DegronMD

Uniprot ID: Q99835

Source protein: Smoothened homolog

Source gene: SMO

Class: DEG_APCC_DBOX_1

Location: 762:770

E3 ligase: APC,CDC20,FZR1

DEGRON score: 0.9772

ASA_SCORE: 71.3444

COIL: 0.7204

CONS_SCORE: 0.3687

DSS_SCORE: 0.4983

HELIX: 0.146

FCONS_SCORE: 0.9923

RIG_SCORE: 0.6436

Degron related mutations and impact score

Mutation	Sample	Cancer	Dataset	Degron	Degron class	Impact score
p.L780R	TCGA-06-5416	GBM	TCGA	RRQGLGPIH	DEG_APCC_DBOX_1	0.0556
p.L780R	DO10880	GBM	ICGC	RRQGLGPIH	DEG_APCC_DBOX_1	0.0556
p.A754T	TCGA-AP-A059	UCEC	TCGA	RRQGLGPIH	DEG_APCC_DBOX_1	0.1111
p.A754T	DO41361	UCEC	ICGC	RRQGLGPIH	DEG_APCC_DBOX_1	0.1111
p.P768S	TCGA-BH-A0B8	BRCA	TCGA	RRQGLGPIH	DEG_APCC_DBOX_1	0.5641
p.P768S	DO5486	BRCA	ICGC	RRQGLGPIH	DEG_APCC_DBOX_1	0.5641
p.S771F	TCGA-ER-A198	SKCM	TCGA	RRQGLGPIH	DEG_APCC_DBOX_1	0.75
p.S771F	DO47563	SKCM	ICGC	RRQGLGPIH	DEG_APCC_DBOX_1	0.75
p.A757V	TCGA-EY-A215	UCEC	TCGA	RRQGLGPIH	DEG_APCC_DBOX_1	0.1944
p.A757V	DO42665	UCEC	ICGC	RRQGLGPIH	DEG_APCC_DBOX_1	0.1944
p.P753L	TCGA-UY-A8OB	BLCA	TCGA	RRQGLGPIH	DEG_APCC_DBOX_1	0.0833
p.P753L	DO219037	BLCA	ICGC	RRQGLGPIH	DEG_APCC_DBOX_1	0.0833
p.W758R	TCGA-ZS-A9CG	LIHC	TCGA	RRQGLGPIH	DEG_APCC_DBOX_1	0.2222
p.W758R	DO52336	LIHC	ICGC	RRQGLGPIH	DEG_APCC_DBOX_1	0.2222
p.Q764H	DO8858	COAD	ICGC	RRQGLGPIH	DEG_APCC_DBOX_1	0.647
p.M776I	DO37432	SKCM	ICGC	RRQGLGPIH	DEG_APCC_DBOX_1	0.1667
p.R772C	SIDM00074	Burkitt's Lymphoma	GDSC	RRQGLGPIH	DEG_APCC_DBOX_1	0.2778
p.R763Q	SIDM00651	Non-Small Cell Lung Carcinoma	GDSC	RRQGLGPIH	DEG_APCC_DBOX_1	0.7329
p.R763Q	SIDM01146	Gastric Carcinoma	GDSC	RRQGLGPIH	DEG_APCC_DBOX_1	0.7329
p.R763Q	ACH-000932	Gastric Cancer	CCLE	RRQGLGPIH	DEG_APCC_DBOX_1	0.7329
p.R763Q	ACH-000980	Lung Cancer	CCLE	RRQGLGPIH	DEG_APCC_DBOX_1	0.7329
p.R763Q	NCI-SNU-1	stomach	COSMIC	RRQGLGPIH	DEG_APCC_DBOX_1	0.7329
p.R763Q	NCI-H1155	lung	COSMIC	RRQGLGPIH	DEG_APCC_DBOX_1	0.7329
p.R772H	SIDM00217	Colorectal Carcinoma	GDSC	RRQGLGPIH	DEG_APCC_DBOX_1	0.2778
p.R772H	ACH-000999	Colon/Colorectal Cancer	CCLE	RRQGLGPIH	DEG_APCC_DBOX_1	0.2778
p.R772H	SNU-1040	large_intestine	COSMIC	RRQGLGPIH	DEG_APCC_DBOX_1	0.2778

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 (Yes)	GDSC	Cyclopamine	143.1287
SIDM00651	UNCLASSIFIED\|lung_NSCLC_large_cell	p.R763Q (Yes)	GDSC	Vismodegib	22.5887
SIDM01174	CESC\|cervix	p.R629* (No)	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 (No)	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 (Yes)	GDSC	Cyclopamine	150.5679
SIDM01146	STAD\|stomach	p.R763Q (Yes)	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: RRQGLGPIH

Degron related mutations and impact score

Drug responses associated with SMO mutations

All proteins holding degron of RRQGLGPIH

Uniprot ID	Source protein	Degron class	Location	Hit	E3 ligase	Degron score	Detail
Q99835	Smoothened homolog	DEG_APCC_DBOX_1	762:770	RRQGLGPIH	APC,CDC20,FZR1	0.9772	More...