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52  structures 449  species 0  interactions 3305  sequences 388  architectures

Family: Polycystin_dom (PF20519)

Summary: Polycystin domain

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 "Polycystin cation channel family". More...

Polycystin cation channel family Edit Wikipedia article

C-terminal Cytosolic Domain of Polycystin-2
File:2KLD asym r 500.jpg
Solution Structure of the Calcium Binding Domain of the C-terminal Cytosolic Domain of Polycystin-2

The Polycystin Cation Channel (PCC) Family (TC# 1.A.5) consists of several transporters ranging in size from 500 to over 4000 amino acyl residues (aas) in length and exhibiting between 5 and 18 transmembrane segments (TMSs). This family is a constituent of the Voltage-Gated Ion Channel (VIC) Superfamily. These transporters generally catalyze the export of cations. A representative list of proteins belonging to the PCC family can be found in the Transporter Classification Database.[1]

Crystal Structures

There are a number of crystal structures available for members of the PCC family. Some of these include:

PKD1: PDB: 1B4R​

Polycystic kidney disease 2-like 1 protein: PDB: 3TE3​, 4GIF​

PKD2: PDB: 2KLD​, 2KLE​, 3HRN​, 3HRO​, 2KQ6​, 2Y4Q​


Human polycystin

Human polycystin 1 is a huge protein of 4303 aas. Its repeated leucine-rich (LRR) segment is found in many proteins. According to the SwissProt description, polycystin 1 contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. However, atomic force microscopy imaging has revealed the domain structure of polycystin-1.[2] It exhibits minimal sequence similarities, but similar domain organization and membrane topology with established cation channels such as the transient receptor potential (TRP) and voltage-gated ion channel (VIC) family proteins (TC# 1.A.4 and TC# 1.A.1, respectively). However, PSI-BLAST without iterations does not pick up these similarities. The PKD2L1-PKD1L3 complex perceives sour taste. Disruption of the PKD2-PKD1 complex, responsible for mechanosensation, leads to development of ADPKD (autosomal-dominant polycystic kidney disease).[3] Besides modulating channel activity and related signaling events, the CRDs (C-terminal regulatory domains) of PKD2 and PKD2L1 play a central role in channel oligomerization. These proteins appear to form trimers.[4]


Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+, while polycystin-2 has been characterized as a Ca2+-permeable cation-selective channel. Two members of the PCC family (polycystin 1 and 2; PKD1 and 2) are mutated in human autosomal dominant polycystic kidney disease, and polycystin-L, very similar and probably orthologous to PKD2, is deleted in mice with renal and retinal defects. PKD1 and 2 interact to form the non-selective cation channel in vitro, but PKD2 can form channels in the absence of any other associated protein. Polycystin-2 transports a variety of organic cations (dimethylamine, tetraethylammonium, tetrabutylammonium, tetrapropylammonium, tetrapentenyl ammonium). The channel diameter was estimated to be at least 1.1 Å.[5] Both are reported to be integral membrane proteins with 7-11 TMSs (PKD1) and 6 TMSs (PKD2), respectively. They share a homologous region of about 400 residues (residues 206-623 in PKD2; residues 3656-4052 in PKD1) which includes five TMSs of both proteins. This may well be the channel domain. PKD2 and polycystin-L have been shown to exhibit voltage-, pH- and divalent cation-dependent channel activity.[6][7] PKD1 may function primarily in regulation, both activating and stabilizing the polycystin-2 channel.[8]

Transient receptor potential proteins

Transient receptor potential (TRP) polycystin 2 and 3 (TRPP2 and 3) are homologous members of the TRP superfamily of cation channels but have different physiological functions. TRPP2 is part of a flow sensor, and is defective in autosomal dominant polycystic kidney disease and implicated in left-right asymmetry development. TRPP3 is implicated in sour tasting in bipolar cells of taste buds of the tongue and in the regulation of pH-sensitive action potential in neurons surrounding the central canal of the spinal cord. TRPP3 is present in both excitable and non-excitable cells in various tissues, such as retina, brain, heart, testis, and kidney.[9][10]


The TRP-ML1 protein (Mucolipin-1) has been shown to be a lysosomal monovalent cation channel that undergoes inactivating proteolytic cleavage.[11] It shows greater sequence similarity to the transmembrane region of polycystin 2 than it does to members of the TRP-CC family (TC# 1.A.4). Therefore, it is included in the former family. Both the PCC and TRP-CC families are members of the VIC superfamily.


Alpha-actinin is an actin-bundling protein known to regulate several types of ion channels. Planer lipid bilayer electrophysiology showed that TRPP3 exhibits cation channel activities that are substantially augmented by alpha-actinin. The TRPP3-alpha-actinin association was documented by co-immunoprecipitation using native cells and tissues, yeast two-hybrid, and in vitro binding assays.[12] TRPP3 is abundant in mouse brain where it associates with alpha-actinin-2. Alpha-actinin attaches TRPP3 to the cytoskeleton and up-regulates its channel function.

Physiological significance

Autosomal recessive polycystic kidney disease is caused by mutations in PKHD1, which encodes the membrane-associated receptor-like protein fibrocystin/polyductin (FPC) (Q8TCZ9, 4074aaa). FPC associates with the primary cilia of epithelial cells and co-localizes with the Pkd2 gene product polycystin-2 (PC2).  Kim et al. (2008) have concluded that a functional and molecular interaction exists between FPC and PC2 in vivo.[13]

See also


  1. ^ "1.A.5 The Polycystin Cation Channel (PCC) Family". TCDB. Retrieved 2016-04-10.
  2. ^ Oatley, Peter; Stewart, Andrew P.; Sandford, Richard; Edwardson, J. Michael (2012-04-03). "Atomic force microscopy imaging reveals the domain structure of polycystin-1". Biochemistry. 51 (13): 2879–2888. doi:10.1021/bi300134b. ISSN 1520-4995. PMID 22409330.
  3. ^ Dalagiorgou, Georgia; Basdra, Efthimia K.; Papavassiliou, Athanasios G. (2010-10-01). "Polycystin-1: function as a mechanosensor". The International Journal of Biochemistry & Cell Biology. 42 (10): 1610–1613. doi:10.1016/j.biocel.2010.06.017. ISSN 1878-5875. PMID 20601082.
  4. ^ Molland, Katrina L.; Narayanan, Anoop; Burgner, John W.; Yernool, Dinesh A. (2010-07-01). "Identification of the structural motif responsible for trimeric assembly of the C-terminal regulatory domains of polycystin channels PKD2L1 and PKD2". The Biochemical Journal. 429 (1): 171–183. doi:10.1042/BJ20091843. ISSN 1470-8728. PMID 20408813.
  5. ^ Anyatonwu, Georgia I.; Ehrlich, Barbara E. (2005-08-19). "Organic cation permeation through the channel formed by polycystin-2". The Journal of Biological Chemistry. 280 (33): 29488–29493. doi:10.1074/jbc.M504359200. ISSN 0021-9258. PMID 15961385.
  6. ^ Gonzalez-Perrett, Silvia; Batelli, Marisa; Kim, Keetae; Essafi, Makram; Timpanaro, Gustavo; Moltabetti, Nicolas; Reisin, Ignacio L.; Arnaout, M. Amin; Cantiello, Horacio F. (2002-07-12). "Voltage dependence and pH regulation of human polycystin-2-mediated cation channel activity". The Journal of Biological Chemistry. 277 (28): 24959–24966. doi:10.1074/jbc.M105084200. ISSN 0021-9258. PMID 11991947.
  7. ^ Liu, Yan; Li, Qiang; Tan, Miao; Zhang, Yu-Yang; Karpinski, Edward; Zhou, Jing; Chen, Xing-Zhen (2002-08-14). "Modulation of the human polycystin-L channel by voltage and divalent cations". FEBS letters. 525 (1–3): 71–76. ISSN 0014-5793. PMID 12163164.
  8. ^ Xu, G. Mark; González-Perrett, Silvia; Essafi, Makram; Timpanaro, Gustavo A.; Montalbetti, Nicolás; Arnaout, M. Amin; Cantiello, Horacio F. (2003-01-17). "Polycystin-1 activates and stabilizes the polycystin-2 channel". The Journal of Biological Chemistry. 278 (3): 1457–1462. doi:10.1074/jbc.M209996200. ISSN 0021-9258. PMID 12407099.
  9. ^ Noben-Trauth, Konrad (2011-01-01). "The TRPML3 channel: from gene to function". Advances in Experimental Medicine and Biology. 704: 229–237. doi:10.1007/978-94-007-0265-3_13. ISSN 0065-2598. PMID 21290299.
  10. ^ Li, Qiang; Dai, Xiao-Qing; Shen, Patrick Y.; Wu, Yuliang; Long, Wentong; Chen, Carl X.; Hussain, Zahir; Wang, Shaohua; Chen, Xing-Zhen (2007-12-01). "Direct binding of alpha-actinin enhances TRPP3 channel activity". Journal of Neurochemistry. 103 (6): 2391–2400. doi:10.1111/j.1471-4159.2007.04940.x. ISSN 1471-4159. PMID 17944866.
  11. ^ Kiselyov, Kirill; Chen, Jin; Rbaibi, Youssef; Oberdick, Daniel; Tjon-Kon-Sang, Sandra; Shcheynikov, Nikolay; Muallem, Shmuel; Soyombo, Abigail (2005-12-30). "TRP-ML1 is a lysosomal monovalent cation channel that undergoes proteolytic cleavage". The Journal of Biological Chemistry. 280 (52): 43218–43223. doi:10.1074/jbc.M508210200. ISSN 0021-9258. PMID 16257972.
  12. ^ Li, Qiang; Dai, Xiao-Qing; Shen, Patrick Y.; Wu, Yuliang; Long, Wentong; Chen, Carl X.; Hussain, Zahir; Wang, Shaohua; Chen, Xing-Zhen (2007-12-01). "Direct binding of alpha-actinin enhances TRPP3 channel activity". Journal of Neurochemistry. 103 (6): 2391–2400. doi:10.1111/j.1471-4159.2007.04940.x. ISSN 1471-4159. PMID 17944866.
  13. ^ Kim, Ingyu; Fu, Yulong; Hui, Kwokyin; Moeckel, Gilbert; Mai, Weiyi; Li, Cunxi; Liang, Dan; Zhao, Ping; Ma, Jie (2008-03-01). "Fibrocystin/polyductin modulates renal tubular formation by regulating polycystin-2 expression and function". Journal of the American Society of Nephrology: JASN. 19 (3): 455–468. doi:10.1681/ASN.2007070770. ISSN 1533-3450. PMC 2391052. PMID 18235088.

As of this edit, this article uses content from "1.A.5 The Polycystin Cation Channel (PCC) Family", which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 3.0 Unported License, but not under the GFDL. All relevant terms must be followed.

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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.

Polycystin domain Provide feedback

This domain represents the polycystin domain from group II of Transient receptor potential (TRP) channels (TRPP) including PKD1, PKD2, PKD2L and mucolipins. The polycystin domain display a sandwich-like shape with five beta-sheets in the tilted middle layer, three alpha-helices on one side and a large loop with two short antiparallel beta-sheets on the other [3].

Literature references

  1. Chen XZ, Vassilev PM, Basora N, Peng JB, Nomura H, Segal Y, Brown EM, Reeders ST, Hediger MA, Zhou J; , Nature 1999;401:383-386.: Polycystin-L is a calcium-regulated cation channel permeable to calcium ions. PUBMED:10517637 EPMC:10517637

  2. Vassilev PM, Guo L, Chen XZ, Segal Y, Peng JB, Basora N, Babakhanlou H, Cruger G, Kanazirska M, Ye Cp, Brown EM, Hediger MA, Zhou J; , Biochem Biophys Res Commun 2001;282:341-350.: Polycystin-2 is a novel cation channel implicated in defective intracellular Ca(2+) homeostasis in polycystic kidney disease. PUBMED:11264013 EPMC:11264013

  3. Su Q, Hu F, Liu Y, Ge X, Mei C, Yu S, Shen A, Zhou Q, Yan C, Lei J, Zhang Y, Liu X, Wang T;, Nat Commun. 2018;9:1192.: Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1. PUBMED:29567962 EPMC:29567962

Internal database links

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

Domain organisation

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

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Pfam Clan

This family is a member of clan Ion_channel (CL0030), which has the following description:

This superfamily contains a diverse range of ion channels that share a pair of transmembrane helices in common. This clan is classified as the VIC (Voltage-gated Ion Channel) superfamily in TCDB.

The clan contains the following 8 members:

Ion_trans Ion_trans_2 IRK KdpA Lig_chan PKD_channel Polycystin_dom TrkH


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...

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

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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.

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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.

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This family is new in this Pfam release.

Seed source: Bateman A
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Chuguransky S
Number in seed: 11
Number in full: 3305
Average length of the domain: 178.5 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 11.59 %

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 23.6 23.6
Trusted cut-off 23.6 23.7
Noise cut-off 23.5 23.5
Model length: 199
Family (HMM) version: 1
Download: download the raw HMM for this family

Species distribution

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


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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 Polycystin_dom domain has been found. There are 52 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.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2K4Q7 View 3D Structure Click here
A0A0N4U9H8 View 3D Structure Click here
A0A2R8Q5E7 View 3D Structure Click here
A0A3P7PS10 View 3D Structure Click here
A0A3Q0KSC6 View 3D Structure Click here
A0A5K4FAK6 View 3D Structure Click here
A2A259 View 3D Structure Click here
D3ZCW6 View 3D Structure Click here
D3ZDT6 View 3D Structure Click here
D4A5F1 View 3D Structure Click here
D4A828 View 3D Structure Click here
E7F2U9 View 3D Structure Click here
F1M1X0 View 3D Structure Click here
F1R6X2 View 3D Structure Click here
H2LRU7 View 3D Structure Click here
M0R5G5 View 3D Structure Click here
O35245 View 3D Structure Click here
Q13563 View 3D Structure Click here
Q2EG98 View 3D Structure Click here
Q4GZT3 View 3D Structure Click here
Q558Y3 View 3D Structure Click here
Q6IVV8 View 3D Structure Click here
Q7TN88 View 3D Structure Click here
Q7Z442 View 3D Structure Click here
Q8R526 View 3D Structure Click here
Q8T8Z2 View 3D Structure Click here
Q9JLG4 View 3D Structure Click here
Q9NTG1 View 3D Structure Click here
Q9NZM6 View 3D Structure Click here
Q9P0L9 View 3D Structure Click here
Q9U1S7 View 3D Structure Click here
Q9VK95 View 3D Structure Click here
Q9VVZ8 View 3D Structure Click here
Q9Z0T6 View 3D Structure Click here
X2JI61 View 3D Structure Click here