Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

SLC2A4

contributors: mct - updated : 22-06-2018

HGNC name	solute carrier family 2 (facilitated glucose transporter), member 4
HGNC id	11009

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001042 11 - 3159 NP_001033 - 509 - 2014 25025572

EXPRESSION

Type	restricted

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 Respiratory respiratory tract larynx     highly Visual eye retina       Rattus norvegicus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Homo sapiens Connective bone       Muscular striatum skeletal   highly Homo sapiens skeleton

cells

System Cell Pubmed Species Stage Rna symbol Visual cone photoreceptor Rattus norvegicus Visual ganglion cell Rattus norvegicus

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	twelve putative transmembrane segments (12TM)
	intracellular N and C termini
	a large extracellular loop, with first intracellular loop of GLUT4 containing the retention motif WLGRK, in which W105 plays a prominent role
	a glycosylation site between TM1 and 2
	a small and a large intracellular loops, respectively between TM2 and 3 and TM8 and 9, both with the conserved RXGRR motif

HOMOLOGY

Homologene

FAMILY	major facilitator superfamily
	sugar transporter family
	glucose transporter subfamily

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic,vesicle
text	stimulation of glucose uptake by insulin requires translocation of SLC24A to intracellular storage sites to cell surface
	AXIN1, TNKS2 and KIF3A are co-localized with SLC2A4 on the trans-Golgi network
	reduced SLC2A4 translocation from intracellular storage compartments to the plasma membrane is a cause of peripheral insulin resistance

basic FUNCTION	facilitated glucose transporter
	mediating insulin-stimulated glucose uptake in adipocytes and muscle by rapidly moving from intracellular storage sites to the plasma membrane
	specific role in glucose homeostasis in conjunction with LNPEP
	mediating the postprandial blood glucose clearance
	role for LNPEP and SLC2A4 in activity-dependent glucose uptake in hippocampal neurones
	dynamically retained through idle cycling among selective intracellular compartments, from whence it undergoes slow recycling to the plasma membrane (PM)
	cardiac glucose utilization is regulated by reversible translocation of the glucose transporter SLC2A4 from intracellular stores to the plasma membrane
	facilitates insulin-stimulated glucose uptake in peripheral tissues including adipose, muscle, and heart
	SLC2A4 and SLC2A8 trafficking is impaired in the diabetic atria and rescued by insulin treatment
	plays a major role in glucose homeostasis and is efficiently retained intracellularly in adipocytes and myocytes

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

facilitated diffusion transport

PATHWAY

metabolism

carbohydrate

signaling

a component

C-ter is required for protein targeting to the perinuclear donor membranes but not to the insulin-responsive vesicles

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca²&
	8314; signals promote SLC2A4 exocytosis and reduce its endocytosis in muscle cells

protein	SLC2A4RG and MEF2A to activate SLC2A4 transcription
	interacting with SGK1 (stimulates glucose transport by enhancing the abundance of SLC2A4 in the cell membrane at least in part via direct SLC2A4 phosphorylation)
	interacting with TBC1D4
	interacting with VAMP4, VAMP8, VAMP2 (requirement for VAMP4 for the initial biosynthetic entry of SLC2A4 from the Golgi apparatus into the insulin-responsive vesicle compartment, VAMP8, for plasma membrane endocytosis and VAMP2 for sorting to the specialized insulin-responsive compartment after plasma membrane endocytosis)
	ARFRP1 appears to be involved in sorting of SLC2A4
	AXIN1 interacts with the ADP-ribosylase tankyrase 2 (TNKS2) and the kinesin motor protein KIF3A, forming a ternary complex crucial for SLC2A4 translocation in response to insulin
	RAB10 is likely involved in insulin-stimulated translocation of SLC2A4 storage vesicle (GSV) to the Plasma membrane, with RAB14 involved in insulin-stimulated translocation of SLC2A4-containing endosome
	insulin promotes SLC2A4 exocytosis by regulating SLC2A4 vesicle arrival at the cell periphery and its subsequent tethering, docking, and fusion with the plasma membrane
	interaction of vesicular MYO1C with cortical actin filaments is required for insulin-mediated tethering of SLC2A4 vesicles and for efficient SLC2A4 surface delivery in muscle cells
	VAMP3, is able to protect insulin-stimulated SLC2A4 translocation during early stages of diet-induced insulin resistance and preserves normal CD36 distribution
	DNAJC5 is involved in insulin resistance by interrupting SLC2A4 vesicle docking with the plasma membrane
	BCAR3 plays an important role in the signaling pathways of insulin leading to cell cycle progression and cytoskeleton reorganization, but not SLC2A4 translocation
	RAB5A activity regulates SLC2A4 sorting into insulin-responsive and non-insulin-responsive endosomal compartments: a potential mechanism for development of insulin resistance
	SIK2 increases SLC2A4 levels, regulates CRTC2, CRTC3, HDAC4 and glucose uptake in adipocytes
	ZNF407 regulates insulin-stimulated glucose uptake and glucose transporter 4 (SLC2A4) mRNA
	TCTEX1D2 is a novel STX4 binding protein that functions as a negative regulator of SLC2A4 plasma membrane translocation (pMID: 26200093)
	TMOD3 is a novel AKT2 effector regulating insulin-stimulated SLC2A4 exocytosis through cortical actin remodeling
	TBC1D4 (AS160) controls trafficking of the glucose transporter SLC2A4 in adipocytes and skeletal muscle cells
	MICALL2 is an effector of insulin-activated RAB13, which links to SLC2A4 through ACTN4, localizing SLC2A4 vesicles at the muscle cell periphery to enable their fusion with the membrane
	transcription factor MEF2A and PLAGL1 mediate MIF-induced SLC2A4 expression through CD74-dependent AMPK activation in cardiomyocytes
	SLC2A4 traffics predominantly through the specialized RAB10-dependent pathway both before and after insulin stimulation
	RAB10 is a regulator of insulin-stimulated translocation of the SLC2A4 glucose transporter to the plasma membrane (PM) of adipocytes, which is essential for whole-body glucose homeostasis
	PID1 serves as an insulin-regulated retention adaptor protein controlling translocation of LRP1 in conjunction with SLC2A4 to the plasma membrane of adipocytes

cell & other

REGULATION

Other	translocated to plasma membrane for insulin stimulated glucose uptake,requiring activation of phosphatidylinositol-3-OH kinase (PI(3)K) and activation of TC10 (essential)
	may be regulated by PLAGL1

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in adipose tissue but preserved in muscle in insuline-resitant states such as obesity and type 2 diabetes

Susceptibility

non insulin dependent diabetes mellitus (type 2)

Variant & Polymorphism	polymorphic variant

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed diabete type 2   promising target for pharmacogenomics of insulin resistance cancer     therapeutic strategy entailing selective SLC2A4, SLC2A11, SLC2A8 inhibition to specifically target aberrant glucose metabolism in cancer

ANIMAL & CELL MODELS

G4A -/- mice