GAM1_ADEG1
ID GAM1_ADEG1 Reviewed; 282 AA.
AC Q64770; Q64778;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 29-SEP-2021, entry version 70.
DE RecName: Full=Protein GAM-1;
DE AltName: Full=Gallus-anti morte protein;
DE AltName: Full=Gam1;
GN ORFNames=8;
OS Fowl adenovirus A serotype 1 (strain CELO / Phelps) (FAdV-1) (Avian
OS adenovirus gal1 (strain Phelps)).
OC Viruses; Varidnaviria; Bamfordvirae; Preplasmiviricota; Tectiliviricetes;
OC Rowavirales; Adenoviridae; Aviadenovirus; Fowl aviadenovirus A.
OX NCBI_TaxID=10553;
OH NCBI_TaxID=8976; Galliformes.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Akopian T.A., Kaverina E.N., Kruglyak V.A., Naroditsky B.S.,
RA Tikhonenko T.T.;
RT "Sequence of an Avian Adenovirus (CELO) DNA fragment (11.2-19.2%).";
RL Submitted (MAY-1993) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=8627769; DOI=10.1128/jvi.70.5.2939-2949.1996;
RA Chiocca S., Kurzbauer R., Schaffner G., Baker A., Mautner V., Cotten M.;
RT "The complete DNA sequence and genomic organization of the avian adenovirus
RT CELO.";
RL J. Virol. 70:2939-2949(1996).
RN [3]
RP IDENTIFICATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-258 AND
RP LEU-265.
RX PubMed=9060680; DOI=10.1128/jvi.71.4.3168-3177.1997;
RA Chiocca S., Baker A., Cotten M.;
RT "Identification of a novel antiapoptotic protein, GAM-1, encoded by the
RT CELO adenovirus.";
RL J. Virol. 71:3168-3177(1997).
RN [4]
RP FUNCTION, AND INTERACTION WITH HOST RETINOBLASTOMA PROTEIN.
RX PubMed=10400747; DOI=10.1128/jvi.73.8.6517-6525.1999;
RA Lehrmann H., Cotten M.;
RT "Characterization of CELO virus proteins that modulate the pRb/E2F
RT pathway.";
RL J. Virol. 73:6517-6525(1999).
RN [5]
RP FUNCTION.
RX PubMed=11001061; DOI=10.1038/35025102;
RA Glotzer J.B., Saltik M., Chiocca S., Michou A.-I., Moseley P., Cotten M.;
RT "Activation of heat-shock response by an adenovirus is essential for virus
RT replication.";
RL Nature 407:207-211(2000).
RN [6]
RP FUNCTION, AND INTERACTION WITH HOST HDAC1.
RX PubMed=11937030; DOI=10.1016/s0960-9822(02)00720-0;
RA Chiocca S., Kurtev V., Colombo R., Boggio R., Sciurpi M.T., Brosch G.,
RA Seiser C., Draetta G.F., Cotten M.;
RT "Histone deacetylase 1 inactivation by an adenovirus early gene product.";
RL Curr. Biol. 12:594-598(2002).
RN [7]
RP FUNCTION.
RX PubMed=12393750; DOI=10.1093/embo-reports/kvf213;
RA Colombo R., Boggio R., Seiser C., Draetta G.F., Chiocca S.;
RT "The adenovirus protein Gam1 interferes with sumoylation of histone
RT deacetylase 1.";
RL EMBO Rep. 3:1062-1068(2002).
RN [8]
RP IDENTIFICATION IN A COMPLEX WITH HUMAN E4F1 AND HDAC1.
RX PubMed=12730668; DOI=10.1038/sj.onc.1206379;
RA Colombo R., Draetta G.F., Chiocca S.;
RT "Modulation of p120E4F transcriptional activity by the Gam1 adenoviral
RT early protein.";
RL Oncogene 22:2541-2547(2003).
RN [9]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH HOST SAE1 AND UBA2.
RX PubMed=15546615; DOI=10.1016/j.molcel.2004.11.007;
RA Boggio R., Colombo R., Hay R.T., Draetta G.F., Chiocca S.;
RT "A mechanism for inhibiting the SUMO pathway.";
RL Mol. Cell 16:549-561(2004).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF TRP-255; LEU-258 AND LEU-265.
RX PubMed=17392274; DOI=10.1074/jbc.m700889200;
RA Boggio R., Passafaro A., Chiocca S.;
RT "Targeting SUMO E1 to ubiquitin ligases: a viral strategy to counteract
RT sumoylation.";
RL J. Biol. Chem. 282:15376-15382(2007).
CC -!- FUNCTION: Early protein essential for viral replication. Strong and
CC global transcriptional activator of both viral and cellular genes.
CC Activates transcription by blocking host retinoblastoma protein (RB)
CC and inhibiting the SUMO pathway. Inhibition of host RB leads to the
CC activation of E2F1-dependent transcription and, in particular, of E2F1-
CC regulated S-phase genes. Stimulation of progression from G1 to S phase
CC allows the virus to efficiently use the cellular DNA replicating
CC machinery to achieve viral genome replication. Blocks the SUMO pathway
CC by targeting the E1 enzyme (SAE1/UBA2 heterodimer) to the ubiquitin-
CC proteasome machinery. Mediates SAE1 degradation possibly through the
CC formation of complexes with either CUL2-elongin BC complex-RBX1 or
CC CUL5-elongin BC complex-RBX1. The degradation of UBA2 is probably a
CC consequent effect of SAE1 disappearance. Inhibits HDAC1 sumoylation,
CC thereby interfering with histone deacetylation mediated by HDAC1,
CC leading to activation of transcription. Mediates induction of heat-
CC shock response. Seems to have an antiapoptotic function.
CC {ECO:0000269|PubMed:10400747, ECO:0000269|PubMed:11001061,
CC ECO:0000269|PubMed:11937030, ECO:0000269|PubMed:12393750,
CC ECO:0000269|PubMed:15546615, ECO:0000269|PubMed:17392274}.
CC -!- SUBUNIT: Interacts with host HDAC1. Interacts with host E1-activating
CC enzyme (SAE1/UBA2 heterodimer). Interacts with host retinoblastoma
CC protein. Seems to form a complex with host E4F1 and HDAC1. Seems to
CC form complexes with either CUL2-elongin BC complex-RBX1 or CUL5-elongin
CC BC complex-RBX1. Interacts with TCEB1/Elongin-C, CUL2 and CUL5 in
CC vitro. {ECO:0000269|PubMed:10400747, ECO:0000269|PubMed:11937030,
CC ECO:0000269|PubMed:12730668, ECO:0000269|PubMed:15546615}.
CC -!- INTERACTION:
CC Q64770; Q66K89: E4F1; Xeno; NbExp=4; IntAct=EBI-8642971, EBI-1227043;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:9060680}.
CC -!- DOMAIN: The BC-box-like motif could mediate the interaction with host
CC cullin RING ubiquitin ligases.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA80482.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; Z22864; CAA80482.1; ALT_FRAME; Genomic_DNA.
DR EMBL; U46933; AAC54927.1; -; Genomic_DNA.
DR PIR; S33491; S33491.
DR RefSeq; NP_043901.1; NC_001720.1.
DR IntAct; Q64770; 2.
DR MINT; Q64770; -.
DR GeneID; 1733455; -.
DR KEGG; vg:1733455; -.
DR Proteomes; UP000001594; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
PE 1: Evidence at protein level;
KW Activator; Early protein; Host nucleus; Host-virus interaction;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..282
FT /note="Protein GAM-1"
FT /id="PRO_0000331618"
FT MOTIF 251..260
FT /note="BC-box-like"
FT MUTAGEN 252
FT /note="L->A: Strong loss of binding to the elongin BC
FT complex."
FT MUTAGEN 255
FT /note="W->A: Strong loss of binding to the elongin BC
FT complex."
FT /evidence="ECO:0000269|PubMed:17392274"
FT MUTAGEN 258
FT /note="L->A: Complete loss of binding to the elongin BC
FT complex, CUL2 and CUL5 proteins. Complete loss of
FT inhibition of sumoylation and antiapoptotic function; when
FT associated with A-265."
FT /evidence="ECO:0000269|PubMed:17392274,
FT ECO:0000269|PubMed:9060680"
FT MUTAGEN 258
FT /note="L->G: Loss of antiapoptotic function; when
FT associated with G-265."
FT /evidence="ECO:0000269|PubMed:17392274,
FT ECO:0000269|PubMed:9060680"
FT MUTAGEN 258
FT /note="L->P: Loss of antiapoptotic function; when
FT associated with P-265."
FT /evidence="ECO:0000269|PubMed:17392274,
FT ECO:0000269|PubMed:9060680"
FT MUTAGEN 265
FT /note="L->A: Complete loss of binding to the elongin BC
FT complex, CUL2 and CUL5 proteins. Complete loss of
FT inhibition of sumoylation and antiapoptotic function; when
FT associated with A-258."
FT /evidence="ECO:0000269|PubMed:17392274,
FT ECO:0000269|PubMed:9060680"
FT MUTAGEN 265
FT /note="L->G: Loss of antiapoptotic function; when
FT associated with G-258."
FT /evidence="ECO:0000269|PubMed:17392274,
FT ECO:0000269|PubMed:9060680"
FT MUTAGEN 265
FT /note="L->P: Loss of antiapoptotic function; when
FT associated with P-258."
FT /evidence="ECO:0000269|PubMed:17392274,
FT ECO:0000269|PubMed:9060680"
FT CONFLICT 144
FT /note="S -> F (in Ref. 1; CAA80482)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 282 AA; 31513 MW; 5F817469544C67A3 CRC64;
MARNPFRMFP GDLPYYMGTI SFTSVVPVDP SQRNPTTSLR EMVTTGLIFN PNLTGEQLRE
YSFSPLVSMG RKAIFADYEG PQRIIHVTIR GRSAEPKTPS EALIMMEKAV RGAFAVPDWV
AREYSDPLPH GITHVGDLGF PIGSVHALKM ALDTLKIHVP RGVGVPGYEG LCGTTTIKAP
RQYRLLTTGV FTKKDLKRTL PEPFFSRFFN QTPEVCAIKT GKNPFSTEIW CMTLGGDSPA
PERNEPRNPH SLQDWARLGV METCLRMSRR GLGSRHHPYH SL
