In molecular biology, ATP-binding domain of ABC transporters is a water-soluble

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined ** Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function *Do ...

of transmembrane

ABC transporters The ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans. ABC transpo ...

. ABC transporters belong to the ATP-Binding Cassette superfamily, which uses the hydrolysis of

ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...

to translocate a variety of compounds across

biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the ...

s. ABC transporters are minimally constituted of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These regions can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.

Biological function

ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain.

Amino acid sequence

The ABC module (approximately two hundred amino acid residues) is known to bind and hydrolyze ATP, thereby coupling transport to ATP hydrolysis in a large number of biological processes. The cassette is duplicated in several subfamilies. Its primary sequence is highly conserved, displaying a typical phosphate-binding loop:

Walker A Walker or The Walker may refer to: People *Walker (given name) *Walker (surname) *Walker (Brazilian footballer) (born 1982), Brazilian footballer Places In the United States *Walker, Arizona, in Yavapai County *Walker, Mono County, California * ...

, and a magnesium binding site: Walker B. Besides these two regions, three other conserved motifs are present in the ABC cassette: the switch region which contains a histidine loop, postulated to polarize the attacking water molecule for hydrolysis, the signature conserved motif (LSGGQ) specific to the ABC transporter, and the Q-motif (between Walker A and the signature), which interacts with the gamma phosphate through a water bond. The Walker A, Walker B, Q-loop and switch region form the nucleotide binding site.

3D structure

The 3D structure of a monomeric ABC module adopts a stubby L-shape with two distinct arms. ArmI (mainly beta-strand) contains Walker A and Walker B. The important residues for ATP hydrolysis and/or binding are located in the P-loop. The ATP-binding pocket is located at the extremity of armI. The perpendicular armII contains mostly the alpha helical subdomain with the signature motif. It only seems to be required for structural integrity of the ABC module. ArmII is in direct contact with the TMD. The hinge between armI and armII contains both the histidine loop and the Q-loop, making contact with the gamma phosphate of the ATP molecule. ATP hydrolysis leads to a conformational change that could facilitate ADP release. In the dimer the two ABC cassettes contact each other through hydrophobic interactions at the antiparallel beta-sheet of armI by a two-fold axis.

Human proteins containing this domain

ABCA1 ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the ''cholesterol efflux regulatory protein'' (CERP) is a protein which in humans is encoded by the ''ABCA1'' gene. This transporter is a major ...

; ABCA10;

ABCA12 ATP-binding cassette sub-family A member 12 also known as ATP-binding cassette transporter 12 is a protein that in humans is encoded by the ''ABCA12'' gene. ABCA12 belongs to a group of genes called the ATP-binding cassette family, which makes ...

; ABCA13;

ABCA2 ATP-binding cassette sub-family A member 2 is a protein that in humans is encoded by the ''ABCA2'' gene. The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC protein ...

;

ABCA3 ATP-binding cassette sub-family A member 3 is a protein that in humans is encoded by the ''ABCA3'' gene. The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins ...

;

ABCA4 ATP-binding cassette, sub-family A (ABC1), member 4, also known as ABCA4 or ABCR, is a protein which in humans is encoded by the ''ABCA4'' gene. ABCA4 is a member of the ATP-binding cassette transporter gene sub-family A (ABC1) found exclusively ...

; ABCA5; ABCA6;

ABCA7 ATP-binding cassette sub-family A member 7 is a protein that in humans is encoded by the ''ABCA7'' gene. Function The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins trans ...

;

ABCA8 ATP-binding cassette sub-family A member 8 is a protein that in humans is encoded by the ''ABCA8'' gene. The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins ...

;

ABCA9 ATP-binding cassette sub-family A member 9 is a protein that in humans is encoded by the ''ABCA9'' gene. Function This gene is a member of the superfamily of ATP-binding cassette (ABC) transporters and the encoded protein contains two tran ...

;

ABCB1 P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...

;

ABCB10 P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...

;

ABCB11 ATP-binding cassette, sub-family B member 11 also known as ABCB11 is a protein which in humans is encoded by the gene. Function The product of the ''ABCB11'' gene is an ABC transporter named BSEP (bile salt export pump), or sPgp (sister of P ...

;

ABCB4 The ATP-binding cassette 4 gene encodes the Multidrug resistance protein 3. ABCB4 is associated with progressive familial intrahepatic cholestasis type 3 and intrahepatic cholestasis of pregnancy. The membrane-associated protein encoded by this ...

;

ABCB5 ATP-binding cassette sub-family B member 5 also known as P-glycoprotein ABCB5 is a plasma membrane-spanning protein that in humans is encoded by the ''ABCB5'' gene. ABCB5 is an ABC transporter and P-glycoprotein family member principally expresse ...

;

ABCB6 ATP-binding cassette super-family B member 6, mitochondrial is a protein that in humans is encoded by the ''ABCB6'' gene. The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporte ...

;

ABCB7 ATP-binding cassette sub-family B member 7, mitochondrial is a protein that in humans is encoded by the ''ABCB7'' gene. Function The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) ...

; ABCB8;

ABCB9 ATP-binding cassette sub-family B member 9 is a protein that in humans is encoded by the ''ABCB9'' gene. The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins ...

;

ABCC1 Multidrug resistance-associated protein 1 (MRP1) is a protein that in humans is encoded by the ''ABCC1'' gene. Function The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins ...

; ABCC10;

ABCC11 ATP-binding cassette transporter sub-family C member 11, also MRP8 (''Multidrug Resistance-Related Protein 8'') is a membrane transporter that exports certain molecules from inside a cell. It is a protein that in humans is encoded by gene ''ABCC1 ...

;

ABCC12 Multidrug resistance-associated protein 9 is a protein that in humans is encoded by the ''ABCC12'' gene. Function This gene is a member of the superfamily of ATP-binding cassette (ABC) transporters and the encoded protein contains two ATP-bin ...

;

ABCC2 Multidrug resistance-associated protein 2 (MRP2) also called canalicular multispecific organic anion transporter 1 (cMOAT) or ATP-binding cassette sub-family C member 2 (ABCC2) is a protein that in humans is encoded by the ''ABCC2'' gene. Functi ...

;

ABCC3 Canalicular multispecific organic anion transporter 2 is a protein that in humans is encoded by the ''ABCC3'' gene. Function The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC protei ...

; ABCC4;

ABCC5 Multidrug resistance-associated protein 5 is a protein that in humans is encoded by the ''ABCC5'' gene. Function The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport ...

;

ABCC6 Multidrug resistance-associated protein 6 (MRP6) also known as ATP-binding cassette sub-family C member 6 (ABCC6) and multi-specific organic anion transporter E (MOAT-E) is a protein that in humans is encoded by the ''ABCC6'' gene. The protein enc ...

;

ABCC8 ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ''ABCC8'' gene. ''ABCC8'' orthologs have been identified in all mammals for which complete genome data are available. The protein encoded by this ...

;

ABCC9 ATP-binding cassette, sub-family C member 9 (ABCC9) also known as sulfonylurea receptor 2 (SUR2) is an ATP-binding cassette transporter that in humans is encoded by the ''ABCC9'' gene. Function The protein encoded by this gene is a member of ...

;

ABCD1 ABCD1 is a protein that transfers fatty acids into peroxisomes. Function The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and i ...

;

ABCD2 ATP-binding cassette sub-family D member 2 is a membrane pump/transporter protein that in humans is encoded by the ''ABCD2'' gene. Function The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transpor ...

; ABCD3;

ABCD4 ATP-binding cassette sub-family D member 4 is a protein that in humans is encoded by the ''ABCD4'' gene. The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various m ...

;

ABCE1 ATP-binding cassette sub-family E member 1 (ABCE1) also known as RNase L inhibitor (RLI) is an enzyme that in humans is encoded by the ABCE1 gene. ABCE1 is an ATPase that is a member of the ATP-binding cassette (ABC) transporters superfamily a ...

;

ABCF1 ATP-binding cassette sub-family F member 1 is a protein that in humans is encoded by the ''ABCF1'' gene. The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various ...

; ABCF2; ABCF3;

ABCG1 ATP-binding cassette sub-family G member 1 is a protein that in humans is encoded by the ''ABCG1'' gene. It is a homolog of the well-known ''Drosophila'' gene ''white''. Function The protein encoded by this gene is a member of the superfamily ...

;

ABCG2 ATP-binding cassette super-family G member 2 is a protein that in humans is encoded by the ''ABCG2'' gene. ABCG2 has also been designated as CDw338 (cluster of differentiation w338). ABCG2 is a translocation protein used to actively pump drugs a ...

;

ABCG4 ATP-binding cassette sub-family G member 4 is a protein that in humans is encoded by the ''ABCG4'' gene. The protein encoded by this gene is included in the ATP-binding cassette transporter (ABC protein) superfamily. ABC proteins transport variou ...

;

ABCG5 ATP-binding cassette sub-family G member 5 is a protein that in humans is encoded by the ''ABCG5'' gene. Function The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transpo ...

;

ABCG8 ATP-binding cassette sub-family G member 8 is a protein that in humans is encoded by the ''ABCG8'' gene. The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various ...

;

CFTR Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the ''CFTR'' gene. Geneticist Lap-Chee Tsui and his team identified the CFTR gene in 1989 as the gene linked wi ...

;

TAP1 Transporter associated with antigen processing 1 (TAP1) is a protein that in humans is encoded by the ''TAP1'' gene. A member of the ATP-binding cassette transporter family, it is also known as ABCB2. Function The membrane-associated protein en ...

;

TAP2 TAP2 is a gene in humans that encodes the protein Antigen peptide transporter 2. Function The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport v ...

; TAPL;

References

* * * {{Cite journal , last1 = Higgins , first1 = C. F. , last2 = Hyde , first2 = S. C. , last3 = Mimmack , first3 = M. M. , last4 = Gileadi , first4 = U. , last5 = Gill , first5 = D. R. , last6 = Gallagher , first6 = M. P. , title = Binding protein-dependent transport systems , journal = Journal of Bioenergetics and Biomembranes , volume = 22 , issue = 4 , pages = 571–592 , year = 1990 , pmid = 2229036 , doi=10.1007/BF00762962 , s2cid = 29046676 Protein domains ATP-binding cassette transporters