CTSR2_MOUSE
ID CTSR2_MOUSE Reviewed; 588 AA.
AC A2ARP9; A2RSK0; Q91ZP5;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Cation channel sperm-associated protein 2;
DE Short=CatSper2;
GN Name=Catsper2;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=129/SvEv;
RX PubMed=11675491; DOI=10.1073/pnas.221454998;
RA Quill T.A., Ren D., Clapham D.E., Garbers D.L.;
RT "A voltage-gated ion channel expressed specifically in spermatozoa.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12527-12531(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14657366; DOI=10.1073/pnas.2136654100;
RA Quill T.A., Sugden S.A., Rossi K.L., Doolittle L.K., Hammer R.E.,
RA Garbers D.L.;
RT "Hyperactivated sperm motility driven by CatSper2 is required for
RT fertilization.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:14869-14874(2003).
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=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 [7]
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 [8]
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 [9]
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 [10]
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 [11]
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:14657366,
CC ECO:0000269|PubMed:16036917, 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:34998468). HSPA1 may be an
CC additional auxiliary complex member (By similarity). 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:Q91ZR5,
CC ECO:0000250|UniProtKB:Q96P56, ECO:0000269|PubMed:21224844,
CC ECO:0000269|PubMed:34225353, ECO:0000269|PubMed:34998468}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane
CC {ECO:0000269|PubMed:11675491}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:34225353}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:11675491}.
CC -!- DEVELOPMENTAL STAGE: Present in testis of 8 day-old. Expressed in
CC pachytene spermatocytes. {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, the sperm lacks CatSper2, while
CC in mice lacking CatSper1, the sperm lacks CatSper1, suggesting that
CC stable expression of CatSper1 requires CatSper2 and vice versa.
CC {ECO:0000269|PubMed:14657366}.
CC -!- SIMILARITY: Belongs to the cation channel sperm-associated (TC
CC 1.A.1.19) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAM24230.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF411816; AAL26489.1; -; mRNA.
DR EMBL; AL845466; CAM24230.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC132140; AAI32141.1; -; mRNA.
DR PDB; 7EEB; EM; 2.90 A; B=1-588.
DR PDBsum; 7EEB; -.
DR AlphaFoldDB; A2ARP9; -.
DR SMR; A2ARP9; -.
DR CORUM; A2ARP9; -.
DR DIP; DIP-60801N; -.
DR IntAct; A2ARP9; 1.
DR STRING; 10090.ENSMUSP00000037222; -.
DR GuidetoPHARMACOLOGY; 389; -.
DR PhosphoSitePlus; A2ARP9; -.
DR PaxDb; A2ARP9; -.
DR PRIDE; A2ARP9; -.
DR ProteomicsDB; 279207; -.
DR MGI; MGI:2387404; Catsper2.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; A2ARP9; -.
DR PhylomeDB; A2ARP9; -.
DR TreeFam; TF343585; -.
DR Reactome; R-MMU-1300642; Sperm Motility And Taxes.
DR ChiTaRS; Catsper2; mouse.
DR PRO; PR:A2ARP9; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; A2ARP9; protein.
DR GO; GO:0036128; C:CatSper complex; IDA:UniProtKB.
DR GO; GO:0036126; C:sperm flagellum; IDA:MGI.
DR GO; GO:0005227; F:calcium activated cation channel activity; IEA:InterPro.
DR GO; GO:0005262; F:calcium channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0009566; P:fertilization; IMP:MGI.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:MGI.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0048240; P:sperm capacitation; IMP:MGI.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR028747; CatSper2.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR46923; PTHR46923; 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..588
FT /note="Cation channel sperm-associated protein 2"
FT /id="PRO_0000295677"
FT TOPO_DOM 1..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 107..129
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 130..138
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 139..164
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 165..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 174..198
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 199..201
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 202..220
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 221..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 238..260
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 261..279
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT INTRAMEM 280..292
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 293..312
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 313..339
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 340..588
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT REGION 376..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 394..435
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 436..503
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 49
FT /note="S -> A (in Ref. 1; AAL26489 and 3; AAI32141)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="D -> N (in Ref. 1; AAL26489)"
FT /evidence="ECO:0000305"
FT CONFLICT 335
FT /note="V -> I (in Ref. 1; AAL26489)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="N -> G (in Ref. 1; AAL26489 and 3; AAI32141)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="K -> E (in Ref. 1; AAL26489 and 3; AAI32141)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="T -> I (in Ref. 1; AAL26489 and 3; AAI32141)"
FT /evidence="ECO:0000305"
FT HELIX 96..102
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 106..128
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 138..165
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 174..195
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 202..209
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 210..215
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 216..220
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 225..238
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 240..260
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 281..292
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 297..305
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 307..310
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 315..325
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 326..328
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 329..373
FT /evidence="ECO:0007829|PDB:7EEB"
SQ SEQUENCE 588 AA; 68572 MW; 93396326105828DA CRC64;
MAQEQGHFQL LRADAIRSKL IDTFSLIEHL QGLSQAVPRH TLREILDPSY QQKLMSGDQE
QLVRFSIKPR RMGHITHSRR LLSRLRVRCS RMPPLSLWAG WVLDSSVFSK FIISLIFLNT
FVLMVEIELM ESTNTALWPV KLALEVADWF ILLSFIVEIL LMWLASFSLF WKDAWNVFDF
FVTLLSLLPE LVVLLGVPAH SVWLQLLRVC RVLRSLKLFA RFRQIKVILL ALVRALKSMT
FLLMLLLIFF YIFAVTGVYF FREYSRSTIE GLEYNMFFSD LLNSLVTVFI LFTLDHWYAV
LQDIWKVPES SRVFSSIYVI LWLLLGSIIF RNIIVAMMVT NFQNIRSELS EEMSHLEVQY
KADMFKQQII QRRQHSESLR GTSLGKVSED IIETSDASDD DDDDDDDDDD DDDDDDDKSD
ATESDNEESD SENSESENSE SEKIDPEKDY AKKSYPEKSH PEKSYPEKSH PEKSYPEKSH
PKKSYDEQAE AEKVKEESKE KAYPVSHSIS SHGSTAADTA FLENLDWETL VHENLPGLMD
MDQDDRIVWP RDSLFRYFEL LEKLQYNLEE RKKLQEFAVQ ALMSFEDK
