LAP_MYXVL
ID LAP_MYXVL Reviewed; 206 AA.
AC Q997C2; Q9Q8F2;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=E3 ubiquitin-protein ligase LAP;
DE EC=2.3.2.27;
DE AltName: Full=Leukemia associated protein;
DE Short=LAP;
DE AltName: Full=RING-type E3 ubiquitin transferase LAP {ECO:0000305};
GN Name=LAP; OrderedLocusNames=m153R;
OS Myxoma virus (strain Lausanne) (MYXV).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Leporipoxvirus.
OX NCBI_TaxID=31530;
OH NCBI_TaxID=9986; Oryctolagus cuniculus (Rabbit).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Toulouse 1;
RX PubMed=11861858; DOI=10.1128/jvi.76.6.2912-2923.2002;
RA Guerin J.L., Gelfi J., Boullier S., Delverdier M., Bellanger F.A.,
RA Bertagnoli S., Drexler I., Sutter G., Messud-Petit F.;
RT "Myxoma virus leukemia-associated protein is responsible for major
RT histocompatibility complex class I and Fas-CD95 down-regulation and defines
RT scrapins, a new group of surface cellular receptor abductor proteins.";
RL J. Virol. 76:2912-2923(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10562494; DOI=10.1006/viro.1999.0001;
RA Cameron C., Hota-Mitchell S., Chen L., Barrett J.W., Cao J.-X.,
RA Macaulay C., Willer D.O., Evans D.H., McFadden G.;
RT "The complete DNA sequence of myxoma virus.";
RL Virology 264:298-318(1999).
RN [3]
RP FUNCTION.
RX PubMed=12502858; DOI=10.1128/jvi.77.2.1427-1440.2003;
RA Mansouri M., Bartee E., Gouveia K., Hovey Nerenberg B.T., Barrett J.,
RA Thomas L., Thomas G., McFadden G., Fruh K.;
RT "The PHD/LAP-domain protein M153R of myxomavirus is a ubiquitin ligase that
RT induces the rapid internalization and lysosomal destruction of CD4.";
RL J. Virol. 77:1427-1440(2003).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16185739; DOI=10.1016/j.virol.2005.07.032;
RA Collin N., Guerin J.L., Drexler I., Blanie S., Gelfi J., Boullier S.,
RA Foucras G., Sutter G., Messud-Petit F.;
RT "The poxviral scrapin MV-LAP requires a myxoma viral infection context to
RT efficiently downregulate MHC-I molecules.";
RL Virology 343:171-178(2005).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which promotes ubiquitination and
CC subsequent degradation of host MHC-I and CD4 molecules, presumably to
CC prevent lysis of infected cells by cytotoxic T-lymphocytes and NK cell.
CC Binds target molecules through transmembrane interaction. The result of
CC this ubiquitination is the enhancement of the endocytosis of the target
CC chain and the delivery to the lysosome, where it is proteolytically
CC destroyed (By similarity). {ECO:0000250, ECO:0000269|PubMed:12502858,
CC ECO:0000269|PubMed:16185739}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Host Golgi apparatus, host trans-Golgi network
CC membrane {ECO:0000269|PubMed:16185739}. Host early endosome membrane
CC {ECO:0000269|PubMed:16185739}.
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity. {ECO:0000255|PROSITE-ProRule:PRU00623}.
CC -!- SIMILARITY: Belongs to the poxviridae LAP protein family.
CC {ECO:0000305}.
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DR EMBL; AF170726; AAF15041.2; -; Genomic_DNA.
DR EMBL; AF229033; AAK00734.1; -; Genomic_DNA.
DR RefSeq; NP_051866.2; NC_001132.2.
DR GeneID; 932099; -.
DR KEGG; vg:932099; -.
DR Proteomes; UP000000867; Genome.
DR GO; GO:0044174; C:host cell endosome; IEA:UniProtKB-KW.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0039648; P:modulation by virus of host protein ubiquitination; IEA:UniProtKB-KW.
DR GO; GO:0046776; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011016; Znf_RING-CH.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF12906; RINGv; 1.
DR SMART; SM00744; RINGv; 1.
DR PROSITE; PS51292; ZF_RING_CH; 1.
PE 3: Inferred from homology;
KW Host endosome; Host Golgi apparatus; Host membrane; Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
KW Inhibition of host MHC class I molecule presentation by virus; Membrane;
KW Metal-binding; Modulation of host ubiquitin pathway by viral E3 ligase;
KW Modulation of host ubiquitin pathway by virus; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..206
FT /note="E3 ubiquitin-protein ligase LAP"
FT /id="PRO_0000396001"
FT TOPO_DOM 1..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 94..114
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 115..129
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..150
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 151..206
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 15..75
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 23
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 26
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 37
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 47
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 50
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
SQ SEQUENCE 206 AA; 23258 MW; AFC6FD51B1D19957 CRC64;
MATVVNMDTV VNLDDVSLAD KCCWICKEAC DIVPNYCKCR GDNKIVHKEC LEEWINTDVV
KNKSCAICES PYNLKRRYKK ITKWRCYKRD CHDSLLVNMS LCLIVGGMGG YLLISTEIVK
LIASEEVSNI AKVFLVSASM GPFMVSALTM VRACIDCRTY FIATRERNTI HEVAEMEDVE
EVEEVNDDDG DEYVDAVEEI VVESPA
