ID A0A2R8YGU4_HUMAN Unreviewed; 1739 AA.
AC A0A2R8YGU4;
DT 20-JUN-2018, integrated into UniProtKB/TrEMBL.
DT 20-JUN-2018, sequence version 1.
DT 24-JAN-2024, entry version 29.
DE SubName: Full=TSC complex subunit 2 {ECO:0000313|Ensembl:ENSP00000496317.1};
GN Name=TSC2 {ECO:0000313|Ensembl:ENSP00000496317.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000313|Ensembl:ENSP00000496317.1, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0000313|Ensembl:ENSP00000496317.1, ECO:0000313|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [2] {ECO:0007829|PubMed:18220336}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.D., Yates J.R.;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [3] {ECO:0007829|PubMed:18691976}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [4] {ECO:0007829|PubMed:18669648}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5] {ECO:0007829|PubMed:19413330}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6] {ECO:0007829|PubMed:19690332}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7] {ECO:0007829|PubMed:20068231}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8] {ECO:0007829|PubMed:21269460}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Burckstummer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9] {ECO:0007829|PubMed:21406692}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10] {ECO:0007829|PubMed:23186163}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=23186163;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11] {ECO:0007829|PubMed:24275569}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12] {ECO:0000313|Ensembl:ENSP00000496317.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2023) to UniProtKB.
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DR EMBL; AC093513; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR SMR; A0A2R8YGU4; -.
DR MassIVE; A0A2R8YGU4; -.
DR PeptideAtlas; A0A2R8YGU4; -.
DR Antibodypedia; 3702; 2363 antibodies from 45 providers.
DR Ensembl; ENST00000644335.1; ENSP00000496317.1; ENSG00000103197.19.
DR HGNC; HGNC:12363; TSC2.
DR VEuPathDB; HostDB:ENSG00000103197; -.
DR GeneTree; ENSGT00950000183139; -.
DR ChiTaRS; TSC2; human.
DR Proteomes; UP000005640; Chromosome 16.
DR Bgee; ENSG00000103197; Expressed in right hemisphere of cerebellum and 187 other cell types or tissues.
DR ExpressionAtlas; A0A2R8YGU4; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:InterPro.
DR GO; GO:0033596; C:TSC1-TSC2 complex; IEA:InterPro.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-UniRule.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IEA:InterPro.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1.
DR Gene3D; 3.40.50.11210; Rap/Ran-GAP; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR035974; Rap/Ran-GAP_sf.
DR InterPro; IPR000331; Rap/Ran_GAP_dom.
DR InterPro; IPR003913; Tuberin.
DR InterPro; IPR018515; Tuberin-type_domain.
DR InterPro; IPR027107; Tuberin/Ral-act_asu.
DR InterPro; IPR024584; Tuberin_N.
DR PANTHER; PTHR10063; TUBERIN; 1.
DR PANTHER; PTHR10063:SF0; TUBERIN; 1.
DR Pfam; PF11864; DUF3384; 1.
DR Pfam; PF02145; Rap_GAP; 1.
DR Pfam; PF03542; Tuberin; 1.
DR PRINTS; PR01431; TUBERIN.
DR SUPFAM; SSF48371; ARM repeat; 1.
DR SUPFAM; SSF111347; Rap/Ran-GAP; 1.
DR PROSITE; PS50085; RAPGAP; 1.
PE 1: Evidence at protein level;
KW GTPase activation {ECO:0000256|ARBA:ARBA00022468, ECO:0000256|PROSITE-
KW ProRule:PRU00165};
KW Proteomics identification {ECO:0007829|EPD:A0A2R8YGU4,
KW ECO:0007829|MaxQB:A0A2R8YGU4};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640}.
FT DOMAIN 1463..1690
FT /note="Rap-GAP"
FT /evidence="ECO:0000259|PROSITE:PS50085"
FT REGION 655..676
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 930..955
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1040..1089
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1105..1131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1265..1286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1298..1422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1697..1725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1040..1059
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1304..1328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1403..1418
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1739 AA; 193121 MW; 94A941D1BC66479C CRC64;
MAKPTSKDSG LKEKFKILLG LGTPRPNPRS AEGKQTEFII TAEILRELSM ECGLNNRIRM
IGQICEVAKT KKFEEHAVEA LWKAVADLLQ PERPLEARHA VLALLKAIVQ GQGERLGVLR
ALFFKVIKDY PSNEDLHERL EVFKALTDNG RHITYLEEEL ADFVLQWMDV GLSSEFLLVL
VNLVKFNSCY LDEYIARMVQ MICLLCVRTA SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI
VTLCRTINVK ELCEPCWKLM RNLLGTHLGH SAIYNMCHLM EDRAYMEDAP LLRGAVFFVG
MALWGAHRLY SLRNSPTSVL PSFYQAMACP NEVVSYEIVL SITRLIKKYR KELQVVAWDI
LLNIIERLLQ QLQTLDSPEL RTIVHDLLTT VEELCDQNEF HGSQERYFEL VERCADQRPE
SSLLNLISYR AQSIHPAKDG WIQNLQALME RFFRSESRGA VRIKVLDVLS FVLLINRQFY
EEELINSVVI SQLSHIPEDK DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS
PPPELEERDV AAYSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYEML VSHIQLHYKH
SYTLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCVCDYME PERGSEKKTS
GPLSPPTGPP GPAPAGPAVR LGSVPYSLLF RVLLQCLKQE SDWKVLKLVL GRLPESLRYK
VLIFTSPCSV DQLCSALCSM LSGPKTLERL RGAPEGFSRT DLHLAVVPVL TALISYHNYL
DKTKQREMVY CLEQGLIHRC ASQCVVALSI CSVEMPDIII KALPVLVVKL THISATASMA
VPLLEFLSTL ARLPHLYRNF AAEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC
RLPFRKDFVP FITKGLRSNV LLSFDDTPEK DSFRARSTSL NERPKSRIQT SLTSASLGSA
DENSVAQADD SLKNLHLELT ETCLDMMARY VFSNFTAVPK RSPVGEFLLA GGRTKTWLVG
NKLVTVTTSV GTGTRSLLGL DSGELQSGPE SSSSPGVHVR QTKEAPAKLE SQAGQQVSRG
ARDRVRSMSG GHGLRVGALD VPASQFLGSA TSPGPRTAPA AKPEKASAGT RVPVQEKTNL
AAYVPLLTQG WAEILVRRPT GNTSWLMSLE NPLSPFSSDI NNMPLQELSN ALMAAERFKE
HRDTALYKSL SVPAASTAKP PPLPRSNTDS AVVMEEGSPG EVPVLVEPPG LEDVEAALGM
DRRTDAYSRS SSVSSQEEKS LHAEELVGRG IPIERVVSSE GGRPSVDLSF QPSQPLSKSS
SSPELQTLQD ILGDPGDKAD VGRLSPEVKA RSQSGTLDGE SAAWSASGED SRGQPEGPLP
SSSPRSPSGL RPRGYTISDS APSRRGKRVE RDALKSRATA SNAEKVPGIN PSFVFLQLYH
SPFFGDESNK PILLPNESFE RSVQLLDQIP SYDTHKIAVL YVGEGQSNSE LAILSNEHGS
YRYTEFLTGL GRLIELKDCQ PDKVYLGGLD VCGEDGQFTY CWHDDIMQAV FHIATLMPTK
DVDKHRCDKK RHLGNDFVSI VYNDSGEDFK LGTIKGQFNF VHVIVTPLDY ECNLVSLQCR
KDMEGLVDTS VAKIVSDRNL PFVARQMALH ANMASQVHHS RSNPTDIYPS KWIARLRHIK
RLRQRICEEA AYSNPSLPLV HPPSHSKAPA QTPAEPTPGY EVGQRKRLIS SVEDFTEFV
//