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Protein

Cation channel sperm-associated protein 4

Gene

CATSPER4

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. 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.2 Publications

GO - Molecular functioni

  1. calcium activated cation channel activity Source: InterPro
  2. voltage-gated calcium channel activity Source: GO_Central

GO - Biological processi

  1. calcium ion import Source: GO_Central
  2. membrane depolarization during action potential Source: GO_Central
  3. multicellular organismal development Source: UniProtKB-KW
  4. multicellular organism reproduction Source: Reactome
  5. single fertilization Source: Reactome
  6. sodium ion transport Source: Ensembl
  7. sperm capacitation Source: Ensembl
  8. sperm-egg recognition Source: Reactome
  9. sperm motility Source: GO_Central
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

ReactomeiREACT_163875. Sperm Motility And Taxes.

Protein family/group databases

TCDBi1.A.1.19.1. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Cation channel sperm-associated protein 4
Short name:
CatSper4
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:23220. CATSPER4.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 9090CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei91 – 11121Helical; Name=Segment S1Sequence AnalysisAdd
BLAST
Topological domaini112 – 13019ExtracellularSequence AnalysisAdd
BLAST
Transmembranei131 – 15121Helical; Name=Segment S2Sequence AnalysisAdd
BLAST
Topological domaini152 – 1576CytoplasmicSequence Analysis
Transmembranei158 – 17821Helical; Name=Segment S3Sequence AnalysisAdd
BLAST
Topological domaini179 – 1791ExtracellularSequence Analysis
Transmembranei180 – 19718Helical; Name=Segment S4Sequence AnalysisAdd
BLAST
Topological domaini198 – 21619CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei217 – 23721Helical; Name=Segment S5Sequence AnalysisAdd
BLAST
Topological domaini238 – 2469ExtracellularSequence Analysis
Intramembranei247 – 26721Helical; Pore-formingSequence AnalysisAdd
BLAST
Topological domaini268 – 28417ExtracellularSequence AnalysisAdd
BLAST
Transmembranei285 – 30521Helical; Name=Segment S6Sequence AnalysisAdd
BLAST
Topological domaini306 – 472167CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. acrosomal vesicle Source: Ensembl
  2. CatSper complex Source: UniProtKB
  3. plasma membrane Source: GO_Central
  4. sperm principal piece Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Flagellum, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134941696.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 472472Cation channel sperm-associated protein 4PRO_0000295681Add
BLAST

Proteomic databases

PaxDbiQ7RTX7.
PRIDEiQ7RTX7.

PTM databases

PhosphoSiteiQ7RTX7.

Expressioni

Tissue specificityi

Testis-specific.2 Publications

Gene expression databases

BgeeiQ7RTX7.
CleanExiHS_CATSPER4.
ExpressionAtlasiQ7RTX7. baseline.
GenevestigatoriQ7RTX7.

Organism-specific databases

HPAiHPA045257.

Interactioni

Subunit structurei

Heterotetramer; possibly composed of CATSPER1, CATSPER2, CATSPER3 and CATSPER4 (Potential). Component of the CatSper complex. Interacts with CATSPER1 (By similarity).By similarityCurated

Protein-protein interaction databases

BioGridi132049. 3 interactions.
STRINGi9606.ENSP00000341006.

Structurei

3D structure databases

ProteinModelPortaliQ7RTX7.
SMRiQ7RTX7. Positions 82-305.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1226.
GeneTreeiENSGT00760000119325.
HOGENOMiHOG000112053.
HOVERGENiHBG102124.
InParanoidiQ7RTX7.
KOiK16892.
PhylomeDBiQ7RTX7.
TreeFamiTF343841.

Family and domain databases

InterProiIPR028744. CatSper4.
IPR005821. Ion_trans_dom.
[Graphical view]
PANTHERiPTHR10037:SF199. PTHR10037:SF199. 1 hit.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7RTX7-1) [UniParc]FASTAAdd to basket

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
MRDNEKAWWQ QWTSHTGLEG WGGTQEDRMG FGGAVAALRG RPSPLQSTIH
60 70 80 90 100
ESYGRPEEQV LINRQEITNK ADAWDMQEFI THMYIKQLLR HPAFQLLLAL
110 120 130 140 150
LLVINAITIA LRTNSYLDQK HYELFSTIDD IVLTILLCEV LLGWLNGFWI
160 170 180 190 200
FWKDGWNILN FIIVFILLLR FFINEINIPS INYTLRALRL VHVCMAVEPL
210 220 230 240 250
ARIIRVILQS VPDMANIMVL ILFFMLVFSV FGVTLFGAFV PKHFQNIQVA
260 270 280 290 300
LYTLFICITQ DGWVDIYSDF QTEKREYAME IGGAIYFTIF ITIGAFIGIN
310 320 330 340 350
LFVIVVTTNL EQMMKAGEQG QQQRITFSET GAEEEEENDQ LPLVHCVVAR
360 370 380 390 400
SEKSGLLQEP LAGGPLSNLS ENTCDNFCLV LEAIQENLRQ YKEIRDELNM
410 420 430 440 450
IVEEVRAIRF NQEQESEVLN RRSSTSGSLE TTSSKDIRQM SQQQDLLSAL
460 470
VSMEKVHDSS SQILLKKHKS SH
Length:472
Mass (Da):54,092
Last modified:December 15, 2003 - v1
Checksum:i5AC94CD0971A25FE
GO
Isoform 2 (identifier: Q7RTX7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     227-242: Missing.
     401-472: Missing.

Note: No experimental confirmation available.

Show »
Length:384
Mass (Da):44,229
Checksum:i00D375891B88F6F3
GO

Sequence cautioni

The sequence AAI28139.1 differs from that shown. Reason: Frameshift at position 21. Curated
The sequence CAH71538.1 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti77 – 771Q → R.
Corresponds to variant rs11247866 [ dbSNP | Ensembl ].
VAR_033310
Natural varianti124 – 1241L → F.
Corresponds to variant rs12138368 [ dbSNP | Ensembl ].
VAR_033311
Natural varianti293 – 2931I → V.
Corresponds to variant rs17257155 [ dbSNP | Ensembl ].
VAR_033312
Natural varianti436 – 4361D → N.
Corresponds to variant rs6657616 [ dbSNP | Ensembl ].
VAR_033313

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei227 – 24216Missing in isoform 2. 1 PublicationVSP_026979Add
BLAST
Alternative sequencei401 – 47272Missing in isoform 2. 1 PublicationVSP_026980Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL355877 Genomic DNA. Translation: CAH71538.1. Different initiation.
BC128138 mRNA. Translation: AAI28139.1. Frameshift.
BC128139 mRNA. Translation: AAI28140.1.
BN000273 mRNA. Translation: CAE30475.1.
CCDSiCCDS30645.1. [Q7RTX7-1]
RefSeqiNP_937770.1. NM_198137.1. [Q7RTX7-1]
UniGeneiHs.123532.

Genome annotation databases

EnsembliENST00000456354; ENSP00000390423; ENSG00000188782. [Q7RTX7-1]
ENST00000518899; ENSP00000429464; ENSG00000188782. [Q7RTX7-2]
GeneIDi378807.
KEGGihsa:378807.
UCSCiuc010oez.2. human. [Q7RTX7-1]

Polymorphism databases

DMDMi74713153.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL355877 Genomic DNA. Translation: CAH71538.1. Different initiation.
BC128138 mRNA. Translation: AAI28139.1. Frameshift.
BC128139 mRNA. Translation: AAI28140.1.
BN000273 mRNA. Translation: CAE30475.1.
CCDSiCCDS30645.1. [Q7RTX7-1]
RefSeqiNP_937770.1. NM_198137.1. [Q7RTX7-1]
UniGeneiHs.123532.

3D structure databases

ProteinModelPortaliQ7RTX7.
SMRiQ7RTX7. Positions 82-305.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi132049. 3 interactions.
STRINGi9606.ENSP00000341006.

Chemistry

GuidetoPHARMACOLOGYi391.

Protein family/group databases

TCDBi1.A.1.19.1. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteiQ7RTX7.

Polymorphism databases

DMDMi74713153.

Proteomic databases

PaxDbiQ7RTX7.
PRIDEiQ7RTX7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000456354; ENSP00000390423; ENSG00000188782. [Q7RTX7-1]
ENST00000518899; ENSP00000429464; ENSG00000188782. [Q7RTX7-2]
GeneIDi378807.
KEGGihsa:378807.
UCSCiuc010oez.2. human. [Q7RTX7-1]

Organism-specific databases

CTDi378807.
GeneCardsiGC01P026517.
HGNCiHGNC:23220. CATSPER4.
HPAiHPA045257.
MIMi609121. gene.
neXtProtiNX_Q7RTX7.
PharmGKBiPA134941696.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1226.
GeneTreeiENSGT00760000119325.
HOGENOMiHOG000112053.
HOVERGENiHBG102124.
InParanoidiQ7RTX7.
KOiK16892.
PhylomeDBiQ7RTX7.
TreeFamiTF343841.

Enzyme and pathway databases

ReactomeiREACT_163875. Sperm Motility And Taxes.

Miscellaneous databases

GeneWikiiCatSper4.
GenomeRNAii378807.
NextBioi100804.
PROiQ7RTX7.
SOURCEiSearch...

Gene expression databases

BgeeiQ7RTX7.
CleanExiHS_CATSPER4.
ExpressionAtlasiQ7RTX7. baseline.
GenevestigatoriQ7RTX7.

Family and domain databases

InterProiIPR028744. CatSper4.
IPR005821. Ion_trans_dom.
[Graphical view]
PANTHERiPTHR10037:SF199. PTHR10037:SF199. 1 hit.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
  3. "Identification of human and mouse CatSper3 and CatSper4 genes: characterisation of a common interaction domain and evidence for expression in testis."
    Lobley A., Pierron V., Reynolds L., Allen L., Michalovich D.
    Reprod. Biol. Endocrinol. 1:53-53(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION, TISSUE SPECIFICITY.
  4. "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(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. "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(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ACTIVATION BY PROGESTERONE.
  6. "Progesterone activates the principal Ca2+ channel of human sperm."
    Lishko P.V., Botchkina I.L., Kirichok Y.
    Nature 471:387-391(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ACTIVATION BY PROGESTERONE.

Entry informationi

Entry nameiCTSR4_HUMAN
AccessioniPrimary (citable) accession number: Q7RTX7
Secondary accession number(s): A1A4W6, Q5VY71
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: December 15, 2003
Last modified: March 4, 2015
This is version 96 of the entry and version 1 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 1
    Human chromosome 1: 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

External Data

Dasty 3

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 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.