ID   HHUA_HAEIF              Reviewed;        1046 AA.
AC   Q48153;
DT   29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT   29-AUG-2001, sequence version 2.
DT   03-AUG-2022, entry version 93.
DE   RecName: Full=Hemoglobin-haptoglobin-binding protein A;
DE   AltName: Full=Hemoglobin-haptoglobin utilization protein A;
DE   Flags: Precursor;
GN   Name=hhuA;
OS   Haemophilus influenzae.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC   Pasteurellaceae; Haemophilus.
OX   NCBI_TaxID=727;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=NTHi TN106;
RX   PubMed=8751920; DOI=10.1128/iai.64.9.3703-3712.1996;
RA   Maciver I., Latimer J.L., Liem H.H., Mueller-Eberhard U., Hrkal Z.,
RA   Hansen E.J.;
RT   "Identification of an outer membrane protein involved in utilization of
RT   hemoglobin-haptoglobin complexes by nontypeable Haemophilus influenzae.";
RL   Infect. Immun. 64:3703-3712(1996).
CC   -!- FUNCTION: Acts as a receptor for the hemoglobin/haptoglobin complex of
CC       the human host and is required for heme uptake. Does not bind
CC       hemoglobin alone.
CC   -!- SUBCELLULAR LOCATION: Cell outer membrane.
CC   -!- MISCELLANEOUS: This protein is subject to phase-variable expression
CC       associated with alteration in the length of the CCAA repeat region.
CC       This mechanism is called slipped-strand mispairing. Addition or loss of
CC       CCAA repeat units would change the reading frame and result in
CC       introduction of stop codons downstream of the repeat region. This may
CC       be a mechanism of regulation and a way to avoid the immunological
CC       response of the host.
CC   -!- SIMILARITY: Belongs to the TonB-dependent receptor family.
CC       Hemoglobin/haptoglobin binding protein subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB36696.1; Type=Frameshift; Note=The actual position is difficult to determine as it occurs within the QPTN repeats.; Evidence={ECO:0000305};
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DR   EMBL; U43198; AAB36696.1; ALT_SEQ; Genomic_DNA.
DR   AlphaFoldDB; Q48153; -.
DR   GO; GO:0009279; C:cell outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR   GO; GO:0006811; P:ion transport; IEA:UniProt.
DR   GO; GO:0071702; P:organic substance transport; IEA:UniProt.
DR   Gene3D; 2.170.130.10; -; 1.
DR   Gene3D; 2.40.170.20; -; 2.
DR   InterPro; IPR039426; BtuB-like.
DR   InterPro; IPR012910; Plug_dom.
DR   InterPro; IPR037066; Plug_dom_sf.
DR   InterPro; IPR006970; PT.
DR   InterPro; IPR000531; TonB-dep_rcpt_b-brl.
DR   InterPro; IPR010949; TonB_Hb/transfer/lactofer_rcpt.
DR   InterPro; IPR036942; TonB_rcpt_b-brl_sf.
DR   InterPro; IPR010917; TonB_rcpt_CS.
DR   PANTHER; PTHR30069; PTHR30069; 1.
DR   Pfam; PF07715; Plug; 1.
DR   Pfam; PF04886; PT; 1.
DR   Pfam; PF00593; TonB_dep_Rec; 1.
DR   TIGRFAMs; TIGR01786; TonB-hemlactrns; 1.
DR   PROSITE; PS01156; TONB_DEPENDENT_REC_2; 1.
PE   3: Inferred from homology;
KW   Cell outer membrane; Membrane; Receptor; Repeat; Signal; TonB box;
KW   Transmembrane; Transmembrane beta strand; Transport.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..1046
FT                   /note="Hemoglobin-haptoglobin-binding protein A"
FT                   /id="PRO_0000034784"
FT   REPEAT          26..29
FT                   /note="1"
FT   REPEAT          30..33
FT                   /note="2"
FT   REPEAT          34..37
FT                   /note="3"
FT   REPEAT          38..41
FT                   /note="4"
FT   REGION          26..41
FT                   /note="4 X 4 AA tandem repeats of Q-P-T-N"
FT   MOTIF           51..58
FT                   /note="TonB box"
FT   MOTIF           1029..1046
FT                   /note="TonB C-terminal box"
SQ   SEQUENCE   1046 AA;  119296 MW;  A5D208A68D27A84E CRC64;
     MTNFRLNLLA YSVMLGLTAG VAYAAQPTNQ PTNQPTNQPT NQDGNVSEQL EQINVLGSDN
     HNDNTPPKIA ETIKTAKKPE KEQAQDVKDL VRYETGITVV EAGRFGNSGF AVRGVDENRV
     AVQIDGLHQA ETISSQGFKE LFEGYGNFNN TRNTAEIETL KQVTIRKGAD SLKSGSGALG
     GSVSFDTKDA RDYLLNKNYY ASYKRGYNTA DNQNLQTLTL AGRYKYFDAI AVITSRKGHE
     LENYGYKNYN DRIQGREREK ADPYRRTQES KLLKFAFQPT ENHRLSVVVD LYKQTSKGHD
     FSYTLKQNTE HMTYDEVELR HTNDKVDRKN LAFTYENFTE TPFWDTLKIS YSHQKITTTA
     RTDDYCDGND KCALAGNPLG MKYNQDNQLV GEDGNLAKYK DINTKQTIHE KLPFTKPNEK
     WRYNRVDWDA LKKKYPGVPI YASCIEENND PSKYCSYDVE IPKKENTFEI NGKQYDLLSE
     ADKNVISDEQ RLPTNSSYLF SCDGLNCDKD TIQGFEKKGT TVNIPFVVIE KNGKKYAKTE
     AVANNQLSGP YIFMPSKTGY QTNLWTQRDL TSETKQINLD LTKHLELGKT QHDLSYGGLW
     SEMEKSMTNI SGDSPMNVKW WAQYPHSCDI FLPSSTPNGA PTLNPERTNT LCNNSNVYSF
     LIPVKTKTGA LYFINDFRVN SHIAFNFGYR YDRVKYDPEY IPGKTPKIPD DMVVNLYVKQ
     PTFDDTKVNL PPEELRKKEA NAAANIKAIV QPKKFSASSY SVGTTLDPLN WLRLQAKYGK
     AFRAPTSDEI YFTFLHPDFS IRPNRDLQAE TAKTKELALT LHNEIGYVTT SVFDTRYRNF
     IDLAYKGLYN VQRHSKLTPY HTYQNVNRPN AKVTGWEIAA QISLGKITQF LNGLNLSYKY
     TYQKGRIDGN IPMNAIQPKT SVYGVSYAHP ADKFGLDLYF THVSAKNAED TYNMFYKEEG
     KKDSTIKWRS KSYTTIDLLG YIKPIKNLTL RAGVYNLTNR KYITWDSARS IRPFGTSNMI
     NQKTGEGINR FYAPGRNYRM SVQFEF