TSC2_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: TSC2_RAT
• UniProt AC: P49816
• Protein Name: Tuberin
• Gene Name: Tsc2
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 1809
• Protein 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 (By similarity). Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (By similarity). May also play a role in microtubule-mediated protein transport. [PubMed: 16707451 Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5]
• Protein Sequence: MAKPTSKDSGLKEKFKILLGLGTSRPNPRCAEGKQTEFIITAEILRELSGECGLNNRIRMIGQICDVAKTKKLEEHAVEALWKAVSDLLQPERPPEARHAVLALLKAIVQGQGDRLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELAEFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIAPMVHMICLLCIRTVSSVDIEVSLQVLDAVVCYNCLPAESLPLFIITLCRTVNVKELCEPCWKLMRNLLGTHLGHSAIYNMCRIMENRSYMEDAPLLRGAVFFVGMALWGAHRLYSLKNSPTSVLPSFYEAMTCPNEVVSYEIVLSITRLIKKYRKELQAVTWDILLDIIERLLQQLQNLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYYELVESYADQRPESSLLNLITYRAQSIHPAKDGWIQNLQLLMERFFRNECRSAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPLELEERDLAVYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYETLISHIQLHYKHGYSLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCLCDCAELDRASEKKASGPLSPPTGPPSPVPTGPAVRLGHLPYSLLFRVLLQCLKQETDWKVLKLVLSKLPESLRYKVLIFTSPCSVDQLSSALCSMLSAPKTLERLRGTPEGFSRTDLHLAVVPVLTALISYHNYLDKTRQREMVYCLEQGLIYRCASQCVVALAICSVEMPDIIIKALPVLVVKLTHISATASMAIPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPYITKGLRSNVLLSFDDTPEKDKFRARSTSLNERPKSLRIARAPKQGLNNSPPVKEFKESCAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSMAQADDNLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGDLQGGSASSSDPGTHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGVLDTSAPYTPGGPASLGAQAAPAARPEKPCAGAQLPAAEKANLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAAGTAKPPTLPRSNTVASFSSLYQPSCQGQLHRSVSWADSAVVLEEGSPGEAHVPVEPPELEDFEAALGTDRHCQRPDAYSRSSSASSQEEKSHLEELAAGGIPIERAISSEGARPTVDLSFQPSQPLSKSSSSPELQTLQDILGDLGDKTDIGRLSPEAKVRSQSGILDGEAATWSAPGEESRITVPPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDNFKSRTAASSAEKVPGINPSFVFLQLYHSPFCGDESNKPILLPNESFERSVQLLDQIPSYDTHKIAVLYVGEGQSSSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIIYNDSGEDFKLGTIKGQFNFVHVIITPLDYKCNLLTLQCRKDMEGLVDTSVAKIVSDRNLSFVARQMALHANMASQVHHRRSNPTDIYPSKWIARLRHIKRLRQRIREEVHYSNPSLPLMHPPAHTKVPAQAPTEATPTYETGQRKRLISSVDDFTEFV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
540	Phosphorylation	KVMARSLSPPLELEE HHHHHCCCCCCCHHH	26.22	-
660	Phosphorylation	RASEKKASGPLSPPT HHHCCCCCCCCCCCC	50.23	27097102
664	Phosphorylation	KKASGPLSPPTGPPS CCCCCCCCCCCCCCC	31.78	27097102
667	Phosphorylation	SGPLSPPTGPPSPVP CCCCCCCCCCCCCCC	66.75	27097102
671	Phosphorylation	SPPTGPPSPVPTGPA CCCCCCCCCCCCCCC	41.48	27097102
675	Phosphorylation	GPPSPVPTGPAVRLG CCCCCCCCCCCCCCC	56.91	25403869
927	Phosphorylation	VLLSFDDTPEKDKFR EEEECCCCCCHHHHH	34.88	-
937	Phosphorylation	KDKFRARSTSLNERP HHHHHHHCCCHHCCC	22.74	28432305
938	Phosphorylation	DKFRARSTSLNERPK HHHHHHCCCHHCCCC	31.51	28432305
939	Phosphorylation	KFRARSTSLNERPKS HHHHHCCCHHCCCCH	30.37	23298284
960	Phosphorylation	PKQGLNNSPPVKEFK CCCCCCCCCCHHHHH	29.52	28432305
979	Phosphorylation	AEAFRCRSISVSEHV HHHHHCCEEEHHHHH	23.88	23984901
981	Phosphorylation	AFRCRSISVSEHVVR HHHCCEEEHHHHHHH	22.34	27097102
983	Phosphorylation	RCRSISVSEHVVRSR HCCEEEHHHHHHHHH	18.39	28432305
993	Phosphorylation	VVRSRIQTSLTSASL HHHHHHHHHHCCCCC	24.27	27097102
994	Phosphorylation	VRSRIQTSLTSASLG HHHHHHHHHCCCCCC	17.18	27097102
996	Phosphorylation	SRIQTSLTSASLGSA HHHHHHHCCCCCCCC	23.24	27097102
997	Phosphorylation	RIQTSLTSASLGSAD HHHHHHCCCCCCCCC	22.58	27097102
999	Phosphorylation	QTSLTSASLGSADEN HHHHCCCCCCCCCCC	32.79	27097102
1002	Phosphorylation	LTSASLGSADENSMA HCCCCCCCCCCCHHH	37.53	27097102
1007	Phosphorylation	LGSADENSMAQADDN CCCCCCCHHHCCCHH	17.28	27097102
1130	Phosphorylation	GARDRVRSMSGGHGL HHHHHHHHCCCCCCE	17.91	25403869
1132	Phosphorylation	RDRVRSMSGGHGLRV HHHHHHCCCCCCEEE	42.75	27097102
1155	Phosphorylation	YTPGGPASLGAQAAP CCCCCCCHHCCCCCC	30.39	-
1203	Phosphorylation	EILVRRPTGNTSWLM EEEEECCCCCCHHHE	41.05	21561859
1252	Phosphorylation	RDTALYKSLSVPAAG HCCHHHHHCCCCCCC	16.60	28432305
1254	Phosphorylation	TALYKSLSVPAAGTA CHHHHHCCCCCCCCC	32.90	22108457
1260	Phosphorylation	LSVPAAGTAKPPTLP CCCCCCCCCCCCCCC	27.12	23984901
1265	Phosphorylation	AGTAKPPTLPRSNTV CCCCCCCCCCCCCCC	58.90	23984901
1269	Phosphorylation	KPPTLPRSNTVASFS CCCCCCCCCCCCCHH	34.61	23984901
1271	Phosphorylation	PTLPRSNTVASFSSL CCCCCCCCCCCHHHH	20.78	23984901
1339	Phosphorylation	RPDAYSRSSSASSQE CCCCCCCCCCCCCHH	23.78	25575281
1340	Phosphorylation	PDAYSRSSSASSQEE CCCCCCCCCCCCHHH	28.90	25575281
1341	Phosphorylation	DAYSRSSSASSQEEK CCCCCCCCCCCHHHH	33.16	25575281
1343	Phosphorylation	YSRSSSASSQEEKSH CCCCCCCCCHHHHHH	34.21	25575281
1344	Phosphorylation	SRSSSASSQEEKSHL CCCCCCCCHHHHHHH	41.13	25575281
1349	Phosphorylation	ASSQEEKSHLEELAA CCCHHHHHHHHHHHH	36.26	25575281
1366	Phosphorylation	IPIERAISSEGARPT CCHHHHHCCCCCCCE	22.73	27097102
1367	Phosphorylation	PIERAISSEGARPTV CHHHHHCCCCCCCEE	33.66	27097102
1373	Phosphorylation	SSEGARPTVDLSFQP CCCCCCCEEECEECC	22.54	27097102
1377	Phosphorylation	ARPTVDLSFQPSQPL CCCEEECEECCCCCC	19.85	22817900
1381	Phosphorylation	VDLSFQPSQPLSKSS EECEECCCCCCCCCC	33.38	22817900
1385	Phosphorylation	FQPSQPLSKSSSSPE ECCCCCCCCCCCCHH	36.86	22817900
1387	Phosphorylation	PSQPLSKSSSSPELQ CCCCCCCCCCCHHHH	31.88	27097102
1388	Phosphorylation	SQPLSKSSSSPELQT CCCCCCCCCCHHHHH	38.27	27097102
1389	Phosphorylation	QPLSKSSSSPELQTL CCCCCCCCCHHHHHH	57.93	23712012
1390	Phosphorylation	PLSKSSSSPELQTLQ CCCCCCCCHHHHHHH	25.09	27097102
1395	Phosphorylation	SSSPELQTLQDILGD CCCHHHHHHHHHHHH	38.72	27097102
1407	Phosphorylation	LGDLGDKTDIGRLSP HHHCCCCCCHHCCCH	37.27	28551015
1413	Phosphorylation	KTDIGRLSPEAKVRS CCCHHCCCHHHHHHC	21.23	29779826
1420	Phosphorylation	SPEAKVRSQSGILDG CHHHHHHCCCCCCCC	31.52	27097102
1422	Phosphorylation	EAKVRSQSGILDGEA HHHHHCCCCCCCCCE	29.10	29779826
1431	Phosphorylation	ILDGEAATWSAPGEE CCCCCEEEECCCCCC	27.31	25575281
1442	Phosphorylation	PGEESRITVPPEGPL CCCCCCCCCCCCCCC	26.33	27097102
1451	Phosphorylation	PPEGPLPSSSPRSPS CCCCCCCCCCCCCCC	51.65	27097102
1452	Phosphorylation	PEGPLPSSSPRSPSG CCCCCCCCCCCCCCC	42.28	27097102
1453	Phosphorylation	EGPLPSSSPRSPSGL CCCCCCCCCCCCCCC	28.77	27097102
1456	Phosphorylation	LPSSSPRSPSGLRPR CCCCCCCCCCCCCCC	27.14	27097102
1458	Phosphorylation	SSSPRSPSGLRPRGY CCCCCCCCCCCCCCE	52.27	27097102
1466	Phosphorylation	GLRPRGYTISDSAPS CCCCCCEECCCCCCC	19.48	18757826
1573	Phosphorylation	NEHGSYRYTEFLTGL CCCCCHHHHHHHHHC	11.46	20484410
1762	Phosphorylation	RIREEVHYSNPSLPL HHHHHHHCCCCCCCC	18.47	25575281
1763	Phosphorylation	IREEVHYSNPSLPLM HHHHHHCCCCCCCCC	27.64	25575281
1766	Phosphorylation	EVHYSNPSLPLMHPP HHHCCCCCCCCCCCC	47.04	25575281
1800	Phosphorylation	GQRKRLISSVDDFTE CCCCEEECCHHHCHH	28.97	22108457
1801	Phosphorylation	QRKRLISSVDDFTEF CCCEEECCHHHCHHC	23.67	25403869
1806	Phosphorylation	ISSVDDFTEFV---- ECCHHHCHHCC----	35.19	28551015

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
939	S	Phosphorylation	Kinase	AKT1	P31749	PSP
939	S	Phosphorylation	Kinase	AKT1	P47196	Uniprot
939	S	Phosphorylation	Kinase	RPS6KA1	Q15418	GPS
1130	S	Phosphorylation	Kinase	AKT1	P31749	PSP
1132	S	Phosphorylation	Kinase	AKT1	P31749	PSP
1203	T	Phosphorylation	Kinase	ROCK1	Q13464	PSP
1203	T	Phosphorylation	Kinase	ROCK1	Q63644	PSP
1373	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
1377	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
1381	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
1385	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
1389	S	Phosphorylation	Kinase	PRKAA1	Q13131	GPS
1466	T	Phosphorylation	Kinase	AKT1	P31749	PSP
1466	T	Phosphorylation	Kinase	AKT1	P47196	Uniprot
1466	T	Phosphorylation	Kinase	RPS6KA1	Q15418	GPS
1800	S	Phosphorylation	Kinase	RPS6KA1	Q63531	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Deleted	D4A722	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
939	S	Phosphorylation	Phosphorylation at Ser-939 and Thr-1466 by PKB/AKT1 is induced by growth factor stimulation.	-
1388	S	Phosphorylation	Phosphorylation at Ser-1388, Ser-1420 or Ser-1422 does not affect interaction with TSC1.	-
1420	S	Phosphorylation	Phosphorylation at Ser-1388, Ser-1420 or Ser-1422 does not affect interaction with TSC1.	-
1422	S	Phosphorylation	Phosphorylation at Ser-1388, Ser-1420 or Ser-1422 does not affect interaction with TSC1.	-
1466	T	Phosphorylation	Phosphorylation at Ser-939 and Thr-1466 by PKB/AKT1 is induced by growth factor stimulation.	-
1800	S	Phosphorylation	Phosphorylated at Ser-1800 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling.	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of TSC2_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
1433B_HUMAN	YWHAB	physical	12582162
TSC1_HUMAN	TSC1	physical	12147258
TSC1_RAT	Tsc1	physical	12147258
1433B_HUMAN	YWHAB	physical	12468542
ESR1_RAT	Esr1	physical	15039427

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.