CTSR2_HUMAN
ID CTSR2_HUMAN Reviewed; 530 AA.
AC Q96P56; Q8NHT9; Q96P54; Q96P55;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Cation channel sperm-associated protein 2;
DE Short=CatSper2;
GN Name=CATSPER2;
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] (ISOFORMS 1; 2 AND 3), AND TISSUE SPECIFICITY.
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 MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Brain, and 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 [3]
RP INVOLVEMENT IN DIS.
RX PubMed=12825070; DOI=10.1038/sj.ejhg.5200991;
RA Avidan N., Tamary H., Dgany O., Cattan D., Pariente A., Thulliez M.,
RA Borot N., Moati L., Barthelme A., Shalmon L., Krasnov T., Ben-Asher E.,
RA Olender T., Khen M., Yaniv I., Zaizov R., Shalev H., Delaunay J.,
RA Fellous M., Lancet D., Beckmann J.S.;
RT "CATSPER2, a human autosomal nonsyndromic male infertility gene.";
RL Eur. J. Hum. Genet. 11:497-502(2003).
RN [4]
RP INTERACTION WITH CACNA1I.
RX PubMed=16740636; DOI=10.1074/jbc.m511288200;
RA Zhang D., Chen J., Saraf A., Cassar S., Han P., Rogers J.C., Brioni J.D.,
RA Sullivan J.P., Gopalakrishnan M.;
RT "Association of Catsper1 or -2 with Ca(v)3.3 leads to suppression of T-type
RT calcium channel activity.";
RL J. Biol. Chem. 281:22332-22341(2006).
RN [5]
RP INVOLVEMENT IN DIS.
RX PubMed=17098888; DOI=10.1136/jmg.2006.045765;
RA Zhang Y., Malekpour M., Al-Madani N., Kahrizi K., Zanganeh M., Mohseni M.,
RA Mojahedi F., Daneshi A., Najmabadi H., Smith R.J.H.;
RT "Sensorineural deafness and male infertility: a contiguous gene deletion
RT syndrome.";
RL J. Med. Genet. 44:233-240(2007).
RN [6]
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 [7]
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 [8]
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 [9]
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: 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, CATSPERG, CATSPERD, CATSPERE,
CC CATSPERZ, C2CD6/CATSPERT, TMEM249, TMEM262 and EFCAB9 (By similarity).
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 (By similarity). The auxiliary CATSPERB,
CC CATSPERG, CATSPERD and CATSPERE subunits form a pavilion-like structure
CC over the pore which stabilizes the complex through interactions with
CC CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (By similarity).
CC TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the
CC complex. C2CD6/CATSPERT interacts at least with CATSPERD and is
CC required for targeting the CatSper complex in the flagellar membrane
CC (By similarity). Interacts with Ca(v)3.3/CACNA1I, leading to
CC suppression of T-type calcium channel activity (PubMed:16740636).
CC {ECO:0000250|UniProtKB:A2ARP9, ECO:0000250|UniProtKB:Q91ZR5,
CC ECO:0000269|PubMed:16740636}.
CC -!- INTERACTION:
CC Q96P56; Q9P0X4: CACNA1I; NbExp=3; IntAct=EBI-2215024, EBI-1220829;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane
CC {ECO:0000250|UniProtKB:A2ARP9}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:A2ARP9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Variant 2;
CC IsoId=Q96P56-1; Sequence=Displayed;
CC Name=2; Synonyms=Variant 1;
CC IsoId=Q96P56-2; Sequence=VSP_026976;
CC Name=3; Synonyms=Variant 3;
CC IsoId=Q96P56-3; Sequence=VSP_026975, VSP_026977;
CC Name=4;
CC IsoId=Q96P56-4; Sequence=VSP_026973, VSP_026974;
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:11675491,
CC ECO:0000269|PubMed:17347248}.
CC -!- DISEASE: Deafness-infertility syndrome (DIS) [MIM:611102]:
CC Characterized by deafness and infertility and is caused by large
CC contiguous gene deletions at 15q15.3 that removes both STRC and
CC CATSPER2 genes. {ECO:0000269|PubMed:12825070,
CC ECO:0000269|PubMed:17098888}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cation channel sperm-associated (TC
CC 1.A.1.19) family. {ECO:0000305}.
CC -!- CAUTION: In mouse, Slco6c1 is an additional auxiliary subunit of the
CC CatSper complex. It is unclear if the related SLCO6A1 protein performs
CC the same role in non-rodent species. {ECO:0000305}.
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DR EMBL; AF411817; AAL26490.1; -; mRNA.
DR EMBL; AF411818; AAL26491.1; -; mRNA.
DR EMBL; AF411819; AAL26492.1; -; mRNA.
DR EMBL; BC028728; AAH28728.1; -; mRNA.
DR EMBL; BC064387; AAH64387.1; -; mRNA.
DR CCDS; CCDS10099.1; -. [Q96P56-1]
DR CCDS; CCDS32216.1; -. [Q96P56-2]
DR RefSeq; NP_001269238.1; NM_001282309.1. [Q96P56-2]
DR RefSeq; NP_473361.1; NM_054020.3.
DR RefSeq; NP_742093.1; NM_172095.2. [Q96P56-1]
DR RefSeq; XP_016877393.1; XM_017021904.1.
DR AlphaFoldDB; Q96P56; -.
DR SMR; Q96P56; -.
DR BioGRID; 125561; 3.
DR IntAct; Q96P56; 3.
DR STRING; 9606.ENSP00000371180; -.
DR DrugCentral; Q96P56; -.
DR GuidetoPHARMACOLOGY; 389; -.
DR TCDB; 1.A.1.19.2; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q96P56; -.
DR PhosphoSitePlus; Q96P56; -.
DR BioMuta; CATSPER2; -.
DR DMDM; 156631018; -.
DR MassIVE; Q96P56; -.
DR PaxDb; Q96P56; -.
DR PeptideAtlas; Q96P56; -.
DR PRIDE; Q96P56; -.
DR ProteomicsDB; 77633; -. [Q96P56-1]
DR ProteomicsDB; 77634; -. [Q96P56-2]
DR ProteomicsDB; 77635; -. [Q96P56-3]
DR ProteomicsDB; 77636; -. [Q96P56-4]
DR Antibodypedia; 11368; 141 antibodies from 17 providers.
DR DNASU; 117155; -.
DR Ensembl; ENST00000321596.6; ENSP00000321463.5; ENSG00000166762.19. [Q96P56-2]
DR Ensembl; ENST00000396879.8; ENSP00000380088.3; ENSG00000166762.19. [Q96P56-1]
DR Ensembl; ENST00000433380.5; ENSP00000389746.1; ENSG00000166762.19. [Q96P56-3]
DR GeneID; 117155; -.
DR KEGG; hsa:117155; -.
DR MANE-Select; ENST00000396879.8; ENSP00000380088.3; NM_172095.4; NP_742093.1.
DR UCSC; uc001zsh.5; human. [Q96P56-1]
DR CTD; 117155; -.
DR DisGeNET; 117155; -.
DR GeneCards; CATSPER2; -.
DR GeneReviews; CATSPER2; -.
DR HGNC; HGNC:18810; CATSPER2.
DR HPA; ENSG00000166762; Tissue enhanced (brain, retina, testis).
DR MalaCards; CATSPER2; -.
DR MIM; 607249; gene.
DR MIM; 611102; phenotype.
DR neXtProt; NX_Q96P56; -.
DR OpenTargets; ENSG00000166762; -.
DR Orphanet; 94064; Deafness-infertility syndrome.
DR PharmGKB; PA38691; -.
DR VEuPathDB; HostDB:ENSG00000166762; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00910000144338; -.
DR HOGENOM; CLU_038828_0_0_1; -.
DR InParanoid; Q96P56; -.
DR OMA; GWVLECK; -.
DR PhylomeDB; Q96P56; -.
DR TreeFam; TF343585; -.
DR PathwayCommons; Q96P56; -.
DR Reactome; R-HSA-1300642; Sperm Motility And Taxes.
DR SignaLink; Q96P56; -.
DR BioGRID-ORCS; 117155; 6 hits in 1065 CRISPR screens.
DR GeneWiki; CatSper2; -.
DR GenomeRNAi; 117155; -.
DR Pharos; Q96P56; Tchem.
DR PRO; PR:Q96P56; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96P56; protein.
DR Bgee; ENSG00000166762; Expressed in cerebellar vermis and 149 other tissues.
DR ExpressionAtlas; Q96P56; baseline and differential.
DR Genevisible; Q96P56; HS.
DR GO; GO:0036128; C:CatSper complex; ISS:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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; 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:0048240; P:sperm capacitation; IBA:GO_Central.
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 Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW Cell membrane; Cell projection; Cilium; Developmental protein;
KW Differentiation; Flagellum; Ion channel; Ion transport; Membrane;
KW Reference proteome; Spermatogenesis; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT CHAIN 1..530
FT /note="Cation channel sperm-associated protein 2"
FT /id="PRO_0000295676"
FT TOPO_DOM 1..108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TRANSMEM 109..131
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TOPO_DOM 132..140
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TRANSMEM 141..166
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TOPO_DOM 167..175
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TRANSMEM 176..200
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TOPO_DOM 201..203
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TRANSMEM 204..222
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TOPO_DOM 223..239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TRANSMEM 240..262
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TOPO_DOM 263..281
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT INTRAMEM 282..294
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TOPO_DOM 295..314
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TRANSMEM 315..341
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT TOPO_DOM 342..530
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:A2ARP9"
FT REGION 378..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..398
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 399..424
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 439..458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 188..199
FT /note="SLLPEVVVLVGV -> VRIEILRVRLVG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026973"
FT VAR_SEQ 200..530
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026974"
FT VAR_SEQ 393..414
FT /note="SSRGASQQRESLDLSEVSEVES -> RSFGLGDSCARKSARANGNGSG (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:11675491"
FT /id="VSP_026975"
FT VAR_SEQ 393..394
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11675491,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_026976"
FT VAR_SEQ 415..530
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11675491"
FT /id="VSP_026977"
FT VARIANT 8
FT /note="E -> G (in dbSNP:rs2614835)"
FT /id="VAR_033307"
FT VARIANT 57
FT /note="V -> I (in dbSNP:rs8042868)"
FT /id="VAR_033308"
FT CONFLICT 46
FT /note="E -> K (in Ref. 2; AAH28728)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 530 AA; 62041 MW; 8561CC0E9F3590B0 CRC64;
MAAYQQEEQM QLPRADAIRS RLIDTFSLIE HLQGLSQAVP RHTIRELLDP SRQKKLVLGD
QHQLVRFSIK PQRIEQISHA QRLLSRLHVR CSQRPPLSLW AGWVLECPLF KNFIIFLVFL
NTIILMVEIE LLESTNTKLW PLKLTLEVAA WFILLIFILE ILLKWLSNFS VFWKSAWNVF
DFVVTMLSLL PEVVVLVGVT GQSVWLQLLR ICRVLRSLKL LAQFRQIQII ILVLVRALKS
MTFLLMLLLI FFYIFAVTGV YVFSEYTRSP RQDLEYHVFF SDLPNSLVTV FILFTLDHWY
ALLQDVWKVP EVSRIFSSIY FILWLLLGSI IFRSIIVAMM VTNFQNIRKE LNEEMARREV
QLKADMFKRQ IIQRRKNMSH EALTSSHSKI EDSSRGASQQ RESLDLSEVS EVESNYGATE
EDLITSASKT EETLSKKREY QSSSCVSSTS SSYSSSSESR FSESIGRLDW ETLVHENLPG
LMEMDQDDRV WPRDSLFRYF ELLEKLQYNL EERKKLQEFA VQALMNLEDK
