CLFA_STAA8
ID CLFA_STAA8 Reviewed; 927 AA.
AC Q2G015;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 25-MAY-2022, entry version 98.
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=SAOUHSC_00812;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC 8325 / PS 47;
RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT "The Staphylococcus aureus NCTC 8325 genome.";
RL (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL D.C. (2006).
RN [2]
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 [3]
RP MUTAGENESIS OF ASN-525; GLU-526; VAL-527; ALA-528; GLY-532; ASP-537;
RP GLU-546 AND GLU-559.
RX PubMed=11044451; DOI=10.1074/jbc.m007979200;
RA Hartford O.M., Wann E.R., Hoeoek M., Foster T.J.;
RT "Identification of residues in the Staphylococcus aureus fibrinogen-binding
RT MSCRAMM clumping factor A (ClfA) that are important for ligand binding.";
RL J. Biol. Chem. 276:2466-2473(2001).
RN [4]
RP SUBCELLULAR LOCATION, AND PROCESSING BY SORTASE A.
RC STRAIN=RN4220;
RX PubMed=11830639; DOI=10.1073/pnas.032523999;
RA Mazmanian S.K., Ton-That H., Su K., Schneewind O.;
RT "An iron-regulated sortase anchors a class of surface protein during
RT Staphylococcus aureus pathogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:2293-2298(2002).
RN [5]
RP SUBCELLULAR LOCATION.
RC STRAIN=RN4220;
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).
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}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE-
CC ProRule:PRU00477, ECO:0000269|PubMed:18800056,
CC ECO:0000305|PubMed:11830639}; Peptidoglycan-anchor
CC {ECO:0000255|PROSITE-ProRule:PRU00477, ECO:0000305|PubMed:11830639}.
CC Note=Found in a ring-like distribution on the cell surface
CC (PubMed:18800056). Does not localize with SasF (PubMed:18800056).
CC Exchanging the ClfA and SasF signal peptides retargets the mature
CC protein on the cell surface (PubMed:18800056). Anchored to the cell
CC wall by sortase A (Probable). {ECO:0000269|PubMed:18800056,
CC ECO:0000305|PubMed:11830639}.
CC -!- SIMILARITY: Belongs to the serine-aspartate repeat-containing protein
CC (SDr) family. {ECO:0000305}.
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DR EMBL; CP000253; ABD29940.1; -; Genomic_DNA.
DR RefSeq; WP_001056234.1; NZ_LS483365.1.
DR RefSeq; YP_499368.1; NC_007795.1.
DR PDB; 2VR3; X-ray; 1.95 A; A/B=229-545.
DR PDBsum; 2VR3; -.
DR AlphaFoldDB; Q2G015; -.
DR SMR; Q2G015; -.
DR STRING; 1280.SAXN108_0856; -.
DR EnsemblBacteria; ABD29940; ABD29940; SAOUHSC_00812.
DR GeneID; 3919375; -.
DR KEGG; sao:SAOUHSC_00812; -.
DR PATRIC; fig|93061.5.peg.734; -.
DR eggNOG; COG2931; Bacteria.
DR eggNOG; COG3266; Bacteria.
DR HOGENOM; CLU_010159_0_0_9; -.
DR OMA; ATEWTTK; -.
DR EvolutionaryTrace; Q2G015; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0070051; F:fibrinogen binding; IMP:CAFA.
DR GO; GO:0001968; F:fibronectin binding; IPI:CAFA.
DR GO; GO:0098630; P:aggregation of unicellular organisms; IMP:CAFA.
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; Reference proteome;
KW Secreted; Signal; Virulence.
FT SIGNAL 1..39
FT /evidence="ECO:0000255"
FT CHAIN 40..893
FT /note="Clumping factor A"
FT /id="PRO_0000249324"
FT PROPEP 894..927
FT /note="Removed by sortase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477,
FT ECO:0000305|PubMed:11830639"
FT /id="PRO_0000249325"
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..898
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 890..894
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..853
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 854..880
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 893
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT MUTAGEN 525
FT /note="N->A: 2-fold reduction in clumping titer compared to
FT wild-type."
FT /evidence="ECO:0000269|PubMed:11044451"
FT MUTAGEN 526..527
FT /note="EV->AS: More than 1000-fold reduction in clumping
FT titer compared to wild-type. No binding to soluble Fg.
FT Dramatic reduction of ability to adhere to immobilized Fg."
FT MUTAGEN 526
FT /note="E->A: 32-fold reduction in clumping titer compared
FT to wild-type. Reduced ability to bind to soluble Fg and to
FT adhere to immobilized Fg."
FT /evidence="ECO:0000269|PubMed:11044451"
FT MUTAGEN 527
FT /note="V->S: 16- to 32-fold reduction in clumping titer
FT compared to wild-type. activity. Reduced ability to bind to
FT soluble Fg and to adhere to immobilized Fg."
FT /evidence="ECO:0000269|PubMed:11044451"
FT MUTAGEN 528
FT /note="A->V: 2-fold reduction in clumping titer compared to
FT wild-type; when associated with A-532."
FT /evidence="ECO:0000269|PubMed:11044451"
FT MUTAGEN 532
FT /note="G->A: 2-fold reduction in clumping titer compared to
FT wild-type; when associated with V-528."
FT /evidence="ECO:0000269|PubMed:11044451"
FT MUTAGEN 537
FT /note="D->A: 2-fold reduction in clumping titer compared to
FT wild-type."
FT /evidence="ECO:0000269|PubMed:11044451"
FT MUTAGEN 546
FT /note="E->A: 2-fold reduction in clumping titer compared to
FT wild-type."
FT /evidence="ECO:0000269|PubMed:11044451"
FT MUTAGEN 559
FT /note="E->A: 2-fold reduction in clumping titer compared to
FT wild-type."
FT /evidence="ECO:0000269|PubMed:11044451"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 237..244
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 257..265
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:2VR3"
FT HELIX 322..325
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 326..339
FT /evidence="ECO:0007829|PDB:2VR3"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 346..356
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 359..367
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 378..388
FT /evidence="ECO:0007829|PDB:2VR3"
FT TURN 389..392
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 393..401
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 407..416
FT /evidence="ECO:0007829|PDB:2VR3"
FT TURN 428..430
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 432..437
FT /evidence="ECO:0007829|PDB:2VR3"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:2VR3"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 462..468
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 471..475
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 487..495
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 505..512
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 518..530
FT /evidence="ECO:0007829|PDB:2VR3"
FT STRAND 533..540
FT /evidence="ECO:0007829|PDB:2VR3"
SQ SEQUENCE 927 AA; 96448 MW; B429AEB92AEFCABB CRC64;
MNMKKKEKHA IRKKSIGVAS VLVGTLIGFG LLSSKEADAS ENSVTQSDSA SNESKSNDSS
SVSAAPKTDD TNVSDTKTSS NTNNGETSVA QNPAQQETTQ SSSTNATTEE TPVTGEATTT
TTNQANTPAT TQSSNTNAEE LVNQTSNETT SNDTNTVSSV NSPQNSTNAE NVSTTQDTST
EATPSNNESA PQSTDASNKD VVNQAVNTSA PRMRAFSLAA VAADAPVAGT 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 SDSDSDSDSD SDSDSDSDSD SASDSDSGSD
SDSSSDSDSE SDSNSDSESV SNNNVVPPNS PKNGTNASNK NEAKDSKEPL PDTGSEDEAN
TSLIWGLLAS IGSLLLFRRK KENKDKK
