CTSR4_MOUSE
ID CTSR4_MOUSE Reviewed; 442 AA.
AC Q8BVN3; A2A9K6;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Cation channel sperm-associated protein 4;
DE Short=CatSper4;
GN Name=Catsper4;
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 [LARGE SCALE MRNA].
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 [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].
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 FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH
RP CATSPER1, AND DISRUPTION PHENOTYPE.
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 [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 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: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:21224844, PubMed:17227845). 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 (Probable). {ECO:0000250|UniProtKB:Q91ZR5,
CC ECO:0000269|PubMed:17227845, ECO:0000269|PubMed:21224844,
CC ECO:0000269|PubMed:34225353, ECO:0000305}.
CC -!- INTERACTION:
CC Q8BVN3; Q91ZR5: Catsper1; NbExp=2; IntAct=EBI-15619199, 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}. Note=Specifically
CC located in the principal piece of the sperm tail.
CC {ECO:0000269|PubMed:17227845, ECO:0000269|PubMed:34225353}.
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=CAM21941.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AK077145; BAC36641.1; -; mRNA.
DR EMBL; AL627314; CAM21940.1; -; Genomic_DNA.
DR EMBL; AL627314; CAM21941.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC108974; AAI08975.1; -; mRNA.
DR EMBL; BC108975; AAI08976.1; -; mRNA.
DR CCDS; CCDS18766.1; -.
DR RefSeq; NP_001123502.1; NM_001130030.1.
DR RefSeq; NP_808534.1; NM_177866.4.
DR PDB; 7EEB; EM; 2.90 A; D=1-442.
DR PDBsum; 7EEB; -.
DR AlphaFoldDB; Q8BVN3; -.
DR SMR; Q8BVN3; -.
DR BioGRID; 236869; 1.
DR CORUM; Q8BVN3; -.
DR DIP; DIP-60803N; -.
DR IntAct; Q8BVN3; 1.
DR STRING; 10090.ENSMUSP00000051694; -.
DR GuidetoPHARMACOLOGY; 391; -.
DR TCDB; 1.A.1.19.3; the voltage-gated ion channel (vic) superfamily.
DR PhosphoSitePlus; Q8BVN3; -.
DR PaxDb; Q8BVN3; -.
DR PRIDE; Q8BVN3; -.
DR ProteomicsDB; 285429; -.
DR Antibodypedia; 51012; 94 antibodies from 21 providers.
DR Ensembl; ENSMUST00000055892; ENSMUSP00000051694; ENSMUSG00000048003.
DR GeneID; 329954; -.
DR KEGG; mmu:329954; -.
DR UCSC; uc008veh.2; mouse.
DR CTD; 378807; -.
DR MGI; MGI:3043288; Catsper4.
DR VEuPathDB; HostDB:ENSMUSG00000048003; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000161879; -.
DR HOGENOM; CLU_042053_0_0_1; -.
DR InParanoid; Q8BVN3; -.
DR OMA; NRRDITS; -.
DR OrthoDB; 1270192at2759; -.
DR PhylomeDB; Q8BVN3; -.
DR TreeFam; TF343841; -.
DR Reactome; R-MMU-1300642; Sperm Motility And Taxes.
DR BioGRID-ORCS; 329954; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Catsper4; mouse.
DR PRO; PR:Q8BVN3; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8BVN3; protein.
DR Bgee; ENSMUSG00000048003; Expressed in spermatid and 33 other tissues.
DR ExpressionAtlas; Q8BVN3; baseline and differential.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:MGI.
DR GO; GO:0036128; C:CatSper complex; IDA:UniProtKB.
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:0051649; P:establishment of localization in cell; 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:0006814; P:sodium ion transport; IMP:MGI.
DR GO; GO:0048240; P:sperm capacitation; IMP:MGI.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR028744; CatSper4.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR47077; PTHR47077; 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..442
FT /note="Cation channel sperm-associated protein 4"
FT /id="PRO_0000295682"
FT TOPO_DOM 1..66
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 67..88
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 89..98
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 99..125
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 126..129
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 130..153
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 154..156
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 157..175
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 176..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 189..212
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 213..222
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT INTRAMEM 223..234
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 235..255
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TRANSMEM 256..283
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000269|PubMed:34225353"
FT TOPO_DOM 284..442
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34225353"
FT HELIX 54..65
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 68..88
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 91..96
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 98..121
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 124..127
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 132..148
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 155..158
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 166..170
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 177..212
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 223..234
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 239..247
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 254..270
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 271..276
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 278..291
FT /evidence="ECO:0007829|PDB:7EEB"
SQ SEQUENCE 442 AA; 51130 MW; B4A41CAA47F0AE21 CRC64;
MSEKHKWWQQ VENIDITHLG PKRKAYELLG RHEEQVLINR RDVMEKKDAW DVQEFITQMY
IKQLLRHPAF QLLLAFLLLS NAITIALRTN SYLGQKHYEL FSTIDDIVLT ILICEVLLGW
LNGFWIFWKD GWNILNFAIV FILFMGFFIK QLDMVAITYP LRVLRLVHVC MAVEPLARII
KVILQSMPDL ANVMALILFF MLVFSVFGVT LFGAFVPKHF QNMGVALYTL FICITQDGWL
DIYTDFQMDE REYAMEVGGA IYFAVFITLG AFIGLNLFVV VVTTNLEQMM KTGEEEGHLN
IKFTETEEDE DWTDELPLVH CTEARKDTST VPKEPLVGGP LSNLTEKTCD NFCLVLEAIQ
ENLMEYKEIR EELNMIVEEV SSIRFNQEQQ NVILHKYTSK SATFLSEPPE GANKQDLITA
LVSREKVSDS NINMVNKHKF SH
