ID CTSR3_MOUSE Reviewed; 395 AA.
AC Q80W99; Q5FWA9; Q9D5T9;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 2.
DT 24-JAN-2024, entry version 135.
DE RecName: Full=Cation channel sperm-associated protein 3;
DE Short=CatSper3;
GN Name=Catsper3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, INTERACTION WITH CATSPER1, AND DISRUPTION PHENOTYPE.
RC STRAIN=BALB/cJ; TISSUE=Testis;
RX PubMed=17227845; DOI=10.1073/pnas.0610286104;
RA Qi H., Moran M.M., Navarro B., Chong J.A., Krapivinsky G., Krapivinsky L.,
RA Kirichok Y., Ramsey I.S., Quill T.A., Clapham D.E.;
RT "All four CatSper ion channel proteins are required for male fertility and
RT sperm cell hyperactivated motility.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1219-1223(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16107607; DOI=10.1095/biolreprod.105.045468;
RA Jin J.-L., O'Doherty A.M., Wang S., Zheng H., Sanders K.M., Yan W.;
RT "Catsper3 and catsper4 encode two cation channel-like proteins exclusively
RT expressed in the testis.";
RL Biol. Reprod. 73:1235-1242(2005).
RN [5]
RP DEVELOPMENTAL STAGE.
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 [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17344468; DOI=10.1095/biolreprod.107.060186;
RA Jin J.-L., Jin N., Zheng H., Ro S., Tafolla D., Sanders K.M., Yan W.;
RT "Catsper3 and catsper4 are essential for sperm hyperactivated motility and
RT male fertility in the mouse.";
RL Biol. Reprod. 77:37-44(2007).
RN [7]
RP LACK OF ACTIVATION BY PROGESTERONE AND PGE1.
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 [8]
RP IDENTIFICATION IN THE CATSPER COMPLEX.
RC STRAIN=C57BL/6J;
RX PubMed=21224844; DOI=10.1038/ncomms1153;
RA Chung J.J., Navarro B., Krapivinsky G., Krapivinsky L., Clapham D.E.;
RT "A novel gene required for male fertility and functional CATSPER channel
RT formation in spermatozoa.";
RL Nat. Commun. 2:153-153(2011).
RN [9]
RP IDENTIFICATION IN THE CATSPER COMPLEX.
RX PubMed=34998468; DOI=10.1016/j.celrep.2021.110226;
RA Hwang J.Y., Wang H., Lu Y., Ikawa M., Chung J.J.;
RT "C2cd6-encoded CatSpertau targets sperm calcium channel to Ca2+ signaling
RT domains in the flagellar membrane.";
RL Cell Rep. 38:110226-110226(2022).
RN [10]
RP STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) OF THE CATSPER COMPLEX,
RP IDENTIFICATION BY MASS SPECTROMETRY, TRANSMEMBRANE DOMAINS, AND TOPOLOGY.
RX PubMed=34225353; DOI=10.1038/s41586-021-03742-6;
RA Lin S., Ke M., Zhang Y., Yan Z., Wu J.;
RT "Structure of a mammalian sperm cation channel complex.";
RL Nature 595:746-750(2021).
CC -!- FUNCTION: Voltage-gated calcium channel that plays a central role in
CC sperm cell hyperactivation. Controls calcium entry to mediate the
CC hyperactivated motility, a step needed for sperm motility which is
CC essential late in the preparation of sperm for fertilization. Activated
CC by intracellular alkalinization. {ECO:0000269|PubMed:17227845,
CC ECO:0000269|PubMed:17344468}.
CC -!- ACTIVITY REGULATION: In contrast to the human ortholog, not activated
CC by progesterone. {ECO:0000269|PubMed:21412339}.
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, CATSPERG2, CATSPERD, CATSPERE,
CC CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9
CC (PubMed:34225353, PubMed:17227845, PubMed:21224844, PubMed:34998468).
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 (PubMed:34225353). The auxiliary CATSPERB,
CC CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like
CC structure over the pore which stabilizes the complex through
CC interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2
CC respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and
CC TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the
CC complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with
CC CATSPERD and is required for targeting the CatSper complex in the
CC flagellar membrane (PubMed:34998468). {ECO:0000250|UniProtKB:Q91ZR5,
CC ECO:0000269|PubMed:17227845, ECO:0000269|PubMed:21224844,
CC ECO:0000269|PubMed:34225353, ECO:0000269|PubMed:34998468}.
CC -!- INTERACTION:
CC Q80W99; Q91ZR5: Catsper1; NbExp=2; IntAct=EBI-15619135, EBI-15619083;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane
CC {ECO:0000269|PubMed:16107607, ECO:0000269|PubMed:17227845}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:34225353}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q80W99-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80W99-2; Sequence=VSP_026978;
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:16107607,
CC ECO:0000269|PubMed:17227845}.
CC -!- DEVELOPMENTAL STAGE: Detected in hte testis during postnatal
CC development at day 15. Restricted to the late-stage germline cells that
CC line the seminiferous tubules. {ECO:0000269|PubMed:17347248}.
CC -!- DISRUPTION PHENOTYPE: Mice are normal but males are sterile. Male
CC sterility is due to defects in sperm motility unability to fertilize
CC intact eggs. {ECO:0000269|PubMed:17227845,
CC ECO:0000269|PubMed:17344468}.
CC -!- SIMILARITY: Belongs to the cation channel sperm-associated (TC
CC 1.A.1.19) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH89518.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.; Evidence={ECO:0000305};
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DR EMBL; AY263400; AAP21831.1; -; mRNA.
DR EMBL; AK014942; BAB29631.1; -; mRNA.
DR EMBL; BC089518; AAH89518.1; ALT_SEQ; mRNA.
DR CCDS; CCDS26555.1; -. [Q80W99-2]
DR CCDS; CCDS56885.1; -. [Q80W99-1]
DR RefSeq; NP_001239416.1; NM_001252487.1. [Q80W99-1]
DR RefSeq; NP_084048.1; NM_029772.4. [Q80W99-2]
DR RefSeq; XP_006517518.1; XM_006517455.2. [Q80W99-1]
DR PDB; 7EEB; EM; 2.90 A; C=1-395.
DR PDBsum; 7EEB; -.
DR AlphaFoldDB; Q80W99; -.
DR EMDB; EMD-31076; -.
DR SMR; Q80W99; -.
DR BioGRID; 218352; 2.
DR CORUM; Q80W99; -.
DR DIP; DIP-60802N; -.
DR IntAct; Q80W99; 1.
DR STRING; 10090.ENSMUSP00000021961; -.
DR GuidetoPHARMACOLOGY; 390; -.
DR TCDB; 1.A.1.19.3; the voltage-gated ion channel (vic) superfamily.
DR PhosphoSitePlus; Q80W99; -.
DR jPOST; Q80W99; -.
DR PaxDb; 10090-ENSMUSP00000021961; -.
DR ProteomicsDB; 285427; -. [Q80W99-1]
DR ProteomicsDB; 285428; -. [Q80W99-2]
DR Antibodypedia; 26383; 75 antibodies from 16 providers.
DR DNASU; 76856; -.
DR Ensembl; ENSMUST00000021961.12; ENSMUSP00000021961.6; ENSMUSG00000021499.13. [Q80W99-1]
DR Ensembl; ENSMUST00000109898.3; ENSMUSP00000105524.3; ENSMUSG00000021499.13. [Q80W99-2]
DR GeneID; 76856; -.
DR KEGG; mmu:76856; -.
DR UCSC; uc007qsb.2; mouse. [Q80W99-2]
DR UCSC; uc007qsc.2; mouse. [Q80W99-1]
DR AGR; MGI:1924106; -.
DR CTD; 347732; -.
DR MGI; MGI:1924106; Catsper3.
DR VEuPathDB; HostDB:ENSMUSG00000021499; -.
DR eggNOG; KOG2302; Eukaryota.
DR GeneTree; ENSGT00940000161455; -.
DR HOGENOM; CLU_058058_0_0_1; -.
DR InParanoid; Q80W99; -.
DR OMA; YTLFQVM; -.
DR OrthoDB; 2911220at2759; -.
DR PhylomeDB; Q80W99; -.
DR TreeFam; TF343841; -.
DR Reactome; R-MMU-1300642; Sperm Motility And Taxes.
DR BioGRID-ORCS; 76856; 1 hit in 78 CRISPR screens.
DR ChiTaRS; Catsper3; mouse.
DR PRO; PR:Q80W99; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q80W99; Protein.
DR Bgee; ENSMUSG00000021499; Expressed in spermatid and 14 other cell types or tissues.
DR ExpressionAtlas; Q80W99; baseline and differential.
DR Genevisible; Q80W99; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:MGI.
DR GO; GO:0036128; C:CatSper complex; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:MGI.
DR GO; GO:0006814; P:sodium ion transport; IMP:MGI.
DR GO; GO:0048240; P:sperm capacitation; IMP:MGI.
DR Gene3D; 1.10.287.70; -; 1.
DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 1.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR47131; CATION CHANNEL SPERM-ASSOCIATED PROTEIN 3; 1.
DR PANTHER; PTHR47131:SF1; CATION CHANNEL SPERM-ASSOCIATED PROTEIN 3; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Cell membrane; Cell projection; Cilium;
KW Developmental protein; Differentiation; Flagellum; Ion channel;
KW Ion transport; Membrane; Reference proteome; Spermatogenesis;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..395
FT /note="Cation channel sperm-associated protein 3"
FT /id="PRO_0000295680"
FT TOPO_DOM 1..48
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 49..71
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 72..80
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 81..107
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 109..131
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 132..143
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 144..160
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 161..168
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 169..195
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 196..216
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT INTRAMEM 217..236
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 237..242
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 243..268
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 269..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT VAR_SEQ 84..96
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_026978"
FT CONFLICT 314
FT /note="S -> T (in Ref. 1; AAP21831)"
FT /evidence="ECO:0000305"
FT HELIX 39..47
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 50..69
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 73..77
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 80..103
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 113..133
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 142..147
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 148..158
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 161..171
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 174..199
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 207..209
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 213..224
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 229..237
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 244..255
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 256..259
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 260..314
FT /evidence="ECO:0007829|PDB:7EEB"
SQ SEQUENCE 395 AA; 45486 MW; 10641E91039210A6 CRC64;
MSQHFHHNPV RVKSGSLFAT ASEALQARLS KIKRKDKECQ AYFRKVIKST FFQIVMITTV
TTNSFLLVLG TNYDIQFEFF RTFEVSELFF VSVYVCEFLM KVYVDPITYW KDGYNILDVI
ILIILTIPYL LRKIKGNHSA YLHFADGIQS LRILKLISYS RGIRTLIIAV GETVYTVASV
LTLLFLLMFV FAILGFCLFG VTDRGDLENW GNLASAFFTL FSLATVDGWT DLQEELDKRK
FTVSRAFTIL FILLASFIFL NMFVGVMIMH TEDSMKKFER DLTLERNLAI MEEKQIILKR
QQEEVNRLMN TQKSGSMNFI DMVEGFKKTL RHTDPMVLDD FSTSLSFIDI YLVTLDNQDV
IVSKLQELYC EIVNVLSLML EDMPKESSSS LSGLS
//
