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   29-SEP-2021, entry version 133.
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: Heterotetramer; possibly composed of CATSPER1, CATSPER2,
CC       CATSPER3 and CATSPER4 (Potential). Component of the CatSper complex.
CC       Interacts with CATSPER1 (By similarity). {ECO:0000250, ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane;
CC       Multi-pass membrane protein. Note=Specifically located in the principal
CC       piece of sperm tail.
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}.
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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   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; 65 antibodies.
DR   DNASU; 347732; -.
DR   Ensembl; ENST00000282611; ENSP00000282611; ENSG00000152705.
DR   GeneID; 347732; -.
DR   KEGG; hsa:347732; -.
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; VMTLESW; -.
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; 4 hits in 1004 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 right testis and 121 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: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..50
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        51..71
FT                   /note="Helical; Name=Segment S1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        72..78
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        79..100
FT                   /note="Helical; Name=Segment S2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        101..115
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        116..136
FT                   /note="Helical; Name=Segment S3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        137..141
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        142..161
FT                   /note="Helical; Name=Segment S4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        162..179
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        180..200
FT                   /note="Helical; Name=Segment S5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        201..209
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        210..230
FT                   /note="Helical; Pore-forming"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        231..248
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        249..269
FT                   /note="Helical; Name=Segment S6"
FT                   /evidence="ECO:0000255"
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
//