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FLASH GENE

Symbol

SLC16A4

contributors: mct - updated : 07-04-2020

HGNC name	solute carrier family 16, member 4 (monocarboxylic acid transporter 5)
HGNC id	10925

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	1p13.3      Physical location : 110.905.504 - 110.933.636
Synonym name	solute carrier family 16 (monocarboxylic acid transporters), member 4
	monocarboxylate transporter 4
	monocarboxylate transporter 5
Synonym symbol(s)	MCT4, MCT5

DNA

TYPE	functioning gene
STRUCTURE	29.12 kb     9 Exon(s)

Genomic sequence alignment details
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_004696 9 - 2529 NP_004687 - 487 - 2019 31101938 NM_001201547 8 - 2496 NP_001188476 - 425 - 2019 31101938 NM_001201546 8 - 2423 NP_001188475 - 439 - 2019 31101938 NM_001201548 7 - 2372 NP_001188477 - 382 - 2019 31101938 NM_001319220 7 - 1930 NP_001306149 - 257 - 2019 31101938 NM_001201549 8 - 2063 NP_001188478 - 319 - 2019 31101938

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 Hearing/Equilibrium ear inner cochlea   highly Nervous brain         Homo sapiens Reproductive female system placenta     highly Urinary kidney       highly Visual eye anterior segment cornea     Homo sapiens

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erythrocyte Homo sapiens Visual epithelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

twelve transmembrane spanning segments with a cytoplasmic loop between TM6 and TM7 ( Arg-278 in TMD8 is a critical residue involved in substrate, L-lactate recognition by SLC16A4)

HOMOLOGY

Homologene

FAMILY	major facilitator superfamily
	monocarboxylate porter family

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	catalyzing the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine
	specific interaction of SLC16A4 with beta(1)-integrin may regulate cell migration through modulation of focal adhesions
	mediates lactic acid efflux from most tissues that are dependent on glycolysis for their ATP production
	hypoxia stimulates lactate release and modulates monocarboxylate transporter (SLC16A1, SLC16A2, and SLC16A4) expression in human adipocytes
	critical role of SLC16A4 in cell proliferation and metastasis in oral squamous cell carcinoma
	SLC16A4 up-regulation represents a positive feedback mechanism in macrophages to maintain a high glycolytic rate that is essential to a fully activated inflammatory response
	lactate homeostasis participates in the regulation of the Schwann cells (SCs) myelination program and reveal that similar to CNS, PNS axon-glial metabolic interactions are most likely mediated by SLC16A4, SLC16A1
	shows highly specific substrate recognition and low-affinity l-lactate transport
	mediate L-lactate transport
	is a critical element for glycolytic metabolism and malignant behaviors in many tumor cells 3)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	monocarboxylate transport

PATHWAY

metabolism

monocarbon

signaling

a component

INTERACTION

DNA

RNA

small molecule
	proton linked

protein	BSG is required for the expression of SLC16A1 and SLC16A4 in the corneal endothelium
	is required for macrophage activation upon TLR2 and TLR4 stimulations
	TMPRSS11B promotes solubilization of BSG, an obligate chaperone of SLC16A4, which enhances lactate export and glycolytic metabolism, thereby promoting tumorigenesis
	TMPRSS11B interacts with BSG and SLC16A4 at the plasma membrane

cell & other

REGULATION

activated by

by hypoxia through a HIF-1alpha-mediated mechanism

Other

SLC16A4, SLC16A1 are regulated via expression of their chaperone, BSG

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in osteosarcoma tissues compared with that in adjacent normal ones, and may predict poor prognosis among osteosarcoma patients tumoral     --over   in urothelial carcinoma is associated with features of aggressive tumor biology and portends a poor prognosis tumoral     --over   is highly overexpressed in malignant cells of acsites in gastric carcinoma constitutional     --low   reduced SLC16A4 and SLC1A3 expression by astrocytes may lead to neuronal hyperexcitability and epileptogenesis in the temporal lobe by reducing the supply of metabolic intermediates and by allowing accumulation of extracellular glutamate tumoral     --over   SLC16A44 and BSG overexpression correlated with higher PSA levels, as well as with perineural invasion and biochemical recurrence in prostate carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	may represent for colorectal cancer with peritoneal carcinomatosis a prognostic indicator
	is prognostic biomarker for clear cell renal cell carcinoma (ccRCC)
Therapy target
	System Type Disorder Pubmed cancer     pharmacological inhibition of SLC16A1 and SLC16A4 combined with metformin treatment is a potential cancer therapy cancer urinary   targeting lactate metabolism via SLC16A4 provides a promising therapeutic approach for invasive urothelial carcinoma, especially in the basal subtype cancer digestive colon may represent a new therapeutic target for colorectal cancer with peritoneal carcinomatosis cancer digestive stomach is a clinically relevant therapy target in GC with peritoneal carcinomatosis

ANIMAL & CELL MODELS