DegronMD - Q9UIU6(SIX4)

FUNCTION: Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a DNA sequence on these target genes and is involved in processes like cell differentiation, cell migration and cell survival. Transactivates gene expression by binding a 5'-[CAT]A[CT][CT][CTG]GA[GAT]-3' motif present in the Trex site and a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 site of the muscle-specific genes enhancer. Acts cooperatively with EYA proteins to transactivate their target genes through interaction and nuclear translocation of EYA protein. Acts synergistically with SIX1 to regulate target genes involved in formation of various organs, including muscle, kidney, gonad, ganglia, olfactory epithelium and cranial skeleton. Plays a role in several important steps of muscle development. Controls the genesis of hypaxial myogenic progenitors in the dermomyotome by transactivating PAX3 and the delamination and migration of the hypaxial precursors from the ventral lip to the limb buds through the transactivation of PAX3, MET and LBX1. Controls myoblast determination by transactivating MYF5, MYOD1 and MYF6. Controls somitic differentiation in myocyte through MYOG transactivation. Plays a role in synaptogenesis and sarcomere organization by participating in myofiber specialization during embryogenesis by activating fast muscle program in the primary myotome resulting in an up-regulation of fast muscle genes, including ATP2A1, MYL1 and TNNT3. Simultaneously, is also able to activate inhibitors of slow muscle genes, such as SOX6, HRASLS, and HDAC4, thereby restricting the activation of the slow muscle genes. During muscle regeneration, negatively regulates differentiation of muscle satellite cells through down-regulation of MYOG expression. During kidney development regulates the early stages of metanephros development and ureteric bud formation through regulation of GDNF, SALL1, PAX8 and PAX2 expression. Plays a role in gonad development by regulating both testis determination and size determination. In gonadal sex determination, transactivates ZFPM2 by binding a MEF3 consensus sequence, resulting in SRY up-regulation. In gonadal size determination, transactivates NR5A1 by binding a MEF3 consensus sequence resulting in gonadal precursor cell formation regulation. During olfactory development mediates the specification and patterning of olfactory placode through fibroblast growth factor and BMP4 signaling pathways and also regulates epithelial cell proliferation during placode formation. Promotes survival of sensory neurons during early trigeminal gangliogenesis. In the developing dorsal root ganglia, up-regulates SLC12A2 transcription. Regulates early thymus/parathyroid organogenesis through regulation of GCM2 and FOXN1 expression. Forms gustatory papillae during development of the tongue. Also plays a role during embryonic cranial skeleton morphogenesis. {ECO:0000250|UniProtKB:Q61321}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.L307V	TCGA-06-5416	GBM	TCGA	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.2222
p.L307V	DO10880	GBM	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.2222
p.S435C	TCGA-94-8035	LUSC	TCGA	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation altering degron motif	0.7541
p.S435C	DO219173	LUSC	ICGC	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation altering degron motif	0.7541
p.S368Y	TCGA-AP-A1DV	UCEC	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	TCGA-CA-6717	COAD	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	TCGA-QF-A5YS	UCEC	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	TCGA-VQ-A8P2	STAD	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	DO8730	COAD	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	DO8264	COAD	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	DO222798	COCA	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	DO51761	STAD	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	DO43186	UCEC	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	DO52426	UCEC	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	SIDM00534	Colorectal Carcinoma	GDSC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	SIDM01611	Endometrial Carcinoma	GDSC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	ACH-000986	Colon/Colorectal Cancer	CCLE	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	ACH-000996	Endometrial/Uterine Cancer	CCLE	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.S368Y	HT-115	large intestine	COSMIC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.F363C	TCGA-B5-A3FA	UCEC	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.25
p.F363C	DO52402	UCEC	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.25
p.S316C	TCGA-CV-A6K2	HNSC	TCGA	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.3056
p.S316C	DO52079	HNSC	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.3056
p.P356H	TCGA-D3-A2JP	SKCM	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation altering degron motif	0.7694
p.P356H	DO47407	SKCM	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation altering degron motif	0.7694
p.T432S	TCGA-D5-6529	COAD	TCGA	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation altering degron motif	0.6005
p.T432S	DO10758	COAD	ICGC	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation altering degron motif	0.6005
p.S360L	TCGA-D9-A6EC	SKCM	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation altering degron motif	0.7667
p.S360L	DO50291	SKCM	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation altering degron motif	0.7667
p.G303V	TCGA-EB-A3XB	SKCM	TCGA	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.1111
p.G303V	DO37856	SKCM	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.1111
p.P438S	TCGA-EO-A22R	UCEC	TCGA	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation rewiring degron network	0.25
p.P438S	DO42713	UCEC	ICGC	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation rewiring degron network	0.25
p.F421L	TCGA-EO-A3B0	UCEC	TCGA	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation rewiring degron network	0.0556
p.F421L	DO219773	UCEC	ICGC	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation rewiring degron network	0.0556
p.P309S	TCGA-FW-A3R5	SKCM	TCGA	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.2778
p.P309S	DO37406	SKCM	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.2778
p.I370F	TCGA-GL-A59R	KIRP	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.0556
p.I370F	DO44525	KIRP	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.0556
p.N367S	TCGA-GS-A9TY	DLBC	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1389
p.N367S	DO219917	DLBC	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1389
p.V440I	TCGA-IB-7651	PAAD	TCGA	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation rewiring degron network	0.1944
p.V440I	DO46657	PAAD	ICGC	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation rewiring degron network	0.1944
p.G347E	TCGA-XF-A8HC	BLCA	TCGA	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.0833
p.G347E	DO51908	BLCA	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.0833
p.D317N	TCGA-XF-A9T3	BLCA	TCGA	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.2778
p.D317N	DO51922	BLCA	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.2778
p.S439G	DO233109	GACA	ICGC	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation blocking phosphorylation signal	0.6667
p.I319T	DO233270	GACA	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.2222
p.P445T	DO229015	LICA	ICGC	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation rewiring degron network	0.0556
p.S323R	DO229034	LICA	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.1111
p.P311T	DO229041	LICA	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation altering degron motif	0.7031
p.P311Q	DO229045	LICA	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation altering degron motif	0.7035
p.H304N	DO229055	LICA	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.1389
p.V84L	DO50951	LICA	ICGC	VQLHSE	LIG_APCC_ABBA_1	84:89	Mutation altering degron motif	0.5654
p.G318V	DO45281	LIRI	ICGC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.25
p.S368F	DO51958	PRAD	ICGC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.1111
p.V423I	SIDM01164	Glioma	GDSC	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation rewiring degron network	0.1111
p.V423I	SW1783	central nervous system	COSMIC	ATTTS	DEG_SPOP_SBC_1	431:435	Mutation rewiring degron network	0.1111
p.G352E	SIDM00516	Melanoma	GDSC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.2222
p.G352E	ACH-002166	Skin Cancer	CCLE	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.2222
p.G352E	MZ7-mel	skin	COSMIC	PASTS	DEG_SPOP_SBC_1	356:360	Mutation rewiring degron network	0.2222
p.S308F	SIDM01033	Bladder Carcinoma	GDSC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.25
p.S308F	ACH-000486	Bladder Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.25
p.S308F	KU-19-19	urinary tract	COSMIC	PLSSS	DEG_SPOP_SBC_1	311:315	Mutation rewiring degron network	0.25
p.A99P	ACH-001638	Lymphoma	CCLE	VQLHSE	LIG_APCC_ABBA_1	84:89	Mutation rewiring degron network	0.0556

Kaplan plot for SIX4 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

SIX4

UniProt ID: Q9UIU6

Entrez ID: 51804

Protein name: Homeobox protein SIX4 (Sine oculis homeobox homolog 4)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SIX4 in