CFA69_HUMAN
ID CFA69_HUMAN Reviewed; 941 AA.
AC A5D8W1; A3KMP9; B4DYW6; B4DZP7; B9EIM7; Q6V705; Q8IY89; Q9H7C2;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 3.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Cilia- and flagella-associated protein 69 {ECO:0000312|HGNC:HGNC:26107};
GN Name=CFAP69 {ECO:0000312|HGNC:HGNC:26107};
GN Synonyms=C7orf63 {ECO:0000312|HGNC:HGNC:26107};
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 MRNA] (ISOFORM 4).
RA Zhou G., Zhong G., Li H., Ke R., Shen C., Yu R., Lin L., Yang S.;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 418-941 (ISOFORM 2), AND VARIANTS MET-490
RP AND MET-885.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANTS
RP MET-490 AND MET-885.
RC TISSUE=Brain;
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INVOLVEMENT IN SPGF24,
RP AND VARIANT SPGF24 255-GLN--THR-941 DEL.
RX PubMed=29606301; DOI=10.1016/j.ajhg.2018.03.007;
RA Dong F.N., Amiri-Yekta A., Martinez G., Saut A., Tek J., Stouvenel L.,
RA Lores P., Karaouzene T., Thierry-Mieg N., Satre V., Brouillet S.,
RA Daneshipour A., Hosseini S.H., Bonhivers M., Gourabi H., Dulioust E.,
RA Arnoult C., Toure A., Ray P.F., Zhao H., Coutton C.;
RT "Absence of CFAP69 Causes Male Infertility due to Multiple Morphological
RT Abnormalities of the Flagella in Human and Mouse.";
RL Am. J. Hum. Genet. 102:636-648(2018).
CC -!- FUNCTION: Cilium- and flagellum-associated protein (PubMed:29606301).
CC In the olfactory epithelium, regulates the speed of activation and
CC termination of the odor response and thus contributes to the robustness
CC of olfactory transduction pathways (By similarity). Required for sperm
CC flagellum assembly and stability (PubMed:29606301).
CC {ECO:0000250|UniProtKB:Q8BH53, ECO:0000269|PubMed:29606301}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q8BH53}. Cell projection, cilium, flagellum
CC {ECO:0000269|PubMed:29606301}. Note=Localizes to the midpiece of the
CC sperm flagellum. {ECO:0000269|PubMed:29606301}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=A5D8W1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A5D8W1-2; Sequence=VSP_031676;
CC Name=3;
CC IsoId=A5D8W1-3; Sequence=VSP_031674, VSP_031675;
CC Name=4;
CC IsoId=A5D8W1-4; Sequence=VSP_031673, VSP_031674, VSP_031675;
CC Name=5;
CC IsoId=A5D8W1-5; Sequence=VSP_036548;
CC -!- TISSUE SPECIFICITY: Highly expressed in the testis, specifically in
CC sperm (at protein level) (PubMed:29606301). Expressed in the brain,
CC kidney, liver, lung, and intestine (PubMed:29606301).
CC {ECO:0000269|PubMed:29606301}.
CC -!- DISEASE: Spermatogenic failure 24 (SPGF24) [MIM:617959]: An autosomal
CC recessive infertility disorder caused by spermatogenesis defects that
CC result in multiple morphologic abnormalities of the flagella, including
CC absent, short, coiled, bent, and irregular-caliber flagella.
CC Malformations of the sperm head have also been observed. In addition,
CC patients exhibit very low sperm concentrations and total sperm counts
CC per ejaculate. {ECO:0000269|PubMed:29606301}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Incomplete sequence. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14972.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY349356; AAQ56720.1; -; mRNA.
DR EMBL; AK024715; BAB14972.1; ALT_INIT; mRNA.
DR EMBL; AK302636; BAG63878.1; -; mRNA.
DR EMBL; AK303034; BAG64159.1; -; mRNA.
DR EMBL; AC002064; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036351; AAH36351.1; -; mRNA.
DR EMBL; BC132771; AAI32772.1; -; mRNA.
DR EMBL; BC140742; AAI40743.1; -; mRNA.
DR EMBL; BC141834; AAI41835.1; -; mRNA.
DR EMBL; BC142655; AAI42656.1; -; mRNA.
DR CCDS; CCDS43613.2; -. [A5D8W1-1]
DR CCDS; CCDS55122.1; -. [A5D8W1-5]
DR RefSeq; NP_001034795.2; NM_001039706.2. [A5D8W1-1]
DR RefSeq; NP_001153610.1; NM_001160138.1. [A5D8W1-5]
DR RefSeq; XP_016868116.1; XM_017012627.1. [A5D8W1-2]
DR AlphaFoldDB; A5D8W1; -.
DR BioGRID; 122937; 8.
DR IntAct; A5D8W1; 2.
DR STRING; 9606.ENSP00000373948; -.
DR iPTMnet; A5D8W1; -.
DR PhosphoSitePlus; A5D8W1; -.
DR BioMuta; CFAP69; -.
DR EPD; A5D8W1; -.
DR MassIVE; A5D8W1; -.
DR PaxDb; A5D8W1; -.
DR PeptideAtlas; A5D8W1; -.
DR PRIDE; A5D8W1; -.
DR ProteomicsDB; 714; -. [A5D8W1-1]
DR ProteomicsDB; 715; -. [A5D8W1-2]
DR ProteomicsDB; 716; -. [A5D8W1-3]
DR ProteomicsDB; 717; -. [A5D8W1-4]
DR ProteomicsDB; 718; -. [A5D8W1-5]
DR Antibodypedia; 67513; 67 antibodies from 16 providers.
DR DNASU; 79846; -.
DR Ensembl; ENST00000389297.8; ENSP00000373948.4; ENSG00000105792.19. [A5D8W1-1]
DR Ensembl; ENST00000451029.5; ENSP00000411234.1; ENSG00000105792.19. [A5D8W1-3]
DR Ensembl; ENST00000497910.5; ENSP00000419549.1; ENSG00000105792.19. [A5D8W1-5]
DR GeneID; 79846; -.
DR KEGG; hsa:79846; -.
DR MANE-Select; ENST00000389297.8; ENSP00000373948.4; NM_001039706.3; NP_001034795.2.
DR UCSC; uc010lep.3; human. [A5D8W1-1]
DR CTD; 79846; -.
DR DisGeNET; 79846; -.
DR GeneCards; CFAP69; -.
DR HGNC; HGNC:26107; CFAP69.
DR HPA; ENSG00000105792; Low tissue specificity.
DR MalaCards; CFAP69; -.
DR MIM; 617959; phenotype.
DR neXtProt; NX_A5D8W1; -.
DR OpenTargets; ENSG00000105792; -.
DR Orphanet; 276234; Non-syndromic male infertility due to sperm motility disorder.
DR PharmGKB; PA162380735; -.
DR VEuPathDB; HostDB:ENSG00000105792; -.
DR eggNOG; ENOG502QV2V; Eukaryota.
DR GeneTree; ENSGT00390000014274; -.
DR HOGENOM; CLU_1209429_0_0_1; -.
DR InParanoid; A5D8W1; -.
DR OMA; MVQCYQN; -.
DR OrthoDB; 640213at2759; -.
DR PhylomeDB; A5D8W1; -.
DR TreeFam; TF328355; -.
DR PathwayCommons; A5D8W1; -.
DR SignaLink; A5D8W1; -.
DR BioGRID-ORCS; 79846; 12 hits in 1068 CRISPR screens.
DR ChiTaRS; CFAP69; human.
DR GenomeRNAi; 79846; -.
DR Pharos; A5D8W1; Tdark.
DR PRO; PR:A5D8W1; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; A5D8W1; protein.
DR Bgee; ENSG00000105792; Expressed in right uterine tube and 151 other tissues.
DR ExpressionAtlas; A5D8W1; baseline and differential.
DR Genevisible; A5D8W1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0097730; C:non-motile cilium; ISS:UniProtKB.
DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:MGI.
DR GO; GO:0042048; P:olfactory behavior; ISS:UniProtKB.
DR GO; GO:1905516; P:positive regulation of fertilization; ISS:UniProtKB.
DR GO; GO:1902093; P:positive regulation of flagellated sperm motility; ISS:UniProtKB.
DR GO; GO:1990834; P:response to odorant; ISS:UniProtKB.
DR GO; GO:0007608; P:sensory perception of smell; IEA:UniProtKB-KW.
DR GO; GO:0007288; P:sperm axoneme assembly; IMP:MGI.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR SUPFAM; SSF48371; SSF48371; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cilium; Differentiation; Flagellum;
KW Olfaction; Reference proteome; Sensory transduction; Spermatogenesis.
FT CHAIN 1..941
FT /note="Cilia- and flagella-associated protein 69"
FT /evidence="ECO:0000305"
FT /id="PRO_0000320596"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 118..119
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_031673"
FT VAR_SEQ 161..178
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036548"
FT VAR_SEQ 228..229
FT /note="EV -> GL (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_031674"
FT VAR_SEQ 230..941
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_031675"
FT VAR_SEQ 685..730
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_031676"
FT VARIANT 22
FT /note="S -> R (in dbSNP:rs17862129)"
FT /id="VAR_039219"
FT VARIANT 255..941
FT /note="Missing (in SPGF24)"
FT /evidence="ECO:0000269|PubMed:29606301"
FT /id="VAR_081046"
FT VARIANT 306
FT /note="R -> C (in dbSNP:rs17866223)"
FT /id="VAR_039220"
FT VARIANT 459
FT /note="P -> L (in dbSNP:rs17865959)"
FT /id="VAR_039221"
FT VARIANT 490
FT /note="V -> M (in dbSNP:rs1029365)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_039222"
FT VARIANT 885
FT /note="T -> M (in dbSNP:rs1134956)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_039223"
FT CONFLICT 101
FT /note="I -> V (in Ref. 2; BAG64159)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="K -> R (in Ref. 1; AAQ56720)"
FT /evidence="ECO:0000305"
FT CONFLICT 420
FT /note="Q -> H (in Ref. 2; BAB14972)"
FT /evidence="ECO:0000305"
FT CONFLICT 854
FT /note="S -> R (in Ref. 2; BAB14972/BAG63878/BAG64159 and 4;
FT AAI32772/AAI41835/AAI42656)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 941 AA; 105883 MW; BE2C49835F217D1F CRC64;
MWTEEAGATA EAQESGIRNK SSSSSQIPVV GVVTEDDEAQ DVFKPMDLNR VIKLLEETDK
DGLEEKQLKF VKKLVQCYQN GLPLRDLAQI FKILNLCSGK IKNQPRFIES AYDIIKLCGL
PFLKKKVSDE ITYAEDTANS IALLGDLMKI PSSELRIQIC KCIVDFYHAE PPKKHIPGYQ
QASSSYKIQM AEVGGLAKTM VQSMTLLENQ LVEKLWVLKV LQHLSTSEVN CTIMMKAQAA
SGICTHLNDP DPSGQLLFRS SEILWNLLEK SSKEEVIQQL SNLECLLALK EVFKNLFMRG
FSHYDRQLRN DILVITTIIA QNPEAPMIEC GFTKDLILFA TFNEVKSQNL LVKGLKLSNS
YEDFELKKLL FNVIVILCKD LPTVQLLIDG KVILALFTYV KKPEKQKIID WSAAQHEELQ
LHAIATLSSV APLLIEEYMS CQGNARVLAF LEWCESEDPF FSHGNSFHGT GGRGNKFAQM
RYSLRLLRAV VYLEDETVNK DLCEKGTIQQ MIGIFKNIIS KPNEKEEAIV LEIQSDILLI
LSGLCENHIQ RKEIFGTEGV DIVLHVMKTD PRKLQSGLGY NVLLFSTLDS IWCCILGCYP
SEDYFLEKEG IFLLLDLLAL NQKKFCNLIL GIMVEFCDNP KTAAHVNAWQ GKKDQTAASL
LIKLWRKEEK ELGVKRDKNG KIIDTKKPLF TSFQEEQKII PLPANCPSIA VMDVSENIRA
KIYAILGKLD FENLPGLSAE DFVTLCIIHR YLDFKIGEIW NEIYEEIKLE KLRPVTTDKK
ALEAITTASE NIGKMVASLQ SDIIESQACQ DMQNEQKVYA KIQATHKQRE LANKSWEDFL
ARTSNAKTLK KAKSLQEKAI EASRYHKRPQ NAIFHQTHIK GLNTTVPSGG VVTVESTPAR
LVGGPLVDTD IALKKLPIRG GALQRVKAVK IVDAPKKSIP T
