An organic cation transport protein mediates the transport of organic

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

s across the

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

. These proteins are members of the

solute carrier family The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO ...

, subfamily 22. This family of proteins can also transport

zwitterion In chemistry, a zwitterion ( ; ), also called an inner salt or dipolar ion, is a molecule that contains an equal number of positively and negatively charged functional groups. : (1,2- dipolar compounds, such as ylides, are sometimes excluded from ...

s and

anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

s, though it is a different subfamily of solute carrier proteins than the organic anion transporters.

Function

Organic cation transport proteins (OCTs) are involved in membrane transport through facilitated diffusion of organic cations and some weak bases. They are crucial for the disposal of many organic cations that come from drugs or other environmental sources. They also allow for the recycling of necessary organic cations. Some of these organic cation transport proteins are compound-specific, and others transport a broad range of cations across the membrane. For example, the disposing of the blood sugar medication

Metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, ...

is dependent on organic cation transport proteins^{/sup>.

Structure

The general structure of an OCT or OCTN consists of 11-12 alpha-helical transmembrane protein

A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...
domains. These create a transmembrane unit that creates loops on both sides of the membrane. There is typically a large extracellular loop with glycosylation

Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...
sites at the beginning of the transporter, followed by many smaller loops that connect the transmembrane protein domains on the extracellular side. The loops found on the inside of the cell contain many sites for phosphorylation

In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writ ...
^{/sup>. There is also an intracellular loop between the transmembrane domains 6 and 7 that contains phosphorylation sites that are believed to contribute to regulation of activity of the organic cation transport protein. Some of these phosphorylation sites are shared between the different organic cation transport proteins^{/sup>.

Nomenclature

The various types of organic cation transport proteins are often referred to in its respective abbreviated form or by the gene that codes it. For example, OCT1 is coded by the SLC22A1

Solute carrier family 22 member 1 is a protein that in humans is encoded by the gene ''SLC22A1''.
Function

Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogen ...
gene. Similarly, OCT2 is often called SLC22A2

Solute carrier family 22 member 2 (also termed ''OCT2'' or ''organic cation transporter-2'') is a protein that in humans is encoded by the ''SLC22A2'' gene.

Poly specific organic cation transporters in the liver, kidney, intestine, and other orga ...
.

Proteins

{, class="wikitable sortable" border="1"
, -
!Abbreviation!!Protein name!!Location!!Transported solute(s), , Associated disorder(s)
, -
, , SLC22A1

Solute carrier family 22 member 1 is a protein that in humans is encoded by the gene ''SLC22A1''.
Function

Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogen ...
, , Solute carrier family 22 member 1, , Liver, brain (cerebellum), , , ,
, -
, , SLC22A2

Solute carrier family 22 member 2 (also termed ''OCT2'' or ''organic cation transporter-2'') is a protein that in humans is encoded by the ''SLC22A2'' gene.

Poly specific organic cation transporters in the liver, kidney, intestine, and other orga ...
, , Solute carrier family 22 member 2, , Primarily in kidney, also in brain, , , ,
, -
, , SLC22A3

Solute carrier family 22 member 3 (SLC22A3) also known as the organic cation transporter 3 (OCT3) or extraneuronal monoamine transporter (EMT) is a protein that in humans is encoded by the ''SLC22A3'' gene.

Polyspecific organic cation transport ...
, , Solute carrier family 22 member 3, , Brain and kidney , , Histamine

Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...
, dopamine

Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
, serotonin

Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...
, norepinephrine

Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
, MPP⁺ , ,
, -
, , SLC22A4

Solute carrier family 22, member 4, also known as SLC22A4, is a human gene; the encoded protein is known as the ergothioneine transporter.
Function
The encoded protein is an integral protein of the plasma membrane containing 12 transmembrane s ...
, , Solute carrier family 22 member 4, , , , Sodium ion and ergothioneine

Ergothioneine is a naturally occurring amino acid and is a thiourea derivative of histidine, containing a sulfur atom on the imidazole ring. This compound occurs in relatively few organisms, notably actinomycetota, cyanobacteria, and certain fun ...
, ,
, -
, , SLC22A5

SLC22A5 is a membrane transport protein associated with primary carnitine deficiency. This protein is involved in the active cellular uptake of carnitine. It acts a symporter, moving sodium ions and other organic cations across the membrane along ...
, , Solute carrier family 22 member 5, , , , , , Primary carnitine deficiency

Systemic primary carnitine deficiency (SPCD)Systemic primary carn ...

, -
, , SLC22A6

The organic anion transporter 1 (OAT1) also known as solute carrier family 22 member 6 (SLC22A6) is a protein that in humans is encoded by the ''SLC22A6'' gene. It is a member of the organic anion transporter#Organic anion transporter (OAT) famil ...
, , Solute carrier family 22 member 6, , , , , ,
, -
, , SLC22A7, , Solute carrier family 22 member 7, , , , , ,
, -
, , SLC22A8

Solute carrier family 22 member 8, or organic anion transporter 3 (OAT3), is a protein that in humans is encoded by the ''SLC22A8'' gene.
Function

OAT3 is involved in the transport and excretion of organic ions some of which are drugs (e.g., ...
, , Solute carrier family 22 member 8, , , , , ,
, -
, , SLC22A9, , Solute carrier family 22 member 9, , , , , ,
, -
, , SLC22A10, , Solute carrier family 22 member 10, , , , , ,
, -
, , SLC22A11, , Solute carrier family 22 member 11, , , , , ,
, -
, , SLC22A12

Solute carrier family 22 (organic anion/cation transporter), member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the ''SLC22A12'' gene.
Function
The protein encoded by this gene is a urate transporter and ura ...
, , Solute carrier family 22 member 12, , Kidney, , Uric acid

Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the Chemical formula, formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the meta ...
, , Hyperuricemia

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 ...
and hypouricemia

Hypouricemia or hypouricaemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper thre ...

, -
, , SLC22A13, , Solute carrier family 22 member 13, , , , , ,
, -
, , SLC22A14, , Solute carrier family 22 member 14, , , , , ,
, -
, , SLC22A15, , Solute carrier family 22 member 15, , , , , ,
, -
, , SLC22A16, , Solute carrier family 22 member 16, , , , , ,
, -
, , SLC22A17, , Solute carrier family 22 member 17, , , , , ,
, -
, , SLC22A18, , Solute carrier family 22 member 18, , , , , , Beckwith-Wiedemann syndrome, Wilms tumor

Wilms' tumor or Wilms tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children (rarely in adults), and occurs most commonly as a renal tumor in child patients. It is named after Max Wilms, the German surge ...
, rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the neoplasm, tumor are identified as rhabdomyoblasts.

The four ...
, adrenocortical carcinoma, and lung, ovarian, and breast cancer
, -
, , SLC22A19, , Solute carrier family 22 member 19, , , , , ,
, -
, , SLC22A20, , Solute carrier family 22 member 20, , , , , ,
, -

References

# Koepsell, H., Endou, H. The SLC22 drug transporter family. ''Pflugers Arch - Eur J Physiol'' 447, 666–676 (2004). https://doi-org.byu.idm.oclc.org/10.1007/s00424-003-1089-9
# Ciarimboli, G., Schlatter, E. Regulation of organic cation transport. ''Pflugers Arch - Eur J Physiol'' 449, 423–441 (2005). https://doi-org.byu.idm.oclc.org/10.1007/s00424-004-1355-5
# Kerb, R. , Brinkmann, U. , Chatskaia, N. , Gorbunov, D. , Gorboulev, V. , Mornhinweg, E. , Keil, A. , Eichelbaum, M. & Koepsell, H. (2002). Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences. ''Pharmacogenetics, 12'' (8), 591-595.

Solute carrier family
Transmembrane transporters
Transport proteins}}}