Q96P56 · CTSR2_HUMAN
- ProteinCation channel sperm-associated protein 2
- GeneCATSPER2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids530 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Pore-forming subunit of the CatSper complex, a sperm-specific voltage-gated calcium channel, that plays a central role in calcium-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acrosome reaction and chemotaxis towards the oocyte.
Catalytic activity
- Ca2+(in) = Ca2+(out)
Activity regulation
The CatSper calcium channel is indirectly activated by extracellular progesterone and prostaglandins following the sequence: progesterone > PGF1-alpha = PGE1 > PGA1 > PGE2 >> PGD2 (PubMed:21412338, PubMed:21412339, PubMed:26989199).
The CatSper calcium channel is directly inhibited by endocannabinoid 2-arachidonoylglycerol (2AG) (PubMed:26989199).
Indirect activation by progesterone takes place via the following mechanism: progesterone binds and activates the acylglycerol lipase ABHD2, which in turn mediates hydrolysis of 2AG inhibitor, relieving inhibition of the CatSper channel (PubMed:26989199).
The primary effect of progesterone activation is to shift voltage dependence towards more physiological, negative membrane potentials; it is not mediated by metabotropic receptors and second messengers (PubMed:21412338, PubMed:21412339).
Sperm capacitation enhances the effect of progesterone by providing additional negative shift. Also activated by the elevation of intracellular pH (PubMed:21412338, PubMed:21412339).
The CatSper calcium channel is directly inhibited by endocannabinoid 2-arachidonoylglycerol (2AG) (PubMed:26989199).
Indirect activation by progesterone takes place via the following mechanism: progesterone binds and activates the acylglycerol lipase ABHD2, which in turn mediates hydrolysis of 2AG inhibitor, relieving inhibition of the CatSper channel (PubMed:26989199).
The primary effect of progesterone activation is to shift voltage dependence towards more physiological, negative membrane potentials; it is not mediated by metabotropic receptors and second messengers (PubMed:21412338, PubMed:21412339).
Sperm capacitation enhances the effect of progesterone by providing additional negative shift. Also activated by the elevation of intracellular pH (PubMed:21412338, PubMed:21412339).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | CatSper complex | |
Cellular Component | motile cilium | |
Cellular Component | plasma membrane | |
Molecular Function | calcium-activated cation channel activity | |
Molecular Function | voltage-gated calcium channel activity | |
Biological Process | calcium ion transport | |
Biological Process | fertilization | |
Biological Process | flagellated sperm motility | |
Biological Process | sperm capacitation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCation channel sperm-associated protein 2
- Short namesCatSper2
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96P56
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell projection, cilium, flagellum membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-108 | Cytoplasmic | ||||
Sequence: MAAYQQEEQMQLPRADAIRSRLIDTFSLIEHLQGLSQAVPRHTIRELLDPSRQKKLVLGDQHQLVRFSIKPQRIEQISHAQRLLSRLHVRCSQRPPLSLWAGWVLECP | ||||||
Transmembrane | 109-131 | Helical; Name=Segment S1 | ||||
Sequence: LFKNFIIFLVFLNTIILMVEIEL | ||||||
Topological domain | 132-140 | Extracellular | ||||
Sequence: LESTNTKLW | ||||||
Transmembrane | 141-166 | Helical; Name=Segment S2 | ||||
Sequence: PLKLTLEVAAWFILLIFILEILLKWL | ||||||
Topological domain | 167-175 | Cytoplasmic | ||||
Sequence: SNFSVFWKS | ||||||
Transmembrane | 176-200 | Helical; Name=Segment S3 | ||||
Sequence: AWNVFDFVVTMLSLLPEVVVLVGVT | ||||||
Topological domain | 201-203 | Extracellular | ||||
Sequence: GQS | ||||||
Transmembrane | 204-222 | Helical; Name=Segment S4 | ||||
Sequence: VWLQLLRICRVLRSLKLLA | ||||||
Topological domain | 223-239 | Cytoplasmic | ||||
Sequence: QFRQIQIIILVLVRALK | ||||||
Transmembrane | 240-262 | Helical; Name=Segment S5 | ||||
Sequence: SMTFLLMLLLIFFYIFAVTGVYV | ||||||
Topological domain | 263-281 | Extracellular | ||||
Sequence: FSEYTRSPRQDLEYHVFFS | ||||||
Intramembrane | 282-294 | Helical; Pore-forming | ||||
Sequence: DLPNSLVTVFILF | ||||||
Topological domain | 295-314 | Extracellular | ||||
Sequence: TLDHWYALLQDVWKVPEVSR | ||||||
Transmembrane | 315-341 | Helical; Name=Segment S6 | ||||
Sequence: IFSSIYFILWLLLGSIIFRSIIVAMMV | ||||||
Topological domain | 342-530 | Cytoplasmic | ||||
Sequence: TNFQNIRKELNEEMARREVQLKADMFKRQIIQRRKNMSHEALTSSHSKIEDSSRGASQQRESLDLSEVSEVESNYGATEEDLITSASKTEETLSKKREYQSSSCVSSTSSSYSSSSESRFSESIGRLDWETLVHENLPGLMEMDQDDRVWPRDSLFRYFELLEKLQYNLEERKKLQEFAVQALMNLEDK |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Deafness-infertility syndrome (DIS)
- Note
- DescriptionCharacterized by deafness and infertility and is caused by large contiguous gene deletions at 15q15.3 that removes both STRC and CATSPER2 genes.
- See alsoMIM:611102
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_033307 | 8 | in dbSNP:rs2614835 | |||
Sequence: E → G | ||||||
Natural variant | VAR_033308 | 57 | in dbSNP:rs8042868 | |||
Sequence: V → I |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 688 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000295676 | 1-530 | Cation channel sperm-associated protein 2 | |||
Sequence: MAAYQQEEQMQLPRADAIRSRLIDTFSLIEHLQGLSQAVPRHTIRELLDPSRQKKLVLGDQHQLVRFSIKPQRIEQISHAQRLLSRLHVRCSQRPPLSLWAGWVLECPLFKNFIIFLVFLNTIILMVEIELLESTNTKLWPLKLTLEVAAWFILLIFILEILLKWLSNFSVFWKSAWNVFDFVVTMLSLLPEVVVLVGVTGQSVWLQLLRICRVLRSLKLLAQFRQIQIIILVLVRALKSMTFLLMLLLIFFYIFAVTGVYVFSEYTRSPRQDLEYHVFFSDLPNSLVTVFILFTLDHWYALLQDVWKVPEVSRIFSSIYFILWLLLGSIIFRSIIVAMMVTNFQNIRKELNEEMARREVQLKADMFKRQIIQRRKNMSHEALTSSHSKIEDSSRGASQQRESLDLSEVSEVESNYGATEEDLITSASKTEETLSKKREYQSSSCVSSTSSSYSSSSESRFSESIGRLDWETLVHENLPGLMEMDQDDRVWPRDSLFRYFELLEKLQYNLEERKKLQEFAVQALMNLEDK |
Proteomic databases
PTM databases
Expression
Tissue specificity
Testis-specific.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, TMEM249, TMEM262 and EFCAB9 (By similarity).
HSPA1 may be an additional auxiliary complex member (By similarity).
The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (By similarity).
The auxiliary CATSPERB, CATSPERG, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (By similarity).
TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex. C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (By similarity).
Interacts with Ca(v)3.3/CACNA1I, leading to suppression of T-type calcium channel activity (PubMed:16740636).
HSPA1 may be an additional auxiliary complex member (By similarity).
The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (By similarity).
The auxiliary CATSPERB, CATSPERG, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (By similarity).
TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex. C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (By similarity).
Interacts with Ca(v)3.3/CACNA1I, leading to suppression of T-type calcium channel activity (PubMed:16740636).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96P56 | CACNA1I Q9P0X4 | 3 | EBI-2215024, EBI-1220829 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 378-398 | Basic and acidic residues | ||||
Sequence: MSHEALTSSHSKIEDSSRGAS | ||||||
Region | 378-458 | Disordered | ||||
Sequence: MSHEALTSSHSKIEDSSRGASQQRESLDLSEVSEVESNYGATEEDLITSASKTEETLSKKREYQSSSCVSSTSSSYSSSSE | ||||||
Compositional bias | 399-424 | Polar residues | ||||
Sequence: QQRESLDLSEVSEVESNYGATEEDLI | ||||||
Compositional bias | 439-458 | Polar residues | ||||
Sequence: EYQSSSCVSSTSSSYSSSSE |
Sequence similarities
Belongs to the cation channel sperm-associated (TC 1.A.1.19) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q96P56-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsVariant 2
- Length530
- Mass (Da)62,041
- Last updated2007-07-24 v2
- Checksum8561CC0E9F3590B0
Q96P56-2
- Name2
- SynonymsVariant 1
- Differences from canonical
- 393-394: Missing
Q96P56-3
- Name3
- SynonymsVariant 3
Q96P56-4
- Name4
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 46 | in Ref. 2; AAH28728 | ||||
Sequence: E → K | ||||||
Alternative sequence | VSP_026973 | 188-199 | in isoform 4 | |||
Sequence: SLLPEVVVLVGV → VRIEILRVRLVG | ||||||
Alternative sequence | VSP_026974 | 200-530 | in isoform 4 | |||
Sequence: Missing | ||||||
Compositional bias | 378-398 | Basic and acidic residues | ||||
Sequence: MSHEALTSSHSKIEDSSRGAS | ||||||
Alternative sequence | VSP_026976 | 393-394 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_026975 | 393-414 | in isoform 3 | |||
Sequence: SSRGASQQRESLDLSEVSEVES → RSFGLGDSCARKSARANGNGSG | ||||||
Compositional bias | 399-424 | Polar residues | ||||
Sequence: QQRESLDLSEVSEVESNYGATEEDLI | ||||||
Alternative sequence | VSP_026977 | 415-530 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 439-458 | Polar residues | ||||
Sequence: EYQSSSCVSSTSSSYSSSSE |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF411817 EMBL· GenBank· DDBJ | AAL26490.1 EMBL· GenBank· DDBJ | mRNA | ||
AF411818 EMBL· GenBank· DDBJ | AAL26491.1 EMBL· GenBank· DDBJ | mRNA | ||
AF411819 EMBL· GenBank· DDBJ | AAL26492.1 EMBL· GenBank· DDBJ | mRNA | ||
BC028728 EMBL· GenBank· DDBJ | AAH28728.1 EMBL· GenBank· DDBJ | mRNA | ||
BC064387 EMBL· GenBank· DDBJ | AAH64387.1 EMBL· GenBank· DDBJ | mRNA |