Summary: PQ loop repeat
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PQ loop repeat Provide feedback
Members of this family are all membrane bound proteins possessing a pair of repeats each spanning two transmembrane helices connected by a loop . The PQ motif found on loop 2 is critical for the localisation of cystinosin to lysosomes . However, the PQ motif appears not to be a general lysosome-targeting motif. It is thought likely to possess a more general function. Most probably this involves a glutamine residue . Family members are membrane transporters since two members, cystinosin and PQLC2, transport cystine and cationic amino acids, respectively, across the lysosomal membrane . The 2nd PQ-loop of cystinosin hosts the substrate-coupled H+ binding site underlying its H+ symport mechanism, suggesting that PQ-loop repeats have functional significance [4,5]. It is thus likely that PQ-loop-containing proteins act as a family of membrane transporters. Some transport cystine and cationic amino acids, respectively, across the lysosomal membrane. Others transport lysine and or arginine across the lysosomal membrane in order to maintain the acidic homoeostasis .
Ponting CP, Mott R, Bork P, Copley RR; , Genome Res 2001;11:1996-2008.: Novel protein domains and repeats in Drosophila melanogaster: insights into structure, function, and evolution. PUBMED:11731489 EPMC:11731489
Cherqui S, Kalatzis V, Trugnan G, Antignac C; , J Biol Chem 2001;276:13314-13321.: The targeting of cystinosin to the lysosomal membrane requires a tyrosine-based signal and a novel sorting motif. PUBMED:11150305 EPMC:11150305
Kalatzis V, Cherqui S, Antignac C, Gasnier B;, EMBO J. 2001;20:5940-5949.: Cystinosin, the protein defective in cystinosis, is a H(+)-driven lysosomal cystine transporter. PUBMED:11689434 EPMC:11689434
Ruivo R, Bellenchi GC, Chen X, Zifarelli G, Sagne C, Debacker C, Pusch M, Supplisson S, Gasnier B;, Proc Natl Acad Sci U S A. 2012;109:E210-E217.: Mechanism of proton/substrate coupling in the heptahelical lysosomal transporter cystinosin. PUBMED:22232659 EPMC:22232659
Jezegou A, Llinares E, Anne C, Kieffer-Jaquinod S, O'Regan S, Aupetit J, Chabli A, Sagne C, Debacker C, Chadefaux-Vekemans B, Journet A, Andre B, Gasnier B;, Proc Natl Acad Sci U S A. 2012;109:E3434-E3443.: Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy. PUBMED:23169667 EPMC:23169667
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR006603
Some membrane bound proteins possess a pair of repeats each spanning two transmembrane helices connected by a loop [PUBMED:11731489]. The PQ motif found on loop 2 is critical for the localisation of cystinosin to lysosomes [PUBMED:11150305]. However, the PQ motif appears not to be a general lysosome-targeting motif. It is thought to possess a more general function; most probably this involves a glutamine residue [PUBMED:11731489].
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The clan forms a large and diverse family of proteins with seven transmembrane helices, common topology and, most likely, similar function. Their coding genes exist in all eukaryota and in several prokaryota. Some are responsible for metabolic diseases (cystinosis, congenital disorder of glycosylation), others are candidate genes for genetic disorders (cleft lip and palate, certain forms of cancer) or solute uptake and efflux (SWEETs) and many have not yet been assigned a function. Comparison with the properties of well-annotated clan members suggests that the proteins could be involved in protein trafficking and serve as cargo receptors in vesicle trafficking .
The clan contains the following 5 members:ER_lumen_recept LAB_N MPC MtN3_slv PQ-loop
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Curation and family details
|Seed source:||TIGRFAMs (release 2.0);|
|Author:||TIGRFAMs, Finn RD|
|Number in seed:||228|
|Number in full:||7326|
|Average length of the domain:||59.40 aa|
|Average identity of full alignment:||21 %|
|Average coverage of the sequence by the domain:||35.74 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||10|
|Download:||download the raw HMM for this family|
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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 PQ-loop domain has been found. There are 8 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 seqence.
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