Q96P56 (CTSR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cation channel sperm-associated protein 2
Short name=CatSper2

Gene names

Name:

CATSPER2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	530 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Voltage-gated calcium channel that plays a central role in calcium-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acrosome reaction and chemotaxis towards the oocyte. Activated by extracellular progesterone and prostaglandins following the sequence: progesterone > PGF1-alpha = PGE1 > PGA1 > PGE2 >> PGD2. The primary effect of progesterone activation is to shift voltage dependence towards more physiological, negative membrane potentials; it is not mediated by metabotropic receptors and second messengers. Sperm capacitation enhances the effect of progesterone by providing additional negative shift. Also activated by the elevation of intracellular pH. Ref.7 Ref.8
Subunit structure	Heterotetramer; possibly composed of CATSPER1, CATSPER2, CATSPER3 and CATSPER4 Potential. Component of the CatSper complex. Interacts with Ca(v)3.3/CACNA1I, leading to suppress T-type calcium channel activity. Ref.4
Subcellular location	Cell projection › cilium › flagellum membrane; Multi-pass membrane protein By similarity. Note: Specifically located in the principal piece of sperm tail.
Tissue specificity	Testis-specific. Ref.1 Ref.6
Involvement in disease	Deafness-infertility syndrome (DIS) [MIM:611102]: Characterized by deafness and infertility and is caused by large contiguous gene deletions at 15q15.3 that removes both STRC and CATSPER2 genes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.5
Sequence similarities	Belongs to the cation channel sperm-associated (TC 1.A.1.19) family. [View classification]

Ontologies

Keywords
Biological process	Calcium transport Differentiation Ion transport Spermatogenesis Transport
Cellular component	Cell membrane Cell projection Cilium Flagellum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Calcium channel Developmental protein Ion channel Voltage-gated channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW ciliary or flagellar motility Inferred from electronic annotation. Source: Compara fertilization Inferred from electronic annotation. Source: Compara multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW sperm motility Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	CatSper complex Inferred from sequence or structural similarity. Source: UniProtKB cilium Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	calcium channel activity Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated ion channel activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CACNA1I	Q9P0X4	3	EBI-2215024,EBI-1220829

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96P56-1)

Also known as: Variant 2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96P56-2)

Also known as: Variant 1;

The sequence of this isoform differs from the canonical sequence as follows:
     393-394: Missing.

Isoform 3 (identifier: Q96P56-3)

Also known as: Variant 3;

The sequence of this isoform differs from the canonical sequence as follows:
     393-414: SSRGASQQRESLDLSEVSEVES → RSFGLGDSCARKSARANGNGSG
     415-530: Missing.

Isoform 4 (identifier: Q96P56-4)

The sequence of this isoform differs from the canonical sequence as follows:
     188-199: SLLPEVVVLVGV → VRIEILRVRLVG
     200-530: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 530	530	Cation channel sperm-associated protein 2		PRO_0000295676
Regions
	Topological domain	1 – 112	112	Cytoplasmic Potential
	Transmembrane	113 – 133	21	Helical; Name=Segment S1; Potential
	Topological domain	134 – 145	12	Extracellular Potential
	Transmembrane	146 – 166	21	Helical; Name=Segment S2; Potential
	Topological domain	167 – 178	12	Cytoplasmic Potential
	Transmembrane	179 – 199	21	Helical; Name=Segment S3; Potential
	Topological domain	200 – 205	6	Extracellular Potential
	Transmembrane	206 – 226	21	Helical; Name=Segment S4; Potential
	Topological domain	227 – 242	16	Cytoplasmic Potential
	Transmembrane	243 – 263	21	Helical; Name=Segment S5; Potential
	Topological domain	264 – 282	19	Extracellular Potential
	Intramembrane	283 – 303	21	Helical; Pore-forming; Potential
	Topological domain	304 – 320	17	Extracellular Potential
	Transmembrane	321 – 341	21	Helical; Name=Segment S6; Potential
	Topological domain	342 – 530	189	Cytoplasmic Potential
	Compositional bias	385 – 464	80	Ser-rich
Natural variations
	Alternative sequence	188 – 199	12	SLLPE…VLVGV → VRIEILRVRLVG in isoform 4.		VSP_026973
	Alternative sequence	200 – 530	331	Missing in isoform 4.		VSP_026974
	Alternative sequence	393 – 414	22	SSRGA…SEVES → RSFGLGDSCARKSARANGNG SG in isoform 3.		VSP_026975
	Alternative sequence	393 – 394	2	Missing in isoform 2.		VSP_026976
	Alternative sequence	415 – 530	116	Missing in isoform 3.		VSP_026977
	Natural variant	8	1	E → G. Corresponds to variant rs2614835 [ dbSNP | Ensembl ].		VAR_033307
	Natural variant	57	1	V → I. Corresponds to variant rs8042868 [ dbSNP | Ensembl ].		VAR_033308
Experimental info
	Sequence conflict	46	1	E → K in AAH28728. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Variant 2) [UniParc]. Last modified July 24, 2007. Version 2. Checksum: 8561CC0E9F3590B0	FASTA	530	62,041
	10 20 30 40 50 60 MAAYQQEEQM QLPRADAIRS RLIDTFSLIE HLQGLSQAVP RHTIRELLDP SRQKKLVLGD 70 80 90 100 110 120 QHQLVRFSIK PQRIEQISHA QRLLSRLHVR CSQRPPLSLW AGWVLECPLF KNFIIFLVFL 130 140 150 160 170 180 NTIILMVEIE LLESTNTKLW PLKLTLEVAA WFILLIFILE ILLKWLSNFS VFWKSAWNVF 190 200 210 220 230 240 DFVVTMLSLL PEVVVLVGVT GQSVWLQLLR ICRVLRSLKL LAQFRQIQII ILVLVRALKS 250 260 270 280 290 300 MTFLLMLLLI FFYIFAVTGV YVFSEYTRSP RQDLEYHVFF SDLPNSLVTV FILFTLDHWY 310 320 330 340 350 360 ALLQDVWKVP EVSRIFSSIY FILWLLLGSI IFRSIIVAMM VTNFQNIRKE LNEEMARREV 370 380 390 400 410 420 QLKADMFKRQ IIQRRKNMSH EALTSSHSKI EDSSRGASQQ RESLDLSEVS EVESNYGATE 430 440 450 460 470 480 EDLITSASKT EETLSKKREY QSSSCVSSTS SSYSSSSESR FSESIGRLDW ETLVHENLPG 490 500 510 520 530 LMEMDQDDRV WPRDSLFRYF ELLEKLQYNL EERKKLQEFA VQALMNLEDK
	Isoform 2 (Variant 1) [UniParc]. Checksum: 4B38C7DC481EE755	FASTA	528	61,867
	10 20 30 40 50 60 MAAYQQEEQM QLPRADAIRS RLIDTFSLIE HLQGLSQAVP RHTIRELLDP SRQKKLVLGD 70 80 90 100 110 120 QHQLVRFSIK PQRIEQISHA QRLLSRLHVR CSQRPPLSLW AGWVLECPLF KNFIIFLVFL 130 140 150 160 170 180 NTIILMVEIE LLESTNTKLW PLKLTLEVAA WFILLIFILE ILLKWLSNFS VFWKSAWNVF 190 200 210 220 230 240 DFVVTMLSLL PEVVVLVGVT GQSVWLQLLR ICRVLRSLKL LAQFRQIQII ILVLVRALKS 250 260 270 280 290 300 MTFLLMLLLI FFYIFAVTGV YVFSEYTRSP RQDLEYHVFF SDLPNSLVTV FILFTLDHWY 310 320 330 340 350 360 ALLQDVWKVP EVSRIFSSIY FILWLLLGSI IFRSIIVAMM VTNFQNIRKE LNEEMARREV 370 380 390 400 410 420 QLKADMFKRQ IIQRRKNMSH EALTSSHSKI EDRGASQQRE SLDLSEVSEV ESNYGATEED 430 440 450 460 470 480 LITSASKTEE TLSKKREYQS SSCVSSTSSS YSSSSESRFS ESIGRLDWET LVHENLPGLM 490 500 510 520 EMDQDDRVWP RDSLFRYFEL LEKLQYNLEE RKKLQEFAVQ ALMNLEDK
	Isoform 3 (Variant 3) [UniParc]. Checksum: B5A474A8DF68C27F	FASTA	414	48,341
	10 20 30 40 50 60 MAAYQQEEQM QLPRADAIRS RLIDTFSLIE HLQGLSQAVP RHTIRELLDP SRQKKLVLGD 70 80 90 100 110 120 QHQLVRFSIK PQRIEQISHA QRLLSRLHVR CSQRPPLSLW AGWVLECPLF KNFIIFLVFL 130 140 150 160 170 180 NTIILMVEIE LLESTNTKLW PLKLTLEVAA WFILLIFILE ILLKWLSNFS VFWKSAWNVF 190 200 210 220 230 240 DFVVTMLSLL PEVVVLVGVT GQSVWLQLLR ICRVLRSLKL LAQFRQIQII ILVLVRALKS 250 260 270 280 290 300 MTFLLMLLLI FFYIFAVTGV YVFSEYTRSP RQDLEYHVFF SDLPNSLVTV FILFTLDHWY 310 320 330 340 350 360 ALLQDVWKVP EVSRIFSSIY FILWLLLGSI IFRSIIVAMM VTNFQNIRKE LNEEMARREV 370 380 390 400 410 QLKADMFKRQ IIQRRKNMSH EALTSSHSKI EDRSFGLGDS CARKSARANG NGSG
	Isoform 4 [UniParc]. Checksum: 57171E69BE875D30	FASTA	199	23,437
	10 20 30 40 50 60 MAAYQQEEQM QLPRADAIRS RLIDTFSLIE HLQGLSQAVP RHTIRELLDP SRQKKLVLGD 70 80 90 100 110 120 QHQLVRFSIK PQRIEQISHA QRLLSRLHVR CSQRPPLSLW AGWVLECPLF KNFIIFLVFL 130 140 150 160 170 180 NTIILMVEIE LLESTNTKLW PLKLTLEVAA WFILLIFILE ILLKWLSNFS VFWKSAWNVF 190 DFVVTMLVRI EILRVRLVG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A voltage-gated ion channel expressed specifically in spermatozoa." Quill T.A., Ren D., Clapham D.E., Garbers D.L. Proc. Natl. Acad. Sci. U.S.A. 98:12527-12531(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4). Tissue: Brain and Testis.
[3]	"CATSPER2, a human autosomal nonsyndromic male infertility gene." Avidan N., Tamary H., Dgany O., Cattan D., Pariente A., Thulliez M., Borot N., Moati L., Barthelme A., Shalmon L., Krasnov T., Ben-Asher E., Olender T., Khen M., Yaniv I., Zaizov R., Shalev H., Delaunay J. , Fellous M., Lancet D., Beckmann J.S. Eur. J. Hum. Genet. 11:497-502(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN DIS.
[4]	"Association of Catsper1 or -2 with Ca(v)3.3 leads to suppression of T-type calcium channel activity." Zhang D., Chen J., Saraf A., Cassar S., Han P., Rogers J.C., Brioni J.D., Sullivan J.P., Gopalakrishnan M. J. Biol. Chem. 281:22332-22341(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CACNA1I.
[5]	"Sensorineural deafness and male infertility: a contiguous gene deletion syndrome." Zhang Y., Malekpour M., Al-Madani N., Kahrizi K., Zanganeh M., Mohseni M., Mojahedi F., Daneshi A., Najmabadi H., Smith R.J.H. J. Med. Genet. 44:233-240(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN DIS.
[6]	"Expression of CatSper family transcripts in the mouse testis during post-natal development and human ejaculated spermatozoa: relationship to sperm motility." Li H.-G., Ding X.-F., Liao A.-H., Kong X.-B., Xiong C.-L. Mol. Hum. Reprod. 13:299-306(2007) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm." Strunker T., Goodwin N., Brenker C., Kashikar N.D., Weyand I., Seifert R., Kaupp U.B. Nature 471:382-386(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION BY PROGESTERONE.
[8]	"Progesterone activates the principal Ca2+ channel of human sperm." Lishko P.V., Botchkina I.L., Kirichok Y. Nature 471:387-391(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION BY PROGESTERONE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF411817 mRNA. Translation: AAL26490.1. AF411818 mRNA. Translation: AAL26491.1. AF411819 mRNA. Translation: AAL26492.1. BC028728 mRNA. Translation: AAH28728.1. BC064387 mRNA. Translation: AAH64387.1.
IPI	IPI00065918. IPI00788611. IPI00797407. IPI00797980.
RefSeq	NP_473361.1. NM_054020.2. NP_742093.1. NM_172095.1. NP_742095.1. NM_172097.1.
UniGene	Hs.662284.
3D structure databases
ProteinModelPortal	Q96P56.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96P56. 1 interaction.
STRING	9606.ENSP00000299989.
Protein family/group databases
TCDB	1.A.1.19.2. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	Q96P56.
Polymorphism databases
DMDM	156631018.
Proteomic databases
PaxDb	Q96P56.
PRIDE	Q96P56.
Protocols and materials databases
DNASU	117155.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299989; ENSP00000299989; ENSG00000166762. ENST00000321596; ENSP00000321463; ENSG00000166762. ENST00000354127; ENSP00000339137; ENSG00000166762. ENST00000355438; ENSP00000347613; ENSG00000166762. ENST00000396879; ENSP00000380088; ENSG00000166762. ENST00000433380; ENSP00000389746; ENSG00000166762.
GeneID	117155.
KEGG	hsa:117155.
UCSC	uc001zsh.3. human. uc001zsi.3. human. uc001zsk.3. human.
Organism-specific databases
CTD	117155.
GeneCards	GC15M043920.
HGNC	HGNC:18810. CATSPER2.
HPA	HPA042709.
MIM	607249. gene. 611102. phenotype.
neXtProt	NX_Q96P56.
Orphanet	94064. Deafness-infertility syndrome.
PharmGKB	PA38691.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG302565.
HOGENOM	HOG000007710.
HOVERGEN	HBG107782.
PhylomeDB	Q96P56.
Gene expression databases
ArrayExpress	Q96P56.
Bgee	Q96P56.
CleanEx	HS_CATSPER2.
Genevestigator	Q96P56.
Family and domain databases
InterPro	IPR005821. Ion_trans_dom. [Graphical view]
Pfam	PF00520. Ion_trans. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CATSPER2. human.
GenomeRNAi	117155.
NextBio	80109.
SOURCE	Search...

Entry information

Entry name

CTSR2_HUMAN

Accession

Primary (citable) accession number: Q96P56
Secondary accession number(s): Q8NHT9, Q96P54, Q96P55

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 24, 2007
Last sequence update:	July 24, 2007
Last modified:	May 1, 2013
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.