DegronMD

Uniprot ID: Q99835

Source protein: Smoothened homolog

Source gene: SMO

Class: DEG_SCF_FBW7_1

Location: 637:644

E3 ligase: FBXW7

DEGRON score: 0.9905

ASA_SCORE: 76.7625

COIL: 0.896

CONS_SCORE: 0.4862

DSS_SCORE: 0.4372

HELIX: 0.025

FCONS_SCORE: 0.9599

RIG_SCORE: 0.7483

Degron related mutations and impact score

Mutation	Sample	Cancer	Dataset	Degron	Degron class	Impact score
p.V642L	TCGA-67-6217	LUAD	TCGA	ISVTPVAT	DEG_SCF_FBW7_1	0.5654
p.V642L	DO25877	LUAD	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.5654
p.P641R	TCGA-69-7979	LUAD	TCGA	ISVTPVAT	DEG_SCF_FBW7_1	0.7512
p.P641R	DO23874	LUAD	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.7512
p.P634L	TCGA-78-7220	LUAD	TCGA	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P634L	DO24409	LUAD	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.Q635H	TCGA-AP-A0LM	UCEC	TCGA	ISVTPVAT	DEG_SCF_FBW7_1	0.2778
p.Q635H	DO43306	UCEC	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.2778
p.P645T	TCGA-CN-A63Y	HNSC	TCGA	ISVTPVAT	DEG_SCF_FBW7_1	0.3056
p.P645T	DO44422	HNSC	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.3056
p.D636N	TCGA-FS-A4F5	SKCM	TCGA	ISVTPVAT	DEG_SCF_FBW7_1	0.3056
p.D636N	DO37881	SKCM	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.3056
p.D636N	ACH-000941	Endometrial/Uterine Cancer	CCLE	ISVTPVAT	DEG_SCF_FBW7_1	0.3056
p.V639A	TCGA-VQ-A8PB	STAD	TCGA	ISVTPVAT	DEG_SCF_FBW7_1	0.5825
p.V639A	DO51766	STAD	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.5825
p.R628Q	DO233112	GACA	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.0833
p.G630E	DO222714	MELA	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.1389
p.Q635K	DO229234	THCA	ICGC	ISVTPVAT	DEG_SCF_FBW7_1	0.2778
p.P647S	SIDM01139	Pancreatic Carcinoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM01878	Non-Cancerous	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM00099	Mesothelioma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM00343	Glioblastoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM00939	Non-Small Cell Lung Carcinoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM00053	Pancreatic Carcinoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM01545	Non-Small Cell Lung Carcinoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM01596	Non-Small Cell Lung Carcinoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM01739	Small Cell Lung Carcinoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM01475	Ovarian Carcinoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.P647S	SIDM01491	Colorectal Carcinoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.25
p.T640A	SIDM00789	Colorectal Carcinoma	GDSC	ISVTPVAT	DEG_SCF_FBW7_1	0.7139
p.T640A	ACH-000997	Colon/Colorectal Cancer	CCLE	ISVTPVAT	DEG_SCF_FBW7_1	0.7139
p.T640A	ACH-001061	Colon/Colorectal Cancer	CCLE	ISVTPVAT	DEG_SCF_FBW7_1	0.7139
p.T640A	HCT-15	large_intestine	COSMIC	ISVTPVAT	DEG_SCF_FBW7_1	0.7139

Drug responses associated with SMO mutations

Sample	Cancer	Mutation (In Degron?)	Dataset	Drug	IC50
SIDM01228	SKCM\|melanoma	p.A572S (No)	GDSC	Vismodegib	25.4128
SIDM00683	PRAD\|prostate	p.C273R (No)	GDSC	Cyclopamine	143.4405
SIDM00683	PRAD\|prostate	p.C273R (No)	GDSC	Vismodegib	111.6448
SIDM00617	LIHC\|liver	p.K575M (No)	GDSC	Vismodegib	54.974
SIDM01034	UNCLASSIFIED\|B_cell_leukemia	p.A729T (No)	GDSC	Vismodegib	26.4624
SIDM01162	KIRC\|kidney	p.Q710E (No)	GDSC	Vismodegib	122.1433
SIDM00651	UNCLASSIFIED\|lung_NSCLC_large_cell	p.R763Q (No)	GDSC	Cyclopamine	143.1287
SIDM00651	UNCLASSIFIED\|lung_NSCLC_large_cell	p.R763Q (No)	GDSC	Vismodegib	22.5887
SIDM01174	CESC\|cervix	p.R629* (Yes)	GDSC	Vismodegib	159.7717
SIDM01132	MB\|medulloblastoma	p.R726Q (No)	GDSC	Vismodegib	81.4368
SIDM00847	UNCLASSIFIED\|rhabdomyosarcoma	p.L23_G24insL (No)	GDSC	Vismodegib	147.3917
SIDM00214	COREAD\|large_intestine	p.V195L (No)	GDSC	Vismodegib	253.3781
SIDM00176	UNCLASSIFIED\|chondrosarcoma	p.L267H (No)	GDSC	Vismodegib	236.543
SIDM00810	UNCLASSIFIED\|lung_NSCLC_not_specified	p.L23_G24insL (No)	GDSC	Vismodegib	59.2223
SIDM00853	UNCLASSIFIED\|soft_tissue_other	p.P698S (No)	GDSC	Vismodegib	11.8752
SIDM00839	COREAD\|large_intestine	p.A324T (No)	GDSC	Vismodegib	68.8611
SIDM00660	COREAD\|large_intestine	p.G191D (No)	GDSC	Cyclopamine	124.9674
SIDM00660	COREAD\|large_intestine	p.G191D (No)	GDSC	Vismodegib	98.0498
SIDM01071	SCLC\|lung_small_cell_carcinoma	p.S574C (No)	GDSC	Cyclopamine	73.2554
SIDM00882	BRCA\|breast	p.S574C (No)	GDSC	Vismodegib	91.0617
SIDM00783	COREAD\|large_intestine	p.V404M (No)	GDSC	Vismodegib	26.1364
SIDM00462	LAML\|acute_myeloid_leukaemia	p.V157M (No)	GDSC	Cyclopamine	147.5119
SIDM00462	LAML\|acute_myeloid_leukaemia	p.V157M (No)	GDSC	Vismodegib	68.4865
SIDM00789	COREAD\|large_intestine	p.T640A (Yes)	GDSC	Vismodegib	107.1264
SIDM00534	COREAD\|large_intestine	p.E194K (No)	GDSC	Vismodegib	160.9463
SIDM00534	COREAD\|large_intestine	p.R668C (No)	GDSC	Vismodegib	160.9463
SIDM01169	OV\|ovary	p.Q581* (No)	GDSC	Vismodegib	30.4305
SIDM00748	UNCLASSIFIED\|lung_NSCLC_large_cell	p.R726Q (No)	GDSC	Cyclopamine	114.6306
SIDM00748	UNCLASSIFIED\|lung_NSCLC_large_cell	p.R726Q (No)	GDSC	Vismodegib	103.0366
SIDM00545	SKCM\|melanoma	p.P505S (No)	GDSC	Vismodegib	132.4395
SIDM00594	LAML\|acute_myeloid_leukaemia	p.L23_G24insL (No)	GDSC	Cyclopamine	59.0949
SIDM00594	LAML\|acute_myeloid_leukaemia	p.L23_G24insL (No)	GDSC	Vismodegib	63.5853
SIDM00241	BRCA\|breast	p.P663S (No)	GDSC	Cyclopamine	119.1991
SIDM00241	BRCA\|breast	p.P663S (No)	GDSC	Vismodegib	74.8944
SIDM00394	CESC\|cervix	p.K575M (No)	GDSC	Vismodegib	111.2709
SIDM00616	LIHC\|liver	p.K575M (No)	GDSC	Vismodegib	43.4426
SIDM00528	BRCA\|breast	p.P698R (No)	GDSC	Vismodegib	96.796
SIDM00373	UCEC\|endometrium	p.Y322H (No)	GDSC	Vismodegib	77.5112
SIDM00511	SCLC\|lung_small_cell_carcinoma	p.G497V (No)	GDSC	Cyclopamine	91.5567
SIDM00511	SCLC\|lung_small_cell_carcinoma	p.G497V (No)	GDSC	Vismodegib	88.6164
SIDM00539	ESCA\|oesophagus	p.R296H (No)	GDSC	Vismodegib	40.4228
SIDM00539	ESCA\|oesophagus	p.Q745R (No)	GDSC	Vismodegib	40.4228
SIDM01146	STAD\|stomach	p.R763Q (No)	GDSC	Cyclopamine	150.5679
SIDM01146	STAD\|stomach	p.R763Q (No)	GDSC	Vismodegib	34.8333
SIDM00123	KIRC\|kidney	p.N608S (No)	GDSC	Vismodegib	68.1094
SIDM01068	LUAD\|lung_NSCLC_adenocarcinoma	p.R576W (No)	GDSC	Vismodegib	78.0998

DegronMD: protein-targeted degradation, mutation and drug response to degrons

Degron: ISVTPVAT

Degron related mutations and impact score

Drug responses associated with SMO mutations

All proteins holding degron of ISVTPVAT

Uniprot ID	Source protein	Degron class	Location	Hit	E3 ligase	Degron score	Detail
Q99835	Smoothened homolog	DEG_SCF_FBW7_1	637:644	ISVTPVAT	FBXW7	0.9905	More...