Q7RTX7 (CTSR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cation channel sperm-associated protein 4
Short name=CatSper4

Gene names

Name:

CATSPER4

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	472 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.5 Ref.6
Subunit structure	Heterotetramer; possibly composed of CATSPER1, CATSPER2, CATSPER3 and CATSPER4 Potential. Component of the CatSper complex. Interacts with CATSPER1 By similarity.
Subcellular location	Cell projection › cilium › flagellum membrane; Multi-pass membrane protein. Note: Specifically located in the principal piece of sperm tail.
Tissue specificity	Testis-specific. Ref.3 Ref.4
Sequence similarities	Belongs to the cation channel sperm-associated (TC 1.A.1.19) family. [View classification]
Sequence caution	The sequence AAI28139.1 differs from that shown. Reason: Frameshift at position 21. The sequence CAH71538.1 differs from that shown. Reason: Erroneous initiation.

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 multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW sodium ion transport Inferred from electronic annotation. Source: Compara 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 acrosomal vesicle Inferred from electronic annotation. Source: Compara cilium Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	calcium activated cation channel activity Inferred from electronic annotation. Source: Compara 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...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7RTX7-1)

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: Q7RTX7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     227-242: Missing.
     401-472: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 472	472	Cation channel sperm-associated protein 4		PRO_0000295681
Regions
	Topological domain	1 – 90	90	Cytoplasmic Potential
	Transmembrane	91 – 111	21	Helical; Name=Segment S1; Potential
	Topological domain	112 – 130	19	Extracellular Potential
	Transmembrane	131 – 151	21	Helical; Name=Segment S2; Potential
	Topological domain	152 – 157	6	Cytoplasmic Potential
	Transmembrane	158 – 178	21	Helical; Name=Segment S3; Potential
	Topological domain	179	1	Extracellular Potential
	Transmembrane	180 – 197	18	Helical; Name=Segment S4; Potential
	Topological domain	198 – 216	19	Cytoplasmic Potential
	Transmembrane	217 – 237	21	Helical; Name=Segment S5; Potential
	Topological domain	238 – 246	9	Extracellular Potential
	Intramembrane	247 – 267	21	Helical; Pore-forming; Potential
	Topological domain	268 – 284	17	Extracellular Potential
	Transmembrane	285 – 305	21	Helical; Name=Segment S6; Potential
	Topological domain	306 – 472	167	Cytoplasmic Potential
Natural variations
	Alternative sequence	227 – 242	16	Missing in isoform 2.		VSP_026979
	Alternative sequence	401 – 472	72	Missing in isoform 2.		VSP_026980
	Natural variant	77	1	Q → R. Corresponds to variant rs11247866 [ dbSNP | Ensembl ].		VAR_033310
	Natural variant	124	1	L → F. Corresponds to variant rs12138368 [ dbSNP | Ensembl ].		VAR_033311
	Natural variant	293	1	I → V. Corresponds to variant rs17257155 [ dbSNP | Ensembl ].		VAR_033312
	Natural variant	436	1	D → N. Corresponds to variant rs6657616 [ dbSNP | Ensembl ].		VAR_033313

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 15, 2003. Version 1. Checksum: 5AC94CD0971A25FE	FASTA	472	54,092
	10 20 30 40 50 60 MRDNEKAWWQ QWTSHTGLEG WGGTQEDRMG FGGAVAALRG RPSPLQSTIH ESYGRPEEQV 70 80 90 100 110 120 LINRQEITNK ADAWDMQEFI THMYIKQLLR HPAFQLLLAL LLVINAITIA LRTNSYLDQK 130 140 150 160 170 180 HYELFSTIDD IVLTILLCEV LLGWLNGFWI FWKDGWNILN FIIVFILLLR FFINEINIPS 190 200 210 220 230 240 INYTLRALRL VHVCMAVEPL ARIIRVILQS VPDMANIMVL ILFFMLVFSV FGVTLFGAFV 250 260 270 280 290 300 PKHFQNIQVA LYTLFICITQ DGWVDIYSDF QTEKREYAME IGGAIYFTIF ITIGAFIGIN 310 320 330 340 350 360 LFVIVVTTNL EQMMKAGEQG QQQRITFSET GAEEEEENDQ LPLVHCVVAR SEKSGLLQEP 370 380 390 400 410 420 LAGGPLSNLS ENTCDNFCLV LEAIQENLRQ YKEIRDELNM IVEEVRAIRF NQEQESEVLN 430 440 450 460 470 RRSSTSGSLE TTSSKDIRQM SQQQDLLSAL VSMEKVHDSS SQILLKKHKS SH
	Isoform 2 [UniParc]. Checksum: 00D375891B88F6F3	FASTA	384	44,229
	10 20 30 40 50 60 MRDNEKAWWQ QWTSHTGLEG WGGTQEDRMG FGGAVAALRG RPSPLQSTIH ESYGRPEEQV 70 80 90 100 110 120 LINRQEITNK ADAWDMQEFI THMYIKQLLR HPAFQLLLAL LLVINAITIA LRTNSYLDQK 130 140 150 160 170 180 HYELFSTIDD IVLTILLCEV LLGWLNGFWI FWKDGWNILN FIIVFILLLR FFINEINIPS 190 200 210 220 230 240 INYTLRALRL VHVCMAVEPL ARIIRVILQS VPDMANIMVL ILFFMLHFQN IQVALYTLFI 250 260 270 280 290 300 CITQDGWVDI YSDFQTEKRE YAMEIGGAIY FTIFITIGAF IGINLFVIVV TTNLEQMMKA 310 320 330 340 350 360 GEQGQQQRIT FSETGAEEEE ENDQLPLVHC VVARSEKSGL LQEPLAGGPL SNLSENTCDN 370 380 FCLVLEAIQE NLRQYKEIRD ELNM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 1 AND 2).
[3]	"Identification of human and mouse CatSper3 and CatSper4 genes: characterisation of a common interaction domain and evidence for expression in testis." Lobley A., Pierron V., Reynolds L., Allen L., Michalovich D. Reprod. Biol. Endocrinol. 1:53-53(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, TISSUE SPECIFICITY.
[4]	"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.
[5]	"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.
[6]	"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	AL355877 Genomic DNA. Translation: CAH71538.1. Different initiation. BC128138 mRNA. Translation: AAI28139.1. Frameshift. BC128139 mRNA. Translation: AAI28140.1. BN000273 mRNA. Translation: CAE30475.1.
IPI	IPI00398709. IPI00854776.
RefSeq	NP_937770.1. NM_198137.1.
UniGene	Hs.123532.
3D structure databases
ProteinModelPortal	Q7RTX7.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000341006.
Protein family/group databases
TCDB	1.A.1.19.1. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	Q7RTX7.
Polymorphism databases
DMDM	74713153.
Proteomic databases
PaxDb	Q7RTX7.
PRIDE	Q7RTX7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000456354; ENSP00000390423; ENSG00000188782. ENST00000518899; ENSP00000429464; ENSG00000188782.
GeneID	378807.
KEGG	hsa:378807.
UCSC	uc010oey.1. human.
Organism-specific databases
CTD	378807.
GeneCards	GC01P026517.
HGNC	HGNC:23220. CATSPER4.
HPA	HPA045257.
MIM	609121. gene.
neXtProt	NX_Q7RTX7.
PharmGKB	PA134941696.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1226.
HOGENOM	HOG000112053.
HOVERGEN	HBG102124.
InParanoid	Q7RTX7.
PhylomeDB	Q7RTX7.
Gene expression databases
Bgee	Q7RTX7.
CleanEx	HS_CATSPER4.
Genevestigator	Q7RTX7.
Family and domain databases
InterPro	IPR005821. Ion_trans_dom. [Graphical view]
Pfam	PF00520. Ion_trans. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	378807.
NextBio	100804.
SOURCE	Search...

Entry information

Entry name

CTSR4_HUMAN

Accession

Primary (citable) accession number: Q7RTX7
Secondary accession number(s): A1A4W6, Q5VY71

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 24, 2007
Last sequence update:	December 15, 2003
Last modified:	April 3, 2013
This is version 76 of the entry and version 1 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.