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Protein

Cation channel sperm-associated protein 2

Gene

CATSPER2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Enzyme regulationi

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).3 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Developmental protein, Ion channel, Voltage-gated channel

Keywords - Biological processi

Calcium transport, Differentiation, Ion transport, Spermatogenesis, Transport

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166762-MONOMER.
ReactomeiR-HSA-1300642. Sperm Motility And Taxes.

Protein family/group databases

TCDBi1.A.1.19.2. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Cation channel sperm-associated protein 2
Short name:
CatSper2
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:18810. CATSPER2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 112CytoplasmicSequence analysisAdd BLAST112
Transmembranei113 – 133Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini134 – 145ExtracellularSequence analysisAdd BLAST12
Transmembranei146 – 166Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini167 – 178CytoplasmicSequence analysisAdd BLAST12
Transmembranei179 – 199Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini200 – 205ExtracellularSequence analysis6
Transmembranei206 – 226Helical; Name=Segment S4Sequence analysisAdd BLAST21
Topological domaini227 – 242CytoplasmicSequence analysisAdd BLAST16
Transmembranei243 – 263Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini264 – 282ExtracellularSequence analysisAdd BLAST19
Intramembranei283 – 303Helical; Pore-formingSequence analysisAdd BLAST21
Topological domaini304 – 320ExtracellularSequence analysisAdd BLAST17
Transmembranei321 – 341Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini342 – 530CytoplasmicSequence analysisAdd BLAST189

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Flagellum, Membrane

Pathology & Biotechi

Involvement in diseasei

Deafness-infertility syndrome (DIS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized by deafness and infertility and is caused by large contiguous gene deletions at 15q15.3 that removes both STRC and CATSPER2 genes.
See also OMIM:611102

Organism-specific databases

DisGeNETi117155.
MalaCardsiCATSPER2.
MIMi611102. phenotype.
OpenTargetsiENSG00000166762.
Orphaneti94064. Deafness-infertility syndrome.
PharmGKBiPA38691.

Chemistry databases

GuidetoPHARMACOLOGYi389.

Polymorphism and mutation databases

BioMutaiCATSPER2.
DMDMi156631018.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002956761 – 530Cation channel sperm-associated protein 2Add BLAST530

Proteomic databases

PaxDbiQ96P56.
PeptideAtlasiQ96P56.
PRIDEiQ96P56.

PTM databases

iPTMnetiQ96P56.
PhosphoSitePlusiQ96P56.

Expressioni

Tissue specificityi

Testis-specific.2 Publications

Gene expression databases

BgeeiENSG00000166762.
CleanExiHS_CATSPER2.
ExpressionAtlasiQ96P56. baseline and differential.
GenevisibleiQ96P56. HS.

Organism-specific databases

HPAiHPA042709.

Interactioni

Subunit structurei

Heterotetramer; possibly composed of CATSPER1, CATSPER2, CATSPER3 and CATSPER4 (Potential). Component of the CatSper complex. Interacts with Ca(v)3.3/CACNA1I, leading to suppress T-type calcium channel activity.Curated1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CACNA1IQ9P0X43EBI-2215024,EBI-1220829

Protein-protein interaction databases

IntActiQ96P56. 1 interactor.
STRINGi9606.ENSP00000299989.

Structurei

3D structure databases

ProteinModelPortaliQ96P56.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi385 – 464Ser-richAdd BLAST80

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410INF6. Eukaryota.
ENOG4111GC6. LUCA.
GeneTreeiENSGT00760000119325.
HOGENOMiHOG000007710.
HOVERGENiHBG107782.
InParanoidiQ96P56.
KOiK16890.
PhylomeDBiQ96P56.
TreeFamiTF343585.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR028747. CatSper2.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PANTHERiPTHR10037:SF189. PTHR10037:SF189. 1 hit.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96P56-1) [UniParc]FASTAAdd to basket
Also known as: Variant 2

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.

« Hide

        10         20         30         40         50
MAAYQQEEQM QLPRADAIRS RLIDTFSLIE HLQGLSQAVP RHTIRELLDP
60 70 80 90 100
SRQKKLVLGD QHQLVRFSIK PQRIEQISHA QRLLSRLHVR CSQRPPLSLW
110 120 130 140 150
AGWVLECPLF KNFIIFLVFL NTIILMVEIE LLESTNTKLW PLKLTLEVAA
160 170 180 190 200
WFILLIFILE ILLKWLSNFS VFWKSAWNVF DFVVTMLSLL PEVVVLVGVT
210 220 230 240 250
GQSVWLQLLR ICRVLRSLKL LAQFRQIQII ILVLVRALKS MTFLLMLLLI
260 270 280 290 300
FFYIFAVTGV YVFSEYTRSP RQDLEYHVFF SDLPNSLVTV FILFTLDHWY
310 320 330 340 350
ALLQDVWKVP EVSRIFSSIY FILWLLLGSI IFRSIIVAMM VTNFQNIRKE
360 370 380 390 400
LNEEMARREV QLKADMFKRQ IIQRRKNMSH EALTSSHSKI EDSSRGASQQ
410 420 430 440 450
RESLDLSEVS EVESNYGATE EDLITSASKT EETLSKKREY QSSSCVSSTS
460 470 480 490 500
SSYSSSSESR FSESIGRLDW ETLVHENLPG LMEMDQDDRV WPRDSLFRYF
510 520 530
ELLEKLQYNL EERKKLQEFA VQALMNLEDK
Length:530
Mass (Da):62,041
Last modified:July 24, 2007 - v2
Checksum:i8561CC0E9F3590B0
GO
Isoform 2 (identifier: Q96P56-2) [UniParc]FASTAAdd to basket
Also known as: Variant 1

The sequence of this isoform differs from the canonical sequence as follows:
     393-394: Missing.

Show »
Length:528
Mass (Da):61,867
Checksum:i4B38C7DC481EE755
GO
Isoform 3 (identifier: Q96P56-3) [UniParc]FASTAAdd to basket
Also known as: Variant 3

The sequence of this isoform differs from the canonical sequence as follows:
     393-414: SSRGASQQRESLDLSEVSEVES → RSFGLGDSCARKSARANGNGSG
     415-530: Missing.

Show »
Length:414
Mass (Da):48,341
Checksum:iB5A474A8DF68C27F
GO
Isoform 4 (identifier: Q96P56-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     188-199: SLLPEVVVLVGV → VRIEILRVRLVG
     200-530: Missing.

Note: No experimental confirmation available.
Show »
Length:199
Mass (Da):23,437
Checksum:i57171E69BE875D30
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti46E → K in AAH28728 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0333078E → G.Corresponds to variant rs2614835dbSNPEnsembl.1
Natural variantiVAR_03330857V → I.Corresponds to variant rs8042868dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_026973188 – 199SLLPE…VLVGV → VRIEILRVRLVG in isoform 4. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_026974200 – 530Missing in isoform 4. 1 PublicationAdd BLAST331
Alternative sequenceiVSP_026975393 – 414SSRGA…SEVES → RSFGLGDSCARKSARANGNG SG in isoform 3. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_026976393 – 394Missing in isoform 2. 2 Publications2
Alternative sequenceiVSP_026977415 – 530Missing in isoform 3. 1 PublicationAdd BLAST116

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF411817 mRNA. Translation: AAL26490.1.
AF411818 mRNA. Translation: AAL26491.1.
AF411819 mRNA. Translation: AAL26492.1.
BC028728 mRNA. Translation: AAH28728.1.
BC064387 mRNA. Translation: AAH64387.1.
CCDSiCCDS10099.1. [Q96P56-1]
CCDS32216.1. [Q96P56-2]
RefSeqiNP_001269238.1. NM_001282309.1. [Q96P56-2]
NP_473361.1. NM_054020.3. [Q96P56-2]
NP_742093.1. NM_172095.2. [Q96P56-1]
XP_016877393.1. XM_017021904.1. [Q96P56-1]
UniGeneiHs.662284.

Genome annotation databases

EnsembliENST00000321596; ENSP00000321463; ENSG00000166762. [Q96P56-1]
ENST00000396879; ENSP00000380088; ENSG00000166762. [Q96P56-2]
ENST00000433380; ENSP00000389746; ENSG00000166762. [Q96P56-3]
GeneIDi117155.
KEGGihsa:117155.
UCSCiuc001zsh.5. human. [Q96P56-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF411817 mRNA. Translation: AAL26490.1.
AF411818 mRNA. Translation: AAL26491.1.
AF411819 mRNA. Translation: AAL26492.1.
BC028728 mRNA. Translation: AAH28728.1.
BC064387 mRNA. Translation: AAH64387.1.
CCDSiCCDS10099.1. [Q96P56-1]
CCDS32216.1. [Q96P56-2]
RefSeqiNP_001269238.1. NM_001282309.1. [Q96P56-2]
NP_473361.1. NM_054020.3. [Q96P56-2]
NP_742093.1. NM_172095.2. [Q96P56-1]
XP_016877393.1. XM_017021904.1. [Q96P56-1]
UniGeneiHs.662284.

3D structure databases

ProteinModelPortaliQ96P56.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ96P56. 1 interactor.
STRINGi9606.ENSP00000299989.

Chemistry databases

GuidetoPHARMACOLOGYi389.

Protein family/group databases

TCDBi1.A.1.19.2. the voltage-gated ion channel (vic) superfamily.

PTM databases

iPTMnetiQ96P56.
PhosphoSitePlusiQ96P56.

Polymorphism and mutation databases

BioMutaiCATSPER2.
DMDMi156631018.

Proteomic databases

PaxDbiQ96P56.
PeptideAtlasiQ96P56.
PRIDEiQ96P56.

Protocols and materials databases

DNASUi117155.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321596; ENSP00000321463; ENSG00000166762. [Q96P56-1]
ENST00000396879; ENSP00000380088; ENSG00000166762. [Q96P56-2]
ENST00000433380; ENSP00000389746; ENSG00000166762. [Q96P56-3]
GeneIDi117155.
KEGGihsa:117155.
UCSCiuc001zsh.5. human. [Q96P56-1]

Organism-specific databases

CTDi117155.
DisGeNETi117155.
GeneCardsiCATSPER2.
GeneReviewsiCATSPER2.
HGNCiHGNC:18810. CATSPER2.
HPAiHPA042709.
MalaCardsiCATSPER2.
MIMi607249. gene.
611102. phenotype.
neXtProtiNX_Q96P56.
OpenTargetsiENSG00000166762.
Orphaneti94064. Deafness-infertility syndrome.
PharmGKBiPA38691.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410INF6. Eukaryota.
ENOG4111GC6. LUCA.
GeneTreeiENSGT00760000119325.
HOGENOMiHOG000007710.
HOVERGENiHBG107782.
InParanoidiQ96P56.
KOiK16890.
PhylomeDBiQ96P56.
TreeFamiTF343585.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166762-MONOMER.
ReactomeiR-HSA-1300642. Sperm Motility And Taxes.

Miscellaneous databases

GeneWikiiCatSper2.
GenomeRNAii117155.
PROiQ96P56.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166762.
CleanExiHS_CATSPER2.
ExpressionAtlasiQ96P56. baseline and differential.
GenevisibleiQ96P56. HS.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR028747. CatSper2.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PANTHERiPTHR10037:SF189. PTHR10037:SF189. 1 hit.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCTSR2_HUMAN
AccessioniPrimary (citable) accession number: Q96P56
Secondary accession number(s): Q8NHT9, Q96P54, Q96P55
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: July 24, 2007
Last modified: November 2, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.