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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 transcript 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:G66-31009-MONOMER.
ReactomeiR-HSA-1300642. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:23220. CATSPER4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 90CytoplasmicSequence analysisAdd BLAST90
Transmembranei91 – 111Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini112 – 130ExtracellularSequence analysisAdd BLAST19
Transmembranei131 – 151Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini152 – 157CytoplasmicSequence analysis6
Transmembranei158 – 178Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini179ExtracellularSequence analysis1
Transmembranei180 – 197Helical; Name=Segment S4Sequence analysisAdd BLAST18
Topological domaini198 – 216CytoplasmicSequence analysisAdd BLAST19
Transmembranei217 – 237Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini238 – 246ExtracellularSequence analysis9
Intramembranei247 – 267Helical; Pore-formingSequence analysisAdd BLAST21
Topological domaini268 – 284ExtracellularSequence analysisAdd BLAST17
Transmembranei285 – 305Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini306 – 472CytoplasmicSequence analysisAdd BLAST167

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Flagellum, Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000188782.
PharmGKBiPA134941696.

Chemistry databases

GuidetoPHARMACOLOGYi391.

Polymorphism and mutation databases

BioMutaiCATSPER4.
DMDMi74713153.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002956811 – 472Cation channel sperm-associated protein 4Add BLAST472

Proteomic databases

PaxDbiQ7RTX7.
PRIDEiQ7RTX7.

PTM databases

iPTMnetiQ7RTX7.
PhosphoSitePlusiQ7RTX7.

Expressioni

Tissue specificityi

Testis-specific.2 Publications

Gene expression databases

BgeeiENSG00000188782.
CleanExiHS_CATSPER4.
ExpressionAtlasiQ7RTX7. baseline and differential.

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. 4 interactors.
STRINGi9606.ENSP00000390423.

Structurei

3D structure databases

ProteinModelPortaliQ7RTX7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410II5Y. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000119325.
HOGENOMiHOG000112053.
HOVERGENiHBG102124.
InParanoidiQ7RTX7.
KOiK16892.
PhylomeDBiQ7RTX7.
TreeFamiTF343841.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR028744. CatSper4.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PANTHERiPTHR10037:SF225. PTHR10037:SF225. 2 hits.
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 differs from that shown. Reason: Frameshift at position 21.Curated
The sequence CAH71538 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03331077Q → R.Corresponds to variant rs11247866dbSNPEnsembl.1
Natural variantiVAR_033311124L → F.Corresponds to variant rs12138368dbSNPEnsembl.1
Natural variantiVAR_033312293I → V.Corresponds to variant rs17257155dbSNPEnsembl.1
Natural variantiVAR_033313436D → N.Corresponds to variant rs6657616dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_026979227 – 242Missing in isoform 2. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_026980401 – 472Missing in isoform 2. 1 PublicationAdd BLAST72

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.
UCSCiuc009vsf.4. human. [Q7RTX7-1]

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi132049. 4 interactors.
STRINGi9606.ENSP00000390423.

Chemistry databases

GuidetoPHARMACOLOGYi391.

Protein family/group databases

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

PTM databases

iPTMnetiQ7RTX7.
PhosphoSitePlusiQ7RTX7.

Polymorphism and mutation databases

BioMutaiCATSPER4.
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.
UCSCiuc009vsf.4. human. [Q7RTX7-1]

Organism-specific databases

CTDi378807.
GeneCardsiCATSPER4.
HGNCiHGNC:23220. CATSPER4.
HPAiHPA045257.
MIMi609121. gene.
neXtProtiNX_Q7RTX7.
OpenTargetsiENSG00000188782.
PharmGKBiPA134941696.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410II5Y. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000119325.
HOGENOMiHOG000112053.
HOVERGENiHBG102124.
InParanoidiQ7RTX7.
KOiK16892.
PhylomeDBiQ7RTX7.
TreeFamiTF343841.

Enzyme and pathway databases

BioCyciZFISH:G66-31009-MONOMER.
ReactomeiR-HSA-1300642. Sperm Motility And Taxes.

Miscellaneous databases

GeneWikiiCatSper4.
GenomeRNAii378807.
PROiQ7RTX7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188782.
CleanExiHS_CATSPER4.
ExpressionAtlasiQ7RTX7. baseline and differential.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR028744. CatSper4.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PANTHERiPTHR10037:SF225. PTHR10037:SF225. 2 hits.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 113 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

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.