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Q96P56 (CTSR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cation channel sperm-associated protein 2

Short name=CatSper2
Gene names
Name:CATSPER2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length530 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Activated by extracellular progesterone and prostaglandins following the sequence: progesterone > PGF1-alpha = PGE1 > PGA1 > PGE2 >> PGD2. 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. Sperm capacitation enhances the effect of progesterone by providing additional negative shift. Also activated by the elevation of intracellular pH. Ref.7 Ref.8

Subunit structure

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. Ref.4

Subcellular location

Cell projectionciliumflagellum membrane; Multi-pass membrane protein By similarity. Note: Specifically located in the principal piece of sperm tail.

Tissue specificity

Testis-specific. Ref.1 Ref.6

Involvement in disease

Deafness-infertility syndrome (DIS) [MIM:611102]: Characterized by deafness and infertility and is caused by large contiguous gene deletions at 15q15.3 that removes both STRC and CATSPER2 genes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.5

Sequence similarities

Belongs to the cation channel sperm-associated (TC 1.A.1.19) family. [View classification]

Ontologies

Keywords
   Biological processCalcium transport
Differentiation
Ion transport
Spermatogenesis
Transport
   Cellular componentCell membrane
Cell projection
Cilium
Flagellum
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionCalcium channel
Developmental protein
Ion channel
Voltage-gated channel
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

multicellular organism reproduction

Traceable author statement. Source: Reactome

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

single fertilization

Traceable author statement. Source: Reactome

sperm motility

Inferred from electronic annotation. Source: InterPro

sperm-egg recognition

Traceable author statement. Source: Reactome

spermatogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentCatSper complex

Inferred from sequence or structural similarity. Source: UniProtKB

cilium

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncalcium activated cation channel activity

Inferred from electronic annotation. Source: InterPro

calcium channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

voltage-gated ion channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CACNA1IQ9P0X43EBI-2215024,EBI-1220829

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96P56-1)

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.
Isoform 2 (identifier: Q96P56-2)

Also known as: Variant 1;

The sequence of this isoform differs from the canonical sequence as follows:
     393-394: Missing.
Isoform 3 (identifier: Q96P56-3)

Also known as: Variant 3;

The sequence of this isoform differs from the canonical sequence as follows:
     393-414: SSRGASQQRESLDLSEVSEVES → RSFGLGDSCARKSARANGNGSG
     415-530: Missing.
Isoform 4 (identifier: Q96P56-4)

The sequence of this isoform differs from the canonical sequence as follows:
     188-199: SLLPEVVVLVGV → VRIEILRVRLVG
     200-530: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 530530Cation channel sperm-associated protein 2
PRO_0000295676

Regions

Topological domain1 – 112112Cytoplasmic Potential
Transmembrane113 – 13321Helical; Name=Segment S1; Potential
Topological domain134 – 14512Extracellular Potential
Transmembrane146 – 16621Helical; Name=Segment S2; Potential
Topological domain167 – 17812Cytoplasmic Potential
Transmembrane179 – 19921Helical; Name=Segment S3; Potential
Topological domain200 – 2056Extracellular Potential
Transmembrane206 – 22621Helical; Name=Segment S4; Potential
Topological domain227 – 24216Cytoplasmic Potential
Transmembrane243 – 26321Helical; Name=Segment S5; Potential
Topological domain264 – 28219Extracellular Potential
Intramembrane283 – 30321Helical; Pore-forming; Potential
Topological domain304 – 32017Extracellular Potential
Transmembrane321 – 34121Helical; Name=Segment S6; Potential
Topological domain342 – 530189Cytoplasmic Potential
Compositional bias385 – 46480Ser-rich

Natural variations

Alternative sequence188 – 19912SLLPE…VLVGV → VRIEILRVRLVG in isoform 4.
VSP_026973
Alternative sequence200 – 530331Missing in isoform 4.
VSP_026974
Alternative sequence393 – 41422SSRGA…SEVES → RSFGLGDSCARKSARANGNG SG in isoform 3.
VSP_026975
Alternative sequence393 – 3942Missing in isoform 2.
VSP_026976
Alternative sequence415 – 530116Missing in isoform 3.
VSP_026977
Natural variant81E → G.
Corresponds to variant rs2614835 [ dbSNP | Ensembl ].
VAR_033307
Natural variant571V → I.
Corresponds to variant rs8042868 [ dbSNP | Ensembl ].
VAR_033308

Experimental info

Sequence conflict461E → K in AAH28728. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Variant 2) [UniParc].

Last modified July 24, 2007. Version 2.
Checksum: 8561CC0E9F3590B0

FASTA53062,041
        10         20         30         40         50         60 
MAAYQQEEQM QLPRADAIRS RLIDTFSLIE HLQGLSQAVP RHTIRELLDP SRQKKLVLGD 

        70         80         90        100        110        120 
QHQLVRFSIK PQRIEQISHA QRLLSRLHVR CSQRPPLSLW AGWVLECPLF KNFIIFLVFL 

       130        140        150        160        170        180 
NTIILMVEIE LLESTNTKLW PLKLTLEVAA WFILLIFILE ILLKWLSNFS VFWKSAWNVF 

       190        200        210        220        230        240 
DFVVTMLSLL PEVVVLVGVT GQSVWLQLLR ICRVLRSLKL LAQFRQIQII ILVLVRALKS 

       250        260        270        280        290        300 
MTFLLMLLLI FFYIFAVTGV YVFSEYTRSP RQDLEYHVFF SDLPNSLVTV FILFTLDHWY 

       310        320        330        340        350        360 
ALLQDVWKVP EVSRIFSSIY FILWLLLGSI IFRSIIVAMM VTNFQNIRKE LNEEMARREV 

       370        380        390        400        410        420 
QLKADMFKRQ IIQRRKNMSH EALTSSHSKI EDSSRGASQQ RESLDLSEVS EVESNYGATE 

       430        440        450        460        470        480 
EDLITSASKT EETLSKKREY QSSSCVSSTS SSYSSSSESR FSESIGRLDW ETLVHENLPG 

       490        500        510        520        530 
LMEMDQDDRV WPRDSLFRYF ELLEKLQYNL EERKKLQEFA VQALMNLEDK 

« Hide

Isoform 2 (Variant 1) [UniParc].

Checksum: 4B38C7DC481EE755
Show »

FASTA52861,867
Isoform 3 (Variant 3) [UniParc].

Checksum: B5A474A8DF68C27F
Show »

FASTA41448,341
Isoform 4 [UniParc].

Checksum: 57171E69BE875D30
Show »

FASTA19923,437

References

« Hide 'large scale' references
[1]"A voltage-gated ion channel expressed specifically in spermatozoa."
Quill T.A., Ren D., Clapham D.E., Garbers D.L.
Proc. Natl. Acad. Sci. U.S.A. 98:12527-12531(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
Tissue: Brain and Testis.
[3]"CATSPER2, a human autosomal nonsyndromic male infertility gene."
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. expand/collapse author list , Fellous M., Lancet D., Beckmann J.S.
Eur. J. Hum. Genet. 11:497-502(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN DIS.
[4]"Association of Catsper1 or -2 with Ca(v)3.3 leads to suppression of T-type calcium channel activity."
Zhang D., Chen J., Saraf A., Cassar S., Han P., Rogers J.C., Brioni J.D., Sullivan J.P., Gopalakrishnan M.
J. Biol. Chem. 281:22332-22341(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CACNA1I.
[5]"Sensorineural deafness and male infertility: a contiguous gene deletion syndrome."
Zhang Y., Malekpour M., Al-Madani N., Kahrizi K., Zanganeh M., Mohseni M., Mojahedi F., Daneshi A., Najmabadi H., Smith R.J.H.
J. Med. Genet. 44:233-240(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN DIS.
[6]"Expression of CatSper family transcripts in the mouse testis during post-natal development and human ejaculated spermatozoa: relationship to sperm motility."
Li H.-G., Ding X.-F., Liao A.-H., Kong X.-B., Xiong C.-L.
Mol. Hum. Reprod. 13:299-306(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm."
Strunker T., Goodwin N., Brenker C., Kashikar N.D., Weyand I., Seifert R., Kaupp U.B.
Nature 471:382-386(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION BY PROGESTERONE.
[8]"Progesterone activates the principal Ca2+ channel of human sperm."
Lishko P.V., Botchkina I.L., Kirichok Y.
Nature 471:387-391(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION BY PROGESTERONE.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001269238.1. NM_001282309.1.
NP_473361.1. NM_054020.3.
NP_742093.1. NM_172095.2.
UniGeneHs.662284.

3D structure databases

ProteinModelPortalQ96P56.
SMRQ96P56. Positions 104-341.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ96P56. 1 interaction.
STRING9606.ENSP00000299989.

Chemistry

GuidetoPHARMACOLOGY389.

Protein family/group databases

TCDB1.A.1.19.2. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteQ96P56.

Polymorphism databases

DMDM156631018.

Proteomic databases

PaxDbQ96P56.
PRIDEQ96P56.

Protocols and materials databases

DNASU117155.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000321596; ENSP00000321463; ENSG00000166762. [Q96P56-1]
ENST00000354127; ENSP00000339137; ENSG00000166762. [Q96P56-2]
ENST00000355438; ENSP00000347613; ENSG00000166762. [Q96P56-3]
ENST00000396879; ENSP00000380088; ENSG00000166762. [Q96P56-2]
ENST00000433380; ENSP00000389746; ENSG00000166762. [Q96P56-3]
GeneID117155.
KEGGhsa:117155.
UCSCuc001zsh.3. human. [Q96P56-1]
uc001zsi.3. human. [Q96P56-2]
uc001zsk.3. human. [Q96P56-4]

Organism-specific databases

CTD117155.
GeneCardsGC15M043920.
HGNCHGNC:18810. CATSPER2.
HPAHPA042709.
MIM607249. gene.
611102. phenotype.
neXtProtNX_Q96P56.
Orphanet94064. Deafness-infertility syndrome.
PharmGKBPA38691.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG302565.
HOGENOMHOG000007710.
HOVERGENHBG107782.
KOK16890.
OrthoDBEOG761BTM.
PhylomeDBQ96P56.
TreeFamTF343585.

Enzyme and pathway databases

ReactomeREACT_163848. Reproduction.

Gene expression databases

ArrayExpressQ96P56.
BgeeQ96P56.
CleanExHS_CATSPER2.
GenevestigatorQ96P56.

Family and domain databases

Gene3D1.20.120.350. 1 hit.
InterProIPR028747. CatSper2.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PANTHERPTHR10037:SF6. PTHR10037:SF6. 1 hit.
PfamPF00520. Ion_trans. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCATSPER2. human.
GeneWikiCatSper2.
GenomeRNAi117155.
NextBio80109.
PROQ96P56.
SOURCESearch...

Entry information

Entry nameCTSR2_HUMAN
AccessionPrimary (citable) accession number: Q96P56
Secondary accession number(s): Q8NHT9, Q96P54, Q96P55
Entry history
Integrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: July 24, 2007
Last modified: April 16, 2014
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM