CLFA_STAAE
ID CLFA_STAAE Reviewed; 933 AA.
AC Q53653; A6QF96;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 133.
DE RecName: Full=Clumping factor A;
DE AltName: Full=Fibrinogen receptor A;
DE AltName: Full=Fibrinogen-binding protein A;
DE Flags: Precursor;
GN Name=clfA; OrderedLocusNames=NWMN_0756;
OS Staphylococcus aureus (strain Newman).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=426430;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8170386; DOI=10.1111/j.1365-2958.1994.tb00304.x;
RA McDevitt D., Francois P., Vaudaux P., Foster T.J.;
RT "Molecular characterization of the clumping factor(fibrogen receptor of
RT Staphylococcus aureus.";
RL Mol. Microbiol. 11:237-248(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Newman;
RX PubMed=17951380; DOI=10.1128/jb.01000-07;
RA Baba T., Bae T., Schneewind O., Takeuchi F., Hiramatsu K.;
RT "Genome sequence of Staphylococcus aureus strain Newman and comparative
RT analysis of staphylococcal genomes: polymorphism and evolution of two major
RT pathogenicity islands.";
RL J. Bacteriol. 190:300-310(2008).
RN [3]
RP REGULATION, INDUCTION, AND MUTAGENESIS OF ASP-310; ASP-312; THR-318 AND
RP ASP-321.
RX PubMed=9506984; DOI=10.1074/jbc.273.12.6821;
RA O'Connell D.P., Nanavathy T., McDevitt D., Gurusiddappa S., Hoeoek M.,
RA Foster T.J.;
RT "The fibrinogen-binding MSCRAMM (clumping factor) of Staphylococcus aureus
RT has a Ca2+-dependent inhibitory site.";
RL J. Biol. Chem. 273:6821-6829(1998).
RN [4]
RP FUNCTION.
RX PubMed=10225887; DOI=10.1128/iai.67.5.2299-2305.1999;
RA Dominiecki M.E., Weiss J.;
RT "Antibacterial action of extracellular mammalian group IIA phospholipase A2
RT against grossly clumped Staphylococcus aureus.";
RL Infect. Immun. 67:2299-2305(1999).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11292731; DOI=10.1128/iai.69.5.3120-3127.2001;
RA Siboo I.R., Cheung A.L., Bayer A.S., Sullam P.M.;
RT "Clumping factor A mediates binding of Staphylococcus aureus to human
RT platelets.";
RL Infect. Immun. 69:3120-3127(2001).
RN [6]
RP FUNCTION, REGULATION, AND INDUCTION.
RX PubMed=12010496; DOI=10.1046/j.1365-2958.2002.02935.x;
RA O'Brien L.M., Kerrigan S.W., Kaw G., Hogan M., Penades J., Litt D.,
RA Fitzgerald D.J., Foster T.J., Cox D.;
RT "Multiple mechanisms for the activation of human platelet aggregation by
RT Staphylococcus aureus: roles for the clumping factors clfA and clfB, the
RT serine-aspartate repeat protein sdrE and protein A.";
RL Mol. Microbiol. 44:1033-1044(2002).
RN [7]
RP FUNCTION.
RX PubMed=14998517; DOI=10.1016/j.micinf.2003.11.005;
RA Palmqvist N., Patti J.M., Tarkowski A., Josefsson E.;
RT "Expression of staphylococcal clumping factor A impedes macrophage
RT phagocytosis.";
RL Microbes Infect. 6:188-195(2004).
RN [8]
RP REGULATION BY SIGMA-B.
RX PubMed=15664942; DOI=10.1128/iai.73.2.990-998.2005;
RA Entenza J.-M., Moreillon P., Senn M.M., Kormanec J., Dunman P.M.,
RA Berger-Baechi B., Projan S., Bischoff M.;
RT "Role of sigmaB in the expression of Staphylococcus aureus cell wall
RT adhesins clfA and fnbA and contribution to infectivity in a rat model of
RT experimental endocarditis.";
RL Infect. Immun. 73:990-998(2005).
RN [9]
RP SUBCELLULAR LOCATION.
RC STRAIN=Newman;
RX PubMed=18800056; DOI=10.1038/emboj.2008.185;
RA DeDent A., Bae T., Missiakas D.M., Schneewind O.;
RT "Signal peptides direct surface proteins to two distinct envelope locations
RT of Staphylococcus aureus.";
RL EMBO J. 27:2656-2668(2008).
RN [10]
RP CRYSTALLIZATION.
RX PubMed=10089377; DOI=10.1107/s0907444998012426;
RA Deivanayagam C.C.S., Perkins S., Danthuluri S., Owens R.T., Bice T.,
RA Nanavathy T., Foster T.J., Hoeoek M., Narayana S.V.L.;
RT "Crystallization of ClfA and ClfB fragments: the fibrinogen-binding surface
RT proteins of Staphylococcus aureus.";
RL Acta Crystallogr. D 55:554-556(1999).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 221-559, AND MUTAGENESIS OF
RP ALA-254; TYR-256; PRO-336; TYR-338; ILE-387 AND LYS-389.
RX PubMed=12485987; DOI=10.1093/emboj/cdf619;
RA Deivanayagam C.C.S., Wann E.R., Chen W., Carson M., Rajashankar K.R.,
RA Hoeoek M., Narayana S.V.;
RT "A novel variant of the immunoglobulin fold in surface adhesins of
RT Staphylococcus aureus: crystal structure of the fibrinogen-binding MSCRAMM,
RT clumping factor A.";
RL EMBO J. 21:6660-6672(2002).
CC -!- FUNCTION: Cell surface-associated protein implicated in virulence.
CC Promotes bacterial attachment exclusively to the gamma-chain of human
CC fibrinogen. Induces formation of bacterial clumps, which diminish the
CC ability of group IIA phospholipase A2 to cause bacterial phospholipid
CC hydrolysis and killing. Significantly decreases macrophage phagocytosis
CC possibly thanks to the clumps, clumped bacteria being too large to be
CC phagocytosed. Dominant factor responsible for human platelet
CC aggregation, which may be an important mechanism for initiating
CC infective endocarditis. Enhances spleen cell proliferative response in
CC vitro, contributing significantly to the immunostimulatory activity of
CC S.aureus. {ECO:0000269|PubMed:10225887, ECO:0000269|PubMed:11292731,
CC ECO:0000269|PubMed:12010496, ECO:0000269|PubMed:14998517}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE-
CC ProRule:PRU00477, ECO:0000269|PubMed:18800056}; Peptidoglycan-anchor
CC {ECO:0000255|PROSITE-ProRule:PRU00477}. Note=Found in a ring-like
CC distribution on the surface (PubMed:18800056). Anchored to the cell
CC wall by sortase A (By similarity). {ECO:0000250|UniProtKB:Q2G015,
CC ECO:0000269|PubMed:18800056}.
CC -!- INDUCTION: Expressed on cells from both exponential and stationary
CC phases. Up-regulated by sigma-B factor during later growth stages.
CC Sigma-B seems to have a transient enhancing effect on bacterial density
CC in the early stages of infection that it lost during later stages of
CC infection. {ECO:0000269|PubMed:12010496, ECO:0000269|PubMed:9506984}.
CC -!- MISCELLANEOUS: Fg-binding activity is regulated by the divalent cations
CC Ca(2+) and Mn(2+).
CC -!- SIMILARITY: Belongs to the serine-aspartate repeat-containing protein
CC (SDr) family. {ECO:0000305}.
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DR EMBL; Z18852; CAA79304.1; -; Genomic_DNA.
DR EMBL; AP009351; BAF67028.1; -; Genomic_DNA.
DR PIR; S41539; S41539.
DR RefSeq; WP_001056178.1; NZ_CP023390.1.
DR PDB; 1N67; X-ray; 1.90 A; A=221-559.
DR PDB; 5JQ6; X-ray; 2.40 A; A=229-545.
DR PDBsum; 1N67; -.
DR PDBsum; 5JQ6; -.
DR AlphaFoldDB; Q53653; -.
DR SMR; Q53653; -.
DR ChEMBL; CHEMBL3856168; -.
DR ABCD; Q53653; 16 sequenced antibodies.
DR EnsemblBacteria; BAF67028; BAF67028; NWMN_0756.
DR KEGG; sae:NWMN_0756; -.
DR HOGENOM; CLU_010159_0_0_9; -.
DR OMA; ATEWTTK; -.
DR EvolutionaryTrace; Q53653; -.
DR PHI-base; PHI:7743; -.
DR Proteomes; UP000006386; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR Gene3D; 2.60.40.1280; -; 1.
DR InterPro; IPR011266; Adhesin_Fg-bd_dom_2.
DR InterPro; IPR008966; Adhesion_dom_sf.
DR InterPro; IPR011252; Fibrogen-bd_dom1.
DR InterPro; IPR019931; LPXTG_anchor.
DR InterPro; IPR041171; SDR_Ig.
DR InterPro; IPR005877; YSIRK_signal_dom.
DR Pfam; PF17961; Big_8; 1.
DR Pfam; PF00746; Gram_pos_anchor; 1.
DR Pfam; PF10425; SdrG_C_C; 1.
DR Pfam; PF04650; YSIRK_signal; 1.
DR SUPFAM; SSF49401; SSF49401; 2.
DR TIGRFAMs; TIGR01168; YSIRK_signal; 1.
DR PROSITE; PS50847; GRAM_POS_ANCHORING; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell wall; Peptidoglycan-anchor; Secreted; Signal; Virulence.
FT SIGNAL 1..39
FT /evidence="ECO:0000255"
FT CHAIN 40..899
FT /note="Clumping factor A"
FT /id="PRO_0000041990"
FT PROPEP 900..933
FT /note="Removed by sortase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT /id="PRO_0000041991"
FT REGION 34..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 40..542
FT /note="Ligand binding A region"
FT REGION 529..904
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 9..20
FT /note="YSIRK-G/S signaling motif"
FT /evidence="ECO:0000305|PubMed:18800056"
FT MOTIF 896..900
FT /note="LPXTG sorting signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT COMPBIAS 36..200
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 552..566
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..614
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 615..859
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 860..886
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 899
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT MUTAGEN 254
FT /note="A->S: Decrease in Fg-binding activity."
FT /evidence="ECO:0000269|PubMed:12485987"
FT MUTAGEN 256
FT /note="Y->A: Decrease in Fg-binding activity."
FT /evidence="ECO:0000269|PubMed:12485987"
FT MUTAGEN 310
FT /note="D->A: Decrease in gamma-chain peptide-binding
FT activity and in the degree of inhibition induced by Ca(2+).
FT 3-fold decrease in gamma-chain peptide binding activity and
FT decrease in the degree of inhibition induced by Ca(2+);
FT when associated with A-312. Dramatic decrease in gamma-
FT chain peptide-binding activity and decrease in the degree
FT of inhibition induced by Ca(2+); when associated with A-
FT 312; A-318 and A-321."
FT /evidence="ECO:0000269|PubMed:9506984"
FT MUTAGEN 312
FT /note="D->A: 3-fold decrease in gamma-chain peptide binding
FT activity and decrease in the degree of inhibition induced
FT by Ca(2+); when associated with A-310. Dramatic decrease in
FT gamma-chain peptide-binding activity and decrease in the
FT degree of inhibition induced by Ca(2+); when associated
FT with A-310; A-318 and A-321."
FT /evidence="ECO:0000269|PubMed:9506984"
FT MUTAGEN 318
FT /note="T->A: Dramatic decrease in gamma-chain peptide-
FT binding activity and decrease in the degree of inhibition
FT induced by Ca(2+); when associated with A-310; A-312 and A-
FT 321."
FT /evidence="ECO:0000269|PubMed:9506984"
FT MUTAGEN 321
FT /note="D->A: Dramatic decrease in gamma-chain peptide-
FT binding activity and decrease in the degree of inhibition
FT induced by Ca(2+); when associated with A-310; A-312 and A-
FT 318."
FT /evidence="ECO:0000269|PubMed:9506984"
FT MUTAGEN 336
FT /note="P->S: Decrease in Fg-binding activity."
FT /evidence="ECO:0000269|PubMed:12485987"
FT MUTAGEN 338
FT /note="Y->A: No Fg-binding."
FT /evidence="ECO:0000269|PubMed:12485987"
FT MUTAGEN 387
FT /note="I->S: Decrease of Fg-binding activity."
FT /evidence="ECO:0000269|PubMed:12485987"
FT MUTAGEN 389
FT /note="K->A: Decrease of Fg-binding activity."
FT /evidence="ECO:0000269|PubMed:12485987"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 237..244
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:1N67"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:5JQ6"
FT STRAND 257..264
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 302..309
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:1N67"
FT HELIX 322..325
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 330..339
FT /evidence="ECO:0007829|PDB:1N67"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 346..356
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 359..367
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 378..382
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:1N67"
FT TURN 389..392
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 393..400
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 407..416
FT /evidence="ECO:0007829|PDB:1N67"
FT TURN 428..430
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 432..439
FT /evidence="ECO:0007829|PDB:1N67"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:1N67"
FT HELIX 452..454
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 455..457
FT /evidence="ECO:0007829|PDB:1N67"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 462..468
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 471..475
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 487..495
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 497..499
FT /evidence="ECO:0007829|PDB:5JQ6"
FT STRAND 503..512
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 519..527
FT /evidence="ECO:0007829|PDB:1N67"
FT STRAND 537..543
FT /evidence="ECO:0007829|PDB:1N67"
SQ SEQUENCE 933 AA; 97058 MW; EB51A6DE2FF759F4 CRC64;
MNMKKKEKHA IRKKSIGVAS VLVGTLIGFG LLSSKEADAS ENSVTQSDSA SNESKSNDSS
SVSAAPKTDD TNVSDTKTSS NTNNGETSVA QNPAQQETTQ SSSTNATTEE TPVTGEATTT
TTNQANTPAT TQSSNTNAEE LVNQTSNETT FNDTNTVSSV NSPQNSTNAE NVSTTQDTST
EATPSNNESA PQSTDASNKD VVNQAVNTSA PRMRAFSLAA VAADAPAAGT DITNQLTNVT
VGIDSGTTVY PHQAGYVKLN YGFSVPNSAV KGDTFKITVP KELNLNGVTS TAKVPPIMAG
DQVLANGVID SDGNVIYTFT DYVNTKDDVK ATLTMPAYID PENVKKTGNV TLATGIGSTT
ANKTVLVDYE KYGKFYNLSI KGTIDQIDKT NNTYRQTIYV NPSGDNVIAP VLTGNLKPNT
DSNALIDQQN TSIKVYKVDN AADLSESYFV NPENFEDVTN SVNITFPNPN QYKVEFNTPD
DQITTPYIVV VNGHIDPNSK GDLALRSTLY GYNSNIIWRS MSWDNEVAFN NGSGSGDGID
KPVVPEQPDE PGEIEPIPED SDSDPGSDSG SDSNSDSGSD SGSDSTSDSG SDSASDSDSA
SDSDSASDSD SASDSDSASD SDSDNDSDSD SDSDSDSDSD SDSDSDSDSD SDSDSDSDSD
SDSDSDSDSD SDSDSDSDSD SDSDSDSDSD SDSDSDSDSD SDSDSDSDSD SDSDSDSDSD
SDSDSDSDSD SDSDSDSDSD SDSDSDSDSD SDSDSDSDSD SDSDSDSASD SDSDSDSDSD
SDSDSDSDSD SDSDSDSDSD SDSDSDSESD SDSESDSDSD SDSDSDSDSD SDSDSDSASD
SDSGSDSDSS SDSDSESDSN SDSESGSNNN VVPPNSPKNG TNASNKNEAK DSKEPLPDTG
SEDEANTSLI WGLLASIGSL LLFRRKKENK DKK
