
ID HETR_NOSS1 Reviewed; 299 AA.
AC P27709;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=DNA-binding transcriptional activator HetR {ECO:0000255|HAMAP-Rule:MF_00781, ECO:0000303|PubMed:26576507};
DE EC=3.4.21.- {ECO:0000255|HAMAP-Rule:MF_00781, ECO:0000305|PubMed:9560210};
DE AltName: Full=Heterocyst differentiation control protein {ECO:0000255|HAMAP-Rule:MF_00781};
GN Name=hetR {ECO:0000255|HAMAP-Rule:MF_00781, ECO:0000303|PubMed:1840555};
GN OrderedLocusNames=alr2339;
OS Nostoc sp. (strain PCC 7120 / SAG 25.82 / UTEX 2576).
OC Bacteria; Cyanobacteria; Nostocales; Nostocaceae; Nostoc.
OX NCBI_TaxID=103690;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INDUCTION BY NITORGEN
RP LIMITATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASN-179.
RC STRAIN=PCC 7120 / SAG 25.82 / UTEX 2576;
RX PubMed=1840555; DOI=10.1101/gad.5.2.321;
RA Buikema W.J., Haselkorn R.;
RT "Characterization of a gene controlling heterocyst differentiation in the
RT cyanobacterium Anabaena 7120.";
RL Genes Dev. 5:321-330(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=PCC 7120 / SAG 25.82 / UTEX 2576;
RX PubMed=11759840; DOI=10.1093/dnares/8.5.205;
RA Kaneko T., Nakamura Y., Wolk C.P., Kuritz T., Sasamoto S., Watanabe A.,
RA Iriguchi M., Ishikawa A., Kawashima K., Kimura T., Kishida Y., Kohara M.,
RA Matsumoto M., Matsuno A., Muraki A., Nakazaki N., Shimpo S., Sugimoto M.,
RA Takazawa M., Yamada M., Yasuda M., Tabata S.;
RT "Complete genomic sequence of the filamentous nitrogen-fixing
RT cyanobacterium Anabaena sp. strain PCC 7120.";
RL DNA Res. 8:205-213(2001).
RN [3]
RP PROTEIN SEQUENCE OF 35-62; 77-83; 94-101; 166-198; 224-233 AND 251-274, AND
RP INDUCTION.
RA Chaurasia A.K., Apte S.K.;
RL Submitted (DEC-2008) to UniProtKB.
RN [4]
RP PROTEIN SEQUENCE OF 146-164, PROTEASE ACTIVITY, PROBABLE DISULFIDE BOND,
RP PROTEOLYTIC CLEAVAGE, ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF
RP SER-179.
RC STRAIN=PCC 7120 / SAG 25.82 / UTEX 2576;
RX PubMed=9560210; DOI=10.1073/pnas.95.9.4959;
RA Zhou R., Wei X., Jiang N., Li H., Dong Y., Hsi K.-L., Zhao J.;
RT "Evidence that HetR protein is an unusual serine-type protease.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:4959-4963(1998).
RN [5]
RP DEVELOPMENTAL STAGE, AND INDUCTION.
RC STRAIN=PCC 7120 / SAG 25.82 / UTEX 2576;
RX PubMed=8412673; DOI=10.1111/j.1365-2958.1993.tb01670.x;
RA Black T.A., Cai Y., Wolk C.P.;
RT "Spatial expression and autoregulation of hetR, a gene involved in the
RT control of heterocyst development in Anabaena.";
RL Mol. Microbiol. 9:77-84(1993).
RN [6]
RP ACTIVE SITE, INDUCTION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF SER-142
RP AND SER-152.
RC STRAIN=PCC 7120 / SAG 25.82 / UTEX 2576;
RX PubMed=10692362; DOI=10.1128/jb.182.6.1575-1579.2000;
RA Dong Y., Huang X., Wu X.-Y., Zhao J.;
RT "Identification of the active site of HetR protease and its requirement for
RT heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC
RT 7120.";
RL J. Bacteriol. 182:1575-1579(2000).
RN [7]
RP FUNCTION, HOMODIMERIZATION, INDUCTION, DISULFIDE BOND, DNA-BINDING, AND
RP MUTAGENESIS OF CYS-48 AND SER-179.
RC STRAIN=PCC 7120 / SAG 25.82 / UTEX 2576;
RX PubMed=15051891; DOI=10.1073/pnas.0400429101;
RA Huang X., Dong Y., Zhao J.;
RT "HetR homodimer is a DNA-binding protein required for heterocyst
RT differentiation, and the DNA-binding activity is inhibited by PatS.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4848-4853(2004).
RN [8] {ECO:0007744|PDB:4HRI}
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH DNA.
RA Hu H.X., Jiang Y.L., Zhao M.X., Zhu P.F., Yang X.Y., Wen B., Zhang Z.,
RA Wu Q., Chen Y., Zhang C.C., Zhou C.Z.;
RT "Structural and biochemical analyses of Anabaena HetR reveal insights into
RT its binding to DNA targets and the inhibitory hexapeptide ERGSGR.";
RL Submitted (OCT-2012) to the PDB data bank.
RN [9] {ECO:0007744|PDB:4LH9}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 256-295.
RA Hu H.X., Jiang Y.L., Zhao M.X., Zhu P., Yang X., Ren Y.M., Wen B.,
RA Zhang Z., Wu Q., Chen Y., Zhang C.C., Zhou C.Z.;
RT "Structural and biochemical analyses of Anabaena HetR reveal insights into
RT the cyanobacterial heterocyst development and pattern formation.";
RL Submitted (JUL-2013) to the PDB data bank.
RN [10] {ECO:0007744|PDB:4YNL, ECO:0007744|PDB:4YRV}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 219-299 (HOOD DOMAIN) IN COMPLEX
RP WITH PATS PEPTIDE, X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH
RP DNA, SUBUNIT, DOMAIN, DNA-BINDING, AND MUTAGENESIS OF ARG-223; GLU-253;
RP GLU-254; ASP-256; 270-ASP--ASP-278; ASP-270 AND ASP-278.
RX PubMed=26576507; DOI=10.1038/srep16470;
RA Hu H.X., Jiang Y.L., Zhao M.X., Cai K., Liu S., Wen B., Lv P., Zhang Y.,
RA Peng J., Zhong H., Yu H.M., Ren Y.M., Zhang Z., Tian C., Wu Q.,
RA Oliveberg M., Zhang C.C., Chen Y., Zhou C.Z.;
RT "Structural insights into HetR-PatS interaction involved in cyanobacterial
RT pattern formation.";
RL Sci. Rep. 5:16470-16470(2015).
CC -!- FUNCTION: Controls heterocyst differentiation. Dimerization is required
CC for DNA-binding. Has both a protease and a DNA-binding activity.
CC {ECO:0000255|HAMAP-Rule:MF_00781}.
CC -!- FUNCTION: Controls heterocyst differentiation; increased expression
CC leads to more heterocysts than usual (PubMed:1840555). Has protease
CC activity (PubMed:9560210). Binds the promoter regions of hetR, hepA and
CC patS and is required for their expression. Dimerization is required for
CC DNA-binding, DNA-binding is inhibited by the PatS6 peptide
CC (PubMed:15051891). In Nostoc filaments, approximately every 10th
CC vegetative cell terminally differentiates into a heterocyst specialized
CC for nitrogen fixation (PubMed:8412673, PubMed:10692362,
CC PubMed:15051891). {ECO:0000269|PubMed:10692362,
CC ECO:0000269|PubMed:15051891, ECO:0000269|PubMed:1840555,
CC ECO:0000269|PubMed:8412673, ECO:0000269|PubMed:9560210}.
CC -!- ACTIVITY REGULATION: Protease activity is inhibited by PMSF, suggesting
CC this is a serine protease. {ECO:0000269|PubMed:9560210}.
CC -!- SUBUNIT: Upon expression in E.coli most protein is monomeric, although
CC varying amounts of homodimer can be seen (Probable). Homodimer;
CC disulfide-linked (PubMed:15051891) (By similarity). Homodimer (Ref.8,
CC PubMed:26576507). Binds the 6 residue C-terminal peptide of PatS; one
CC peptide binds to each subunit (PubMed:26576507). {ECO:0000255|HAMAP-
CC Rule:MF_00781, ECO:0000269|PubMed:15051891,
CC ECO:0000269|PubMed:26576507, ECO:0000269|Ref.8,
CC ECO:0000305|PubMed:9560210}.
CC -!- INTERACTION:
CC P27709; P27709: hetR; NbExp=2; IntAct=EBI-15592082, EBI-15592082;
CC -!- DEVELOPMENTAL STAGE: Accumulates only in cells that are going to
CC differentiate into heterocysts. {ECO:0000305|PubMed:8412673}.
CC -!- INDUCTION: By nitrogen deficiency (at protein level). Activates its own
CC expression (PubMed:10692362, PubMed:1840555, PubMed:8412673).
CC Transcription increases quickly upon nitrogen reduction and remains
CC high during heterocyst differentiation (at least 24 hours).
CC Transcription is blocked by the C-terminal PatS peptide (sequence Arg-
CC Gly-Ser-Gly-Arg) (PubMed:15051891). {ECO:0000269|PubMed:10692362,
CC ECO:0000269|PubMed:15051891, ECO:0000269|PubMed:1840555,
CC ECO:0000269|PubMed:8412673, ECO:0000269|Ref.3}.
CC -!- DOMAIN: Has an N-terminal DNA-binding domain that inserts into the DNA
CC major groove, a central flap domain and C-terminal hood domain. The
CC hood domain binds the PatS6 peptide. Upon PatS6 binding the flap domain
CC probably moves considerably. {ECO:0000269|PubMed:26576507}.
CC -!- PTM: Probably autodegrades. {ECO:0000305|PubMed:10692362,
CC ECO:0000305|PubMed:9560210}.
CC -!- DISRUPTION PHENOTYPE: Unable to differentiate heterocysts, normal
CC vegetative growth. {ECO:0000269|PubMed:1840555}.
CC -!- SIMILARITY: Belongs to the peptidase S48 family. {ECO:0000255|HAMAP-
CC Rule:MF_00781}.
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DR EMBL; M37779; AAA21998.1; -; Genomic_DNA.
DR EMBL; BA000019; BAB74038.1; -; Genomic_DNA.
DR PIR; A38705; A38705.
DR PIR; AD2098; AD2098.
DR RefSeq; WP_010996495.1; NZ_RSCN01000004.1.
DR PDB; 4HRI; X-ray; 2.95 A; A/B=1-299.
DR PDB; 4LH9; X-ray; 2.05 A; A=256-295.
DR PDB; 4YNL; X-ray; 2.10 A; A/B/M/N=219-299.
DR PDB; 4YRV; X-ray; 2.80 A; A/B=1-299.
DR PDBsum; 4HRI; -.
DR PDBsum; 4LH9; -.
DR PDBsum; 4YNL; -.
DR PDBsum; 4YRV; -.
DR AlphaFoldDB; P27709; -.
DR SMR; P27709; -.
DR DIP; DIP-61232N; -.
DR IntAct; P27709; 1.
DR STRING; 103690.17131431; -.
DR MEROPS; S48.001; -.
DR EnsemblBacteria; BAB74038; BAB74038; BAB74038.
DR GeneID; 58722805; -.
DR KEGG; ana:alr2339; -.
DR eggNOG; ENOG502Z96Q; Bacteria.
DR OMA; HHIEPKR; -.
DR OrthoDB; 590352at2; -.
DR Proteomes; UP000002483; Chromosome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0043158; P:heterocyst differentiation; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.1670; -; 1.
DR Gene3D; 1.10.10.1680; -; 1.
DR HAMAP; MF_00781; HetR; 1.
DR InterPro; IPR040949; HetR_C.
DR InterPro; IPR041936; HetR_DNA-bd_N.
DR InterPro; IPR041935; HetR_flap.
DR InterPro; IPR005319; Pept_S48_HetR.
DR Pfam; PF18460; HetR_C; 1.
DR Pfam; PF03574; Peptidase_S48; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Autocatalytic cleavage; Direct protein sequencing;
KW Disulfide bond; DNA-binding; Heterocyst; Hydrolase; Protease;
KW Reference proteome; Serine protease; Transcription;
KW Transcription regulation.
FT CHAIN 1..299
FT /note="DNA-binding transcriptional activator HetR"
FT /id="PRO_0000208478"
FT REGION 1..98
FT /note="DNA-binding domain"
FT /evidence="ECO:0000269|PubMed:26576507"
FT REGION 99..216
FT /note="Flap domain"
FT /evidence="ECO:0000269|PubMed:26576507"
FT REGION 217..299
FT /note="Hood domain"
FT /evidence="ECO:0000269|PubMed:26576507"
FT ACT_SITE 152
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00781,
FT ECO:0000269|PubMed:10692362"
FT BINDING 34..40
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000269|PubMed:26576507"
FT BINDING 60..76
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000269|PubMed:26576507"
FT BINDING 179..181
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000269|PubMed:26576507"
FT DISULFID 48
FT /note="Interchain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00781,
FT ECO:0000269|PubMed:15051891, ECO:0000305|PubMed:9560210"
FT MUTAGEN 48
FT /note="C->A: Loss of homodimerization, does not form
FT heterocysts, not dominant to wild-type protein. Does not
FT bind DNA."
FT /evidence="ECO:0000269|PubMed:15051891"
FT MUTAGEN 142
FT /note="S->A: Behaves like wild-type."
FT /evidence="ECO:0000269|PubMed:10692362"
FT MUTAGEN 152
FT /note="S->A: Loss of protease activity, does not form
FT heterocysts, does not down-regulate its own expression."
FT /evidence="ECO:0000269|PubMed:10692362"
FT MUTAGEN 179
FT /note="S->N: In strain 216; unable to control heterocyst
FT differentiation, has no protease activity, homodimerizes,
FT binds DNA, dominant to wild-type protein."
FT /evidence="ECO:0000269|PubMed:15051891,
FT ECO:0000269|PubMed:1840555, ECO:0000269|PubMed:9560210"
FT MUTAGEN 223
FT /note="R->W: Greatly decreased PatS6 binding."
FT /evidence="ECO:0000269|PubMed:26576507"
FT MUTAGEN 253
FT /note="E->A: Loss of PatS6 binding, PatS6 no longer blocks
FT DNA-binding."
FT /evidence="ECO:0000269|PubMed:26576507"
FT MUTAGEN 254
FT /note="E->A: Decreased PatS6 binding, PatS still blocks
FT DNA-binding."
FT /evidence="ECO:0000269|PubMed:26576507"
FT MUTAGEN 256
FT /note="D->A: Decreased PatS6 binding."
FT /evidence="ECO:0000269|PubMed:26576507"
FT MUTAGEN 270..278
FT /note="DEIIRTWAD->AEIIRTWAA: Loss of PatS6 binding, PatS6
FT no longer blocks DNA-binding."
FT /evidence="ECO:0000269|PubMed:26576507"
FT MUTAGEN 270
FT /note="D->A: Decreased PatS6 binding."
FT /evidence="ECO:0000269|PubMed:26576507"
FT MUTAGEN 278
FT /note="D->A: Decreased PatS6 binding."
FT /evidence="ECO:0000269|PubMed:26576507"
FT HELIX 5..9
FT /evidence="ECO:0007829|PDB:4YRV"
FT HELIX 15..28
FT /evidence="ECO:0007829|PDB:4YRV"
FT HELIX 35..56
FT /evidence="ECO:0007829|PDB:4YRV"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:4HRI"
FT HELIX 61..68
FT /evidence="ECO:0007829|PDB:4YRV"
FT HELIX 72..87
FT /evidence="ECO:0007829|PDB:4YRV"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:4YRV"
FT HELIX 101..104
FT /evidence="ECO:0007829|PDB:4YRV"
FT HELIX 106..113
FT /evidence="ECO:0007829|PDB:4YRV"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:4YRV"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:4HRI"
FT HELIX 130..139
FT /evidence="ECO:0007829|PDB:4YRV"
FT HELIX 152..168
FT /evidence="ECO:0007829|PDB:4YRV"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:4YRV"
FT HELIX 180..192
FT /evidence="ECO:0007829|PDB:4YRV"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:4YRV"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:4HRI"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:4YRV"
FT HELIX 223..242
FT /evidence="ECO:0007829|PDB:4YNL"
FT STRAND 249..257
FT /evidence="ECO:0007829|PDB:4YNL"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:4YNL"
FT HELIX 263..280
FT /evidence="ECO:0007829|PDB:4LH9"
FT STRAND 285..296
FT /evidence="ECO:0007829|PDB:4YNL"
SQ SEQUENCE 299 AA; 34969 MW; 74AF6CA9D87F9126 CRC64;
MSNDIDLIKR LGPSAMDQIM LYLAFSAMRT SGHRHGAFLD AAATAAKCAI YMTYLEQGQN
LRMTGHLHHL EPKRVKIIVE EVRQALMEGK LLKTLGSQEP RYLIQFPYVW MEQYPWIPGR
SRIPGTSLTS EEKRQIEHKL PSNLPDAQLV TSFEFLELIE FLHKRSQEDL PPEHRMELSE
ALAEHIKRRL LYSGTVTRID SPWGMPFYAL TRPFYAPADD QERTYIMVED TARYFRMMKD
WAEKRPNAMR ALEELDVPPE RWDEAMQELD EIIRTWADKY HQVGGIPMIL QMVFGRKED
