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<entry dataset="Swiss-Prot" created="2006-12-12" modified="2026-06-10" version="111" xmlns="http://uniprot.org/uniprot">
  <accession>Q0T9X8</accession>
  <name>NRFA_ECOL5</name>
  <protein>
    <recommendedName>
      <fullName evidence="1">Cytochrome c-552</fullName>
      <ecNumber evidence="1">1.7.2.2</ecNumber>
    </recommendedName>
    <alternativeName>
      <fullName evidence="1">Ammonia-forming cytochrome c nitrite reductase</fullName>
      <shortName evidence="1">Cytochrome c nitrite reductase</shortName>
    </alternativeName>
  </protein>
  <gene>
    <name evidence="1" type="primary">nrfA</name>
    <name type="ordered locus">ECP_4303</name>
  </gene>
  <organism>
    <name type="scientific">Escherichia coli O6:K15:H31 (strain 536 / UPEC)</name>
    <dbReference type="NCBI Taxonomy" id="362663"/>
    <lineage>
      <taxon>Bacteria</taxon>
      <taxon>Pseudomonadati</taxon>
      <taxon>Pseudomonadota</taxon>
      <taxon>Gammaproteobacteria</taxon>
      <taxon>Enterobacterales</taxon>
      <taxon>Enterobacteriaceae</taxon>
      <taxon>Escherichia</taxon>
    </lineage>
  </organism>
  <reference key="1">
    <citation type="journal article" date="2006" name="Mol. Microbiol." volume="61" first="584" last="595">
      <title>Role of pathogenicity island-associated integrases in the genome plasticity of uropathogenic Escherichia coli strain 536.</title>
      <authorList>
        <person name="Hochhut B."/>
        <person name="Wilde C."/>
        <person name="Balling G."/>
        <person name="Middendorf B."/>
        <person name="Dobrindt U."/>
        <person name="Brzuszkiewicz E."/>
        <person name="Gottschalk G."/>
        <person name="Carniel E."/>
        <person name="Hacker J."/>
      </authorList>
      <dbReference type="PubMed" id="16879640"/>
      <dbReference type="DOI" id="10.1111/j.1365-2958.2006.05255.x"/>
    </citation>
    <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    <source>
      <strain>536 / UPEC</strain>
    </source>
  </reference>
  <comment type="function">
    <text evidence="1">Catalyzes the reduction of nitrite to ammonia, consuming six electrons in the process.</text>
  </comment>
  <comment type="catalytic activity">
    <reaction evidence="1">
      <text>6 Fe(III)-[cytochrome c] + NH4(+) + 2 H2O = 6 Fe(II)-[cytochrome c] + nitrite + 8 H(+)</text>
      <dbReference type="Rhea" id="RHEA:13089"/>
      <dbReference type="Rhea" id="RHEA-COMP:10350"/>
      <dbReference type="Rhea" id="RHEA-COMP:14399"/>
      <dbReference type="ChEBI" id="CHEBI:15377"/>
      <dbReference type="ChEBI" id="CHEBI:15378"/>
      <dbReference type="ChEBI" id="CHEBI:16301"/>
      <dbReference type="ChEBI" id="CHEBI:28938"/>
      <dbReference type="ChEBI" id="CHEBI:29033"/>
      <dbReference type="ChEBI" id="CHEBI:29034"/>
      <dbReference type="EC" id="1.7.2.2"/>
    </reaction>
  </comment>
  <comment type="cofactor">
    <cofactor evidence="1">
      <name>Ca(2+)</name>
      <dbReference type="ChEBI" id="CHEBI:29108"/>
    </cofactor>
    <text evidence="1">Binds 1 Ca(2+) ion per monomer.</text>
  </comment>
  <comment type="cofactor">
    <cofactor evidence="1">
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
    </cofactor>
    <text evidence="1">Binds 5 heme c groups covalently per monomer.</text>
  </comment>
  <comment type="pathway">
    <text evidence="1">Nitrogen metabolism; nitrate reduction (assimilation).</text>
  </comment>
  <comment type="subcellular location">
    <subcellularLocation>
      <location evidence="1">Periplasm</location>
    </subcellularLocation>
  </comment>
  <comment type="similarity">
    <text evidence="1">Belongs to the cytochrome c-552 family.</text>
  </comment>
  <dbReference type="EC" id="1.7.2.2" evidence="1"/>
  <dbReference type="EMBL" id="CP000247">
    <property type="protein sequence ID" value="ABG72251.1"/>
    <property type="molecule type" value="Genomic_DNA"/>
  </dbReference>
  <dbReference type="RefSeq" id="WP_000196879.1">
    <property type="nucleotide sequence ID" value="NC_008253.1"/>
  </dbReference>
  <dbReference type="AlphaFoldDB" id="Q0T9X8"/>
  <dbReference type="SMR" id="Q0T9X8"/>
  <dbReference type="KEGG" id="ecp:ECP_4303"/>
  <dbReference type="HOGENOM" id="CLU_035040_1_0_6"/>
  <dbReference type="UniPathway" id="UPA00653"/>
  <dbReference type="AbasyAtlas" id="Q0T9X8"/>
  <dbReference type="GO" id="GO:0030288">
    <property type="term" value="C:outer membrane-bounded periplasmic space"/>
    <property type="evidence" value="ECO:0000501"/>
    <property type="project" value="TreeGrafter"/>
  </dbReference>
  <dbReference type="GO" id="GO:0005509">
    <property type="term" value="F:calcium ion binding"/>
    <property type="evidence" value="ECO:0000501"/>
    <property type="project" value="UniProtKB-UniRule"/>
  </dbReference>
  <dbReference type="GO" id="GO:0020037">
    <property type="term" value="F:heme binding"/>
    <property type="evidence" value="ECO:0000501"/>
    <property type="project" value="InterPro"/>
  </dbReference>
  <dbReference type="GO" id="GO:0005506">
    <property type="term" value="F:iron ion binding"/>
    <property type="evidence" value="ECO:0000501"/>
    <property type="project" value="UniProtKB-UniRule"/>
  </dbReference>
  <dbReference type="GO" id="GO:0042279">
    <property type="term" value="F:nitrite reductase (cytochrome, ammonia-forming) activity"/>
    <property type="evidence" value="ECO:0000501"/>
    <property type="project" value="UniProtKB-UniRule"/>
  </dbReference>
  <dbReference type="GO" id="GO:0019645">
    <property type="term" value="P:anaerobic electron transport chain"/>
    <property type="evidence" value="ECO:0000501"/>
    <property type="project" value="TreeGrafter"/>
  </dbReference>
  <dbReference type="GO" id="GO:0042128">
    <property type="term" value="P:nitrate assimilation"/>
    <property type="evidence" value="ECO:0000501"/>
    <property type="project" value="UniProtKB-UniRule"/>
  </dbReference>
  <dbReference type="CDD" id="cd00548">
    <property type="entry name" value="NrfA-like"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="FunFam" id="1.10.1130.10:FF:000002">
    <property type="entry name" value="Cytochrome c-552"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="FunFam" id="1.20.140.10:FF:000014">
    <property type="entry name" value="Cytochrome c-552"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="Gene3D" id="1.20.140.10">
    <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="Gene3D" id="1.10.1130.10">
    <property type="entry name" value="Flavocytochrome C3, Chain A"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="HAMAP" id="MF_01182">
    <property type="entry name" value="Cytochrom_C552"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="InterPro" id="IPR003321">
    <property type="entry name" value="Cyt_c552"/>
  </dbReference>
  <dbReference type="InterPro" id="IPR017570">
    <property type="entry name" value="Cyt_c_NO2Rdtase_formate-dep"/>
  </dbReference>
  <dbReference type="InterPro" id="IPR036280">
    <property type="entry name" value="Multihaem_cyt_sf"/>
  </dbReference>
  <dbReference type="NCBIfam" id="TIGR03152">
    <property type="entry name" value="cyto_c552_HCOOH"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="NCBIfam" id="NF008339">
    <property type="entry name" value="PRK11125.1"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="PANTHER" id="PTHR30633:SF0">
    <property type="entry name" value="CYTOCHROME C-552"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="PANTHER" id="PTHR30633">
    <property type="entry name" value="CYTOCHROME C-552 RESPIRATORY NITRITE REDUCTASE"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="Pfam" id="PF02335">
    <property type="entry name" value="Cytochrom_C552"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="PIRSF" id="PIRSF000243">
    <property type="entry name" value="Cyt_c552"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="SUPFAM" id="SSF48695">
    <property type="entry name" value="Multiheme cytochromes"/>
    <property type="match status" value="1"/>
  </dbReference>
  <dbReference type="PROSITE" id="PS51008">
    <property type="entry name" value="MULTIHEME_CYTC"/>
    <property type="match status" value="1"/>
  </dbReference>
  <proteinExistence type="inferred from homology"/>
  <keyword id="KW-0106">Calcium</keyword>
  <keyword id="KW-0249">Electron transport</keyword>
  <keyword id="KW-0349">Heme</keyword>
  <keyword id="KW-0408">Iron</keyword>
  <keyword id="KW-0479">Metal-binding</keyword>
  <keyword id="KW-0560">Oxidoreductase</keyword>
  <keyword id="KW-0574">Periplasm</keyword>
  <keyword id="KW-0732">Signal</keyword>
  <keyword id="KW-0813">Transport</keyword>
  <feature type="signal peptide" evidence="1">
    <location>
      <begin position="1"/>
      <end position="26"/>
    </location>
  </feature>
  <feature type="chain" id="PRO_0000268965" description="Cytochrome c-552">
    <location>
      <begin position="27"/>
      <end position="478"/>
    </location>
  </feature>
  <feature type="binding site" description="axial binding residue" evidence="1">
    <location>
      <position position="94"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>3</label>
    </ligand>
    <ligandPart>
      <name>Fe</name>
      <dbReference type="ChEBI" id="CHEBI:18248"/>
    </ligandPart>
  </feature>
  <feature type="binding site" description="covalent" evidence="1">
    <location>
      <position position="122"/>
    </location>
    <ligand>
      <name>heme</name>
      <dbReference type="ChEBI" id="CHEBI:30413"/>
      <label>1</label>
    </ligand>
  </feature>
  <feature type="binding site" description="covalent" evidence="1">
    <location>
      <position position="125"/>
    </location>
    <ligand>
      <name>heme</name>
      <dbReference type="ChEBI" id="CHEBI:30413"/>
      <label>1</label>
    </ligand>
  </feature>
  <feature type="binding site" description="axial binding residue" evidence="1">
    <location>
      <position position="126"/>
    </location>
    <ligand>
      <name>heme</name>
      <dbReference type="ChEBI" id="CHEBI:30413"/>
      <label>1</label>
    </ligand>
    <ligandPart>
      <name>Fe</name>
      <dbReference type="ChEBI" id="CHEBI:18248"/>
    </ligandPart>
  </feature>
  <feature type="binding site" description="covalent" evidence="1">
    <location>
      <position position="160"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>2</label>
    </ligand>
  </feature>
  <feature type="binding site" description="covalent" evidence="1">
    <location>
      <position position="163"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>2</label>
    </ligand>
  </feature>
  <feature type="binding site" description="axial binding residue" evidence="1">
    <location>
      <position position="164"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>2</label>
    </ligand>
    <ligandPart>
      <name>Fe</name>
      <dbReference type="ChEBI" id="CHEBI:18248"/>
    </ligandPart>
  </feature>
  <feature type="binding site" description="covalent" evidence="1">
    <location>
      <position position="209"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>3</label>
    </ligand>
  </feature>
  <feature type="binding site" description="covalent" evidence="1">
    <location>
      <position position="212"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>3</label>
    </ligand>
  </feature>
  <feature type="binding site" description="axial binding residue" evidence="1">
    <location>
      <position position="213"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>3</label>
    </ligand>
    <ligandPart>
      <name>Fe</name>
      <dbReference type="ChEBI" id="CHEBI:18248"/>
    </ligandPart>
  </feature>
  <feature type="binding site" evidence="1">
    <location>
      <position position="215"/>
    </location>
    <ligand>
      <name>Ca(2+)</name>
      <dbReference type="ChEBI" id="CHEBI:29108"/>
    </ligand>
  </feature>
  <feature type="binding site" evidence="1">
    <location>
      <position position="216"/>
    </location>
    <ligand>
      <name>Ca(2+)</name>
      <dbReference type="ChEBI" id="CHEBI:29108"/>
    </ligand>
  </feature>
  <feature type="binding site" evidence="1">
    <location>
      <position position="216"/>
    </location>
    <ligand>
      <name>substrate</name>
    </ligand>
  </feature>
  <feature type="binding site" evidence="1">
    <location>
      <position position="261"/>
    </location>
    <ligand>
      <name>Ca(2+)</name>
      <dbReference type="ChEBI" id="CHEBI:29108"/>
    </ligand>
  </feature>
  <feature type="binding site" evidence="1">
    <location>
      <position position="263"/>
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    <ligand>
      <name>Ca(2+)</name>
      <dbReference type="ChEBI" id="CHEBI:29108"/>
    </ligand>
  </feature>
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    <location>
      <position position="264"/>
    </location>
    <ligand>
      <name>substrate</name>
    </ligand>
  </feature>
  <feature type="binding site" description="axial binding residue" evidence="1">
    <location>
      <position position="275"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>5</label>
    </ligand>
    <ligandPart>
      <name>Fe</name>
      <dbReference type="ChEBI" id="CHEBI:18248"/>
    </ligandPart>
  </feature>
  <feature type="binding site" description="covalent" evidence="1">
    <location>
      <position position="282"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>4</label>
    </ligand>
  </feature>
  <feature type="binding site" description="covalent" evidence="1">
    <location>
      <position position="285"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
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    </ligand>
  </feature>
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      <position position="286"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>4</label>
    </ligand>
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      <name>Fe</name>
      <dbReference type="ChEBI" id="CHEBI:18248"/>
    </ligandPart>
  </feature>
  <feature type="binding site" description="axial binding residue" evidence="1">
    <location>
      <position position="301"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>2</label>
    </ligand>
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      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>5</label>
    </ligand>
  </feature>
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    <location>
      <position position="317"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>5</label>
    </ligand>
  </feature>
  <feature type="binding site" description="axial binding residue" evidence="1">
    <location>
      <position position="318"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>5</label>
    </ligand>
    <ligandPart>
      <name>Fe</name>
      <dbReference type="ChEBI" id="CHEBI:18248"/>
    </ligandPart>
  </feature>
  <feature type="binding site" description="axial binding residue" evidence="1">
    <location>
      <position position="393"/>
    </location>
    <ligand>
      <name>heme c</name>
      <dbReference type="ChEBI" id="CHEBI:61717"/>
      <label>4</label>
    </ligand>
    <ligandPart>
      <name>Fe</name>
      <dbReference type="ChEBI" id="CHEBI:18248"/>
    </ligandPart>
  </feature>
  <evidence type="ECO:0000255" key="1">
    <source>
      <dbReference type="HAMAP-Rule" id="MF_01182"/>
    </source>
  </evidence>
  <sequence length="478" mass="53676" checksum="ED06CDA0A5849707" modified="2006-09-05" version="1" precursor="true">MTRIKINARRIFSLLIPFFFFTSVHAEQTAAPATPVTVEAKNETFAPQHPDQYLSWKATSEQSERVDALAEDPRLVILWAGYPFSRDYNKPRGHAFAVTDVRETLRTGAPKNAEDGPLPMACWSCKSPDVARLIQKDGEDGYFHGKWARGGPEIVNNLGCADCHNTASPEFAKGKPELTLSRPYAARAMEAIGKPFEKAGRFDQQSMVCGQCHVEYYFDGKNKAVKFPWDDGMKVENMEQYYDKIAFSDWTNSLSKTPMLKAQHPEYETWTAGIHGKNNVTCIDCHMPKVQNAEGKLYTDHKIGNPFDNFAQTCANCHTQDKAALQKVVAERKQSINDLKIKVEDQLVHAHFEAKAALDAGATEAEMKPIQDDIRHAQWRWDLAIASHGIHMHAPEEGLRMLGTAMDKAADARTKLARLLATKGITHEIQIPDISTKEKAQQAIGLNMEQIKAEKQDFIKTVIPQWEEQARKNGLLSQ</sequence>
</entry>
<copyright>
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms Distributed under the Creative Commons Attribution (CC BY 4.0) License
</copyright>
</uniprot>