GH_HCMVM
ID GH_HCMVM Reviewed; 742 AA.
AC Q6SW67; D2K3N3;
DT 11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 68.
DE RecName: Full=Envelope glycoprotein H {ECO:0000255|HAMAP-Rule:MF_04033};
DE Short=gH {ECO:0000255|HAMAP-Rule:MF_04033};
DE Flags: Precursor;
GN Name=gH {ECO:0000255|HAMAP-Rule:MF_04033}; Synonyms=UL75;
OS Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=295027;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15105547; DOI=10.1099/vir.0.79888-0;
RA Dolan A., Cunningham C., Hector R.D., Hassan-Walker A.F., Lee L.,
RA Addison C., Dargan D.J., McGeoch D.J., Gatherer D., Emery V.C.,
RA Griffiths P.D., Sinzger C., McSharry B.P., Wilkinson G.W.G., Davison A.J.;
RT "Genetic content of wild-type human cytomegalovirus.";
RL J. Gen. Virol. 85:1301-1312(2004).
RN [2]
RP FUNCTION, AND INTERACTION WITH GL; UL128; UL130 AND UL131A.
RX PubMed=17942555; DOI=10.1128/jvi.01910-07;
RA Ryckman B.J., Rainish B.L., Chase M.C., Borton J.A., Nelson J.A.,
RA Jarvis M.A., Johnson D.C.;
RT "Characterization of the human cytomegalovirus gH/gL/UL128-131 complex that
RT mediates entry into epithelial and endothelial cells.";
RL J. Virol. 82:60-70(2008).
RN [3]
RP FUNCTION.
RX PubMed=23853586; DOI=10.1371/journal.ppat.1003463;
RA Nogalski M.T., Chan G.C., Stevenson E.V., Collins-McMillen D.K.,
RA Yurochko A.D.;
RT "The HCMV gH/gL/UL128-131 complex triggers the specific cellular activation
RT required for efficient viral internalization into target monocytes.";
RL PLoS Pathog. 9:E1003463-E1003463(2013).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=23804643; DOI=10.1128/jvi.01167-13;
RA Zhou M., Yu Q., Wechsler A., Ryckman B.J.;
RT "Comparative analysis of gO isoforms reveals that strains of human
RT cytomegalovirus differ in the ratio of gH/gL/gO and gH/gL/UL128-131 in the
RT virion envelope.";
RL J. Virol. 87:9680-9690(2013).
RN [5]
RP REVIEW.
RX PubMed=24957713; DOI=10.4149/av_2014_02_103;
RA Tao R., Xu J., Gao H., Zhao W., Shang S.;
RT "Characteristics and functions of human cytomegalovirus UL128
RT gene/protein.";
RL Acta Virol. 58:103-107(2014).
RN [6]
RP INTERACTION WITH UL116.
RC STRAIN=TR;
RX PubMed=26937030; DOI=10.1128/jvi.02517-15;
RA Calo S., Cortese M., Ciferri C., Bruno L., Gerrein R., Benucci B.,
RA Monda G., Gentile M., Kessler T., Uematsu Y., Maione D., Lilja A.E.,
RA Carfi A., Merola M.;
RT "The Human Cytomegalovirus UL116 Gene Encodes an Envelope Glycoprotein
RT Forming a Complex with gH Independently from gL.";
RL J. Virol. 90:4926-4938(2016).
RN [7]
RP FUNCTION, AND INTERACTION WITH GO; GL AND HOST PDGFRA.
RX PubMed=28403202; DOI=10.1371/journal.ppat.1006281;
RA Wu Y., Prager A., Boos S., Resch M., Brizic I., Mach M., Wildner S.,
RA Scrivano L., Adler B.;
RT "Human cytomegalovirus glycoprotein complex gH/gL/gO uses PDGFR-alpha as a
RT key for entry.";
RL PLoS Pathog. 13:E1006281-E1006281(2017).
RN [8]
RP FUNCTION, AND INTERACTION WITH HOST NRP2.
RX PubMed=30057110; DOI=10.1016/j.cell.2018.06.028;
RA Martinez-Martin N., Marcandalli J., Huang C.S., Arthur C.P., Perotti M.,
RA Foglierini M., Ho H., Dosey A.M., Shriver S., Payandeh J., Leitner A.,
RA Lanzavecchia A., Perez L., Ciferri C.;
RT "An Unbiased Screen for Human Cytomegalovirus Identifies Neuropilin-2 as a
RT Central Viral Receptor.";
RL Cell 0:0-0(2018).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (3.02 ANGSTROMS) OF 1-715, FUNCTION, AND INTERACTION
RP WITH GL; UL128; UL130 AND UL131A.
RX PubMed=28783665; DOI=10.1126/sciimmunol.aan1457;
RA Chandramouli S., Malito E., Nguyen T., Luisi K., Donnarumma D., Xing Y.,
RA Norais N., Yu D., Carfi A.;
RT "Structural basis for potent antibody-mediated neutralization of human
RT cytomegalovirus.";
RL Sci. Immunol. 2:0-0(2017).
CC -!- FUNCTION: The heterodimer glycoprotein H-glycoprotein L is required for
CC the fusion of viral and plasma membranes leading to virus entry into
CC the host cell. Following initial binding to host receptor, membrane
CC fusion is mediated by the fusion machinery composed of gB and the
CC heterodimer gH/gL. May also be involved in the fusion between the
CC virion envelope and the outer nuclear membrane during virion
CC morphogenesis (By similarity). In human cytomegalovirus, forms two
CC distincts complexes to mediate viral entry, a trimer and a pentamer at
CC the surface of the virion envelope. The gH-gL-gO trimer is required for
CC infection in fibroblasts by interacting with host PDGFRA
CC (PubMed:28403202). The gH-gL-UL128-UL130-UL131A pentamer is essential
CC for viral entry in epithelial, endothelial and myeloid cells via
CC interaction with host NRP2 (PubMed:17942555, PubMed:23853586,
CC PubMed:30057110, PubMed:28783665). {ECO:0000255|HAMAP-Rule:MF_04033,
CC ECO:0000269|PubMed:17942555, ECO:0000269|PubMed:23853586,
CC ECO:0000269|PubMed:28403202, ECO:0000269|PubMed:28783665,
CC ECO:0000269|PubMed:30057110}.
CC -!- SUBUNIT: Interacts with glycoprotein L (gL); this interaction is
CC necessary for the correct processing and cell surface expression of gH.
CC The heterodimer gH/gL seems to interact with gB trimers during fusion
CC (By similarity). Forms the envelope pentamer complex (PC) composed of
CC gH, gL, UL128, UL130, and UL131A (PubMed:17942555, PubMed:28783665).
CC The pentamer interacts with host NRP2 (PubMed:30057110). Forms the
CC envelope trimer complex composed of gH, gL, and gO. The trimer
CC interacts with host PDGFRA (PubMed:28403202). Interacts with UL116
CC (PubMed:26937030). {ECO:0000255|HAMAP-Rule:MF_04033,
CC ECO:0000269|PubMed:17942555, ECO:0000269|PubMed:26937030,
CC ECO:0000269|PubMed:28403202, ECO:0000269|PubMed:28783665,
CC ECO:0000269|PubMed:30057110}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04033,
CC ECO:0000269|PubMed:23804643}; Single-pass type I membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_04033}. Host cell membrane
CC {ECO:0000255|HAMAP-Rule:MF_04033}; Single-pass type I membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_04033}. Host endosome membrane
CC {ECO:0000255|HAMAP-Rule:MF_04033}; Single-pass type I membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_04033}. Note=During virion morphogenesis,
CC this protein probably accumulates in the endosomes and trans-Golgi
CC where secondary envelopment occurs. It is probably transported to the
CC cell surface from where it is endocytosed and directed to the trans-
CC Golgi network (TGN). {ECO:0000255|HAMAP-Rule:MF_04033}.
CC -!- PTM: N-glycosylated, O-glycosylated, and sialylated.
CC {ECO:0000255|HAMAP-Rule:MF_04033}.
CC -!- SIMILARITY: Belongs to the herpesviridae glycoprotein H family.
CC {ECO:0000255|HAMAP-Rule:MF_04033}.
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DR EMBL; AY446894; AAR31627.1; -; Genomic_DNA.
DR RefSeq; YP_081523.1; NC_006273.2.
DR PDB; 5VOB; X-ray; 3.02 A; A=1-715.
DR PDB; 5VOC; X-ray; 3.99 A; A=1-715.
DR PDB; 5VOD; X-ray; 5.90 A; A=1-715.
DR PDB; 7LBE; EM; 2.90 A; A=1-715.
DR PDB; 7LBF; EM; 2.80 A; A=1-715.
DR PDB; 7LBG; EM; 2.60 A; A=1-715.
DR PDBsum; 5VOB; -.
DR PDBsum; 5VOC; -.
DR PDBsum; 5VOD; -.
DR PDBsum; 7LBE; -.
DR PDBsum; 7LBF; -.
DR PDBsum; 7LBG; -.
DR SMR; Q6SW67; -.
DR TCDB; 1.G.22.1.1; the cytomegalovirus (human herpesvirus 5) glycoprotein go (go) family.
DR PRIDE; Q6SW67; -.
DR GeneID; 3077450; -.
DR KEGG; vg:3077450; -.
DR Reactome; R-HSA-9609690; HCMV Early Events.
DR Reactome; R-HSA-9610379; HCMV Late Events.
DR Proteomes; UP000000938; Genome.
DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0019031; C:viral envelope; TAS:Reactome.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098670; P:entry receptor-mediated virion attachment to host cell; IEA:UniProtKB-KW.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.3190; -; 1.
DR HAMAP; MF_04033; HSV_GH; 1.
DR InterPro; IPR003493; Herpes_gH.
DR InterPro; IPR035305; Herpes_glycoH_C.
DR InterPro; IPR038172; Herpes_glycoH_C_sf.
DR Pfam; PF17488; Herpes_glycoH_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Fusion of virus membrane with host cell membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW Membrane; Reference proteome; Sialic acid; Signal; Transmembrane;
KW Transmembrane helix; Viral attachment to host cell;
KW Viral attachment to host entry receptor; Viral envelope protein;
KW Viral penetration into host cytoplasm; Virion; Virus entry into host cell.
FT SIGNAL 1..23
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT CHAIN 24..742
FT /note="Envelope glycoprotein H"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT /id="PRO_0000436654"
FT TOPO_DOM 24..719
FT /note="Virion surface"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT TRANSMEM 720..740
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT TOPO_DOM 741..742
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT REGION 217..280
FT /note="Interaction with gL"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT CARBOHYD 641
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT CARBOHYD 700
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 64..72
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 75..83
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 86..92
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 100..106
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 115..121
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 128..131
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 147..150
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 172..175
FT /evidence="ECO:0007829|PDB:5VOB"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 222..229
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 231..241
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 246..251
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 264..267
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 276..280
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 283..285
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 290..293
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 295..298
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 299..302
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 309..315
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 317..327
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 335..351
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 359..362
FT /evidence="ECO:0007829|PDB:7LBF"
FT HELIX 363..383
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:5VOB"
FT HELIX 397..408
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 409..412
FT /evidence="ECO:0007829|PDB:5VOB"
FT HELIX 416..428
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 432..434
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 437..453
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 454..456
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 461..474
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 481..493
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 497..506
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:5VOB"
FT HELIX 515..518
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 521..523
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 524..528
FT /evidence="ECO:0007829|PDB:5VOB"
FT HELIX 532..537
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 541..543
FT /evidence="ECO:0007829|PDB:7LBE"
FT HELIX 548..558
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 567..571
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 578..581
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 584..594
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 597..603
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 614..619
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 646..649
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 650..658
FT /evidence="ECO:0007829|PDB:7LBG"
FT TURN 659..661
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 662..669
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 672..679
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 681..683
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 693..697
FT /evidence="ECO:0007829|PDB:7LBG"
FT STRAND 703..705
FT /evidence="ECO:0007829|PDB:7LBG"
FT HELIX 707..709
FT /evidence="ECO:0007829|PDB:7LBG"
SQ SEQUENCE 742 AA; 84321 MW; A4E837BA88DFF4DB CRC64;
MRPGLPSYLI ILAVCLFSHL LSSRYGAEAV SEPLDKAFHL LLNTYGRPIR FLRENTTQCT
YNSSLRNSTV VRENAISFNF FQSYNQYYVF HMPRCLFAGP LAEQFLNQVD LTETLERYQQ
RLNTYALVSK DLASYRSFSQ QLKAQDSLGE QPTTVPPPID LSIPHVWMPP QTTPHGWTES
HTTSGLHRPH FNQTCILFDG HDLLFSTVTP CLHQGFYLID ELRYVKITLT EDFFVVTVSI
DDDTPMLLIF GHLPRVLFKA PYQRDNFILR QTEKHELLVL VKKDQLNRHS YLKDPDFLDA
ALDFNYLDLS ALLRNSFHRY AVDVLKSGRC QMLDRRTVEM AFAYALALFA AARQEEAGAQ
VSVPRALDRQ AALLQIQEFM ITCLSQTPPR TTLLLYPTAV DLAKRALWTP NQITDITSLV
RLVYILSKQN QQHLIPQWAL RQIADFALKL HKTHLASFLS AFARQELYLM GSLVHSMLVH
TTERREIFIV ETGLCSLAEL SHFTQLLAHP HHEYLSDLYT PCSSSGRRDH SLERLTRLFP
DATVPATVPA ALSILSTMQP STLETFPDLF CLPLGESFSA LTVSEHVSYI VTNQYLIKGI
SYPVSTTVVG QSLIITQTDS QTKCELTRNM HTTHSITVAL NISLENCAFC QSALLEYDDT
QGVINIMYMH DSDDVLFALD PYNEVVVSSP RTHYLMLLKN GTVLEVTDVV VDATDSRLLM
MSVYALSAII GIYLLYRMLK TC
