PADA_STRGC
ID PADA_STRGC Reviewed; 3646 AA.
AC A8AZP4;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 1.
DT 25-MAY-2022, entry version 86.
DE RecName: Full=Platelet adherence protein A {ECO:0000303|PubMed:19884334};
DE AltName: Full=Adhesin PadA {ECO:0000305};
DE Flags: Precursor;
GN Name=padA {ECO:0000303|PubMed:19884334}; OrderedLocusNames=SGO_2005;
OS Streptococcus gordonii (strain Challis / ATCC 35105 / BCRC 15272 / CH1 /
OS DL1 / V288).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=467705;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Challis / ATCC 35105 / BCRC 15272 / CH1 / DL1 / V288;
RX PubMed=17720781; DOI=10.1128/jb.01023-07;
RA Vickerman M.M., Iobst S., Jesionowski A.M., Gill S.R.;
RT "Genome-wide transcriptional changes in Streptococcus gordonii in response
RT to competence signaling peptide.";
RL J. Bacteriol. 189:7799-7807(2007).
RN [2]
RP S.GORDONII IN INFECTIVE ENDOCARDITIS.
RX PubMed=8366515; DOI=10.1099/00222615-39-3-179;
RA Douglas C.W., Heath J., Hampton K.K., Preston F.E.;
RT "Identity of viridans streptococci isolated from cases of infective
RT endocarditis.";
RL J. Med. Microbiol. 39:179-182(1993).
RN [3]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, DOMAIN, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=Challis / ATCC 35105 / BCRC 15272 / CH1 / DL1 / V288;
RX PubMed=19884334; DOI=10.1128/iai.00664-09;
RA Petersen H.J., Keane C., Jenkinson H.F., Vickerman M.M., Jesionowski A.,
RA Waterhouse J.C., Cox D., Kerrigan S.W.;
RT "Human platelets recognize a novel surface protein, PadA, on Streptococcus
RT gordonii through a unique interaction involving fibrinogen receptor
RT GPIIbIIIa.";
RL Infect. Immun. 78:413-422(2010).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Challis / ATCC 35105 / BCRC 15272 / CH1 / DL1 / V288;
RX PubMed=21071690; DOI=10.1161/atvbaha.110.216515;
RA Keane C., Petersen H., Reynolds K., Newman D.K., Cox D., Jenkinson H.F.,
RA Newman P.J., Kerrigan S.W.;
RT "Mechanism of outside-in {alpha}IIb{beta}3-mediated activation of human
RT platelets by the colonizing Bacterium, Streptococcus gordonii.";
RL Arterioscler. Thromb. Vasc. Biol. 30:2408-2415(2010).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 416-ARG--THR-418 AND
RP 486-GLY-ASP-487.
RC STRAIN=Challis / ATCC 35105 / BCRC 15272 / CH1 / DL1 / V288;
RX PubMed=24136582; DOI=10.1160/th13-07-0580;
RA Keane C., Petersen H.J., Tilley D., Haworth J., Cox D., Jenkinson H.F.,
RA Kerrigan S.W.;
RT "Multiple sites on Streptococcus gordonii surface protein PadA bind to
RT platelet GPIIbIIIa.";
RL Thromb. Haemost. 110:1278-1287(2013).
RN [6]
RP FUNCTION IN ADHESION TO HOST CELLS AND BIOFILM FORMATION, SUBCELLULAR
RP LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 214-ASN--ARG-216;
RP 416-ARG--THR-418 AND 486-GLY-ASP-487.
RC STRAIN=Challis / ATCC 35105 / BCRC 15272 / CH1 / DL1 / V288;
RX PubMed=27616700; DOI=10.1111/cmi.12667;
RA Haworth J.A., Jenkinson H.F., Petersen H.J., Back C.R., Brittan J.L.,
RA Kerrigan S.W., Nobbs A.H.;
RT "Concerted functions of Streptococcus gordonii surface proteins PadA and
RT Hsa mediate activation of human platelets and interactions with
RT extracellular matrix.";
RL Cell. Microbiol. 19:0-0(2017).
CC -!- FUNCTION: A cell wall protein involved with Hsa in host cell
CC interactions required for colonization and pathogenesis
CC (PubMed:19884334, PubMed:21071690, PubMed:24136582, PubMed:27616700).
CC Involved in recognition of platelets. Interacts with human platelet
CC integrin receptor GPIIbIIIa (a complex of ITGA2B and ITGB3)
CC (PubMed:19884334). Involved in platelet spreading, presumably by
CC activation of outside-in signaling leading to platelet activation and
CC then spreading. Spreading also involves GPIIbIIIa (PubMed:21071690).
CC Binding to platelets under static conditions causes platelet dense
CC granules to secrete ADP (similar to release induced by fibrinogen
CC binding), has no effect on platelet alpha granule release. The N-
CC terminal 656 aa residue fragment (called F2) also binds platelets,
CC causes dense granule secretion and allows platelet spreading
CC (PubMed:24136582). Acts in concert with Hsa to promote binding to human
CC fibronectin (FN1) and vitronectin (VTN), and biofilm formation. F2 bind
CC activated platelets more strongly than unactivated platelets. Binding
CC to both FN1 and VTN is mediated at least in part by their glycosylation
CC (PubMed:27616700). {ECO:0000269|PubMed:19884334,
CC ECO:0000269|PubMed:21071690, ECO:0000269|PubMed:24136582,
CC ECO:0000269|PubMed:27616700}.
CC -!- ACTIVITY REGULATION: Whole bacterial adhesion to Chinese hamster ovary
CC cells expressing GPIIbIIIa is abrogated by integrin inhibitor RGDS and
CC GPIIbIIIa inhibitor Abciximab. {ECO:0000269|PubMed:19884334}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE-
CC ProRule:PRU00477, ECO:0000269|PubMed:19884334,
CC ECO:0000269|PubMed:27616700}; Peptidoglycan-anchor
CC {ECO:0000255|PROSITE-ProRule:PRU00477}.
CC -!- DOMAIN: The central region (709-3205) contains 17 RrgB repeats and may
CC serve as a flexible extension that holds the N-terminus away from the
CC bacterial surface (Probable). Immobilized protein fragments 34-690
CC (also called F2) and 34-1328 bind to human platelets but 34-359 does
CC not (PubMed:19884334). Three integrin-like recognition motifs (NGR, RGT
CC and AGD) are involved together in platelet recognition, but not in
CC fibronectin- or vitronectin-binding, nor biofilm formation
CC (PubMed:24136582, PubMed:27616700). {ECO:0000269|PubMed:19884334,
CC ECO:0000269|PubMed:24136582, ECO:0000269|PubMed:27616700,
CC ECO:0000305|PubMed:27616700}.
CC -!- DISRUPTION PHENOTYPE: Bacteria bind less well to human platelets; no
CC change in platelet aggregation (PubMed:19884334, PubMed:21071690).
CC Platelets no longer spread on S.gordonii (PubMed:21071690). Platelets
CC roll on immobilized bacteria but do not adhere under low shear or
CC static conditions (PubMed:24136582). Single mutant binds less well to
CC vitronectin (VTN) and fibronectin (FN1), slightly less well to salivary
CC pellicle and makes less biofilm on salivary pellicle. Double hsa-padA
CC deletions bind less well to human platelets than does the single padA
CC deletion and make no biofilm on saliva-covered slides
CC (PubMed:27616700). {ECO:0000269|PubMed:19884334,
CC ECO:0000269|PubMed:21071690, ECO:0000269|PubMed:24136582,
CC ECO:0000269|PubMed:27616700}.
CC -!- MISCELLANEOUS: S.gordonii, a commensal oral cavity bacteria, is among
CC the bacteria most frequently identified as being the primary
CC etiological agents of subacute infective endocarditis (found in 13% of
CC cases). {ECO:0000269|PubMed:8366515}.
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DR EMBL; CP000725; ABV10352.1; -; Genomic_DNA.
DR RefSeq; WP_012130981.1; NC_009785.1.
DR SMR; A8AZP4; -.
DR STRING; 467705.SGO_2005; -.
DR EnsemblBacteria; ABV10352; ABV10352; SGO_2005.
DR KEGG; sgo:SGO_2005; -.
DR eggNOG; COG2304; Bacteria.
DR eggNOG; COG4932; Bacteria.
DR HOGENOM; CLU_000386_0_0_9; -.
DR OMA; KASSVCD; -.
DR Proteomes; UP000001131; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0098785; P:biofilm matrix assembly; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0090604; P:surface biofilm formation; IMP:UniProtKB.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR026466; Fim_isopep_form_D2_dom.
DR InterPro; IPR019931; LPXTG_anchor.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR SUPFAM; SSF53300; SSF53300; 1.
DR TIGRFAMs; TIGR04226; RrgB_K2N_iso_D2; 17.
DR PROSITE; PS50847; GRAM_POS_ANCHORING; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell wall; Coiled coil; Peptidoglycan-anchor;
KW Reference proteome; Secreted; Signal; Virulence.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..3646
FT /note="Platelet adherence protein A"
FT /evidence="ECO:0000255"
FT /id="PRO_5002719352"
FT PROPEP 3618..3646
FT /note="Removed by sortase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT /id="PRO_5018372630"
FT DOMAIN 75..373
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT REGION 34..1328
FT /note="Binds platelets"
FT /evidence="ECO:0000269|PubMed:19884334"
FT REGION 34..690
FT /note="F2, binds platelets, fibronectin, vitronectin,
FT salivary pellicle, causes ADP secretion by dense granules"
FT /evidence="ECO:0000269|PubMed:19884334,
FT ECO:0000269|PubMed:24136582, ECO:0000269|PubMed:27616700"
FT REGION 34..359
FT /note="Does not bind platelets"
FT /evidence="ECO:0000269|PubMed:19884334"
FT REGION 439..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 709..3205
FT /note="Central region with RrgB repeats"
FT /evidence="ECO:0000255"
FT REGION 1124..1153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1563..1589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2011..2036
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2170..2198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2320..2343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2467..2492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2611..2644
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2767..2792
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2916..2948
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3202..3252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3371..3412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3550..3618
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 3326..3376
FT /evidence="ECO:0000255"
FT COILED 3408..3475
FT /evidence="ECO:0000255"
FT MOTIF 214..216
FT /note="Integrin-like recognition motif NGR"
FT /evidence="ECO:0000303|PubMed:27616700"
FT MOTIF 416..418
FT /note="Integrin-like recognition motif RGT"
FT /evidence="ECO:0000303|PubMed:24136582"
FT MOTIF 485..487
FT /note="Integrin-like recognition motif AGD"
FT /evidence="ECO:0000303|PubMed:24136582"
FT MOTIF 3614..3618
FT /note="LPXTG sorting signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT COMPBIAS 3202..3219
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3221..3236
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3563..3610
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 3617
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT MUTAGEN 214..216
FT /note="NGR->AAA: No change in binding to activated
FT platelets. No change in platelet spreading. No binding to
FT activated platelets; when associated with 416-A--A-418 and
FT 486-A-A-487. Triple mutant shows no change in binding to
FT fibronectin, vitronectin or salivary pellicle."
FT /evidence="ECO:0000269|PubMed:27616700"
FT MUTAGEN 416..418
FT /note="RGT->AAA: Decreased ADP release by dense granules,
FT decreased platelet spreading. No change in binding to
FT activated platelets. No binding to activated platelets;
FT when associated with 214-A--A-216 and 486-A-A-487. Triple
FT mutant shows no change in binding to fibronectin,
FT vitronectin or salivary pellicle."
FT /evidence="ECO:0000269|PubMed:24136582,
FT ECO:0000269|PubMed:27616700"
FT MUTAGEN 486..487
FT /note="GD->AA: No change in ADP release by dense granules,
FT decreased platelet spreading. No change in binding to
FT activated platelets. No binding to activated platelets;
FT when associated with 214-A--A-216 and 416-A--A-418. Triple
FT mutant shows no change in binding to fibronectin,
FT vitronectin or salivary pellicle."
FT /evidence="ECO:0000269|PubMed:24136582,
FT ECO:0000269|PubMed:27616700"
SQ SEQUENCE 3646 AA; 397342 MW; 6BA2319080A0F3F6 CRC64;
MKDFLKKVLI LFTVLLMSMP SSVLNLGTSV VRADDPLNIE TRRIDEHTTI TQNGCYRKIE
KTDATDWTVP RKPIDLVILQ DASGSFRTTI PSVKNALKRL TTYVSPEQYD ENDPHLVKTD
DPRTTDRVFV ASYQGLDQVR YFENNDFSGN PANVYTDANS TGKNYTYGNS GLTSDQNKVH
NFIDNIAVDG GTPTVPAIDD TIAQYNRVKG NMENGRKTVF LLVTDGVANG YRLPGTNTVV
MDKSWTRTDA IQKAWRVDSY PEAAQDIIGR ANELKAAGNQ LKAAVGSEGS VVVGFWERVD
NFTEKYYQYG PAYLNGFGNT INIGDNRSVQ AIFHDALQSM ASPDKVVNGK NVSFYVNEQN
NIDVFSQKIL ESVAAALVKD DITGEFDITE GYKVDAIRIN GKKIVPKVTD PSKEIRGTIT
QTGNKVKISV PDSVFNPGKN SFDYDLSKEA RAPETDEDSE VDPPENYVPE KEEITVPELT
GKFKAGDFET RQIGGRNQTV EVQKLEYCYP SATKTVKDAD ASNDIGVIPD PLELTKKPSY
SAQLSKKDEE FTYTVDYNFN NVPYEFEKNV MLTDPIDYRL EVVSHSAQGP DGQSWPTRVV
TQQDAGGNSQ SVVVADVPPQ GKDYNYLIMK KAKLKMTVRL KEEYRKNQAS KAYLAILQNN
NGYGLVNQGN IMWNGEDDSP NQDAHAKTKD KASTIRRSNP IYVKPPLDTE VDKKVNEKEH
EGLQADGEEF EYKVTAPWPG IADKFTLTDT VVDELEIVPN SAKVTVAGKS YNALTKAISI
NGQTIDITLD KAQLTSLNRL ISRRGGSEVQ EIELIFKAKI RPGADLSKYK KNGAVNIPNT
ADVILNDKKK TSKEVTVTPP KPKEPTVSKK INNTLDSLVT FDGQPYTYNI TTAVPSDVAG
YKKFVISDKL DADLEFDGQA SISGPLADVF EIQTNGQTVT ATVKEGKFKE LAKYSFVELT
IPAKVKAGVT GKTIENKAKI SFTNENNVAK EVESNPVTVT PPPVTKKINE NLDHLDIATG
QPYKYNVKTT LPSDITSYKE FVITDTLEDE LSVINEGTDK PVISGPAAEF FDVTVSGQKV
TATMKNFAGA SALAGQEIEL VIPAKINDGV TRSNIPNKAT FSFKDKNDHK GEKETIPVTV
TPPTEPNVSK KINGDQDNAT IAAETDFTYN IKTTLPNDID TYKSFAITDT LDENLGVVNP
EPSISEEAKK FFDITVSGNT VTATMKDFAK ASALANKEIE LVIHAKVKKE SVLPEIPNTA
KITYTNKNNE SKEKETEPVK VTPPPITKKV NGKDQEDLAS LTSTFKYTVD SKVPIVADKF
VLSDTLEEVL TFDGDATVTI DGQTVTDVTV AKKDQKLTVT FDKDQVKKYA GKAVQVAFDA
KIKSGYTVDQ LVAKYPNGDK AAIPNKASFV VNDNPETEKF SNPVTVTPPP PNTPEIEKKV
NGADSYNLQT RLEEFTYSLN TAMPTNATEF TVTDELKSVL EFAGKKGDVQ VKIDGKAAND
QATISTDKNT LTVAFAEKAV KANAGKSIEV TFKAKIREGA NLLDYLVPGQ GIRIPNKASY
DIDHNPKFHK DSNEVPVTPP SPEQPPIEKD VNDKAEATLE ARDEEFTYHV KTKIPYEATA
FNITDTLKEV LDFSGEKGQA EATVDGKKLS DDHIAINGQT ITVTLNQEEL KANADKEIKL
TFKAKIRPNA NLAAYVVGDK VVINNQASYN VDLPDNPGVH KDSNIVPVTP PSPEKPEIEK
TVNDAKEATL ANRDEIFTYK VKTKVPFDAT AFSIDDTIKD VLEFADAGSA TLNGEALEAD
RISIADQKIT LTLTEDQVKN NGGKEVVLTF KAKIRQGANL SGYIEKGKTV INNQASYNAA
FPNDPNFHKD SNIVPVTPPN PENPPIEKKV NEAESANLGA RDEEFTYTID TTVPLDVTGF
AVYDTIEKVL EFSGENGQAS ATVDGQPLDA SHITIKGQKI TVKLTEDEAK ALGGKAVHVS
FKAKIKAGAN LSDYIEKDGT TRIYNTAKYN FNNDPGTEQS SKPVPVIPPT PTEPELKKEV
NGKEAETLAN RDDVFTYTVK TTVPQDATAF SISDSLVPVL EFAGEDAEAS LTLNGEKLDA
KQIKLKDQTI SAELTEAQVK ANGGKEVVLN FKAKIREGAN LADYIEADGV TRVPNKASYV
ANFPHRPKVE KDSNIVPVTP PSPENPPVEK KVNNKPSATL DSRDEEFTYT IDTKVPVDAT
GFKITDELKD VLEFSGKKGQ AEVTVDGDKD VIEDSQITVD KQVLTVTLTK DQVKKYGNKA
VHVSFKAKIR KNVSLAGYIE ADGVTRIPNI AKYIINDDPK TEKSTEPVPV IPPSPEEPGI
KKEVNGQPEA TLKERYEEFT YKVTTSVPQD ATAFSVSDTL VPVLEFSGEK GQATATLDGQ
EIDANRINVA DQTISMALTE DEVKANGGKE VTLTFKAKIR EGANLSAYIE KGKTSIPNTA
SYTAGFPNRP EIHKDSNRVP VTPPTPEEPE IKKDVNGKEE ETLANRNDEF TYHINTKVPF
DATAFSINDE LKDVLEFADG TGRATASLNG QALDADRISI NGQTITVNLT EEQVKNNGGK
DVNLTFTAKI RQGVNLSGYI KDGKTSIPNK ASYRVDFPNN PGVTKDSNEV PVTPPSPENP
PIEKKVNEAE SANLGARDEE FTYTIDTTVP LDVTGFAVYD TIEKVLEFSG ENGQASATVD
GQPLDASHIT IKGQKITVKL TEDEAKALGG KAVHVSFKAK IKAGANLSDY IEKDGTTRIY
NTAKYNFNND PGTEQSSKPV PVIPPTPTEP ELKKEVNGKE AETLANRDDV FTYTVKTTVP
QDATAFSISD KLEDVLEFAG ESSATLAGED LKADQITTDG QIIKLTLTED QVKANGGKEV
VLNFKAKIRE GANLSAYMKA DKAEVPNKAS YTVGFPNKPA VTKDSNEVPV TPPSPEQPPI
EKDVNSKPSE TIADRTEEFT YNIHTTMPQD ATGFTVTDEL KDVLEFAGDV QVTLGGKKAD
AAVAKNGQTL EVTFPEETVK ANGGKKVQVT FKAKIKADAD LTPYETANSY SVPNTASYLI
NNNPTSKKET KPVTVEVPKQ PGPEVTKKIN RTLDHLDVDR DVPYMYNVNT QIPKDIRLYK
EFTVTDTLEP VLEITGTPVA YVDGYATDAV ETKVEGNTVT VTVKDFARIS GYKEIQLYIP
AKLKADSDLS AYENQTVPNK ATIAFKDSNG KNGTKESNPV TVRPRDPEKP EEPKPNEPAK
TVGPADGSNP STAYRLKELK EGFRFDVTAK VPTDPVDESG NPIKDAQGRD VKTELNSFTV
TDELEKVLKV DRVAVKVEEN KVAEAIAKIT AKIEKAESDL KELEGKETNG TFAKKLAEAE
KKVEELTAQL AAAKEKAAAA PATPAPASDS DAGNATATPA PADNNAEVAA LEESLKAAQA
ELEQLKADGA KAGNLATPEE QKVEQDKLNK NLEQLKESKE KLEKALEAFT TVNDKGEITD
EALAKIAKVT VEGQKVTVEV TDKAVLEALK GSTFRVIIYS SIKDGADLSS YLNKENNETK
IPNKATVTFN DKPKVTNTVN VYPPEPTTPP QTPPHTPPTT PGTPPPTTPD TPPAPKGDLP
PAPTPEPEKP KNILPKTGTS ATMVNEVIIG MILVLMGLLL RRKPKH
