ITP_HHV11
ID ITP_HHV11 Reviewed; 1123 AA.
AC P10221;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Inner tegument protein {ECO:0000255|HAMAP-Rule:MF_04043};
DE EC=3.5.1.- {ECO:0000269|PubMed:27866900, ECO:0000269|PubMed:30092200};
DE EC=3.5.1.44 {ECO:0000269|PubMed:30092200};
DE AltName: Full=Viral deamidase UL37;
GN Name=UL37;
OS Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10299;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2839594; DOI=10.1099/0022-1317-69-7-1531;
RA McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D.,
RA Perry L.J., Scott J.E., Taylor P.;
RT "The complete DNA sequence of the long unique region in the genome of
RT herpes simplex virus type 1.";
RL J. Gen. Virol. 69:1531-1574(1988).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=7856080; DOI=10.1006/viro.1995.1028;
RA Schmitz J.B., Albright A.G., Kinchington P.R., Jenkins F.J.;
RT "The UL37 protein of herpes simplex virus type 1 is associated with the
RT tegument of purified virions.";
RL Virology 206:1055-1065(1995).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=17223150; DOI=10.1016/j.virol.2006.11.031;
RA Bucks M.A., O'Regan K.J., Murphy M.A., Wills J.W., Courtney R.J.;
RT "Herpes simplex virus type 1 tegument proteins VP1/2 and UL37 are
RT associated with intranuclear capsids.";
RL Virology 361:316-324(2007).
RN [4]
RP INTERACTION WITH THE LARGE TEGUMENT PROTEIN.
RC STRAIN=KOS;
RX PubMed=18787001; DOI=10.1128/jvi.00956-08;
RA Desai P., Sexton G.L., Huang E., Person S.;
RT "Localization of herpes simplex virus type 1 UL37 in the Golgi complex
RT requires UL36 but not capsid structures.";
RL J. Virol. 82:11354-11361(2008).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20505007; DOI=10.1099/vir.0.022053-0;
RA Pasdeloup D., Beilstein F., Roberts A.P., McElwee M., McNab D., Rixon F.J.;
RT "Inner tegument protein pUL37 of herpes simplex virus type 1 is involved in
RT directing capsids to the trans-Golgi network for envelopment.";
RL J. Gen. Virol. 91:2145-2151(2010).
RN [6]
RP FUNCTION, AND INTERACTION WITH HOST DST.
RX PubMed=23269794; DOI=10.1128/jvi.02676-12;
RA Pasdeloup D., McElwee M., Beilstein F., Labetoulle M., Rixon F.J.;
RT "Herpesvirus tegument protein pUL37 interacts with dystonin/BPAG1 to
RT promote capsid transport on microtubules during egress.";
RL J. Virol. 87:2857-2867(2013).
RN [7]
RP FUNCTION, AND INTERACTION WITH LARGE TEGUMENT PROTEIN.
RX PubMed=24725933; DOI=10.1016/j.virol.2014.02.003;
RA Kelly B.J., Bauerfeind R., Binz A., Sodeik B., Laimbacher A.S., Fraefel C.,
RA Diefenbach R.J.;
RT "The interaction of the HSV-1 tegument proteins pUL36 and pUL37 is
RT essential for secondary envelopment during viral egress.";
RL Virology 454:67-77(2014).
RN [8]
RP FUNCTION, INTERACTION WITH HOST DDX58, AND MUTAGENESIS OF CYS-819 AND
RP CYS-850.
RX PubMed=27866900; DOI=10.1016/j.chom.2016.10.011;
RA Zhao J., Zeng Y., Xu S., Chen J., Shen G., Yu C., Knipe D., Yuan W.,
RA Peng J., Xu W., Zhang C., Xia Z., Feng P.;
RT "A Viral Deamidase Targets the Helicase Domain of RIG-I to Block RNA-
RT Induced Activation.";
RL Cell Host Microbe 20:770-784(2016).
RN [9]
RP FUNCTION.
RX PubMed=29216315; DOI=10.1371/journal.ppat.1006741;
RA Richards A.L., Sollars P.J., Pitts J.D., Stults A.M., Heldwein E.E.,
RA Pickard G.E., Smith G.A.;
RT "The pUL37 tegument protein guides alpha-herpesvirus retrograde axonal
RT transport to promote neuroinvasion.";
RL PLoS Pathog. 13:E1006741-E1006741(2017).
RN [10]
RP FUNCTION, INTERACTION WITH HOST CGAS, AND MUTAGENESIS OF CYS-819.
RX PubMed=30092200; DOI=10.1016/j.chom.2018.07.004;
RA Zhang J., Zhao J., Xu S., Li J., He S., Zeng Y., Xie L., Xie N., Liu T.,
RA Lee K., Seo G.J., Chen L., Stabell A.C., Xia Z., Sawyer S.L., Jung J.,
RA Huang C., Feng P.;
RT "Species-Specific Deamidation of cGAS by Herpes Simplex Virus UL37 Protein
RT Facilitates Viral Replication.";
RL Cell Host Microbe 24:234-248(2018).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.51 ANGSTROMS) OF 1-575.
RX PubMed=28768862; DOI=10.1128/jvi.01244-17;
RA Koenigsberg A.L., Heldwein E.E.;
RT "Crystal Structure of the N-Terminal Half of the Traffic Controller UL37
RT from Herpes Simplex Virus 1.";
RL J. Virol. 91:0-0(2017).
CC -!- FUNCTION: Plays an essential role in cytoplasmic secondary envelopment
CC during viral egress. Interacts with the capsid via the large tegument
CC protein/LTP and participates in its transport to the host trans-Golgi
CC network (TGN) where secondary envelopment occurs. Modulates
CC tegumentation and capsid accumulation at the viral assembly complex (By
CC similarity). Plays a role in microtubule-based retrograde axonal
CC transport to promote neuroinvasion (PubMed:29216315). Also plays a role
CC in the inhibition of host immune response by acting as a viral
CC deamidase (PubMed:27866900). Deamidates host DDX58/RIG-I on two
CC asparagines which becomes unable to sense viral dsRNA. In turn, its
CC ability to trigger antiviral immune response and restrict viral
CC replication is inhibited (PubMed:27866900). Deamidates also a critical
CC asparagine on host CGAS which abolishes cGAMP synthesis and downstream
CC innate immune activation (PubMed:30092200). {ECO:0000255|HAMAP-
CC Rule:MF_04043, ECO:0000269|PubMed:20505007,
CC ECO:0000269|PubMed:23269794, ECO:0000269|PubMed:24725933,
CC ECO:0000269|PubMed:27866900, ECO:0000269|PubMed:29216315,
CC ECO:0000269|PubMed:30092200}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-asparaginyl-[protein] = L-aspartyl-[protein] + NH4(+);
CC Xref=Rhea:RHEA:57416, Rhea:RHEA-COMP:9867, Rhea:RHEA-COMP:12804,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29961,
CC ChEBI:CHEBI:50347; Evidence={ECO:0000269|PubMed:27866900,
CC ECO:0000269|PubMed:30092200};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutaminyl-[protein] = L-glutamyl-[protein] + NH4(+);
CC Xref=Rhea:RHEA:16441, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:10208,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29973,
CC ChEBI:CHEBI:30011; EC=3.5.1.44;
CC Evidence={ECO:0000269|PubMed:30092200};
CC -!- SUBUNIT: Interacts (via C-terminus) with the large tegument protein/LTP
CC (via N-terminus) (By similarity) (PubMed:18787001, PubMed:24725933).
CC Interacts with host DST (PubMed:23269794). Interacts with host DDX58;
CC this interaction inhibits DDX58 activation (PubMed:27866900). Interacts
CC with host CGAS; this interaction inhibits host CGAS activation
CC (PubMed:30092200). {ECO:0000255|HAMAP-Rule:MF_04043,
CC ECO:0000269|PubMed:18787001, ECO:0000269|PubMed:23269794,
CC ECO:0000269|PubMed:24725933, ECO:0000269|PubMed:27866900,
CC ECO:0000269|PubMed:30092200}.
CC -!- INTERACTION:
CC P10221; P10220: UL36; NbExp=2; IntAct=EBI-6880600, EBI-7694334;
CC P10221; P10221: UL37; NbExp=2; IntAct=EBI-6880600, EBI-6880600;
CC P10221; Q9Y4K3: TRAF6; Xeno; NbExp=3; IntAct=EBI-6880600, EBI-359276;
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000255|HAMAP-Rule:MF_04043,
CC ECO:0000269|PubMed:7856080}. Host cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_04043, ECO:0000269|PubMed:20505007,
CC ECO:0000269|PubMed:7856080}. Host nucleus {ECO:0000255|HAMAP-
CC Rule:MF_04043, ECO:0000269|PubMed:17223150,
CC ECO:0000269|PubMed:7856080}. Host Golgi apparatus, host trans-Golgi
CC network {ECO:0000255|HAMAP-Rule:MF_04043, ECO:0000269|PubMed:20505007}.
CC -!- SIMILARITY: Belongs to the herpesviridae inner tegument protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04043}.
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; X14112; CAA32312.1; -; Genomic_DNA.
DR PIR; A30088; WMBEH7.
DR PDB; 5VYL; X-ray; 3.51 A; A=1-575.
DR PDBsum; 5VYL; -.
DR SASBDB; P10221; -.
DR SMR; P10221; -.
DR BioGRID; 971403; 8.
DR ELM; P10221; -.
DR IntAct; P10221; 7.
DR MINT; P10221; -.
DR PRIDE; P10221; -.
DR Proteomes; UP000009294; Genome.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019033; C:viral tegument; IDA:CAFA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050568; F:protein-glutamine glutaminase activity; IEA:UniProtKB-EC.
DR GO; GO:0039701; P:microtubule-dependent intracellular transport of viral material towards cell periphery; IDA:UniProtKB.
DR GO; GO:0039540; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity; IDA:UniProtKB.
DR GO; GO:0019068; P:virion assembly; IEA:UniProtKB-UniRule.
DR HAMAP; MF_04043; HSV_ITP; 1.
DR InterPro; IPR005655; Herpes_UL37.
DR InterPro; IPR034738; HSV_ITP.
DR Pfam; PF03970; Herpes_UL37_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cytoplasm; Host Golgi apparatus; Host nucleus;
KW Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host RIG-I by virus; Inhibition of host RLR pathway by virus;
KW Reference proteome; Viral immunoevasion; Virion; Virion tegument.
FT CHAIN 1..1123
FT /note="Inner tegument protein"
FT /id="PRO_0000116044"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 568..1123
FT /note="Interaction with large tegument protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04043"
FT REGION 1047..1123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1083..1102
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 819
FT /note="C->S: Complete loss of deamidase activity."
FT /evidence="ECO:0000269|PubMed:27866900,
FT ECO:0000269|PubMed:30092200"
FT MUTAGEN 850
FT /note="C->S: Complete loss of deamidase activity."
FT /evidence="ECO:0000269|PubMed:27866900"
SQ SEQUENCE 1123 AA; 120556 MW; 18425792B4D7EC9D CRC64;
MADRGLPSEA PVVTTSPAGP PSDGPMQRLL ASLAGLRQPP TPTAETANGA DDPAFLATAK
LRAAMAAFLL SGTAIAPADA RDCWRPLLEH LCALHRAHGL PETALLAENL PGLLVHRLVV
ALPEAPDQAF REMEVIKDTI LAVTGSDTSH ALDSAGLRTA AALGPVRVRQ CAVEWIDRWQ
TVTKSCLAMS PRTSIEALGE TSLKMAPVPL GQPSANLTTP AYSLLFPAPF VQEGLRFLAL
VSNRVTLFSA HLQRIDDATL TPLTRALFTL ALVDEYLTTP ERGAVVPPPL LAQFQHTVRE
IDPAIMIPPL EANKMVRSRE EVRVSTALSR VSPRSACAPP GTLMARVRTD VAVFDPDVPF
LSSSALAVFQ PAVSSLLQLG EQPSAGAQQR LLALLQQTWT LIQNTNSPSV VINTLIDAGF
TPSHCTHYLS ALEGFLAAGV PARTPTGHGL GEVQQLFGCI ALAGSNVFGL AREYGYYANY
VKTFRRVQGA SEHTHGRLCE AVGLSGGVLS QTLARIMGPA VPTEHLASLR RALVGEFETA
ERRFSSGQPS LLRETALIWI DVYGQTHWDI TPTTPATPLS ALLPVGQPSH APSVHLAAAT
QIRFPALEGI HPNVLADPGF VPYVLALVVG DALRATCSAA YLPRPVEFAL RVLAWARDFG
LGYLPTVEGH RTKLGALITL LEPAARGGLG PTMQMADNIE QLLRELYVIS RGAVEQLRPL
VQLQPPPPPE VGTSLLLISM YALAARGVLQ DLAERADPLI RQLEDAIVLL RLHMRTLSAF
FECRFESDGR RLYAVVGDTP DRLGPWPPEA MGDAVSQYCS MYHDAKRALV ASLASLRSVI
TETTAHLGVC DELAAQVSHE DNVLAVVRRE IHGFLSVVSG IHARASKLLS GDQVPGFCFM
GQFLARWRRL SACYQAARAA AGPEPVAEFV QELHDTWKGL QTERAVVVAP LVSSADQRAA
AIREVMAHAP EDAPPQSPAA DRVVLTSRRD LGAWGDYSLG PLGQTTAVPD SVDLSRQGLA
VTLSMDWLLM NELLRVTDGV FRASAFRPLA GPESPRDLEV RDAGNSLPAP MPMDAQKPEA
YGHGPRQADR EGAPHSNTPV EDDEMIPEDT VAPPTDLPLT SYQ
