CAPSD_AAV2S
ID CAPSD_AAV2S Reviewed; 735 AA.
AC P03135; O56652; O56653; O92917;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 2.
DT 23-FEB-2022, entry version 106.
DE RecName: Full=Capsid protein VP1;
GN Name=VP1;
OS Adeno-associated virus 2 (isolate Srivastava/1982) (AAV-2).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Quintoviricetes;
OC Piccovirales; Parvoviridae; Parvovirinae; Dependoparvovirus.
OX NCBI_TaxID=648242;
OH NCBI_TaxID=40674; Mammalia.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6300419; DOI=10.1128/jvi.45.2.555-564.1983;
RA Srivastava A., Lusby E.W., Berns K.I.;
RT "Nucleotide sequence and organization of the adeno-associated virus 2
RT genome.";
RL J. Virol. 45:555-564(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7996133; DOI=10.1099/0022-1317-75-12-3385;
RA Ruffing M., Heid H., Kleinschmidt J.A.;
RT "Mutations in the carboxy terminus of adeno-associated virus 2 capsid
RT proteins affect viral infectivity: lack of an RGD integrin-binding motif.";
RL J. Gen. Virol. 75:3385-3392(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Berns K.I., Bohenzky R.A., Cassinotti P., Colvin D., Donahue B.A., Dull T.,
RA Horer M., Kleinschmidt J.A., Ruffing M., Snyder R.O., Tratschin J.-D.,
RA Weitz M.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP ALTERNATIVE SPLICING.
RX PubMed=2839699; DOI=10.1128/jvi.62.8.2745-2754.1988;
RA Becerra S.P., Koczot F., Fabisch P., Rose J.A.;
RT "Synthesis of adeno-associated virus structural proteins requires both
RT alternative mRNA splicing and alternative initiations from a single
RT transcript.";
RL J. Virol. 62:2745-2754(1988).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=8995658; DOI=10.1128/jvi.71.2.1341-1352.1997;
RA Wistuba A., Kern A., Weger S., Grimm D., Kleinschmidt J.A.;
RT "Subcellular compartmentalization of adeno-associated virus type 2
RT assembly.";
RL J. Virol. 71:1341-1352(1997).
RN [6]
RP FUNCTION.
RX PubMed=9445046; DOI=10.1128/jvi.72.2.1438-1445.1998;
RA Summerford C., Samulski R.J.;
RT "Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-
RT associated virus type 2 virions.";
RL J. Virol. 72:1438-1445(1998).
RN [7]
RP FUNCTION.
RX PubMed=10684294; DOI=10.1128/jvi.74.6.2777-2785.2000;
RA Bartlett J.S., Wilcher R., Samulski R.J.;
RT "Infectious entry pathway of adeno-associated virus and adeno-associated
RT virus vectors.";
RL J. Virol. 74:2777-2785(2000).
RN [8]
RP FUNCTION OF VP1.
RX PubMed=11961250; DOI=10.1099/0022-1317-83-5-973;
RA Girod A., Wobus C.E., Zadori Z., Ried M., Leike K., Tijssen P.,
RA Kleinschmidt J.A., Hallek M.;
RT "The VP1 capsid protein of adeno-associated virus type 2 is carrying a
RT phospholipase A2 domain required for virus infectivity.";
RL J. Gen. Virol. 83:973-978(2002).
RN [9]
RP FUNCTION.
RX PubMed=16940508; DOI=10.1128/jvi.00843-06;
RA Asokan A., Hamra J.B., Govindasamy L., Agbandje-McKenna M., Samulski R.J.;
RT "Adeno-associated virus type 2 contains an integrin alpha5beta1 binding
RT domain essential for viral cell entry.";
RL J. Virol. 80:8961-8969(2006).
RN [10]
RP BIOTECHNOLOGY.
RX PubMed=18369962; DOI=10.1007/978-1-59745-210-6_2;
RA Van Vliet K.M., Blouin V., Brument N., Agbandje-McKenna M., Snyder R.O.;
RT "The role of the adeno-associated virus capsid in gene transfer.";
RL Methods Mol. Biol. 437:51-91(2008).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 217-735.
RX PubMed=12136130; DOI=10.1073/pnas.162250899;
RA Xie Q., Bu W., Bhatia S., Hare J., Somasundaram T., Azzi A., Chapman M.S.;
RT "The atomic structure of adeno-associated virus (AAV-2), a vector for human
RT gene therapy.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10405-10410(2002).
CC -!- FUNCTION: Capsid protein self-assembles to form an icosahedral capsid
CC with a T=1 symmetry, about 22 nm in diameter, and consisting of 60
CC copies of three size variants of the capsid protein VP1, VP2 and VP3
CC which differ in their N-terminus. The capsid encapsulates the genomic
CC ssDNA. Binds to host cell heparan sulfate and uses host ITGA5-ITGB1 as
CC coreceptor on the cell surface to provide virion attachment to target
CC cell. This attachment induces virion internalization predominantly
CC through clathrin-dependent endocytosis. Binding to the host receptor
CC also induces capsid rearrangements leading to surface exposure of VP1
CC N-terminus, specifically its phospholipase A2-like region and putative
CC nuclear localization signal(s). VP1 N-terminus might serve as a
CC lipolytic enzyme to breach the endosomal membrane during entry into
CC host cell and might contribute to virus transport to the nucleus.
CC {ECO:0000269|PubMed:10684294, ECO:0000269|PubMed:11961250,
CC ECO:0000269|PubMed:16940508, ECO:0000269|PubMed:9445046}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000305}. Host nucleus, host
CC nucleolus {ECO:0000269|PubMed:8995658}. Note=Capid proteins are first
CC observed in the host nucleolus where capsid assembly may occur, and
CC then are present over the whole nucleoplasm where encapsidation of the
CC viral DNA takes place.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Name=VP1;
CC IsoId=P03135-1; Sequence=Displayed;
CC Name=VP2;
CC IsoId=P03135-2; Sequence=VSP_040829, VSP_040830;
CC Name=VP3;
CC IsoId=P03135-3; Sequence=VSP_040828;
CC -!- DOMAIN: The N-terminus of VP1 is sequestered within the mature capsid.
CC It contains a phospholipase A2-like region and putative nuclear
CC localization signals.
CC -!- BIOTECHNOLOGY: AAV capsids serve as viral gene transfer vectors that
CC have been shown to affect long-term gene expression and disease
CC correction with low toxicity in animal models, and are well tolerated
CC in human clinical trials. {ECO:0000305|PubMed:18369962}.
CC -!- MISCELLANEOUS: the ratio at which VP1, VP2 and VP3 proteins are
CC synthesized in vivo is about 1:1:10, which is the same as in the mature
CC virus particle. {ECO:0000305|PubMed:18369962}.
CC -!- MISCELLANEOUS: [Isoform VP1]: Produced by alternative splicing (2.6 kb
CC mRNA). {ECO:0000269|PubMed:2839699}.
CC -!- MISCELLANEOUS: [Isoform VP2]: Produced by alternative splicing (2.3 kb
CC mRNA), with initiatory methionine encoded by an ACG codon.
CC {ECO:0000269|PubMed:2839699}.
CC -!- MISCELLANEOUS: [Isoform VP3]: Produced by alternative initiation of the
CC 2.3 kb mRNA. {ECO:0000269|PubMed:2839699}.
CC -!- SIMILARITY: Belongs to the parvoviridae capsid protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA42376.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; J01901; AAA42376.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AF043303; AAC03779.1; -; Genomic_DNA.
DR EMBL; AF043303; AAC03780.1; -; Genomic_DNA.
DR EMBL; AF043303; AAC03778.1; -; Genomic_DNA.
DR PIR; A03698; VCPV3A.
DR RefSeq; YP_680426.1; NC_001401.2.
DR RefSeq; YP_680427.1; NC_001401.2.
DR RefSeq; YP_680428.1; NC_001401.2.
DR PDB; 1LP3; X-ray; 3.00 A; A=217-735.
DR PDB; 3J1S; EM; 8.50 A; A=217-735.
DR PDB; 3J4P; EM; 4.80 A; A=221-735.
DR PDB; 5IPI; EM; 3.80 A; 1/2/3/4/5/6/7/8/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=1-735.
DR PDB; 5IPK; EM; 3.70 A; 1/2/3/4/5/6/7/8/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=1-735.
DR PDB; 6CBE; EM; 2.78 A; 0/1/2/3/4/5/6/7/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=1-735.
DR PDB; 6E9D; EM; 1.86 A; 1/2/3/4/5/6/7/8/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=1-735.
DR PDB; 6IH9; EM; 2.80 A; A=219-735.
DR PDB; 6IHB; EM; 2.84 A; A=1-735.
DR PDB; 6NZ0; EM; 2.40 A; A=1-735.
DR PDB; 6U0R; EM; 2.91 A; 1/2/3/4/5/6/7/8/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=219-735.
DR PDB; 6U0V; EM; 3.02 A; 1/2/3/4/5/6/7/8/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=214-735.
DR PDB; 7RWL; EM; 3.14 A; 1/2/3/4/5/6/7/8/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=1-735.
DR PDB; 7RWT; EM; 2.43 A; 1/2/3/4/5/6/7/8/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=1-735.
DR PDBsum; 1LP3; -.
DR PDBsum; 3J1S; -.
DR PDBsum; 3J4P; -.
DR PDBsum; 5IPI; -.
DR PDBsum; 5IPK; -.
DR PDBsum; 6CBE; -.
DR PDBsum; 6E9D; -.
DR PDBsum; 6IH9; -.
DR PDBsum; 6IHB; -.
DR PDBsum; 6NZ0; -.
DR PDBsum; 6U0R; -.
DR PDBsum; 6U0V; -.
DR PDBsum; 7RWL; -.
DR PDBsum; 7RWT; -.
DR SMR; P03135; -.
DR DIP; DIP-46114N; -.
DR ELM; P03135; -.
DR PRIDE; P03135; -.
DR ABCD; P03135; 1 sequenced antibody.
DR DNASU; 4192015; -.
DR GeneID; 4192015; -.
DR GeneID; 4192016; -.
DR GeneID; 4192017; -.
DR KEGG; vg:4192015; -.
DR KEGG; vg:4192016; -.
DR KEGG; vg:4192017; -.
DR BRENDA; 3.1.1.4; 11447.
DR EvolutionaryTrace; P03135; -.
DR Proteomes; UP000008469; Genome.
DR Proteomes; UP000180764; Genome.
DR GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0039615; C:T=1 icosahedral viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0039665; P:permeabilization of host organelle membrane involved in viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0099008; P:viral entry via permeabilization of inner membrane; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR Gene3D; 2.170.30.10; -; 1.
DR InterPro; IPR016184; Capsid/spike_ssDNA_virus.
DR InterPro; IPR001403; Parvovirus_coat.
DR InterPro; IPR013607; Phospholipase_A2-like.
DR InterPro; IPR036952; VP1/VP2.
DR Pfam; PF00740; Parvo_coat; 1.
DR Pfam; PF08398; Phospholip_A2_4; 1.
DR SUPFAM; SSF88645; SSF88645; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Alternative splicing; Capsid protein;
KW Clathrin-mediated endocytosis of virus by host; Host nucleus;
KW Host-virus interaction; Reference proteome; T=1 icosahedral capsid protein;
KW Viral attachment to host cell; Viral penetration into host cytoplasm;
KW Viral penetration via permeabilization of host membrane; Virion;
KW Virus endocytosis by host; Virus entry into host cell.
FT CHAIN 1..735
FT /note="Capsid protein VP1"
FT /id="PRO_0000222455"
FT REGION 22..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 52..97
FT /note="Phospholipase A2-like"
FT /evidence="ECO:0000250"
FT REGION 136..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..209
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..202
FT /note="Missing (in isoform VP3)"
FT /evidence="ECO:0000305"
FT /id="VSP_040828"
FT VAR_SEQ 1..137
FT /note="Missing (in isoform VP2)"
FT /evidence="ECO:0000305"
FT /id="VSP_040829"
FT VAR_SEQ 138
FT /note="T -> M (in isoform VP2)"
FT /evidence="ECO:0000305"
FT /id="VSP_040830"
FT CONFLICT 520..521
FT /note="Missing (in Ref. 3; AAA42376)"
FT /evidence="ECO:0000305"
FT CONFLICT 553
FT /note="D -> N (in Ref. 3; AAA42376)"
FT /evidence="ECO:0000305"
FT CONFLICT 566
FT /note="R -> G (in Ref. 3; AAA42376)"
FT /evidence="ECO:0000305"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:1LP3"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:6IH9"
FT STRAND 238..249
FT /evidence="ECO:0007829|PDB:6NZ0"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 258..262
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:6IH9"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 273..281
FT /evidence="ECO:0007829|PDB:6NZ0"
FT HELIX 287..289
FT /evidence="ECO:0007829|PDB:6NZ0"
FT HELIX 293..300
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 303..326
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 329..337
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 374..378
FT /evidence="ECO:0007829|PDB:6NZ0"
FT HELIX 395..397
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 409..414
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 425..428
FT /evidence="ECO:0007829|PDB:6NZ0"
FT HELIX 430..432
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 436..438
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 441..452
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 455..464
FT /evidence="ECO:0007829|PDB:6NZ0"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:1LP3"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 487..491
FT /evidence="ECO:0007829|PDB:6NZ0"
FT HELIX 492..494
FT /evidence="ECO:0007829|PDB:6NZ0"
FT TURN 501..504
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 507..510
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 513..516
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 524..526
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 533..535
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 536..539
FT /evidence="ECO:0007829|PDB:6IH9"
FT STRAND 541..543
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 549..551
FT /evidence="ECO:0007829|PDB:6NZ0"
FT HELIX 554..556
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:6NZ0"
FT HELIX 563..567
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 576..580
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 586..588
FT /evidence="ECO:0007829|PDB:6IH9"
FT STRAND 592..598
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 618..620
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 635..641
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 646..650
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 672..688
FT /evidence="ECO:0007829|PDB:6NZ0"
FT STRAND 711..714
FT /evidence="ECO:0007829|PDB:1LP3"
FT STRAND 731..733
FT /evidence="ECO:0007829|PDB:6NZ0"
SQ SEQUENCE 735 AA; 81945 MW; 980BEEF46908390B CRC64;
MAADGYLPDW LEDTLSEGIR QWWKLKPGPP PPKPAERHKD DSRGLVLPGY KYLGPFNGLD
KGEPVNEADA AALEHDKAYD RQLDSGDNPY LKYNHADAEF QERLKEDTSF GGNLGRAVFQ
AKKRVLEPLG LVEEPVKTAP GKKRPVEHSP VEPDSSSGTG KAGQQPARKR LNFGQTGDAD
SVPDPQPLGQ PPAAPSGLGT NTMATGSGAP MADNNEGADG VGNSSGNWHC DSTWMGDRVI
TTSTRTWALP TYNNHLYKQI SSQSGASNDN HYFGYSTPWG YFDFNRFHCH FSPRDWQRLI
NNNWGFRPKR LNFKLFNIQV KEVTQNDGTT TIANNLTSTV QVFTDSEYQL PYVLGSAHQG
CLPPFPADVF MVPQYGYLTL NNGSQAVGRS SFYCLEYFPS QMLRTGNNFT FSYTFEDVPF
HSSYAHSQSL DRLMNPLIDQ YLYYLSRTNT PSGTTTQSRL QFSQAGASDI RDQSRNWLPG
PCYRQQRVSK TSADNNNSEY SWTGATKYHL NGRDSLVNPG PAMASHKDDE EKFFPQSGVL
IFGKQGSEKT NVDIEKVMIT DEEEIRTTNP VATEQYGSVS TNLQRGNRQA ATADVNTQGV
LPGMVWQDRD VYLQGPIWAK IPHTDGHFHP SPLMGGFGLK HPPPQILIKN TPVPANPSTT
FSAAKFASFI TQYSTGQVSV EIEWELQKEN SKRWNPEIQY TSNYNKSVNV DFTVDTNGVY
SEPRPIGTRY LTRNL
