ABCD proteins

January 16th, 2011 |

Stephan Kemp, Ph.D.

The ABC protein family

ATP-binding cassette (ABC) proteins form the largest family of transmembrane proteins. Members of this family have been found in each organism examined so far, including bacteria and plants. At least 48 human ABC proteins have been identified in the human genome. ABC transporters bind and hydrolyze ATP and use the energy to drive the transport of various molecules across cellular membranes often against steep concentration gradients

The typical structure of a ABC transporter is composed of two transmembrane domains (TMD) and two ATP-binding cassettes (ABC). There are several different arrangements of the TMD and ABC domains found among the human ABC proteins. But in general, a full functional transporter is build up following the TMD-ABC-TMD-ABC composition. The four domains may be present in one polypeptide (like the MDR P-glycoproteins), or they can be formed by dimerization of two ABC half-transporters, TAP1 (ABCB2) and TAP2 (ABCB3).

ALDP is a half-transporter that must dimerize with another half-transporter to form a full-transporter

The peroxisomal ABC transporters (ABCD)

The peroxisomal ABC half-transporters ALDP (ABCD1), adrenoleukodystrophy-related protein (ALDRP, ABCD2)) and the 70 kDa peroxisomal membrane protein (PMP70, ABCD3) form a separate subclass of the ABC proteins (subclass D). Ever since its identification it was anticipated that PMP69 (or P70R, ABCD4) would be localized to the peroxisome as well. In 2009, however, Kashiwayama and colleagues demonstrated that endogenous P70R localizes to the endoplasmic reticulum and not to the peroxisome.

protein	gene name	Cellular localization	chromosomal location
ALDP	ABCD1	peroxisomal	Xq28
ALDRP	ABCD2	peroxisomal	12q11
PMP70	ABCD3	peroxisomal	1p21-22
PMP69 or P70R	ABCD4	ER	14q24.3

Alignment peroxisomal ABCD proteins

ABCD1           ----MPVLSRPRPWRGNTLKRTAVLLALAAYGAHKVYPLVRQCLAP-ARGLQAPAGEPTQ 55
ABCD2           MTHMLNAAADRVKWTRSSAAKRAACLVAAAYALKTLYPIIGKRLKQSGHGKKKAAAYPAA 60
ABCD3           ----MAAFSKYLTARNSSLAGAAFLLLCLLHKRRRALGLHGK-----------KSGKPPL 45
                    : . :       .:    *  *    :  :    :  :            :. *. 

ABCD1           EASGVAAAKA--------GMNRVFLQRLLWLLRLLFPRVLCRETGLLALHSAALVSRTFL 107
ABCD2           ENTEILHCTETICEKPSPGVNADFFKQLLELRKILFPKLVTTETGWLCLHSVALISRTFL 120
ABCD3           QNNEKEGKKER------AVVDKVFFSRLIQILKIMVPRTFCKETGYLVLIAVMLVSRTYC 99
                : .     .          ::  *:.:*: : :::.*: .  *** * * :. *:***: 

ABCD1           SVYVARLDGRLARCIVRKDPRAFGWQLLQWLLIALPATFVNSAIRYLEGQLALSFRSRLV 167
ABCD2           SIYVAGLDGKIVKSIVEKKPRTFIIKLIKWLMIAIPATFVNSAIRYLECKLALAFRTRLV 180
ABCD3           DVWMIQNGTLIESGIIGRSRKDFKRYLLNFIAAMPLISLVNNFLKYGLNELKLCFRVRLT 159
                .:::   .  :   *: :. : *   *::::      ::**. ::*   :* *.** **.

ABCD1           AHAYRLYFSQQTYYRVSNMDGRLRNPDQSLTEDVVAFAASVAHLYSNLTKPLLDVAVTSY 227
ABCD2           DHAYETYFTNQTYYKVINMDGRLANPDQSLTEDIMMFSQSVAHLYSNLTKPILDVMLTSY 240
ABCD3           KYLYEEYLQAFTYYKMGNLDNRIANPDQLLTQDVEKFCNSVVDLYSNLSKPFLDIVLYIF 219
                 : *. *:   ***:: *:*.*: **** **:*:  *. **..*****:**:**: :  :

ABCD1           TLLRAARSRGAGTAWPSAIAGLVVFLTANVLRAFSPKFGELVAEEARRKGELRYMHSRVV 287
ABCD2           TLIQTATSRGASPIGPTLLAGLVVYATAKVLKACSPKFGKLVAEEAHRKGYLRYVHSRII 300
ABCD3           KLTSAIGAQGP----ASMMAYLVVSG--LFLTRLRRPIGKMTITEQKYEGEYRYVNSRLI 273
                .*  :  ::*.    .: :* ***     .*      :*::.  * : :*  **::**::

ABCD1           ANSEEIAFYGGHEVELALLQRSYQDLASQINLILLERLWYVMLEQFLMKYVWSASGLLMV 347
ABCD2           ANVEEIAFYRGHKVEMKQLQKSYKALADQMNLILSKRLWYIMIEQFLMKYVWSSSGLIMV 360
ABCD3           TNSEEIAFYNGNKREKQTVHSVFRKLVEHLHNFILFRFSMGFIDSIIAKYLATVVGYLVV 333
                :* ****** *:: *   ::  :: *..::: ::  *:   :::.:: **: :  * ::*

ABCD1           AVPIITATGYSESDAEAVKKAALEKKEEELVSERTEAFTIARNLLTAAADAIERIMSSYK 407
ABCD2           AIPIITATGFADGE---------DGQKQVMVSERTEAFTTARNLLASGADAIERIMSSYK 411
ABCD3           SRPFLDLS--------------HPRHLKSTHSELLEDYYQSGRMLLRMSQALGRIVLAGR 379
                : *::  :                 : :   **  * :  : .:*   ::*: **: : :

ABCD1           EVTELAGYTARVHEMFQVFEDVQRCHFKRPRELEDAQAGSGTIGRSGVRVEGPLKIRGQV 467
ABCD2           EVTELAGYTARVYNMFWVFDEVKRGIYKRTAVIQESESHSKNGAKVELPLSDTLAIKGKV 471
ABCD3           EMTRLAGFTARITELMQVLKDLNHGKYERTMVSQQEK------GIEGVQVIPLIPGAGEI 433
                *:*.***:***: ::: *:.::::  ::*.   :: :      .   : :   :   *::

ABCD1           VDVEQGIICENIPIVTPSGEVVVASLNIRVEEGMHLLITGPNGCGKSSLFRILGGLWPTY 527
ABCD2           IDVDHGIICENVPIITPAGEVVASRLNFKVEEGMHLLITGPNGCGKSSLFRILSGLWPVY 531
ABCD3           IIADNIIKFDHVPLATPNGDVLIRDLNFEVRSGANVLICGPNGCGKSSLFRVLGELWPLF 493
                : .:: *  :::*: ** *:*:   **:.*..* ::** ************:*. *** :

ABCD1           GGVLYKPPPQRMFYIPQRPYMSVGSLRDQVIYPDSVEDMQRKGYSEQDLEAILDVVHLHH 587
ABCD2           EGVLYKPPPQHMFYIPQRPYMSLGSLRDQVIYPDSVDDMHDKGYTDQDLERILHNVHLYH 591
ABCD3           GGRLTKPERGKLFYVPQRPYMTLGTLRDQVIYPDGREDQKRKGISDLVLKEYLDNVQLGH 553
                 * * **   ::**:******::*:*********. :* : ** ::  *:  *. *:* *

ABCD1           ILQREGGWEAMCDWKDVLSGGEKQRIGMARMFYHRPKYALLDECTSAVSIDVEGKIFQAA 647
ABCD2           IVQREGGWDAVMDWKDVLSGGEKQRMGMARMFYHKPKYALLDECTSAVSIDVEGKIFQAA 651
ABCD3           ILEREGGWDSVQDWMDVLSGGEKQRMAMARLFYHKPQFAILDECTSAVSVDVEGYIYSHC 613
                *::*****::: ** **********:.***:***:*::*:*********:**** *:. .

ABCD1           KDAGIALLSITHRPSLWKYHTHLLQFDGEGGWKFEKLDSAARLSLTEEKQRLEQQLAGIP 707
ABCD2           KGAGISLLSITHRPSLWKYHTHLLQFDGEGGWRFEQLDTAIRLTLSEEKQKLESQLAGIP 711
ABCD3           RKVGITLFTVSHRKSLWKHHEYYLHMDGRGNYEFKQIT--------EDTVEFGS------ 659
                : .**:*::::** ****:* : *::**.*.:.*:::         *:. .: .      

ABCD1           KMQRRLQELCQILGEAVAPAHVPAPSPQGPGGLQGAST 745
ABCD2           KMQQRLNELCKILGEDSVLKTIKNEDETS--------- 740
ABCD3           --------------------------------------