P49815

PTMD Annotation Information

※ Protein Information

Tag	Content
UniProt Accession	TSC2_HUMAN; P49815;
Entrez ID	7249
GenBank Protein ID	NM_000548.4; NM_001077183.2; NM_001114382.2; NM_001318827.1; NM_001318829.1; NM_001318831.1; NM_001318832.1; XM_005255529.4; XM_017023616.1;
GenBank Nucleotide ID	NP_000539.2; NP_001070651.1; NP_001107854.1; NP_001305756.1; NP_001305758.1; NP_001305760.1; NP_001305761.1; XP_005255586.2; XP_016879105.1;
Protein Name	Tuberin (Tuberous sclerosis 2 protein)
Gene Name	TSC2; TSC4
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. May also play a role in microtubule-mediated protein transport. Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5. Functional Description In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. May also play a role in microtubule-mediated protein transport. Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5.
Sequence (Fasta)	MAKPTSKDSG LKEKFKILLG LGTPRPNPRS AEGKQTEFII TAEILRELSM ECGLNNRIRM 60 IGQICEVAKT KKFEEHAVEA LWKAVADLLQ PERPLEARHA VLALLKAIVQ GQGERLGVLR 120 ALFFKVIKDY PSNEDLHERL EVFKALTDNG RHITYLEEEL ADFVLQWMDV GLSSEFLLVL 180 VNLVKFNSCY LDEYIARMVQ MICLLCVRTA SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI 240 VTLCRTINVK ELCEPCWKLM RNLLGTHLGH SAIYNMCHLM EDRAYMEDAP LLRGAVFFVG 300 MALWGAHRLY SLRNSPTSVL PSFYQAMACP NEVVSYEIVL SITRLIKKYR KELQVVAWDI 360 LLNIIERLLQ QLQTLDSPEL RTIVHDLLTT VEELCDQNEF HGSQERYFEL VERCADQRPE 420 SSLLNLISYR AQSIHPAKDG WIQNLQALME RFFRSESRGA VRIKVLDVLS FVLLINRQFY 480 EEELINSVVI SQLSHIPEDK DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS 540 PPPELEERDV AAYSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYEML VSHIQLHYKH 600 SYTLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCVCDYME PERGSEKKTS 660 GPLSPPTGPP GPAPAGPAVR LGSVPYSLLF RVLLQCLKQE SDWKVLKLVL GRLPESLRYK 720 VLIFTSPCSV DQLCSALCSM LSGPKTLERL RGAPEGFSRT DLHLAVVPVL TALISYHNYL 780 DKTKQREMVY CLEQGLIHRC ASQCVVALSI CSVEMPDIII KALPVLVVKL THISATASMA 840 VPLLEFLSTL ARLPHLYRNF AAEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC 900 RLPFRKDFVP FITKGLRSNV LLSFDDTPEK DSFRARSTSL NERPKSLRIA RPPKQGLNNS 960 PPVKEFKESS AAEAFRCRSI SVSEHVVRSR IQTSLTSASL GSADENSVAQ ADDSLKNLHL 1020 ELTETCLDMM ARYVFSNFTA VPKRSPVGEF LLAGGRTKTW LVGNKLVTVT TSVGTGTRSL 1080 LGLDSGELQS GPESSSSPGV HVRQTKEAPA KLESQAGQQV SRGARDRVRS MSGGHGLRVG 1140 ALDVPASQFL GSATSPGPRT APAAKPEKAS AGTRVPVQEK TNLAAYVPLL TQGWAEILVR 1200 RPTGNTSWLM SLENPLSPFS SDINNMPLQE LSNALMAAER FKEHRDTALY KSLSVPAAST 1260 AKPPPLPRSN TVASFSSLYQ SSCQGQLHRS VSWADSAVVM EEGSPGEVPV LVEPPGLEDV 1320 EAALGMDRRT DAYSRSSSVS SQEEKSLHAE ELVGRGIPIE RVVSSEGGRP SVDLSFQPSQ 1380 PLSKSSSSPE LQTLQDILGD PGDKADVGRL SPEVKARSQS GTLDGESAAW SASGEDSRGQ 1440 PEGPLPSSSP RSPSGLRPRG YTISDSAPSR RGKRVERDAL KSRATASNAE KVPGINPSFV 1500 FLQLYHSPFF GDESNKPILL PNESQSFERS VQLLDQIPSY DTHKIAVLYV GEGQSNSELA 1560 ILSNEHGSYR YTEFLTGLGR LIELKDCQPD KVYLGGLDVC GEDGQFTYCW HDDIMQAVFH 1620 IATLMPTKDV DKHRCDKKRH LGNDFVSIVY NDSGEDFKLG TIKGQFNFVH VIVTPLDYEC 1680 NLVSLQCRKD MEGLVDTSVA KIVSDRNLPF VARQMALHAN MASQVHHSRS NPTDIYPSKW 1740 IARLRHIKRL RQRICEEAAY SNPSLPLVHP PSHSKAPAQT PAEPTPGYEV GQRKRLISSV 1800 EDFTEFV 1808 Fasta Sequence >P49815\|TSC2; TSC4\|Homo sapiens (Human) MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Serine Phosphorylation	Tuberous sclerosis complex		U	S664	17671177
1	[Reference]: Identification of S664 TSC2 phosphorylation as a marker for extracellular signal-regulated kinase mediated mTOR activation in tuberous sclerosis and human cancer.
2	Serine Phosphorylation	Tuberous sclerosis complex		U	S939	12150915
2	[Reference]: We also show that S939 and T1462 of tuberin are PI3K-regulated phosphorylation sites and that T1462 is constitutively phosphorylated in PTEN(-/-) tumor-derived cell lines.

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	pulmonary lymphangioleiomyomatosis (LAM), renal angiomyolipoma, HNSCC hamartoma, renal cell carcinoma, tuberous sclerosis tuber Tuberous sclerosis 2
CTD (Curated) (count: 18) (view all)	MESH:D001321 ; Autistic Disorder MESH:D001927 ; Brain Diseases MESH:D002294 ; Carcinoma, Squamous Cell MESH:D004827 ; Epilepsy MESH:C537067 ; Focal cortical dysplasia of Taylor MESH:D007249 ; Inflammation MESH:D007680 ; Kidney Neoplasms MESH:D007889 ; Leiomyoma MESH:D015470 ; Leukemia, Myeloid, Acute MESH:D018192 ; Lymphangioleiomyomatosis MESH:D009062 ; Mouth Neoplasms MESH:D009410 ; Nerve Degeneration MESH:D010190 ; Pancreatic Neoplasms MESH:D011230 ; Precancerous Conditions MESH:D012640 ; Seizures MESH:D013036 ; Spasms, Infantile MESH:D014402 ; Tuberous Sclerosis MESH:C566021 ; Tuberous Sclerosis 2
GWASdb (count: 2)	rs8059880; Salmonella-induced pyroptosis; Null rs45502703; Obesity-related traits; obesity

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 88) (view all)	1002 LTSASLGSADENSVA dbPAF 1057 FLLAGGRTKTWLVGN dbPAF 1090 LDSGELQSGPESSSS dbPAF 1094 ELQSGPESSSSPGVH dbPAF 1095 LQSGPESSSSPGVHV dbPAF 1096 QSGPESSSSPGVHVR dbPAF 1097 SGPESSSSPGVHVRQ dbPAF 1130 GARDRVRSMSGGHGL dbPAF 1132 RDRVRSMSGGHGLRV dbPAF 1152 PASQFLGSATSPGPR dbPAF 1154 SQFLGSATSPGPRTA dbPAF 1155 QFLGSATSPGPRTAP dbPAF 1186 EKTNLAAYVPLLTQG dbPAF 1250 EHRDTALYKSLSVPA dbPAF 1252 RDTALYKSLSVPAAS dbPAF 1254 TALYKSLSVPAASTA dbPAF 1259 SLSVPAASTAKPPPL dbPAF 1274 PRSNTVASFSSLYQS dbPAF 1290 CQGQLHRSVSWADSA dbPAF 1304 AVVMEEGSPGEVPVL dbPAF 1330 ALGMDRRTDAYSRSS dbPAF 1334 DRRTDAYSRSSSVSS dbPAF 1337 TDAYSRSSSVSSQEE dbPAF 1338 DAYSRSSSVSSQEEK dbPAF 1340 YSRSSSVSSQEEKSL dbPAF 1341 SRSSSVSSQEEKSLH dbPAF 1346 VSSQEEKSLHAEELV dbPAF 1364 IPIERVVSSEGGRPS dbPAF 1365 PIERVVSSEGGRPSV dbPAF 1371 SSEGGRPSVDLSFQP dbPAF 1375 GRPSVDLSFQPSQPL dbPAF 1379 VDLSFQPSQPLSKSS dbPAF 1383 FQPSQPLSKSSSSPE dbPAF 1385 PSQPLSKSSSSPELQ dbPAF 1386 SQPLSKSSSSPELQT dbPAF 1387 QPLSKSSSSPELQTL dbPAF 1388 PLSKSSSSPELQTLQ dbPAF 1393 SSSPELQTLQDILGD dbPAF 1411 KADVGRLSPEVKARS dbPAF 1418 SPEVKARSQSGTLDG dbPAF 1420 EVKARSQSGTLDGES dbPAF 1422 KARSQSGTLDGESAA dbPAF 1427 SGTLDGESAAWSASG dbPAF 1433 ESAAWSASGEDSRGQ dbPAF 1447 QPEGPLPSSSPRSPS dbPAF 1448 PEGPLPSSSPRSPSG dbPAF 1449 EGPLPSSSPRSPSGL dbPAF 1452 LPSSSPRSPSGLRPR dbPAF 1454 SSSPRSPSGLRPRGY dbPAF 1461 SGLRPRGYTISDSAP dbPAF 1462 GLRPRGYTISDSAPS dbPAF 1464 RPRGYTISDSAPSRR dbPAF 1466 RGYTISDSAPSRRGK dbPAF 1469 TISDSAPSRRGKRVE dbPAF 1571 NEHGSYRYTEFLTGL dbPAF 1647 HLGNDFVSIVYNDSG dbPAF 1650 NDFVSIVYNDSGEDF dbPAF 1653 VSIVYNDSGEDFKLG dbPAF 1684 DYECNLVSLQCRKDM dbPAF 1697 DMEGLVDTSVAKIVS dbPAF 1704 TSVAKIVSDRNLPFV dbPAF 1736 RSNPTDIYPSKWIAR dbPAF 1760 RICEEAAYSNPSLPL dbPAF 1761 ICEEAAYSNPSLPLV dbPAF 1764 EAAYSNPSLPLVHPP dbPAF 1788 PAEPTPGYEVGQRKR dbPAF 1798 GQRKRLISSVEDFTE dbPAF 1799 QRKRLISSVEDFTEF dbPAF 188 VNLVKFNSCYLDEYI dbPAF 23 KILLGLGTPRPNPRS dbPAF 540 KVMARSLSPPPELEE dbPAF 602 QLHYKHSYTLPIASS dbPAF 608 SYTLPIASSIRLQAF dbPAF 659 ERGSEKKTSGPLSPP dbPAF 664 KKTSGPLSPPTGPPG dbPAF 760 APEGFSRTDLHLAVV dbPAF 927 VLLSFDDTPEKDSFR dbPAF 932 DDTPEKDSFRARSTS dbPAF 937 KDSFRARSTSLNERP dbPAF 938 DSFRARSTSLNERPK dbPAF 939 SFRARSTSLNERPKS dbPAF 946 SLNERPKSLRIARPP dbPAF 960 PKQGLNNSPPVKEFK dbPAF 979 AEAFRCRSISVSEHV dbPAF 981 AFRCRSISVSEHVVR dbPAF 983 RCRSISVSEHVVRSR dbPAF 997 RIQTSLTSASLGSAD dbPAF 999 QTSLTSASLGSADEN dbPAF
Ubiquitination (count: 35) (view all)	1016 AQADDSLKNLHLELT PLMD 1043 SNFTAVPKRSPVGEF PLMD 1058 LLAGGRTKTWLVGNK PLMD 106 HAVLALLKAIVQGQG PLMD 1106 GVHVRQTKEAPAKLE PLMD 1111 QTKEAPAKLESQAGQ PLMD 1168 APAAKPEKASAGTRV PLMD 1180 TRVPVQEKTNLAAYV PLMD 1242 LMAAERFKEHRDTAL PLMD 125 VLRALFFKVIKDYPS PLMD 1251 HRDTALYKSLSVPAA PLMD 1262 VPAASTAKPPPLPRS PLMD 128 ALFFKVIKDYPSNED PLMD 14 KDSGLKEKFKILLGL PLMD 144 HERLEVFKALTDNGR PLMD 1585 LGRLIELKDCQPDKV PLMD 16 SGLKEKFKILLGLGT PLMD 1658 NDSGEDFKLGTIKGQ PLMD 1689 LVSLQCRKDMEGLVD PLMD 1701 LVDTSVAKIVSDRNL PLMD 1739 PTDIYPSKWIARLRH PLMD 1775 VHPPSHSKAPAQTPA PLMD 250 LCRTINVKELCEPCW PLMD 258 ELCEPCWKLMRNLLG PLMD 34 NPRSAEGKQTEFIIT PLMD 438 AQSIHPAKDGWIQNL PLMD 634 HRLGLPNKDGVVRFS PLMD 658 PERGSEKKTSGPLSP PLMD 69 GQICEVAKTKKFEEH PLMD 7 *MAKPTSKDSGLKEK PLMD 71 ICEVAKTKKFEEHAV PLMD 72 CEVAKTKKFEEHAVE PLMD 782 SYHNYLDKTKQREMV PLMD 914 DFVPFITKGLRSNVL PLMD 930 SFDDTPEKDSFRARS PLMD
Glycation (count: 1)	574 LLVILQTKLYTLPAS PLMD

※ Protein-Protein Interaction

Network

Interaction

A

B

Source

P03372	P49815	HPRD
P27361	P49815	HPRD
P28482	P49815	HPRD
P31749	P49815	HPRD
P31751	P49815	HPRD
P31947	P49815	HPRD; MINT
P46527	P49815	HPRD
P49137	P49815	HPRD
P49815	P67775	HPRD
P49815	Q13131	MINT
P49815	Q13526	MINT
P49815	Q15276	HPRD
P49815	Q15796	HPRD
P49815	Q96EB6	IntAct