MT_POVMA
ID MT_POVMA Reviewed; 421 AA.
AC P03077;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Middle T antigen;
DE Short=MT;
DE Short=MT-AG;
OS Murine polyomavirus (strain A2) (MPyV).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Sepolyvirales; Polyomaviridae; Alphapolyomavirus.
OX NCBI_TaxID=10636;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6243401; DOI=10.1038/283445a0;
RA Soeda E., Arrand J.R., Smolar N., Walsh J.E., Griffin B.E.;
RT "Coding potential and regulatory signals of the polyoma virus genome.";
RL Nature 283:445-453(1980).
RN [2]
RP INTERACTION WITH HOST YES1.
RX PubMed=6304524; DOI=10.1038/303435a0;
RA Courtneidge S.A., Smith A.E.;
RT "Polyoma virus transforming protein associates with the product of the c-
RT src cellular gene.";
RL Nature 303:435-439(1983).
RN [3]
RP INTERACTION WITH HOST SRC.
RX PubMed=3027584; DOI=10.1038/325171a0;
RA Kornbluth S., Sudol M., Hanafusa H.;
RT "Association of the polyomavirus middle-T antigen with c-yes protein.";
RL Nature 325:171-173(1987).
RN [4]
RP INTERACTION WITH HOST FYN.
RX PubMed=2463167; DOI=10.1002/j.1460-2075.1988.tb03270.x;
RA Cheng S.H., Harvey R., Espino P.C., Semba K., Yamamoto T., Toyoshima K.,
RA Smith A.E.;
RT "Peptide antibodies to the human c-fyn gene product demonstrate pp59c-fyn
RT is capable of complex formation with the middle-T antigen of
RT polyomavirus.";
RL EMBO J. 7:3845-3855(1988).
RN [5]
RP INTERACTION WITH HOST PPP2/PP2A.
RX PubMed=2153055; DOI=10.1016/0092-8674(90)90726-u;
RA Pallas D.C., Shahrik L.K., Martin B.L., Jaspers S., Miller T.B. Jr.,
RA Brautigan D.L., Roberts T.M.;
RT "Polyoma small and middle T antigens and SV40 small t antigen form stable
RT complexes with protein phosphatase 2A.";
RL Cell 60:167-176(1990).
RN [6]
RP MUTAGENESIS OF THR-160.
RX PubMed=7690142; DOI=10.1073/pnas.90.17.8113;
RA Perez L., Paasinen A., Schnierle B., Kach S., Senften M., Ballmer-Hofer K.;
RT "Mitosis-specific phosphorylation of polyomavirus middle-sized tumor
RT antigen and its role during cell transformation.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:8113-8117(1993).
RN [7]
RP MUTAGENESIS OF PRO-248 AND TYR-250, INTERACTION WITH HOST SHC1, DOMAIN, AND
RP PHOSPHORYLATION AT TYR-250.
RX PubMed=8022784; DOI=10.1073/pnas.91.14.6344;
RA Campbell K.S., Ogris E., Burke B., Su W., Auger K.R., Druker B.J.,
RA Schaffhausen B.S., Roberts T.M., Pallas D.C.;
RT "Polyoma middle tumor antigen interacts with SHC protein via the NPTY (Asn-
RT Pro-Thr-Tyr) motif in middle tumor antigen.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6344-6348(1994).
RN [8]
RP INTERACTION WITH HOST 14-3-3 PROTEINS.
RX PubMed=8036498; DOI=10.1126/science.8036498;
RA Pallas D.C., Fu H., Haehnel L.C., Weller W., Collier R.J., Roberts T.M.;
RT "Association of polyomavirus middle tumor antigen with 14-3-3 proteins.";
RL Science 265:535-537(1994).
RN [9]
RP MUTAGENESIS OF TYR-315 AND TYR-322, INTERACTION WITH HOST PLCG1 AND P85,
RP AND PHOSPHORYLATION AT TYR-315 AND TYR-322.
RX PubMed=7759472; DOI=10.1074/jbc.270.21.12331;
RA Su W., Liu W., Schaffhausen B.S., Roberts T.M.;
RT "Association of Polyomavirus middle tumor antigen with phospholipase C-
RT gamma 1.";
RL J. Biol. Chem. 270:12331-12334(1995).
RN [10]
RP MUTAGENESIS OF SER-257, AND PHOSPHORYLATION AT SER-257.
RX PubMed=9420259; DOI=10.1128/jvi.72.1.558-563.1998;
RA Cullere X., Rose P., Thathamangalam U., Chatterjee A., Mullane K.P.,
RA Pallas D.C., Benjamin T.L., Roberts T.M., Schaffhausen B.S.;
RT "Serine 257 phosphorylation regulates association of polyomavirus middle T
RT antigen with 14-3-3 proteins.";
RL J. Virol. 72:558-563(1998).
RN [11]
RP FUNCTION.
RX PubMed=16840310; DOI=10.1128/jvi.00679-06;
RA Chen L., Wang X., Fluck M.M.;
RT "Independent contributions of polyomavirus middle T and small T to the
RT regulation of early and late gene expression and DNA replication.";
RL J. Virol. 80:7295-7307(2006).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 248-251.
RX PubMed=15684325; DOI=10.1084/jem.20041890;
RA Nam H.J., Poy F., Saito H., Frederick C.A.;
RT "Structural basis for the function and regulation of the receptor protein
RT tyrosine phosphatase CD45.";
RL J. Exp. Med. 201:441-452(2005).
CC -!- FUNCTION: Plays a role in transformation by modulating the activities
CC of cellular proteins involved in control of cell proliferation and by
CC acting as a functional homolog of an activated tyrosine kinase-
CC associated growth-factor receptor. Recruits upon association with host
CC Ppp2/PP2A the Src tyrosine kinase components Src, Yes and Fyn, thereby
CC activating their kinase activity. Activation of Shc1, Pclg1 and p85
CC mediate signal transduction pathways leading to cell cycle progression
CC and cell division. MT also plays a role in regulation of early and late
CC gene expression and in viral DNA replication.
CC {ECO:0000269|PubMed:16840310}.
CC -!- SUBUNIT: Interacts with host Ppp2/PP2A A and C subunits; this
CC interaction alters Ppp2/PP2A substrate specificity and localization.
CC Interacts with host Src, Yes1, and Fyn. Interacts with host Shc1, Plcg1
CC and p85; these interactions lead to cell cycle progression. Interacts
CC with host 14-3-3 proteins. {ECO:0000269|PubMed:2153055,
CC ECO:0000269|PubMed:2463167, ECO:0000269|PubMed:3027584,
CC ECO:0000269|PubMed:6304524, ECO:0000269|PubMed:7759472,
CC ECO:0000269|PubMed:8022784, ECO:0000269|PubMed:8036498}.
CC -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Middle T antigen;
CC IsoId=P03077-1; Sequence=Displayed;
CC Name=Small t antigen;
CC IsoId=P68835-1; Sequence=External;
CC Name=Large T antigen;
CC IsoId=P03073-1; Sequence=External;
CC -!- DOMAIN: The NPTY motif is required for interaction with host Shc1
CC protein. {ECO:0000269|PubMed:8022784}.
CC -!- PTM: Tyrosine-phosphorylated on three residues 250, 315 and 322,
CC providing docking sites for host Shc1, p85, and Plcg1, respectively.
CC {ECO:0000269|PubMed:7759472, ECO:0000269|PubMed:8022784,
CC ECO:0000269|PubMed:9420259}.
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DR EMBL; J02288; AAB59900.1; -; Genomic_DNA.
DR PDB; 1YGU; X-ray; 2.90 A; C/D=248-251.
DR PDBsum; 1YGU; -.
DR SMR; P03077; -.
DR ELM; P03077; -.
DR iPTMnet; P03077; -.
DR EvolutionaryTrace; P03077; -.
DR Proteomes; UP000008479; Genome.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR Gene3D; 1.10.287.110; -; 1.
DR Gene3D; 1.20.120.1860; -; 1.
DR IDEAL; IID90016; -.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR036869; J_dom_sf.
DR InterPro; IPR003354; Papo_T_antigen.
DR InterPro; IPR036092; Papo_T_antigensf.
DR Pfam; PF02380; Papo_T_antigen; 1.
DR SMART; SM00271; DnaJ; 1.
DR SUPFAM; SSF161240; SSF161240; 1.
DR SUPFAM; SSF46565; SSF46565; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Early protein; Host membrane;
KW Host-virus interaction; Membrane; Oncogene; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..421
FT /note="Middle T antigen"
FT /id="PRO_0000115049"
FT TOPO_DOM 1..394
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 395..415
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 416..421
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 12..75
FT /note="J"
FT REGION 215..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 250
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000269|PubMed:8022784"
FT MOD_RES 257
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:9420259"
FT MOD_RES 315
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000269|PubMed:7759472"
FT MOD_RES 322
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000269|PubMed:7759472"
FT MUTAGEN 160
FT /note="T->A: Complete loss of transformation ability."
FT /evidence="ECO:0000269|PubMed:7690142"
FT MUTAGEN 248
FT /note="P->H: Complete loss of association with host Shc1."
FT /evidence="ECO:0000269|PubMed:8022784"
FT MUTAGEN 250
FT /note="Y->F: Complete loss of association with host Shc1."
FT /evidence="ECO:0000269|PubMed:8022784"
FT MUTAGEN 257
FT /note="S->A: Complete loss of interaction with host Ywhaz."
FT /evidence="ECO:0000269|PubMed:9420259"
FT MUTAGEN 315
FT /note="Y->F: 90% loss of association with host p85."
FT /evidence="ECO:0000269|PubMed:7759472"
FT MUTAGEN 322
FT /note="Y->F: Complete loss of association with host Plcg1."
FT /evidence="ECO:0000269|PubMed:7759472"
SQ SEQUENCE 421 AA; 48622 MW; CA0C25C4984CACB7 CRC64;
MDRVLSRADK ERLLELLKLP RQLWGDFGRM QQAYKQQSLL LHPDKGGSHA LMQELNSLWG
TFKTEVYNLR MNLGGTGFQV RRLHADGWNL STKDTFGDRY YQRFCRMPLT CLVNVKYSSC
SCILCLLRKQ HRELKDKCDA RCLVLGECFC LECYMQWFGT PTRDVLNLYA DFIASMPIDW
LDLDVHSVYN PKRRSEELRR AATVHYTMTT GHSAMEASTS QGNGMISSES GTPATSRRLR
LPSLLSNPTY SVMRSHSYPP TRVLQQIHPH ILLEEDEILV LLSPMTAYPR TPPELLYPES
DQDQLEPLEE EEEEYMPMED LYLDILPGEQ VPQLIPPPII PRAGLSPWEG LILRDLQRAH
FDPILDASQR MRATHRAALR AHSMQRHLRR LGRTLLLVTF LAALLGICLM LFILIKRSRH
F
