ID   NEC1_HCMVA              Reviewed;         376 AA.
AC   P16794; Q7M6N0;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   24-JAN-2024, entry version 76.
DE   RecName: Full=Nuclear egress protein 1 {ECO:0000255|HAMAP-Rule:MF_04023};
GN   Name=NEC1 {ECO:0000255|HAMAP-Rule:MF_04023}; OrderedLocusNames=UL53;
OS   Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Betaherpesvirinae; Cytomegalovirus;
OC   Cytomegalovirus humanbeta5; Human cytomegalovirus.
OX   NCBI_TaxID=10360;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3029980; DOI=10.1016/0042-6822(87)90282-0;
RA   Kouzarides T., Bankier A.T., Satchwell S.C., Weston K.M., Tomlinson P.,
RA   Barrell B.G.;
RT   "Large-scale rearrangement of homologous regions in the genomes of HCMV and
RT   EBV.";
RL   Virology 157:397-413(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=2161319; DOI=10.1007/978-3-642-74980-3_6;
RA   Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R.,
RA   Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A.,
RA   Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G.;
RT   "Analysis of the protein-coding content of the sequence of human
RT   cytomegalovirus strain AD169.";
RL   Curr. Top. Microbiol. Immunol. 154:125-169(1990).
RN   [3]
RP   GENOME REANNOTATION.
RX   PubMed=12533697; DOI=10.1099/vir.0.18606-0;
RA   Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA   McGeoch D.J., Hayward G.S.;
RT   "The human cytomegalovirus genome revisited: comparison with the chimpanzee
RT   cytomegalovirus genome.";
RL   J. Gen. Virol. 84:17-28(2003).
RN   [4]
RP   ERRATUM OF PUBMED:12533697.
RA   Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA   McGeoch D.J., Hayward G.S.;
RL   J. Gen. Virol. 84:1053-1053(2003).
RN   [5]
RP   SUBCELLULAR LOCATION.
RX   PubMed=11961254; DOI=10.1099/0022-1317-83-5-1005;
RA   Dal Monte P., Pignatelli S., Zini N., Maraldi N.M., Perret E.,
RA   Prevost M.C., Landini M.P.;
RT   "Analysis of intracellular and intraviral localization of the human
RT   cytomegalovirus UL53 protein.";
RL   J. Gen. Virol. 83:1005-1012(2002).
RN   [6]
RP   INTERACTION WITH UL50.
RX   PubMed=17005637; DOI=10.1128/jvi.01662-06;
RA   Schnee M., Ruzsics Z., Bubeck A., Koszinowski U.H.;
RT   "Common and specific properties of herpesvirus UL34/UL31 protein family
RT   members revealed by protein complementation assay.";
RL   J. Virol. 80:11658-11666(2006).
RN   [7]
RP   FUNCTION, PHOSPHORYLATION AT SER-19, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP   OF SER-19.
RX   PubMed=25339763; DOI=10.1128/jvi.02426-14;
RA   Sharma M., Bender B.J., Kamil J.P., Lye M.F., Pesola J.M., Reim N.I.,
RA   Hogle J.M., Coen D.M.;
RT   "Human cytomegalovirus UL97 phosphorylates the viral nuclear egress
RT   complex.";
RL   J. Virol. 89:523-534(2015).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) OF 4-168, INTERACTION WITH NEC2,
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-79; CYS-122; CYS-125 AND
RP   HIS-211.
RX   PubMed=26511021; DOI=10.15252/embj.201592651;
RA   Lye M.F., Sharma M., El Omari K., Filman D.J., Schuermann J.P., Hogle J.M.,
RA   Coen D.M.;
RT   "Unexpected features and mechanism of heterodimer formation of a
RT   herpesvirus nuclear egress complex.";
RL   EMBO J. 34:2937-2952(2015).
RN   [9] {ECO:0007744|PDB:6T3X}
RP   X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 1-171, INTERACTION WITH NEC2, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=31980459; DOI=10.1074/jbc.ra119.011546;
RA   Muller Y.A., Hage S., Alkhashrom S., Hollriegl T., Weigert S., Dolles S.,
RA   Hof K., Walzer S.A., Egerer-Sieber C., Conrad M., Holst S., Losing J.,
RA   Sonntag E., Sticht H., Eichler J., Marschall M.;
RT   "High-resolution crystal structures of two prototypical beta- and gamma-
RT   herpesviral nuclear egress complexes unravel the determinants of subfamily
RT   specificity.";
RL   J. Biol. Chem. 295:3189-3201(2020).
CC   -!- FUNCTION: Plays an essential role in virion nuclear egress, the first
CC       step of virion release from infected cell. Within the host nucleus,
CC       NEC1 interacts with the newly formed capsid through the vertexes and
CC       directs it to the inner nuclear membrane by associating with NEC2.
CC       Induces the budding of the capsid at the inner nuclear membrane as well
CC       as its envelopment into the perinuclear space. There, the NEC1/NEC2
CC       complex promotes the fusion of the enveloped capsid with the outer
CC       nuclear membrane and the subsequent release of the viral capsid into
CC       the cytoplasm where it will reach the secondary budding sites in the
CC       host Golgi or trans-Golgi network. {ECO:0000255|HAMAP-Rule:MF_04023,
CC       ECO:0000269|PubMed:25339763}.
CC   -!- SUBUNIT: Forms a heterohexameric complex with NEC2. Interacts with
CC       capsid vertex specific component 2/CVC2; this interaction directs the
CC       capsid to the host inner nuclear membrane to initiate budding.
CC       {ECO:0000255|HAMAP-Rule:MF_04023, ECO:0000269|PubMed:26511021,
CC       ECO:0000269|PubMed:31980459}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus inner membrane {ECO:0000255|HAMAP-
CC       Rule:MF_04023, ECO:0000269|PubMed:11961254,
CC       ECO:0000269|PubMed:25339763, ECO:0000269|PubMed:26511021,
CC       ECO:0000269|PubMed:31980459}. Note=Remains attached to the nucleus
CC       inner membrane through interaction with NEC2. {ECO:0000255|HAMAP-
CC       Rule:MF_04023, ECO:0000269|PubMed:26511021}.
CC   -!- PTM: Phosphorylated at serine residues in the N-terminus. This
CC       phosphorylation regulates the localization within the inner nuclear
CC       membrane (By similarity). Phosphorylation by viral kinase UL97 at Ser-
CC       19 plays an important role for correct viral nuclear egress complex
CC       (NEC) localization (PubMed:25339763). {ECO:0000255|HAMAP-Rule:MF_04023,
CC       ECO:0000269|PubMed:25339763}.
CC   -!- SIMILARITY: Belongs to the herpesviridae NEC1 protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04023}.
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DR   EMBL; M17209; AAA46007.1; -; Genomic_DNA.
DR   EMBL; X17403; CAA35412.1; -; Genomic_DNA.
DR   EMBL; BK000394; DAA00158.1; -; Genomic_DNA.
DR   PIR; S09816; QQBEW2.
DR   PDB; 5DOB; X-ray; 2.47 A; A=61-289.
DR   PDB; 5DOC; X-ray; 1.94 A; A/B=88-290.
DR   PDB; 5DOE; X-ray; 3.00 A; B=72-290.
DR   PDB; 6T3X; X-ray; 1.48 A; A/C=59-87.
DR   PDBsum; 5DOB; -.
DR   PDBsum; 5DOC; -.
DR   PDBsum; 5DOE; -.
DR   PDBsum; 6T3X; -.
DR   SMR; P16794; -.
DR   iPTMnet; P16794; -.
DR   Proteomes; UP000008991; Genome.
DR   Proteomes; UP000008992; Genome.
DR   GO; GO:0044201; C:host cell nuclear inner membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0046765; P:viral budding from nuclear membrane; IEA:InterPro.
DR   HAMAP; MF_04023; HSV_NEC1; 1.
DR   InterPro; IPR021152; Herpes_UL31.
DR   Pfam; PF02718; Herpes_UL31; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Host membrane; Host nucleus; Membrane; Metal-binding;
KW   Phosphoprotein; Reference proteome; Zinc; Zinc-finger.
FT   CHAIN           1..376
FT                   /note="Nuclear egress protein 1"
FT                   /id="PRO_0000116013"
FT   ZN_FING         106..211
FT                   /note="CCCH-type"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04023"
FT   REGION          22..57
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          316..376
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        31..48
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        316..350
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        360..376
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         19
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:25339763"
FT   MUTAGEN         19
FT                   /note="S->A: No effect on replication kinetics."
FT                   /evidence="ECO:0000269|PubMed:25339763"
FT   MUTAGEN         79
FT                   /note="L->A: Loss of interaction and co-localization with
FT                   NEC1."
FT                   /evidence="ECO:0000269|PubMed:25339763"
FT   MUTAGEN         122
FT                   /note="C->S: Partial relocalization in the host
FT                   nucleoplasm."
FT                   /evidence="ECO:0000269|PubMed:31980459"
FT   MUTAGEN         125
FT                   /note="C->S: Partial relocalization in the host
FT                   nucleoplasm."
FT                   /evidence="ECO:0000269|PubMed:31980459"
FT   MUTAGEN         211
FT                   /note="H->A: Partial relocalization in the host
FT                   nucleoplasm."
FT                   /evidence="ECO:0000269|PubMed:31980459"
FT   HELIX           61..70
FT                   /evidence="ECO:0007829|PDB:6T3X"
FT   HELIX           72..81
FT                   /evidence="ECO:0007829|PDB:6T3X"
FT   STRAND          89..91
FT                   /evidence="ECO:0007829|PDB:5DOB"
FT   STRAND          94..97
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           98..100
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   STRAND          105..110
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   STRAND          113..118
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   TURN            119..121
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           134..142
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           144..146
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   TURN            148..151
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           152..156
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   TURN            157..160
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           162..168
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           172..184
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   STRAND          186..195
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   STRAND          198..208
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   STRAND          210..212
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           214..224
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   TURN            225..227
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   STRAND          228..235
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   STRAND          238..246
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           257..266
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           271..279
FT                   /evidence="ECO:0007829|PDB:5DOC"
FT   HELIX           281..288
FT                   /evidence="ECO:0007829|PDB:5DOC"
SQ   SEQUENCE   376 AA;  42313 MW;  BF44D5F8DE2B88B9 CRC64;
     MSSVSGVRTP RERRSALRSL LRKRRQRELA SKVASTVNGA TSANNHGEPP SPADARPRLT
     LHDLHDIFRE HPELELKYLN MMKMAITGKE SICLPFNFHS HRQHTCLDIS PYGNEQVSRI
     ACTSCEDNRI LPTASDAMVA FINQTSNIMK NRNFYYGFCK SSELLKLSTN QPPIFQIYYL
     LHAANHDIVP FMHAEDGRLH MHVIFENPDV HIPCDCITQM LTAAREDYSV TLNIVRDHVV
     ISVLCHAVSA SSVKIDVTIL QRKIDEMDIP NDVSESFERY KELIQELCQS SGNNLYEEAT
     SSYAIRSPLT ASPLHVVSTN GCGPSSSSQS TPPHLHPPSQ ATQPHHYSHH QSQSQQHHHR
     PQSPPPPLFL NSIRAP
//