NADA1_NEIMB
ID NADA1_NEIMB Reviewed; 362 AA.
AC Q9JXK7;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 2.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Neisseria adhesin A {ECO:0000303|PubMed:12045242};
DE Short=NadA variant 1 {ECO:0000303|PubMed:12045242};
DE Flags: Precursor;
GN Name=nadA {ECO:0000303|PubMed:12045242}; Synonyms=nadA1 {ECO:0000305};
GN OrderedLocusNames=NMB1994 {ECO:0000303|PubMed:10710307};
OS Neisseria meningitidis serogroup B (strain MC58).
OC Bacteria; Proteobacteria; Betaproteobacteria; Neisseriales; Neisseriaceae;
OC Neisseria.
OX NCBI_TaxID=122586;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MC58;
RX PubMed=10710307; DOI=10.1126/science.287.5459.1809;
RA Tettelin H., Saunders N.J., Heidelberg J.F., Jeffries A.C., Nelson K.E.,
RA Eisen J.A., Ketchum K.A., Hood D.W., Peden J.F., Dodson R.J., Nelson W.C.,
RA Gwinn M.L., DeBoy R.T., Peterson J.D., Hickey E.K., Haft D.H.,
RA Salzberg S.L., White O., Fleischmann R.D., Dougherty B.A., Mason T.M.,
RA Ciecko A., Parksey D.S., Blair E., Cittone H., Clark E.B., Cotton M.D.,
RA Utterback T.R., Khouri H.M., Qin H., Vamathevan J.J., Gill J., Scarlato V.,
RA Masignani V., Pizza M., Grandi G., Sun L., Smith H.O., Fraser C.M.,
RA Moxon E.R., Rappuoli R., Venter J.C.;
RT "Complete genome sequence of Neisseria meningitidis serogroup B strain
RT MC58.";
RL Science 287:1809-1815(2000).
RN [2]
RP FUNCTION, SUBUNIT, INDUCTION, AND BIOTECHNOLOGY.
RC STRAIN=MC58;
RX PubMed=12045242; DOI=10.1084/jem.20020407;
RA Comanducci M., Bambini S., Brunelli B., Adu-Bobie J., Arico B.,
RA Capecchi B., Giuliani M.M., Masignani V., Santini L., Savino S.,
RA Granoff D.M., Caugant D.A., Pizza M., Rappuoli R., Mora M.;
RT "NadA, a novel vaccine candidate of Neisseria meningitidis.";
RL J. Exp. Med. 195:1445-1454(2002).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=MC58;
RX PubMed=15660996; DOI=10.1111/j.1365-2958.2004.04423.x;
RA Capecchi B., Adu-Bobie J., Di Marcello F., Ciucchi L., Masignani V.,
RA Taddei A., Rappuoli R., Pizza M., Arico B.;
RT "Neisseria meningitidis NadA is a new invasin which promotes bacterial
RT adhesion to and penetration into human epithelial cells.";
RL Mol. Microbiol. 55:687-698(2005).
RN [4]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RC STRAIN=MC58;
RX PubMed=19400792; DOI=10.1111/j.1365-2958.2009.06710.x;
RA Schielke S., Huebner C., Spatz C., Naegele V., Ackermann N., Frosch M.,
RA Kurzai O., Schubert-Unkmeir A.;
RT "Expression of the meningococcal adhesin NadA is controlled by a
RT transcriptional regulator of the MarR family.";
RL Mol. Microbiol. 72:1054-1067(2009).
RN [5]
RP EXPRESSION IN Y.ENTEROCOLITICA, INTERACTION WITH HUMAN INTEGRIN BETA-1,
RP PROBABLE SUBUNIT, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=MC58;
RX PubMed=21471204; DOI=10.1074/jbc.m110.188326;
RA Naegele V., Heesemann J., Schielke S., Jimenez-Soto L.F., Kurzai O.,
RA Ackermann N.;
RT "Neisseria meningitidis adhesin NadA targets beta1 integrins: functional
RT similarity to Yersinia invasin.";
RL J. Biol. Chem. 286:20536-20546(2011).
RN [6]
RP DISRUPTION PHENOTYPE.
RC STRAIN=MC58;
RX PubMed=22066472; DOI=10.1111/j.1462-5822.2011.01722.x;
RA Montanari P., Bozza G., Capecchi B., Caproni E., Barrile R., Norais N.,
RA Capitani M., Sallese M., Cecchini P., Ciucchi L., Gao Z., Rappuoli R.,
RA Pizza M., Arico B., Merola M.;
RT "Human heat shock protein (Hsp) 90 interferes with Neisseria meningitidis
RT adhesin A (NadA)-mediated adhesion and invasion.";
RL Cell. Microbiol. 14:368-385(2012).
CC -!- FUNCTION: Adheres to and induces bacterial uptake by human epithelial
CC cells (Probable). Upon expression in engineered Y.enterocolitica
CC confers an 11- to 15-fold increase in bacterial adherence and uptake by
CC human epithelial cell lines; part of the uptake is mediated by integrin
CC beta-1 (ITGB1) suggesting it may be a human receptor for NadA
CC (PubMed:21471204). A bacterial cell surface protein; antisera against
CC this protein induce complement-mediated killing of this and other
CC strains (PubMed:12045242). {ECO:0000269|PubMed:12045242,
CC ECO:0000269|PubMed:21471204, ECO:0000305|PubMed:15660996}.
CC -!- SUBUNIT: Forms high molecular weight oligomers in whole cell extracts
CC that are not disrupted by boiling in SDS buffer (PubMed:12045242).
CC Homotrimer (Probable). A fragment containing the N-terminal half of the
CC mature protein (residues 24-210, head domain plus part of the stalk)
CC binds human integrin beta-1 (ITGB1). It was not seen to bind
CC immobilized purified CEACAMs 1, 3, 5, 6 or 8 nor commercially prepared
CC type I collagen, fibronectin or matrigel (PubMed:21471204).
CC {ECO:0000269|PubMed:12045242, ECO:0000269|PubMed:21471204,
CC ECO:0000305|PubMed:21471204}.
CC -!- SUBCELLULAR LOCATION: Cell surface {ECO:0000269|PubMed:19400792,
CC ECO:0000305|PubMed:21471204}. Cell outer membrane
CC {ECO:0000305|PubMed:21471204}. Note=Cell outer membrane localization
CC shown in Y.enterocolitica. {ECO:0000269|PubMed:21471204}.
CC -!- INDUCTION: Barely visible in early log phase, levels increase to a
CC maximum in stationary phase cells (at protein level) (PubMed:12045242).
CC Transcription is repressed by NadR (FarR) (PubMed:19400792).
CC {ECO:0000269|PubMed:12045242, ECO:0000269|PubMed:19400792}.
CC -!- DOMAIN: The signal peptide, cleaved at the inner membrane, guides the
CC autotransporter protein to the periplasmic space. Insertion of the C-
CC terminal translocator domain in the outer membrane forms a hydrophilic
CC pore for the translocation of the passenger domain to the bacterial
CC cell surface (By similarity). The trimeric head domain (about residues
CC 24-169) is highly antigenic, it sits at the end of a coiled-coil stalk
CC (about residues 170-307) (By similarity).
CC {ECO:0000250|UniProtKB:A0ELI2, ECO:0000250|UniProtKB:P0C2W0}.
CC -!- DISRUPTION PHENOTYPE: Bacteria adhere 3-fold less well to human cells,
CC a double unencapsulated nadA-saiD deletion is 3-fold less invasive, a
CC triple nadA-opc-siaD deletion is about 10-fold less invasive
CC (PubMed:15660996). No change in invasion of human epithelial cell lines
CC that express or not integrin beta-1 (PubMed:21471204). Bacteria clump
CC more in the presence of human Chang cells, few clumps are associated
CC with human HSP90 (PubMed:22066472). {ECO:0000269|PubMed:15660996,
CC ECO:0000269|PubMed:21471204, ECO:0000269|PubMed:22066472}.
CC -!- BIOTECHNOLOGY: Several alleles exist that vary in length, this is
CC variant 1; alleles 1, 2 and 3 generate cross-bactericidal antibodies,
CC making this protein a good candidate for a serogroup B vaccine
CC molecule. About 50% of hypervirulent serogroup B N.meningitidis encode
CC this protein. {ECO:0000305|PubMed:12045242}.
CC -!- SIMILARITY: Belongs to the autotransporter-2 (AT-2) (TC 1.B.40) family.
CC {ECO:0000305}.
CC -!- CAUTION: The gene name nadA has also been given to quinolinate
CC synthase.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF42321.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305|PubMed:12045242};
CC -!- WEB RESOURCE: Name=Bexsero meningococcal group B Vaccine (4CMenB);
CC URL="https://www.ema.europa.eu/en/medicines/human/EPAR/bexsero";
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DR EMBL; AE002098; AAF42321.1; ALT_INIT; Genomic_DNA.
DR PIR; A81019; A81019.
DR RefSeq; NP_274986.1; NC_003112.2.
DR STRING; 122586.NMB1994; -.
DR PaxDb; Q9JXK7; -.
DR ABCD; Q9JXK7; 7 sequenced antibodies.
DR EnsemblBacteria; AAF42321; AAF42321; NMB1994.
DR KEGG; nme:NMB1994; -.
DR PATRIC; fig|122586.8.peg.2547; -.
DR HOGENOM; CLU_638628_0_0_4; -.
DR OMA; NAVDIDM; -.
DR Proteomes; UP000000425; Chromosome.
DR GO; GO:0009279; C:cell outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR InterPro; IPR045584; Pilin-like.
DR InterPro; IPR005594; YadA_C.
DR Pfam; PF03895; YadA_anchor; 1.
DR SUPFAM; SSF54523; SSF54523; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell outer membrane; Coiled coil; Membrane;
KW Reference proteome; Signal; Transmembrane; Transmembrane beta strand;
KW Transport; Virulence.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..362
FT /note="Neisseria adhesin A"
FT /evidence="ECO:0000255"
FT /id="PRO_5004329313"
FT TRANSMEM 307..317
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:A1JUB7"
FT TRANSMEM 321..332
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:A1JUB7"
FT TRANSMEM 339..345
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:A1JUB7"
FT TRANSMEM 351..362
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:A1JUB7"
FT REGION 24..169
FT /note="Head domain"
FT /evidence="ECO:0000250|UniProtKB:A0ELI2"
FT REGION 170..307
FT /note="Coiled stalk domain"
FT /evidence="ECO:0000250|UniProtKB:A0ELI2,
FT ECO:0000305|PubMed:15660996"
FT REGION 308..362
FT /note="Translocator domain"
FT /evidence="ECO:0000250|UniProtKB:P0C2W0"
FT COILED 90..146
FT /evidence="ECO:0000305|PubMed:12045242"
FT COILED 183..288
FT /evidence="ECO:0000305|PubMed:12045242"
SQ SEQUENCE 362 AA; 37754 MW; AF04A2CC6EF1ED3B CRC64;
MKHFPSKVLT TAILATFCSG ALAATSDDDV KKAATVAIVA AYNNGQEING FKAGETIYDI
GEDGTITQKD ATAADVEADD FKGLGLKKVV TNLTKTVNEN KQNVDAKVKA AESEIEKLTT
KLADTDAALA DTDAALDETT NALNKLGENI TTFAEETKTN IVKIDEKLEA VADTVDKHAE
AFNDIADSLD ETNTKADEAV KTANEAKQTA EETKQNVDAK VKAAETAAGK AEAAAGTANT
AADKAEAVAA KVTDIKADIA TNKADIAKNS ARIDSLDKNV ANLRKETRQG LAEQAALSGL
FQPYNVGRFN VTAAVGGYKS ESAVAIGTGF RFTENFAAKA GVAVGTSSGS SAAYHVGVNY
EW
