EFCB9_MOUSE
ID EFCB9_MOUSE Reviewed; 216 AA.
AC Q9DAM2; Q9D5P6;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=EF-hand calcium-binding domain-containing protein 9 {ECO:0000305};
GN Name=Efcab9 {ECO:0000312|MGI:MGI:1916556};
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].
RC TISSUE=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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, INTERACTION WITH CATSPERZ, AND MUTAGENESIS OF ASP-72
RP AND GLU-160.
RX PubMed=31056283; DOI=10.1016/j.cell.2019.03.047;
RA Hwang J.Y., Mannowetz N., Zhang Y., Everley R.A., Gygi S.P., Bewersdorf J.,
RA Lishko P.V., Chung J.J.;
RT "Dual sensing of physiologic pH and calcium by EFCAB9 regulates sperm
RT motility.";
RL Cell 0:0-0(2019).
RN [5]
RP STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) OF THE CATSPER COMPLEX,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND FUNCTION.
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: Auxiliary component of the CatSper complex, a complex
CC involved in sperm cell hyperactivation (PubMed:34225353,
CC PubMed:31056283). pH-dependent Ca(2+) sensor required to activate the
CC CatSper channel (PubMed:31056283). Sperm cell hyperactivation is needed
CC for sperm motility which is essential late in the preparation of sperm
CC for fertilization (PubMed:31056283). Associates with the CatSper
CC complex via direct interaction with CATSPERZ, and senses intracellular
CC Ca(2+) (PubMed:31056283). Together with CATSPERZ, associates with the
CC CatSper channel pore and is required for the two-row structure of each
CC single CatSper channel (PubMed:31056283). {ECO:0000269|PubMed:31056283,
CC ECO:0000269|PubMed:34225353}.
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). HSPA1 may be an additional auxiliary complex member
CC (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3
CC and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The
CC auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a
CC pavilion-like structure over the pore which stabilizes the complex
CC through 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). Interacts with CATSPERZ; the interaction
CC is direct, Ca(2+)-dependent and connects EFCAB9 with the CatSper
CC complex (PubMed:31056283). Dissociates from CATSPERZ at elevated pH
CC (PubMed:31056283). {ECO:0000250|UniProtKB:Q91ZR5,
CC ECO:0000269|PubMed:31056283, ECO:0000269|PubMed:34225353, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:31056283}. Cell
CC projection, cilium, flagellum {ECO:0000269|PubMed:31056283}.
CC Note=Localizes to the principal piece of the sperm tail.
CC {ECO:0000269|PubMed:31056283}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:31056283}.
CC -!- DEVELOPMENTAL STAGE: Only expressed after meiosis in testis.
CC {ECO:0000269|PubMed:31056283}.
CC -!- DISRUPTION PHENOTYPE: Mice are normal but males show severe male
CC subfertility despite normal sperm morphology (PubMed:31056283).
CC Subfertility is caused by defects in sperm motility: spermatozoa have a
CC lower basal level of intracellular calcium and aberrant Ca(2+)
CC homeostasis (PubMed:31056283). {ECO:0000269|PubMed:31056283}.
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DR EMBL; AK005716; BAB24202.1; -; mRNA.
DR EMBL; AK015057; BAB29694.1; -; mRNA.
DR EMBL; AK161300; BAE36307.1; -; mRNA.
DR EMBL; AL669844; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC087911; AAH87911.1; -; mRNA.
DR CCDS; CCDS24528.1; -.
DR RefSeq; NP_081307.2; NM_027031.3.
DR RefSeq; XP_011242049.1; XM_011243747.2.
DR PDB; 7EEB; EM; 2.90 A; I=1-216.
DR PDBsum; 7EEB; -.
DR AlphaFoldDB; Q9DAM2; -.
DR SMR; Q9DAM2; -.
DR STRING; 10090.ENSMUSP00000060205; -.
DR PhosphoSitePlus; Q9DAM2; -.
DR PaxDb; Q9DAM2; -.
DR PRIDE; Q9DAM2; -.
DR ProteomicsDB; 277551; -.
DR DNASU; 69306; -.
DR Ensembl; ENSMUST00000054327; ENSMUSP00000060205; ENSMUSG00000044056.
DR GeneID; 69306; -.
DR KEGG; mmu:69306; -.
DR UCSC; uc007ijs.2; mouse.
DR CTD; 285588; -.
DR MGI; MGI:1916556; Efcab9.
DR VEuPathDB; HostDB:ENSMUSG00000044056; -.
DR eggNOG; KOG0027; Eukaryota.
DR GeneTree; ENSGT00390000007501; -.
DR HOGENOM; CLU_106342_0_0_1; -.
DR InParanoid; Q9DAM2; -.
DR OMA; EFYMLVC; -.
DR OrthoDB; 1306120at2759; -.
DR PhylomeDB; Q9DAM2; -.
DR TreeFam; TF328944; -.
DR BioGRID-ORCS; 69306; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Efcab9; mouse.
DR PRO; PR:Q9DAM2; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9DAM2; protein.
DR Bgee; ENSMUSG00000044056; Expressed in spermatid and 50 other tissues.
DR ExpressionAtlas; Q9DAM2; baseline and differential.
DR Genevisible; Q9DAM2; MM.
DR GO; GO:0036128; C:CatSper complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0097228; C:sperm principal piece; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0061891; F:calcium ion sensor activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0030317; P:flagellated sperm motility; IDA:UniProtKB.
DR GO; GO:0048240; P:sperm capacitation; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IDA:UniProtKB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR042798; EFCAB9.
DR PANTHER; PTHR47065; PTHR47065; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Calmodulin-binding; Cell projection; Cilium;
KW Cytoplasm; Differentiation; Flagellum; Metal-binding; Reference proteome;
KW Repeat; Spermatogenesis.
FT CHAIN 1..216
FT /note="EF-hand calcium-binding domain-containing protein 9"
FT /id="PRO_0000340649"
FT DOMAIN 59..94
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 100..135
FT /note="EF-hand 2"
FT /evidence="ECO:0000305|PubMed:15489334"
FT DOMAIN 136..171
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 60
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 62
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 69
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 149
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 153
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 160
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT MUTAGEN 72
FT /note="D->N: Reduced interaction with CATSPERZ due to
FT defects in Ca(2+)-binding; when associated with Q-160."
FT /evidence="ECO:0000269|PubMed:31056283"
FT MUTAGEN 160
FT /note="E->Q: Reduced interaction with CATSPERZ due to
FT defects in Ca(2+)-binding; when associated with N-72."
FT /evidence="ECO:0000269|PubMed:31056283"
FT CONFLICT 15
FT /note="D -> G (in Ref. 1; BAB24202)"
FT /evidence="ECO:0000305"
FT HELIX 5..17
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 25..36
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 46..56
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 61..71
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 81..91
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 97..105
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:7EEB"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 124..133
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 138..148
FT /evidence="ECO:0007829|PDB:7EEB"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:7EEB"
FT HELIX 158..173
FT /evidence="ECO:0007829|PDB:7EEB"
SQ SEQUENCE 216 AA; 26125 MW; 4BBEC60A157FD52A CRC64;
MKLTPGCFLW YLYMDKIYCL LSLRNVKALM VYFHLLDVHH RNTLNDVLFF HFLQHVTNLN
KSQIGMIFDL LDWTAVGEIG FDQFYVLICI LLAHQDHLED HFMYRHSRPV FELLDLDGEM
NIGAANFQNY RFLFNIKKQE LRDLFHDFDI TGDRLLNYKE FKLYTIFCTD KSIDRKKRRK
DREAAREREK EKGKDKEKYL HLKKIYSSML SHRSIL
