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FLASH GENE

Symbol

SCRIB

contributors: mct/pgu - updated : 24-08-2016

HGNC name	scribbled homolog (Drosophila)
HGNC id	30377

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	24.46 kb     37 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015356 - - 5201 NP_056171 - 1630 - 2006 16611247 variant 3 - - 5109 isoform 3 - 1601 - 2006 16611247 NM_182706 - - 5276 NP_874365 - 1655 - 2006 16611247

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly Endocrine pancreas         Nervous nerve       highly Respiratory lung         Skin/Tegument skin       highly Urinary kidney         Visual eye       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	18 leucine-rich (LRR) repeats
	four PDZ(DHR) domains

mono polymer

heteromer , complex

HOMOLOGY

interspecies

homolog to drosophila tumor suppressor Scribble

Homologene

FAMILY

LAP (LRR and PDZ) protein family

CATEGORY

signaling

SUBCELLULAR LOCALIZATION	plasma membrane,junction,tight
	intracellular
	intracellular,cytoplasm,cytosolic
text	localized to cell junctions
	co-localized with APC at the synaptic sites of hippocampal neuron and at the tip of membrane protrusion in the epithelial cell line
	instead of a membrane association seen in normal epithelia, tumor-associated SCRIB is mislocalized and found predominantly in the cytosol
	NOS1AP colocalizes with both SCRIB and VANGL1 along cellular protrusions in metastatic breast cancer cells, but does not colocalize with either SCRIB or VANGL1 at cell junctions in normal breast cells

basic FUNCTION	playing a role in planar cell polarity
	may be required for polarization of epithelia
	may participate in the DLG1-APC complex through its PDZ domains and regulate cell cycle and neural function by associating with APC
	participating in oncogenic processes
	implicated in vesicle trafficking in neurons and receptor recycling in thyroid cells
	playing a role in cell migration
	crucial regulator of brain development and spine morphology
	apical-basal polarity determinant and an essential component of the adherens junction
	critical contributor to the clustering of immature T cells, an event shown here to be necessary for efficient developmental progression
	Scribble complex is one of at least three interacting protein complexes that have a critical role in establishing and maintaining epithelial polarity
	negatively regulate the MAPK cascade to suppress tumorigenesis
	in epithelial cancer cells, SCRIB is an upstream activator of the Hippo pathway leading to WWTR1 inhibition
	ERBIN, LRRC1, and SCRIB act at the post-synaptic membrane of NMJs in a concerted fashion to regulate nicotinic acetylcholine receptors cluster morphology and neural transmission

CELLULAR PROCESS

cell migration & motility

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	forming a complex Scrib-ARHGEF7-GIT1
	part of DLG1/SCRIB/LLGL1 tumour suppressor complex, interacting with tSNARE syntaxin 4
	ARHGEF7 forms a complex with cadherin, CTNNB1, and SCRIB at synapses and enhances localized actin polymerization in rat hippocampal neurons

INTERACTION

DNA

RNA

small molecule

protein	binding to k-ras and n-ras
	interacting with APC and LPP
	interacting through its PDZ domains with VANGL2
	also interacting with TRIP6
	interacting with UBE3A through its PDZ domains and C-terminal PDZ domain-binding motif of UBE3A protein
	interacting with Tax protein and this complex is present in human T cell leukemia virus type 1-infected T cells
	interacting with the E6 oncoprotein encoded by HPV16
	interacting through its PDZ domains with ARHGEF7
	interaction between p21-activated kinase proteins and Scrib-ARHGEF7-GIT1 complex
	interacting with MCC
	SCRIB-NOS1AP association is direct and is mediated through the phosphotyrosine-binding (PTB) domain of NOS1AP and the fourth PDZ domain of SCRIB
	a functional interaction between PHLPP1 and SCRIB in negatively regulating AKT signalling
	when CD74 is overexpressed in cancer and noncancerous epithelial cells, it interacts and interferes with the function of SCRIB, a product of a well-known tumor suppressor gene
	ZDHHC7-mediated SCRIB palmitoylation is critical for SCRIB membrane targeting, cell polarity and tumor suppression

cell & other

REGULATION

inhibited by

Tax protein

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --other   deregulation strongly correlated with poor survival in human prostate cancer tumoral     --low   and changed localization of SCRIB were associated with clinical stage, histopathological differentiation, and lymph node metastasis in endometrial cancer

Susceptibility

to craniorachischisis (CRN)

Variant & Polymorphism other	missense variants in SCRIB may represent a cause of CRN

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Scrib1-deficient mice exhibit enhanced learning and memory abilities and impaired social behavior, two features relevant to autistic spectrum disorders
	in Drosophila, loss of Scribbled (Scrib), a cell polarity regulator and neoplastic tumor suppressor, results in impaired Hippo pathway signaling in the epithelial tissues of both the eye and wing imaginal disc