ID   EFCB9_HUMAN             Reviewed;         197 AA.
AC   A8MZ26;
DT   10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT   10-JUN-2008, sequence version 2.
DT   24-JAN-2024, entry version 107.
DE   RecName: Full=EF-hand calcium-binding domain-containing protein 9 {ECO:0000305};
GN   Name=EFCAB9 {ECO:0000312|HGNC:HGNC:34530};
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 [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
CC   -!- FUNCTION: Auxiliary component of the CatSper complex, a complex
CC       involved in sperm cell hyperactivation. pH-dependent Ca(2+) sensor
CC       required to activate the CatSper channel. Sperm cell hyperactivation is
CC       needed for sperm motility which is essential late in the preparation of
CC       sperm for fertilization. Associates with the CatSper complex via direct
CC       interaction with CATSPERZ, and senses intracellular Ca(2+). Together
CC       with CATSPERZ, associates with the CatSper channel pore and is required
CC       for the two-row structure of each single CatSper channel.
CC       {ECO:0000250|UniProtKB:Q9DAM2}.
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 CATSPERZ; the interaction is direct,
CC       Ca(2+)-dependent and connects EFCAB9 with the CatSper complex (By
CC       similarity). Dissociates from CATSPERZ at elevated pH (By similarity).
CC       {ECO:0000250|UniProtKB:Q91ZR5, ECO:0000250|UniProtKB:Q9DAM2}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9DAM2}. Cell
CC       projection, cilium, flagellum {ECO:0000250|UniProtKB:Q9DAM2}.
CC       Note=Localizes to the principal piece of the sperm tail.
CC       {ECO:0000250|UniProtKB:Q9DAM2}.
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; AC024561; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS54946.1; -.
DR   RefSeq; NP_001164654.1; NM_001171183.1.
DR   AlphaFoldDB; A8MZ26; -.
DR   SMR; A8MZ26; -.
DR   STRING; 9606.ENSP00000381247; -.
DR   TCDB; 1.A.1.19.1; the voltage-gated ion channel (vic) superfamily.
DR   iPTMnet; A8MZ26; -.
DR   PhosphoSitePlus; A8MZ26; -.
DR   BioMuta; EFCAB9; -.
DR   EPD; A8MZ26; -.
DR   jPOST; A8MZ26; -.
DR   MassIVE; A8MZ26; -.
DR   PaxDb; 9606-ENSP00000381247; -.
DR   PeptideAtlas; A8MZ26; -.
DR   ProteomicsDB; 2449; -.
DR   DNASU; 285588; -.
DR   Ensembl; ENST00000398186.5; ENSP00000381247.4; ENSG00000214360.5.
DR   GeneID; 285588; -.
DR   KEGG; hsa:285588; -.
DR   MANE-Select; ENST00000398186.5; ENSP00000381247.4; NM_001171183.2; NP_001164654.1.
DR   UCSC; uc021yhr.2; human.
DR   AGR; HGNC:34530; -.
DR   CTD; 285588; -.
DR   DisGeNET; 285588; -.
DR   GeneCards; EFCAB9; -.
DR   HGNC; HGNC:34530; EFCAB9.
DR   HPA; ENSG00000214360; Tissue enriched (testis).
DR   MIM; 618520; gene.
DR   neXtProt; NX_A8MZ26; -.
DR   PharmGKB; PA164718963; -.
DR   VEuPathDB; HostDB:ENSG00000214360; -.
DR   eggNOG; KOG0027; Eukaryota.
DR   GeneTree; ENSGT00390000007501; -.
DR   HOGENOM; CLU_106342_0_0_1; -.
DR   InParanoid; A8MZ26; -.
DR   OMA; EFYMLVC; -.
DR   OrthoDB; 3740718at2759; -.
DR   PhylomeDB; A8MZ26; -.
DR   TreeFam; TF328944; -.
DR   PathwayCommons; A8MZ26; -.
DR   SignaLink; A8MZ26; -.
DR   BioGRID-ORCS; 285588; 13 hits in 1136 CRISPR screens.
DR   ChiTaRS; EFCAB9; human.
DR   GenomeRNAi; 285588; -.
DR   Pharos; A8MZ26; Tdark.
DR   PRO; PR:A8MZ26; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; A8MZ26; Protein.
DR   Bgee; ENSG00000214360; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 36 other cell types or tissues.
DR   GO; GO:0036128; C:CatSper complex; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0097228; C:sperm principal piece; ISS:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0061891; F:calcium ion sensor activity; ISS:UniProtKB.
DR   GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB.
DR   GO; GO:0048240; P:sperm capacitation; ISS:UniProtKB.
DR   GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR   Gene3D; 1.10.238.10; EF-hand; 1.
DR   InterPro; IPR011992; EF-hand-dom_pair.
DR   InterPro; IPR002048; EF_hand_dom.
DR   InterPro; IPR042798; EFCAB9.
DR   PANTHER; PTHR47065; EF-HAND CALCIUM-BINDING DOMAIN-CONTAINING PROTEIN 9; 1.
DR   PANTHER; PTHR47065:SF1; EF-HAND CALCIUM-BINDING DOMAIN-CONTAINING PROTEIN 9; 1.
DR   Pfam; PF13499; EF-hand_7; 1.
DR   SUPFAM; SSF47473; EF-hand; 1.
DR   PROSITE; PS50222; EF_HAND_2; 2.
PE   3: Inferred from homology;
KW   Calcium; Cell projection; Cilium; Cytoplasm; Flagellum; Metal-binding;
KW   Reference proteome; Repeat.
FT   CHAIN           1..197
FT                   /note="EF-hand calcium-binding domain-containing protein 9"
FT                   /id="PRO_0000340648"
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:0000250|UniProtKB:Q9DAM2"
FT   DOMAIN          136..171
FT                   /note="EF-hand 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   REGION          177..197
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        177..191
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         58
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         155
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"
SQ   SEQUENCE   197 AA;  23937 MW;  248012FD9746D508 CRC64;
     MRLKQGSFLW YLYLDKIYCL LSVRNVKALA EYFHILDVHG KNTLNDVLFY HFLHHVTDLK
     KAQINIVFDM LDWNAVGEID FEKFYMLVCM LLAHQNHLEG QFMYRHSRPV FDLLDLKGDL
     RIGAKNFEMY RFLFNIQKQE LKDLFRDFDI TGDNRLNYQE FKLYTIIYTD KLQKRQKTEE
     KEKGERKRSL YSKCHIK
//