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CatSper2

Family: CatSper and Two-Pore channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Tissue Distribution
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 528 15q14 CATSPER2 cation channel, sperm associated 2 5
Mouse 6 1 588 2 E5 Catsper2 cation channel, sperm associated 2 5
Rat 6 1 584 3q35 Catsper2 cation channel, sperm associated 2
Previous and Unofficial Names
Cation channel of sperm; 2
Catsper2_predicted
LOC366174
cation channel sperm-associated protein 2
cation channel, sperm associated 2
cation channel, sperm associated 2 (predicted)
Database Links
Ensembl ENSG00000166762 (Hs), ENSMUSG00000033486 (Mm), ENSRNOG00000023064 (Rn)
Entrez Gene 117155 (Hs), 212670 (Mm), 366174 (Rn)
GeneCards CATSPER2 (Hs)
GenitoUrinary Development Molecular Anatomy Project Catsper2 (Mm)
HomoloGene 77423 (Hs)
Human Protein Reference Database 16236 (Hs)
InterPro Q96P56 (Hs), A2ARP9 (Mm), Q6AXP6 (Rn)
KEGG Gene hsa:117155 (Hs), mmu:212670 (Mm), rno:366174 (Rn)
OMIM 607249 (Hs)
Orphanet Gene ORPHA159339 (Hs)
PharmGKB Gene PA38691 (Hs)
PhosphoSitePlus Q96P56 (Hs), A2ARP9 (Mm), Q6AXP6 (Rn)
Protein Ontology (PRO) PRO:000000670 (Hs)
RefSeq Nucleotide NM_054020 (Hs), NM_172097 (Hs), NM_172095 (Hs), NM_153075 (Mm), NM_001012220 (Rn)
RefSeq Protein NP_742093 (Hs), NP_473361 (Hs), NP_742095 (Hs), NP_694715 (Mm), NP_001012220 (Rn)
TreeFam ENSG00000166762 (Hs), ENSMUSG00000033486 (Mm), ENSRNOG00000023064 (Rn)
UniGene Hs. 662284 (Hs)
UniProt Q96P56 (Hs), A2ARP9 (Mm), Q6AXP6 (Rn)
Wikipedia CatSper2
CatSper and Two-Pore channels
Search for 3D structures on the PDB
Search by keyword: CatSper and Two-Pore channels CatSper2 Search by accession number: Q96P56, Q6AXP6, A2ARP9
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
CatSper4 4
CatSper3 4
CatSper2 4-5
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Not determined
Associated Protein Comments
CatSper1-4 appear to function only as a heterotetramer, producing a current known as ICatSper. All functional data for this channel can be found in CatSper1.
Tissue Distribution
Testis.
Species:  Mouse
Technique:  Northern Blot
References:  5
Testis (principal piece of the tail of spermatozoa).
Species:  Mouse
Technique:  Immunocytochemistry
References:  5
Mature spermatozoa.
Species:  Mouse
Technique:  In situ hybridisation
References:  5
Physiological Functions
CatSper 1-4 together form a channel that is required for mouse sperm hyperactivation of motility, and consequently fertility.
Species:  Mouse
Tissue:  Spermatozoa
References:  2-5,7
Physiological Functions Comments
Sperm cells are slightly acidic internally (pH 6.8) in the vagina (~ pH 5) thus the pH dependence of ICatSper activation leaves it inactive at resting membrane potential. As the pH shifts to ~8 in the cervix and upper female reproductive tract the internal sperm cell pH also becomes alkaline (> pH 7.5) and ICatSper is activated, leading to hyperactivation of motility.
Physiological Consequences of Altering Gene Expression
Infertility as a consequence of loss of hyperactivation of motility
Species:  Mouse
Tissue:  Spermatozoa
Technique:  CatSper2 knockout
References:  6
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Catsper2tm1Gar Catsper2tm1Gar/Catsper2tm1Gar
involves: 129S6/SvEvTac		 MGI:2387404  MP:0002674 abnormal sperm motility PMID: 17227845 
Catsper2tm1Gar Catsper2tm1Gar/Catsper2tm1Gar
involves: 129S6/SvEvTac		 MGI:2387404  MP:0004543 abnormal sperm physiology PMID: 17227845 
Catsper2tm1Gar Catsper2tm1Gar/Catsper2tm1Gar
involves: 129S6/SvEvTac * C57BL/6J		 MGI:2387404  MP:0002675 asthenozoospermia PMID: 14657366 
Catsper2tm1Gar Catsper2tm1Gar/Catsper2tm1Gar
involves: 129S6/SvEvTac		 MGI:2387404  MP:0002675 asthenozoospermia PMID: 17227845 
Catsper2tm1Gar Catsper2tm1Gar/Catsper2tm1Gar
involves: 129S6/SvEvTac * C57BL/6J		 MGI:2387404  MP:0004542 impaired acrosome reaction PMID: 14657366 
Catsper2tm1Gar Catsper2tm1Gar/Catsper2tm1Gar
involves: 129S6/SvEvTac * C57BL/6J		 MGI:2387404  MP:0000242 impaired fertilization PMID: 14657366 
Catsper2tm1Gar Catsper2tm1Gar/Catsper2tm1Gar
involves: 129S6/SvEvTac * C57BL/6J		 MGI:2387404  MP:0001925 male infertility PMID: 14657366 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Male infertility
References:  1
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human Final two exons 1
Disease:  Male infertility segregating with sensorineural deafness.
OMIM:  611102
Orphanet:  94064
Comments:  This syndrome is caused by a large contiguous gene deletion at 15q15.3 including four genes (KIAA0377, CKMT1B, STRC and CATSPER2).
References:  8
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human Entire gene 8
Biologically Significant Variants
Nucleotide accession:  AF411819 
Protein accession:  AAL26492 
Amino acids:  414
Type:  Splice variant
Species:  Human
References:  5
Nucleotide accession:  NM_172097 
Protein accession:  NP_742095 
Amino acids:  199
Type:  Splice variant
Species:  Human
References: 
Nucleotide accession:  NM_172095 
Protein accession:  NP_742093 
Amino acids:  530
Type:  Splice variant
Species:  Human
References:  5
Nucleotide accession:  NM_054020 
Protein accession:  NP_473361 
Amino acids:  528
Type:  Splice variant
Species:  Human
References: 

REFERENCES

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1. Avidan, N; Tamary, H; Dgany, O; Cattan, D; Pariente, A; Thulliez, M; Borot, N; Moati, L; Barthelme, A; Shalmon, L; Krasnov, T; Ben-Asher, E; Olender, T; Khen, M; Yaniv, I; Zaizov, R; Shalev, H; Delaunay, J; Fellous, M; Lancet, D; Beckmann, JS. (2003) CATSPER2, a human autosomal nonsyndromic male infertility gene. Eur. J. Hum. Genet., 11 (7): 497-502. [PMID:12825070]

2. Carlson, AE; Westenbroek, RE; Quill, T; Ren, D; Clapham, DE; Hille, B; Garbers, DL; Babcock, DF. (2003) CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm. Proc. Natl. Acad. Sci. U.S.A., 100 (25): 14864-8. [PMID:14657352]

3. Kirichok, Y; Navarro, B; Clapham, DE. (2006) Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel. Nature, 439 (7077): 737-40. [PMID:16467839]

4. Qi, H; Moran, MM; Navarro, B; Chong, JA; Krapivinsky, G; Krapivinsky, L; Kirichok, Y; Ramsey, IS; Quill, TA; Clapham, DE. (2007) All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility. Proc. Natl. Acad. Sci. U.S.A., 104 (4): 1219-23. [PMID:17227845]

5. Quill, TA; Ren, D; Clapham, DE; Garbers, DL. (2001) A voltage-gated ion channel expressed specifically in spermatozoa. Proc. Natl. Acad. Sci. U.S.A., 98 (22): 12527-31. [PMID:11675491]

6. Quill, TA; Sugden, SA; Rossi, KL; Doolittle, LK; Hammer, RE; Garbers, DL. (2003) Hyperactivated sperm motility driven by CatSper2 is required for fertilization. Proc. Natl. Acad. Sci. U.S.A., 100 (25): 14869-74. [PMID:14657366]

7. Ren, D; Navarro, B; Perez, G; Jackson, AC; Hsu, S; Shi, Q; Tilly, JL; Clapham, DE. (2001) A sperm ion channel required for sperm motility and male fertility. Nature, 413 (6856): 603-9. [PMID:11595941]

8. Zhang, Y; Malekpour, M; Al-Madani, N; Kahrizi, K; Zanganeh, M; Lohr, NJ; Mohseni, M; Mojahedi, F; Daneshi, A; Najmabadi, H; Smith, RJ. (2007) Sensorineural deafness and male infertility: a contiguous gene deletion syndrome. J. Med. Genet., 44 (4): 233-40. [PMID:17098888]

To cite this database page, please use the following:

David E. Clapham.
CatSper and Two-Pore channels: CatSper2. Last modified on 01/07/2010. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=389.


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