CTSR1_MOUSE
ID CTSR1_MOUSE Reviewed; 686 AA.
AC Q91ZR5; Q4PZC3; Q4PZC4; Q4PZC5; Q4PZC6; Q4PZD2;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Cation channel sperm-associated protein 1;
DE Short=CatSper1;
GN Name=Catsper1;
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], FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY,
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=11595941; DOI=10.1038/35098027;
RA Ren D., Navarro B., Perez G., Jackson A.C., Hsu S., Shi Q., Tilly J.L.,
RA Clapham D.E.;
RT "A sperm ion channel required for sperm motility and male fertility.";
RL Nature 413:603-609(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 19-307, AND VARIANTS HIS-PRO-25 INS;
RP ARG-52; GLN-160 DEL; ILE-270 AND SER-276.
RC STRAIN=2, 35, 41, 47, 49, 51, 58, 61, 63, and 72;
RX PubMed=15930155; DOI=10.1093/molbev/msi178;
RA Podlaha O., Webb D.M., Tucker P.K., Zhang J.;
RT "Positive selection for indel substitutions in the rodent sperm protein
RT catsper1.";
RL Mol. Biol. Evol. 22:1845-1852(2005).
RN [3]
RP FUNCTION.
RX PubMed=14657352; DOI=10.1073/pnas.2536658100;
RA Carlson A.E., Westenbroek R.E., Quill T., Ren D., Clapham D.E., Hille B.,
RA Garbers D.L., Babcock D.F.;
RT "CatSper1 required for evoked Ca2+ entry and control of flagellar function
RT in sperm.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:14864-14868(2003).
RN [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=14688170; DOI=10.1093/humrep/deh043;
RA Nikpoor P., Mowla S.J., Movahedin M., Ziaee S.A.-M., Tiraihi T.;
RT "CatSper gene expression in postnatal development of mouse testis and in
RT subfertile men with deficient sperm motility.";
RL Hum. Reprod. 19:124-128(2004).
RN [5]
RP FUNCTION.
RX PubMed=16036917; DOI=10.1074/jbc.m501430200;
RA Carlson A.E., Quill T.A., Westenbroek R.E., Schuh S.M., Hille B.,
RA Babcock D.F.;
RT "Identical phenotypes of CatSper1 and CatSper2 null sperm.";
RL J. Biol. Chem. 280:32238-32244(2005).
RN [6]
RP FUNCTION.
RX PubMed=16467839; DOI=10.1038/nature04417;
RA Kirichok Y., Navarro B., Clapham D.E.;
RT "Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-
RT activated Ca2+ channel.";
RL Nature 439:737-740(2006).
RN [7]
RP FUNCTION.
RX PubMed=17174296; DOI=10.1016/j.ydbio.2006.11.007;
RA Marquez B., Ignotz G., Suarez S.S.;
RT "Contributions of extracellular and intracellular Ca2+ to regulation of
RT sperm motility: release of intracellular stores can hyperactivate CatSper1
RT and CatSper2 null sperm.";
RL Dev. Biol. 303:214-221(2007).
RN [8]
RP IDENTIFICATION IN A COMPLEX WITH CATSPERB AND HSPA1B.
RX PubMed=17478420; DOI=10.1074/jbc.m701083200;
RA Liu J., Xia J., Cho K.-H., Clapham D.E., Ren D.;
RT "CatSperbeta, a novel transmembrane protein in the CatSper channel
RT complex.";
RL J. Biol. Chem. 282:18945-18952(2007).
RN [9]
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 [10]
RP INTERACTION WITH CATSPER3 AND CATSPER4.
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 [11]
RP IDENTIFICATION IN A COMPLEX WITH CATSPERB; CATSPERG2 AND HSPA1B.
RX PubMed=19516020; DOI=10.1095/biolreprod.109.077107;
RA Wang H., Liu J., Cho K.-H., Ren D.;
RT "A novel, single, transmembrane protein CATSPERG is associated with
RT CATSPER1 channel protein.";
RL Biol. Reprod. 81:539-544(2009).
RN [12]
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 [13]
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 [14]
RP IDENTIFICATION IN THE CATSPER COMPLEX, AND SUBCELLULAR LOCATION.
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 [15]
RP STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) OF THE CATSPER COMPLEX,
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, TRANSMEMBRANE
RP 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:11595941,
CC ECO:0000269|PubMed:14657352, ECO:0000269|PubMed:16036917,
CC ECO:0000269|PubMed:16467839, ECO:0000269|PubMed:17174296}.
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:21224844, PubMed:17478420, PubMed:19516020,
CC PubMed:17227845, PubMed:34998468). HSPA1 may be an additional auxiliary
CC complex member (PubMed:17478420, PubMed:19516020). The core complex
CC members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a
CC 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). Interacts with Ca(v)3.3/CACNA1I,
CC leading to suppression of T-type calcium channel activity (By
CC similarity). {ECO:0000250|UniProtKB:Q8NEC5,
CC ECO:0000269|PubMed:17227845, ECO:0000269|PubMed:17478420,
CC ECO:0000269|PubMed:19516020, ECO:0000269|PubMed:21224844,
CC ECO:0000269|PubMed:34225353, ECO:0000269|PubMed:34998468}.
CC -!- INTERACTION:
CC Q91ZR5; Q80W99: Catsper3; NbExp=2; IntAct=EBI-15619083, EBI-15619135;
CC Q91ZR5; Q8BVN3: Catsper4; NbExp=2; IntAct=EBI-15619083, EBI-15619199;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane
CC {ECO:0000269|PubMed:11595941, ECO:0000269|PubMed:34998468}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:34225353}. Note=Specifically
CC located in the principal piece of the sperm tail.
CC {ECO:0000269|PubMed:34225353, ECO:0000269|PubMed:34998468}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:11595941}.
CC -!- DEVELOPMENTAL STAGE: Detected only after round spermatids are produced
CC approximately at day 18. {ECO:0000269|PubMed:14688170,
CC 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. In mice lacking Catsper1, sperm lacks CatSper2 protein,
CC while in mice lacking CatSper1, sperm lacks CatSper1 protein,
CC suggesting that stable expression of CatSper1 protein requires CatSper2
CC and vice versa. {ECO:0000269|PubMed:11595941}.
CC -!- SIMILARITY: Belongs to the cation channel sperm-associated (TC
CC 1.A.1.19) family. {ECO:0000305}.
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DR EMBL; AF407332; AAL14104.1; -; mRNA.
DR EMBL; DQ021482; AAY63820.1; -; Genomic_DNA.
DR EMBL; DQ021483; AAY63821.1; -; Genomic_DNA.
DR EMBL; DQ021484; AAY63822.1; -; Genomic_DNA.
DR EMBL; DQ021485; AAY63823.1; -; Genomic_DNA.
DR EMBL; DQ021486; AAY63824.1; -; Genomic_DNA.
DR EMBL; DQ021488; AAY63826.1; -; Genomic_DNA.
DR EMBL; DQ021489; AAY63827.1; -; Genomic_DNA.
DR EMBL; DQ021490; AAY63828.1; -; Genomic_DNA.
DR EMBL; DQ021491; AAY63829.1; -; Genomic_DNA.
DR EMBL; DQ021492; AAY63830.1; -; Genomic_DNA.
DR CCDS; CCDS29456.1; -.
DR RefSeq; NP_647462.1; NM_139301.2.
DR PDB; 7EEB; EM; 2.90 A; A=1-686.
DR PDBsum; 7EEB; -.
DR AlphaFoldDB; Q91ZR5; -.
DR SMR; Q91ZR5; -.
DR BioGRID; 230434; 7.
DR CORUM; Q91ZR5; -.
DR DIP; DIP-60800N; -.
DR IntAct; Q91ZR5; 3.
DR STRING; 10090.ENSMUSP00000045430; -.
DR ChEMBL; CHEMBL3886121; -.
DR GuidetoPHARMACOLOGY; 388; -.
DR TCDB; 1.A.1.19.3; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q91ZR5; -.
DR PhosphoSitePlus; Q91ZR5; -.
DR PaxDb; Q91ZR5; -.
DR PRIDE; Q91ZR5; -.
DR ProteomicsDB; 285426; -.
DR Antibodypedia; 58041; 128 antibodies from 24 providers.
DR DNASU; 225865; -.
DR Ensembl; ENSMUST00000043380; ENSMUSP00000045430; ENSMUSG00000038498.
DR GeneID; 225865; -.
DR KEGG; mmu:225865; -.
DR UCSC; uc008gcp.1; mouse.
DR CTD; 117144; -.
DR MGI; MGI:2179947; Catsper1.
DR VEuPathDB; HostDB:ENSMUSG00000038498; -.
DR eggNOG; KOG2302; Eukaryota.
DR GeneTree; ENSGT00940000162437; -.
DR HOGENOM; CLU_016037_0_0_1; -.
DR InParanoid; Q91ZR5; -.
DR OMA; EVRGEWY; -.
DR OrthoDB; 753273at2759; -.
DR PhylomeDB; Q91ZR5; -.
DR TreeFam; TF329330; -.
DR Reactome; R-MMU-1300642; Sperm Motility And Taxes.
DR BioGRID-ORCS; 225865; 3 hits in 76 CRISPR screens.
DR PRO; PR:Q91ZR5; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q91ZR5; protein.
DR Bgee; ENSMUSG00000038498; Expressed in seminiferous tubule of testis and 3 other tissues.
DR ExpressionAtlas; Q91ZR5; baseline and differential.
DR Genevisible; Q91ZR5; MM.
DR GO; GO:0036128; C:CatSper complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0097228; C:sperm principal piece; IDA:UniProtKB.
DR GO; GO:0005227; F:calcium activated cation channel activity; IEA:InterPro.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IMP:MGI.
DR GO; GO:0006816; P:calcium ion transport; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:MGI.
DR GO; GO:0007342; P:fusion of sperm to egg plasma membrane involved in single fertilization; IMP:MGI.
DR GO; GO:0051924; P:regulation of calcium ion transport; IMP:MGI.
DR GO; GO:0060296; P:regulation of cilium beat frequency involved in ciliary motility; IMP:MGI.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR028746; CatSper1.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR47193; PTHR47193; 1.
DR Pfam; PF00520; Ion_trans; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 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..686
FT /note="Cation channel sperm-associated protein 1"
FT /id="PRO_0000295675"
FT TOPO_DOM 1..351
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 352..373
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 374..382
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 383..404
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 405..412
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 413..435
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 436..446
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 447..469
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 470..487
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 488..510
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 511..521
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT INTRAMEM 522..534
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 535..551
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 552..577
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 578..686
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT REGION 1..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 97..177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 207..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..143
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..159
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..174
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..248
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 25
FT /note="S -> SHP (in strain: 72)"
FT VARIANT 52
FT /note="M -> R (in strain: 2, 47 and 58)"
FT /evidence="ECO:0000269|PubMed:15930155"
FT VARIANT 160
FT /note="Missing (in strain: 47)"
FT /evidence="ECO:0000269|PubMed:15930155"
FT VARIANT 270
FT /note="T -> I (in strain: 72)"
FT /evidence="ECO:0000269|PubMed:15930155"
FT VARIANT 276
FT /note="Y -> S (in strain: 72)"
FT /evidence="ECO:0000269|PubMed:15930155"
FT HELIX 340..348
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 353..370
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 373..376
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 377..380
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 381..412
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 414..434
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 440..443
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 446..456
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 457..460
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 461..469
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 472..475
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 476..510
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 516..519
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 522..532
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 533..535
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 538..548
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 553..567
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 569..593
FT /evidence="ECO:0007829|PDB:7EEB"
SQ SEQUENCE 686 AA; 78706 MW; 2E85FFE72B3147BC CRC64;
MDQSSRRDES YHETHPGSLD PSHQSHPHPH PHPTLHRPNQ GGVYYDSPQH GMFQQPYQQH
GGFHQQNELQ HLREFSDSHD NAFSHHSYQQ DRAGVSTLPN NISHAYGGSH PLAESQHSGG
PQSGPRIDPN HHPHQDDPHR PSEPLSHPSS TGSHQGTTHQ QYHERSHHLN PQQNRDHADT
ISYRSSTRFY RSHAPFSRQE RPHLHADHHH EGHHAHSHHG EHPHHKEQRH YHGDHMHHHI
HHRSPSASQL SHKSHSTLAT SPSHVGSKST ASGARYTFGA RSQIFGKAQS RESLRESASL
SEGEDHVQKR KKAQRAHKKA HTGNIFQLLW EKISHLLLGL QQMILSLTQS LGFETFIFIV
VCLNTVILVA QTFTELEIRG EWYFMVLDSI FLSIYVLEAV LKLIALGLEY FYDPWNNLDF
FIMVMAVLDF VLLQINSLSY SFYNHSLFRI LKVFKSMRAL RAIRVLRRLS ILTSLHEVAG
TLSGSLPSIT AILTLMFTCL FLFSVVLRAL FQDSDPKRFQ NIFTTLFTLF TMLTLDDWSL
IYIDNRAQGA WYIIPILMIY IVIQYFIFLN LVIAVLVDNF QMALLKGLEK VKLEQAARVH
EKLLDDSLTD LNKADANAQM TEEALKMQLI EGMFGNMTVK QRVLHFQFLQ LVAAVEQHQQ
KFRSQAYVID ELVDMAFEAG DDDYGK
