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Q8NEC5 (CTSR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cation channel sperm-associated protein 1

Short name=CatSper1
Short name=hCatSper
Gene names
Name:CATSPER1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length780 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.9 Ref.10

Subunit structure

Heterotetramer; possibly composed of CATSPER1, CATSPER2, CATSPER3 and CATSPER4 Potential. Component of the CatSper complex. Interacts with CATSPER3 and CATSPER4 By similarity. Interacts with Ca(v)3.3/CACNA1I, leading to suppress T-type calcium channel activity. Ref.6

Subcellular location

Cell projectionciliumflagellum membrane; Multi-pass membrane protein. Note: Specifically located in the principal piece of sperm tail. Ref.5

Tissue specificity

Testis-specific. Ref.1 Ref.5 Ref.7

Developmental stage

Expressed meiotically and post-meiotically. Ref.5

Induction

Down-regulated in patients lacking sperm motility. Ref.4

Involvement in disease

Spermatogenic failure 7 (SPGF7) [MIM:612997]: An infertility disorder characterized by non-motile sperm or sperm motility below the normal threshold, low sperm count, increased abnormally structured spermatozoa, and reduced semen volume.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

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 diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionCalcium channel
Developmental protein
Ion channel
Voltage-gated channel
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium ion import

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

cilium or flagellum-dependent cell motility

Inferred from electronic annotation. Source: Ensembl

fusion of sperm to egg plasma membrane

Inferred from electronic annotation. Source: Ensembl

membrane depolarization during action potential

Inferred from Biological aspect of Ancestor. Source: RefGenome

multicellular organism reproduction

Traceable author statement. Source: Reactome

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of calcium ion transport

Inferred from electronic annotation. Source: Ensembl

single fertilization

Traceable author statement. Source: Reactome

sperm motility

Inferred from Biological aspect of Ancestor. Source: RefGenome

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

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functioncalcium activated cation channel activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction Ref.6. Source: IntAct

voltage-gated calcium channel activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CACNA1IQ9P0X45EBI-744545,EBI-1220829

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 780780Cation channel sperm-associated protein 1
PRO_0000295674

Regions

Topological domain1 – 445445Cytoplasmic Potential
Transmembrane446 – 46621Helical; Name=Segment S1; Potential
Topological domain467 – 48519Extracellular Potential
Transmembrane486 – 50621Helical; Name=Segment S2; Potential
Topological domain507 – 5159Cytoplasmic Potential
Transmembrane516 – 53621Helical; Name=Segment S3; Potential
Topological domain537 – 5415Extracellular Potential
Transmembrane542 – 56221Helical; Name=Segment S4; Potential
Topological domain563 – 57917Cytoplasmic Potential
Transmembrane580 – 60021Helical; Name=Segment S5; Potential
Topological domain601 – 61515Extracellular Potential
Intramembrane616 – 63621Helical; Pore-forming; Potential
Topological domain637 – 64610Extracellular Potential
Transmembrane647 – 66721Helical; Name=Segment S6; Potential
Topological domain668 – 780113Cytoplasmic Potential
Compositional bias26 – 315290His-rich

Natural variations

Natural variant1331G → S.
Corresponds to variant rs1203998 [ dbSNP | Ensembl ].
VAR_033304
Natural variant6521V → I. Ref.1 Ref.3
Corresponds to variant rs3814747 [ dbSNP | Ensembl ].
VAR_033305
Natural variant7301T → P.
Corresponds to variant rs34958219 [ dbSNP | Ensembl ].
VAR_033306

Experimental info

Sequence conflict881G → V in AAH32950. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q8NEC5 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: E09C4339F8AF5044

FASTA78090,091
        10         20         30         40         50         60 
MDQNSVPEKA QNEADTNNAD RFFRSHSSPP HHRPGHSRAL HHYELHHHGV PHQRGESHHP 

        70         80         90        100        110        120 
PEFQDFHDQA LSSHVHQSHH HSEARNHGRA HGPTGFGLAP SQGAVPSHRS YGEDYHDELQ 

       130        140        150        160        170        180 
RDGRRHHDGS QYGGFHQQSD SHYHRGSHHG RPQYLGENLS HYSSGVPHHG EASHHGGSYL 

       190        200        210        220        230        240 
PHGPNPYSES FHHSEASHLS GLQHDESQHH QVPHRGWPHH HQVHHHGRSR HHEAHQHGKS 

       250        260        270        280        290        300 
PHHGETISPH SSVGSYQRGI SDYHSEYHQG DHHPSEYHHG DHPHHTQHHY HQTHRHRDYH 

       310        320        330        340        350        360 
QHQDHHGAYH SSYLHGDYVQ STSQLSIPHT SRSLIHDAPG PAASRTGVFP YHVAHPRGSA 

       370        380        390        400        410        420 
HSMTRSSSTI RSRVTQMSKK VHTQDISTKH SEDWGKEEGQ FQKRKTGRLQ RTRKKGHSTN 

       430        440        450        460        470        480 
LFQWLWEKLT FLIQGFREMI RNLTQSLAFE TFIFFVVCLN TVMLVAQTFA EVEIRGEWYF 

       490        500        510        520        530        540 
MALDSIFFCI YVVEALLKII ALGLSYFFDF WNNLDFFIMA MAVLDFLLMQ THSFAIYHQS 

       550        560        570        580        590        600 
LFRILKVFKS LRALRAIRVL RRLSFLTSVQ EVTGTLGQSL PSIAAILILM FTCLFLFSAV 

       610        620        630        640        650        660 
LRALFRKSDP KRFQNIFTTI FTLFTLLTLD DWSLIYMDSR AQGAWYIIPI LVIYIIIQYF 

       670        680        690        700        710        720 
IFLNLVITVL VDSFQTALFK GLEKAKQERA ARIQEKLLED SLTELRAAEP KEVASEGTML 

       730        740        750        760        770        780 
KRLIEKKFGT MTEKQQELLF HYLQLVASVE QEQQKFRSQA AVIDEIVDTT FEAGEEDFRN 

« Hide

References

« Hide 'large scale' references
[1]"A sperm ion channel required for sperm motility and male fertility."
Ren D., Navarro B., Perez G., Jackson A.C., Hsu S., Shi Q., Tilly J.L., Clapham D.E.
Nature 413:603-609(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT ILE-652.
[2]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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], VARIANT ILE-652.
Tissue: Testis.
[4]"CatSper gene expression in postnatal development of mouse testis and in subfertile men with deficient sperm motility."
Nikpoor P., Mowla S.J., Movahedin M., Ziaee S.A.-M., Tiraihi T.
Hum. Reprod. 19:124-128(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[5]"The expression and significance of CATSPER1 in human testis and ejaculated spermatozoa."
Li H.-G., Liao A.-H., Ding X.-F., Zhou H., Xiong C.-L.
Asian J. Androl. 8:301-306(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[6]"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.
[7]"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.
[8]"Human male infertility caused by mutations in the CATSPER1 channel protein."
Avenarius M.R., Hildebrand M.S., Zhang Y., Meyer N.C., Smith L.L.H., Kahrizi K., Najmabadi H., Smith R.J.H.
Am. J. Hum. Genet. 84:505-510(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SPGF7.
[9]"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.
[10]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF407333 mRNA. Translation: AAL14105.1.
AP006287 Genomic DNA. No translation available.
BC032950 mRNA. Translation: AAH32950.1.
BC036522 mRNA. Translation: AAH36522.1.
CCDSCCDS8127.1.
RefSeqNP_444282.3. NM_053054.3.
UniGeneHs.189105.

3D structure databases

ProteinModelPortalQ8NEC5.
SMRQ8NEC5. Positions 449-699.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125556. 7 interactions.
IntActQ8NEC5. 9 interactions.
MINTMINT-1453027.
STRING9606.ENSP00000309052.

Chemistry

ChEMBLCHEMBL1628462.
GuidetoPHARMACOLOGY388.

Protein family/group databases

TCDB1.A.1.19.1. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteQ8NEC5.

Polymorphism databases

DMDM296439381.

Proteomic databases

PaxDbQ8NEC5.
PRIDEQ8NEC5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000312106; ENSP00000309052; ENSG00000175294.
GeneID117144.
KEGGhsa:117144.
UCSCuc001ogt.3. human.

Organism-specific databases

CTD117144.
GeneCardsGC11M065784.
GeneReviewsCATSPER1.
H-InvDBHIX0201680.
HGNCHGNC:17116. CATSPER1.
MIM606389. gene.
612997. phenotype.
neXtProtNX_Q8NEC5.
Orphanet276234. Non syndromic male infertility due to sperm motility disorder.
PharmGKBPA38438.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG270165.
HOGENOMHOG000112051.
HOVERGENHBG098336.
InParanoidQ8NEC5.
KOK16889.
OMAEWYFMAL.
OrthoDBEOG7FV3Q9.
PhylomeDBQ8NEC5.
TreeFamTF329330.

Enzyme and pathway databases

ReactomeREACT_163848. Reproduction.

Gene expression databases

BgeeQ8NEC5.
CleanExHS_CATSPER1.
GenevestigatorQ8NEC5.

Family and domain databases

Gene3D1.20.120.350. 1 hit.
InterProIPR028746. CatSper1.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PANTHERPTHR10037:SF32. PTHR10037:SF32. 1 hit.
PfamPF00520. Ion_trans. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCatSper1.
GenomeRNAi117144.
NextBio80091.
PROQ8NEC5.
SOURCESearch...

Entry information

Entry nameCTSR1_HUMAN
AccessionPrimary (citable) accession number: Q8NEC5
Secondary accession number(s): Q96P76
Entry history
Integrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 103 of the entry and version 3 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 11

Human chromosome 11: entries, gene names and cross-references to MIM