CTSR3_HUMAN
ID CTSR3_HUMAN Reviewed; 398 AA.
AC Q86XQ3; Q86XS6;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Cation channel sperm-associated protein 3;
DE Short=CatSper3;
DE AltName: Full=Ca(v)-like protein;
DE AltName: Full=One-repeat calcium channel-like protein;
GN Name=CATSPER3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=12646162; DOI=10.1016/s0006-291x(03)00276-6;
RA Arias J.M., Murbartian J., Perez-Reyes E.;
RT "Cloning of a novel one-repeat calcium channel-like gene.";
RL Biochem. Biophys. Res. Commun. 303:31-36(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Cerebellum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION, AND TISSUE SPECIFICITY.
RX PubMed=12932298; DOI=10.1186/1477-7827-1-53;
RA Lobley A., Pierron V., Reynolds L., Allen L., Michalovich D.;
RT "Identification of human and mouse CatSper3 and CatSper4 genes:
RT characterisation of a common interaction domain and evidence for expression
RT in testis.";
RL Reprod. Biol. Endocrinol. 1:53-53(2003).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=17347248; DOI=10.1093/molehr/gam009;
RA Li H.-G., Ding X.-F., Liao A.-H., Kong X.-B., Xiong C.-L.;
RT "Expression of CatSper family transcripts in the mouse testis during post-
RT natal development and human ejaculated spermatozoa: relationship to sperm
RT motility.";
RL Mol. Hum. Reprod. 13:299-306(2007).
RN [5]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=21412338; DOI=10.1038/nature09769;
RA Strunker T., Goodwin N., Brenker C., Kashikar N.D., Weyand I., Seifert R.,
RA Kaupp U.B.;
RT "The CatSper channel mediates progesterone-induced Ca2+ influx in human
RT sperm.";
RL Nature 471:382-386(2011).
RN [6]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=21412339; DOI=10.1038/nature09767;
RA Lishko P.V., Botchkina I.L., Kirichok Y.;
RT "Progesterone activates the principal Ca2+ channel of human sperm.";
RL Nature 471:387-391(2011).
RN [7]
RP ACTIVITY REGULATION.
RX PubMed=26989199; DOI=10.1126/science.aad6887;
RA Miller M.R., Mannowetz N., Iavarone A.T., Safavi R., Gracheva E.O.,
RA Smith J.F., Hill R.Z., Bautista D.M., Kirichok Y., Lishko P.V.;
RT "Unconventional endocannabinoid signaling governs sperm activation via sex
RT hormone progesterone.";
RL Science 352:555-559(2016).
CC -!- FUNCTION: Voltage-gated calcium channel that plays a central role in
CC calcium-dependent physiological responses essential for successful
CC fertilization, such as sperm hyperactivation, acrosome reaction and
CC chemotaxis towards the oocyte. {ECO:0000269|PubMed:21412338,
CC ECO:0000269|PubMed:21412339}.
CC -!- ACTIVITY REGULATION: The CatSper calcium channel is indirectly
CC activated by extracellular progesterone and prostaglandins following
CC the sequence: progesterone > PGF1-alpha = PGE1 > PGA1 > PGE2 >> PGD2
CC (PubMed:21412338, PubMed:21412339, PubMed:26989199). The CatSper
CC calcium channel is directly inhibited by endocannabinoid 2-
CC arachidonoylglycerol (2AG) (PubMed:26989199). Indirect activation by
CC progesterone takes place via the following mechanism: progesterone
CC binds and activates the acylglycerol lipase ABHD2, which in turn
CC mediates hydrolysis of 2AG inhibitor, relieving inhibition of the
CC CatSper channel (PubMed:26989199). The primary effect of progesterone
CC activation is to shift voltage dependence towards more physiological,
CC negative membrane potentials; it is not mediated by metabotropic
CC receptors and second messengers (PubMed:21412338, PubMed:21412339).
CC Sperm capacitation enhances the effect of progesterone by providing
CC additional negative shift. Also activated by the elevation of
CC intracellular pH (PubMed:21412338, PubMed:21412339).
CC {ECO:0000269|PubMed:21412338, ECO:0000269|PubMed:21412339,
CC ECO:0000269|PubMed:26989199}.
CC -!- SUBUNIT: Component of the CatSper complex or CatSpermasome composed of
CC the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4
CC as well as auxiliary members CATSPERB, CATSPERG, CATSPERD, CATSPERE,
CC CATSPERZ, C2CD6/CATSPERT, TMEM249, TMEM262 and EFCAB9 (By similarity).
CC HSPA1 may be an additional auxiliary complex member (By similarity).
CC The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form
CC a heterotetrameric channel. The auxiliary CATSPERB, CATSPERG, CATSPERD
CC and CATSPERE subunits form a pavilion-like structure over the pore
CC which stabilizes the complex through interactions with CATSPER4,
CC CATSPER3, CATSPER1 and CATSPER2 respectively (By similarity).
CC TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the
CC complex. C2CD6/CATSPERT interacts at least with CATSPERD and is
CC required for targeting the CatSper complex in the flagellar membrane
CC (By similarity). {ECO:0000250|UniProtKB:Q80W99,
CC ECO:0000250|UniProtKB:Q91ZR5}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane
CC {ECO:0000250|UniProtKB:Q80W99}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q80W99}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:12646162,
CC ECO:0000269|PubMed:12932298, ECO:0000269|PubMed:17347248}.
CC -!- SIMILARITY: Belongs to the cation channel sperm-associated (TC
CC 1.A.1.19) family. {ECO:0000305}.
CC -!- CAUTION: In mouse, Slco6c1 is an additional auxiliary subunit of the
CC CatSper complex. It is unclear if the related SLCO6A1 protein performs
CC the same role in non-rodent species. {ECO:0000305}.
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DR EMBL; AF432876; AAO85416.1; -; mRNA.
DR EMBL; AY156951; AAO13012.1; -; mRNA.
DR EMBL; BC101692; AAI01693.1; -; mRNA.
DR EMBL; BC110384; AAI10385.1; -; mRNA.
DR EMBL; BN000272; CAE30476.1; -; mRNA.
DR CCDS; CCDS4181.1; -.
DR RefSeq; NP_821138.1; NM_178019.2.
DR AlphaFoldDB; Q86XQ3; -.
DR SMR; Q86XQ3; -.
DR STRING; 9606.ENSP00000282611; -.
DR DrugCentral; Q86XQ3; -.
DR GuidetoPHARMACOLOGY; 390; -.
DR TCDB; 1.A.1.19.1; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q86XQ3; -.
DR PhosphoSitePlus; Q86XQ3; -.
DR BioMuta; CATSPER3; -.
DR DMDM; 74714131; -.
DR MassIVE; Q86XQ3; -.
DR PaxDb; Q86XQ3; -.
DR PeptideAtlas; Q86XQ3; -.
DR PRIDE; Q86XQ3; -.
DR ProteomicsDB; 70315; -.
DR Antibodypedia; 26383; 66 antibodies from 16 providers.
DR DNASU; 347732; -.
DR Ensembl; ENST00000282611.8; ENSP00000282611.6; ENSG00000152705.8.
DR GeneID; 347732; -.
DR KEGG; hsa:347732; -.
DR MANE-Select; ENST00000282611.8; ENSP00000282611.6; NM_178019.3; NP_821138.1.
DR UCSC; uc003lag.3; human.
DR CTD; 347732; -.
DR DisGeNET; 347732; -.
DR GeneCards; CATSPER3; -.
DR HGNC; HGNC:20819; CATSPER3.
DR HPA; ENSG00000152705; Tissue enriched (testis).
DR MIM; 609120; gene.
DR neXtProt; NX_Q86XQ3; -.
DR OpenTargets; ENSG00000152705; -.
DR PharmGKB; PA134911185; -.
DR VEuPathDB; HostDB:ENSG00000152705; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000161455; -.
DR HOGENOM; CLU_058058_0_0_1; -.
DR InParanoid; Q86XQ3; -.
DR OMA; YTLFQVM; -.
DR OrthoDB; 1269955at2759; -.
DR PhylomeDB; Q86XQ3; -.
DR TreeFam; TF343841; -.
DR PathwayCommons; Q86XQ3; -.
DR Reactome; R-HSA-1300642; Sperm Motility And Taxes.
DR BioGRID-ORCS; 347732; 11 hits in 1065 CRISPR screens.
DR GeneWiki; CatSper3; -.
DR GenomeRNAi; 347732; -.
DR Pharos; Q86XQ3; Tchem.
DR PRO; PR:Q86XQ3; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q86XQ3; protein.
DR Bgee; ENSG00000152705; Expressed in sperm and 99 other tissues.
DR Genevisible; Q86XQ3; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IBA:GO_Central.
DR GO; GO:0036128; C:CatSper complex; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0030317; P:flagellated sperm motility; IBA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0006814; P:sodium ion transport; IBA:GO_Central.
DR GO; GO:0048240; P:sperm capacitation; IBA:GO_Central.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR Pfam; PF00520; Ion_trans; 1.
PE 2: Evidence at transcript level;
KW Calcium; Calcium channel; Calcium transport; Cell membrane;
KW Cell projection; Cilium; Developmental protein; Differentiation; Flagellum;
KW Ion channel; Ion transport; Membrane; Reference proteome; Spermatogenesis;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..398
FT /note="Cation channel sperm-associated protein 3"
FT /id="PRO_0000295679"
FT TOPO_DOM 1..48
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TRANSMEM 49..71
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TOPO_DOM 72..80
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TRANSMEM 81..107
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TOPO_DOM 108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TRANSMEM 109..131
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TOPO_DOM 132..143
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TRANSMEM 144..160
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TOPO_DOM 161..168
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TRANSMEM 169..195
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TOPO_DOM 196..216
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT INTRAMEM 217..236
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TOPO_DOM 237..242
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TRANSMEM 243..268
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT TOPO_DOM 269..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q80W99"
FT VARIANT 204
FT /note="N -> K (in dbSNP:rs3896260)"
FT /id="VAR_033309"
SQ SEQUENCE 398 AA; 46422 MW; FB460F66F367DB69 CRC64;
MSQHRHQRHS RVISSSPVDT TSVGFCPTFK KFKRNDDECR AFVKRVIMSR FFKIIMISTV
TSNAFFMALW TSYDIRYRLF RLLEFSEIFF VSICTSELSM KVYVDPINYW KNGYNLLDVI
IIIVMFLPYA LRQLMGKQFT YLYIADGMQS LRILKLIGYS QGIRTLITAV GQTVYTVASV
LLLLFLLMYI FAILGFCLFG SPDNGDHDNW GNLAAAFFTL FSLATVDGWT DLQKQLDNRE
FALSRAFTII FILLASFIFL NMFVGVMIMH TEDSIRKFER ELMLEQQEML MGEKQVILQR
QQEEISRLMH IQKNADCTSF SELVENFKKT LSHTDPMVLD DFGTSLPFID IYFSTLDYQD
TTVHKLQELY YEIVHVLSLM LEDLPQEKPQ SLEKVDEK
