Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
24  structures 3048  species 0  interactions 7172  sequences 14  architectures

Family: BCCT (PF02028)

Summary: BCCT, betaine/carnitine/choline family transporter

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Betaine transporter". More...

Betaine transporter Edit Wikipedia article

BCCT family transporter
BetP 3po3.png
BetP (betaine transporter) from Cornyebacterium glutamicum. PDB 3p03
OPM superfamily64
OPM protein4ain

Proteins of the Betaine/Carnitine/Choline Transporter (BCCT) family are found in Gram-negative and Gram-positive bacteria and archaea. The BCCT family is a member a large group of secondary transporters, the APC superfamily. Their common functional feature is that they all transport molecules with a quaternary ammonium group [R-N (CH3)3]. The BCCT family proteins vary in length between 481 and 706 amino acyl residues and possess 12 putative transmembrane α-helical spanners (TMSs). The x-ray structures reveal two 5 TMS repeats with the total number of TMSs being 10. These porters catalyze bidirectional uniport or are energized by pmf-driven or smf-driven proton or sodium ion symport, respectively, or else by substrate:substrate antiport. Some of these permeases exhibit osmosensory and osmoregulatory properties inherent to their polypeptide chains.[1]


The structures of the sodium-independent carnitine/butyrobetaine antiporter CaiT from Proteus mirabilis (PmCaiT) (4M8J​) and from E. coli (EcCaiT)(3HFX​) were determined.[2]

Most members of the BCCT family are Na+- or H+-dependent, whereas EcCaiT is a Na+- and H+-independent substrate:product antiporter. The three-dimensional architecture of CaiT resembles that of the Na+-dependent transporters LeuT and BetP, but in CaiT, a methionine sulphur takes the place of the Na+ to coordinate the substrate in the central transport site, accounting for Na+ independence. Both CaiT structures (SWSW​, 4M8J​) show the fully open, inward-facing conformation, and thus complete the set of functional states that describe the alternating access mechanism. EcCaiT (SWSX​, 3HFX​) contains two bound butyrobetaine substrate molecules, one in the central transport site, the other in an extracellular binding pocket. In the structure of PmCaiT, a tryptophan side chain occupies the transport site, and access to the extracellular site is blocked. Binding of both substrates to CaiT reconstituted into proteoliposomes is cooperative, with Hill coefficients of up to 1.7, indicating that the extracellular site is regulatory. Schulze et al. (2010) proposed a mechanism whereby the occupied regulatory site increases the binding affinity of the transport site and initiates substrate translocation.[2] Glycine betaine transporters have been found to contain a conserved region with four tryptophans in their central region.[3]


Most secondary-active transporters transport their substrates using an electrochemical ion gradient, but the carnitine transporter (CaiT) is an ion-independent, L-carnitine/gamma-butyrobetaine antiporter. Crystal structures of CaiT from E. coli and Proteus mirabilis revealed the inverted five-transmembrane-helix repeat similar to that in the amino acid/Na+ symporter, LeuT. Kalayil et al. (2013) showed that mutations of arginine 262 (R262) made CaiT Na+-dependent with increased transport activity in the presence of a membrane potential, in agreement with substrate/Na+ cotransport. R262 also plays a role in substrate binding by stabilizing the partly unwound TM1' helix.[4]

Modeling CaiT from P. mirabilis in the outward-open and closed states on the corresponding structures of the related symporter BetP revealed alternating orientations of the buried R262 side chain, which mimic sodium binding and unbinding in the Na+-coupled substrate symporters. A similar mechanism may be operative in other Na+/H+-independent transporters, in which a positively charged amino acid replaces the cotransported cation. The oscillation of the R262 side chain in CaiT indicates how a positive charge triggers the change between outward-open and inward-open conformations.[4]

Transport reactions

The generalized transport reactions catalyzed by members of the BCCT family are:[1]

Substrate (out) + nH+ (out) → Substrate (in) + nH+ (in)
Substrate (out) + Na+ (out) → Substrate (in) + Na+ (in)
Substrate-1 (out) + Substrate-2 (in) → Substrate-1 (in) + Substrate-2 (out)
Substrate (out) ⇌ Substrate (in)
Substrate = a quaternary amine

Other betaine transporters

See also


  1. ^ a b Saier, MH Jr. "2.A.15 The Betaine/Carnitine/Choline Transporter (BCCT) Family". Transporter Classification Database. Saier Lab Bioinformatics Group.
  2. ^ a b Schulze, S; Köster, S; Geldmacher, U; Terwisscha van Scheltinga, AC; Kühlbrandt, W (September 9, 2010). "Structural basis of Na(+)-independent and cooperative substrate/product antiport in CaiT" (PDF). Nature. 467 (7312): 233–6. Bibcode:2010Natur.467..233S. doi:10.1038/nature09310. PMID 20829798. S2CID 4341977.
  3. ^ Kempf B, Bremer E, Kappes RM (1996). "Three transport systems for the osmoprotectant glycine betaine operate in Bacillus subtilis: characterization of OpuD". J. Bacteriol. 178 (17): 5071–5079. doi:10.1128/jb.178.17.5071-5079.1996. PMC 178300. PMID 8752321.
  4. ^ a b Kalayil, S; Schulze, S; Kühlbrandt, W (October 22, 2013). "Arginine oscillation explains Na+ independence in the substrate/product antiporter CaiT". Proc. Natl. Acad. Sci. U.S.A. 110 (43): 17296–301. Bibcode:2013PNAS..11017296K. doi:10.1073/pnas.1309071110. PMC 3808595. PMID 24101465.
This article incorporates text from the public domain Pfam and InterPro: IPR000060

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

BCCT, betaine/carnitine/choline family transporter Provide feedback

No Pfam abstract.

Literature references

  1. Jung H, Buchholz M, Clausen J, Nietschke M, Revermann A, Schmid R, Jung K;, J Biol Chem. 2002;277:39251-39258. : CaiT of Escherichia coli, a new transporter catalyzing L-carnitine/gamma -butyrobetaine exchange. PUBMED:12163501 EPMC:12163501

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000060

These prokaryotic transport proteins belong to a family known as BCCT (for Betaine/Carnitine/Choline Transporters) [ PUBMED:20923416 ] and are specific for compounds containing a quaternary nitrogen atom. The BCCT proteins contain 12 transmembrane regions and are energised by proton symport. They contain a conserved region with four tryptophans in their central region [ PUBMED:8752321 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan APC (CL0062), which has the following description:

This large superfamily contains a variety of transporters including amino acid permeases that according to TCDB belong to the APC (Amino acid-Polyamine-organoCation) superfamily.

The clan contains the following 21 members:

AA_permease AA_permease_2 AA_permease_C Aa_trans BCCT BenE Branch_AA_trans CstA DUF3360 HCO3_cotransp K_trans MFS_MOT1 Na_Ala_symp Nramp SNF Spore_permease SSF Sulfate_transp Transp_cyt_pur Trp_Tyr_perm Xan_ur_permease


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: IPR000060
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Mian N , Bateman A
Number in seed: 77
Number in full: 7172
Average length of the domain: 470.40 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 86.16 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 27.0 27.1
Noise cut-off 26.9 26.8
Model length: 485
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the BCCT domain has been found. There are 24 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...