GP_HTRV
ID GP_HTRV Reviewed; 1076 AA.
AC J3WAX0; J3SPZ8;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Envelopment polyprotein;
DE AltName: Full=M polyprotein;
DE Contains:
DE RecName: Full=Glycoprotein N {ECO:0000250|UniProtKB:P21401};
DE Short=Gn;
DE AltName: Full=Glycoprotein G1;
DE Contains:
DE RecName: Full=Glycoprotein C {ECO:0000250|UniProtKB:P21401};
DE Short=Gc;
DE AltName: Full=Glycoprotein G2;
DE Flags: Precursor;
GN Name=GP;
OS Heartland virus (HTRV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Phenuiviridae; Bandavirus;
OC Heartland bandavirus.
OX NCBI_TaxID=1216928;
OH NCBI_TaxID=999462; Alces americanus (American moose).
OH NCBI_TaxID=6943; Amblyomma americanum (Lone star tick).
OH NCBI_TaxID=9614; Canis latrans (Coyote).
OH NCBI_TaxID=9267; Didelphis virginiana (North American opossum) (Didelphis marsupialis virginiana).
OH NCBI_TaxID=9796; Equus caballus (Horse).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9874; Odocoileus virginianus (White-tailed deer).
OH NCBI_TaxID=9654; Procyon lotor (Raccoon).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate Human/United States/1/2009, and
RC Isolate Human/United States/2/2009;
RA McMullan L.K., Folk S.M., Kelly A.J., MacNeil A., Goldsmith C.S.,
RA Metcalfe M.G., Batten B.C., Albarino C.G., Zaki S.R., Rollin P.E.,
RA Nicholson W.L., Nichol S.T.;
RT "A newly discovered phlebovirus associated with severe febrile illness
RT following tick bite in two patients in Missouri.";
RL N. Engl. J. Med. 367:834-841(2012).
RN [2]
RP FUNCTION (GLYCOPROTEIN N), AND FUNCTION (GLYCOPROTEIN C).
RX PubMed=33561699; DOI=10.1016/j.virol.2020.10.006;
RA Kimura M., Egawa K., Ozawa T., Kishi H., Shimojima M., Taniguchi S.,
RA Fukushi S., Fujii H., Yamada H., Tan L., Sano K., Katano H., Suzuki T.,
RA Morikawa S., Saijo M., Tani H.;
RT "Characterization of pseudotyped vesicular stomatitis virus bearing the
RT heartland virus envelope glycoprotein.";
RL Virology 556:124-132(2021).
RN [3] {ECO:0007829|PDB:5YOW}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 567-998, DISULFIDE BONDS,
RP FUNCTION (GLYCOPROTEIN C), AND SUBUNIT (GLYCOPROTEIN C).
RX PubMed=29070692; DOI=10.1128/jvi.01558-17;
RA Zhu Y., Wu Y., Chai Y., Qi J., Peng R., Feng W.H., Gao G.F.;
RT "The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports
RT Taxonomic Separation of the Bunyaviral Families Phenuiviridae and
RT Hantaviridae.";
RL J. Virol. 92:0-0(2017).
CC -!- FUNCTION: [Glycoprotein N]: Structural component of the virion that
CC interacts with glycoprotein C (By similarity). It shields the
CC hydrophobic fusion loops of the glycoprotein C, preventing premature
CC fusion (By similarity). The glycoprotein protrusions are arranged on an
CC icosahedral lattice, with T=12 triangulation (By similarity). They are
CC able to attach the virion to the host cell receptor CD209/DC-SIGN and
CC to promote fusion of membranes with the late endosome after endocytosis
CC of the virion (Probable). Plays a role in the packaging of
CC ribonucleoproteins during virus assembly (By similarity).
CC {ECO:0000250|UniProtKB:P03518, ECO:0000250|UniProtKB:P09613,
CC ECO:0000250|UniProtKB:P21401, ECO:0000305|PubMed:33561699}.
CC -!- FUNCTION: [Glycoprotein C]: Structural component of the virion that
CC interacts with glycoprotein N (By similarity). Acts as a class II
CC fusion protein that is activated upon acidification and subsequent
CC repositioning of the glycoprotein N (PubMed:29070692). The glycoprotein
CC protrusions are arranged on an icosahedral lattice, with T=12
CC triangulation (By similarity). They are able to attach the virion to
CC the host cell receptor CD209/DC-SIGN and to promote fusion of membranes
CC with the late endosome after endocytosis of the virion (Probable).
CC {ECO:0000250|UniProtKB:P03518, ECO:0000250|UniProtKB:P09613,
CC ECO:0000269|PubMed:29070692, ECO:0000305|PubMed:33561699}.
CC -!- SUBUNIT: [Glycoprotein N]: Heterodimer with glycoprotein C.
CC {ECO:0000250|UniProtKB:P03518}.
CC -!- SUBUNIT: [Glycoprotein C]: Heterodimer with glycoprotein N (By
CC similarity). Homotrimer (postfusion) (PubMed:29070692).
CC {ECO:0000250|UniProtKB:P03518, ECO:0000269|PubMed:29070692}.
CC -!- SUBCELLULAR LOCATION: [Glycoprotein N]: Virion membrane
CC {ECO:0000250|UniProtKB:P09613}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P09613}. Host Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P03518}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P09613}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P09613}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P09613}. Note=Interaction between Glycoprotein N
CC and Glycoprotein C is essential for proper targeting of Glycoprotein C
CC to the Golgi complex, where virion budding occurs.
CC {ECO:0000250|UniProtKB:P09613}.
CC -!- SUBCELLULAR LOCATION: [Glycoprotein C]: Virion membrane
CC {ECO:0000250|UniProtKB:P09613}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P09613}. Host Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P03518}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P09613}. Note=Interaction between Glycoprotein N
CC and Glycoprotein C is essential for proper targeting of Glycoprotein C
CC to the Golgi complex, where virion budding occurs.
CC {ECO:0000250|UniProtKB:P09613}.
CC -!- DOMAIN: [Glycoprotein N]: Contains a Golgi retention signal on its C-
CC terminus. The cytoplasmic tail specifically interacts with the
CC ribonucleoproteins and is critical for genome packaging.
CC {ECO:0000250|UniProtKB:P09613}.
CC -!- PTM: [Envelopment polyprotein]: Specific enzymatic cleavages in vivo
CC yield mature proteins Glycoprotein C, and Glycoprotein N.
CC {ECO:0000250|UniProtKB:P21401}.
CC -!- PTM: [Glycoprotein N]: Glycosylated. {ECO:0000250|UniProtKB:P09613}.
CC -!- PTM: [Glycoprotein C]: Glycosylated. {ECO:0000250|UniProtKB:P09613}.
CC -!- PTM: [Glycoprotein C]: Palmitoylated. {ECO:0000250|UniProtKB:P09613}.
CC -!- MISCELLANEOUS: The sequence shown is that of isolate Human/United
CC States/1/2009. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the phlebovirus envelope glycoprotein family.
CC {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; JX005844; AFP33393.1; -; Genomic_RNA.
DR EMBL; JX005845; AFP33394.1; -; Genomic_RNA.
DR RefSeq; YP_009047241.1; NC_024494.1.
DR PDB; 5YOW; X-ray; 2.10 A; A=567-998.
DR PDBsum; 5YOW; -.
DR GeneID; 19893498; -.
DR KEGG; vg:19893498; -.
DR Proteomes; UP000173982; Genome.
DR Proteomes; UP000203778; Genome.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR InterPro; IPR043603; Phlebo_G2_C.
DR InterPro; IPR010826; Phlebovirus_G1.
DR InterPro; IPR009878; Phlebovirus_G2_fusion.
DR Pfam; PF19019; Phlebo_G2_C; 1.
DR Pfam; PF07243; Phlebovirus_G1; 1.
DR Pfam; PF07245; Phlebovirus_G2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond;
KW Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host endoplasmic reticulum; Host Golgi apparatus; Host membrane;
KW Host-virus interaction; Lipoprotein; Membrane; Palmitate; Signal;
KW Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW Viral penetration into host cytoplasm; Virion; Virus entry into host cell.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..1076
FT /note="Envelopment polyprotein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455547"
FT CHAIN 19..566
FT /note="Glycoprotein N"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455548"
FT CHAIN 567..1076
FT /note="Glycoprotein C"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455549"
FT TOPO_DOM 19..455
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P09613"
FT TRANSMEM 456..476
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 477..539
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P09613"
FT TOPO_DOM 567..1040
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1041..1061
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1062..1076
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P09613"
FT REGION 477..523
FT /note="Golgi retention signal"
FT /evidence="ECO:0000250|UniProtKB:P09613"
FT REGION 544..566
FT /note="Internal signal sequence for glycoprotein C"
FT /evidence="ECO:0000250|UniProtKB:P09613"
FT REGION 654..660
FT /note="Fusion loop"
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT REGION 695..709
FT /note="Fusion loop"
FT /evidence="ECO:0000269|PubMed:29070692"
FT SITE 103..104
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT SITE 566..567
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P09613"
FT SITE 1074
FT /note="Important for glycoprotein C and glycoprotein N
FT subcellular location"
FT /evidence="ECO:0000250|UniProtKB:P09613"
FT CARBOHYD 857
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 918
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 940
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 28..51
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 145..158
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 182..329
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 208..218
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 260..307
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 289..294
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 351..354
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 358..426
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 378..383
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 567..608
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 580..590
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 633..729
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 648..845
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 654..702
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 660..709
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 664..691
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 695..700
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 782..797
FT /evidence="ECO:0000250|UniProtKB:R4V2Q5"
FT DISULFID 813..827
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 912..982
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT DISULFID 922..925
FT /evidence="ECO:0000250|UniProtKB:P21401"
FT VARIANT 3..9
FT /note="VPIVLFL -> APVVLFF"
FT /evidence="ECO:0000269|PubMed:29070692"
FT VARIANT 15
FT /note="E -> Q (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 197
FT /note="V -> I (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 210
FT /note="I -> V (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 406
FT /note="N -> K (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 462
FT /note="I -> V (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 493
FT /note="A -> V (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 526
FT /note="V -> I (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 538..540
FT /note="QGY -> LGH (in strain: Isolate Human/United States/
FT 2/2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 546
FT /note="I -> V (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 613
FT /note="V -> M (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 737
FT /note="T -> I (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 864
FT /note="T -> I (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 889
FT /note="R -> K (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 974
FT /note="I -> V (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
FT VARIANT 1053
FT /note="M -> L (in strain: Isolate Human/United States/2/
FT 2009)"
FT /evidence="ECO:0000269|Ref.1"
SQ SEQUENCE 1076 AA; 116766 MW; FCB6EAE2EE82B348 CRC64;
MIVPIVLFLT LCPSELSAWG SPGDPIVCGV RTETNKSIQI EWKEGRSEKL CQIDRLGHVT
SWLRNHSSFQ GLIGQVKGRP SVSYFPEGAS YPRWSGLLSP CDAEWLGLIA VSKAGDTDMI
VPGPTYKGKI FVERPTYNGY KGWGCADGKS LSHSGTYCET DSSVSSGLIQ GDRVLWVGEV
VCQRGTPVPE DVFSELVSLS QSEFPDVCKI DGVALNQCEQ ESIPQPLDVA WIDVGRSHKV
LMREHKTKWV QESSAKDFVC FKVGQGPCSK QEEDDCMSKG NCHGDEVFCR MAGCSARMQD
NQEGCRCELL QKPGEIIVNY GGVSVRPTCY GFSRMMATLE VHKPDRELTG CTGCHLECIE
GGVKIVTLTS ELRSATVCAS HFCASAKGGS KTTDILFHTG ALVGPNSIRI TGQLLDGSKF
SFDGHCIFPD GCMALDCTFC KEFLRNPQCY PVKKWLFLVV VIMCCYCALM LLTNILRAIG
VWGTWVFAPI KLALALGLRL AKLSKKGLVA VVTRGQMIVN DELHQVRVER GEQNEGRQGY
GPRGPIRHWL YSPALILILT TSICSGCDEL VHAESKSITC KSASGNEKEC SVTGRALLPA
VNPGQEACLH FSVPGSPDSK CLKIKVKSIN LRCKQASSYY VPEAKARCTS VRRCRWAGDC
QSGCPTYFSS NSFSDDWANR MDRAGLGMSG CSDGCGGAAC GCFNAAPSCI FWRKWVENPS
NRVWKVSPCA SWVLAATIEL TLPSGEVKTL EPVTGQATQM FKGVAITYLG SSIEIVGMTR
LCEMKEMGTG IMALAPCNDP GHAIMGNVGE IQCSSIESAK HIRSDGCIWN ADLVGIELRV
DDAVCFSKLT SVEAVANFSK IPATISGVRF DQGNHGESRI YGSPLDITRV SGEFSVSFRG
MRLKLSEISA SCTGEITNVS GCYSCMTGAS VSIKLHSSKN TTGHLKCDSD ETAFSVMEGT
HTYRPHMSFD KAVIDEECVL NCGGHSSKLL LKGSLVFMDV PRFVDGSYVQ TYHSKVPAGG
RVPNPVDWLN ALFGDGITRW ILGIIGVLLA CVMLFVVVVA ITRRLIKGLT QRAKVA
