Tuberin - Homo sapiens (Human)

Sequence

>sp|P49815|TSC2_HUMAN Tuberin OS=Homo sapiens GN=TSC2 PE=1 SV=1 MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRM IGQICEVAKTKKFEEHAVEALWKAVADLLQPERTLEARHAVLALLKAIVQGQGERLGVLR ALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVL VNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFI VTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVG MALWGAHRLYSLRNSPTSVFPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDI LLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPE SSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFY EEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLS PPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKH SYTLPIASSIRLQAFDFLFLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTS GPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYK VLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYL DKTKQREMVYCLEQGLIHRCARQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMA VPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRC RLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNS PPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHL ELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSL LGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVG ALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVR RPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAAST AKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDV EAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQ PLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQ PEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFV FLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELA ILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFH IATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYEC NLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKW IARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSV EDFTEFV

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Sequence length	1807 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

Function	Implicated as a tumor suppressor. May have a function in vesicular transport, but may also play a role in the regulation of cell growth arrest and in the regulation of transcription mediated by steroid receptors. Interaction between TSC1 and TSC2 may facilitate vesicular docking. Specifically stimulates the intrinsic GTPase activity of the Ras-related protein RAP1A and RAB5. Suggesting a possible mechanism for its role in regulating cellular growth. Mutations in TSC2 leads to constitutive activation of RAP1A in tumors.
Subunit structure	Interacts with TSC1 and HERC1; the interaction with TSC1 stabilizes TSC2 and prevents the interaction with HERC1. May also interact with the adapter molecule RABEP1. The final complex contains TSC2 and RABEP1 linked to RAB5 Probable. Interacts with HSPA1 and HSPA8.
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein. Note= At steady state found in association with membranes.
Tissue specificity	Liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle, kidney, lung and placenta.
Post-translational modification	Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1.
Involvement in disease	Defects in TSC2 are the cause of tuberous sclerosis complex (TSC) [MIM:191100]. The molecular basis of TSC is a functional impairment of the tuberin-hamartin complex. TSC is an autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. TSC is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical symptoms can range from benign hypopigmented macules of the skin to profound mental retardation with intractable seizures to premature death from a variety of disease-associated causes. Defects in TSC2 are a cause of lymphangioleiomyomatosis (LAM) [MIM:606690]. LAM is a progressive and often fatal lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. It affects almost exclusively young women and can occur as an isolated disorder or in association with tuberous sclerosis complex.
Sequence similarities	Contains 1 Rap-GAP domain.

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Molecular function	Anti-oncogene GTPase activation
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	heart development Inferred from sequence or structural similarity. Source: UniProtKB insulin-like growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of phosphoinositide 3-kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB neural tube closure Inferred from sequence or structural similarity. Source: UniProtKB positive chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of GTPase activity Inferred from electronic annotation. Source: InterPro protein import into nucleus Inferred from sequence or structural similarity. Source: UniProtKB regulation of endocytosis Inferred from sequence or structural similarity. Source: UniProtKB regulation of insulin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi apparatus Ref.9 Inferred from direct assay. Source: UniProtKB TSC1-TSC2 complex Ref.8 Inferred from direct assay. Source: UniProtKB membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane fraction Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	GTPase activator activity Ref.7 Inferred from direct assay. Source: UniProtKB protein homodimerization activity Ref.9 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

With	Entry	#Exp.	IntAct	Notes
TSC1	Q92574	3	EBI-396587,EBI-1386638
YWHAQ	P27348	1	EBI-396587,EBI-359854

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] Notes: Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: P49815-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P49815-2) The sequence of this isoform differs from the canonical sequence as follows: 946-988: Missing.

Isoform 3 (identifier: P49815-3) The sequence of this isoform differs from the canonical sequence as follows: 946-989: Missing.

Isoform 4 (identifier: P49815-4) The sequence of this isoform differs from the canonical sequence as follows: 1272-1294: Missing.

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations