ACTL9_HUMAN
ID ACTL9_HUMAN Reviewed; 416 AA.
AC Q8TC94; A8K893; Q6X960;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Actin-like protein 9;
GN Name=ACTL9 {ECO:0000312|HGNC:HGNC:28494}; Synonyms=ACTL7C; ORFNames=HSD21;
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], AND VARIANT HIS-227.
RC TISSUE=Testis;
RA Yang C.B., Miao S.Y., Zhang X.D., Qiao Y., Liang G., Wang L.F.;
RT "A new spermatogenesis-related gene.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PHE-37; VAL-51 AND
RP HIS-227.
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=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [6]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-42 AND THR-332.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [7]
RP INVOLVEMENT IN SPGF53, VARIANTS SPGF53 LEU-345; LEU-380 AND
RP 403-TYR--TYR-416 DEL, CHARACTERIZATION OF VARIANTS SPGF53 LEU-345; LEU-380
RP AND 403-TYR--TYR-416 DEL, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP INTERACTION WITH ACTL7A, AND FUNCTION.
RX PubMed=33626338; DOI=10.1016/j.ajhg.2021.02.004;
RA Dai J., Zhang T., Guo J., Zhou Q., Gu Y., Zhang J., Hu L., Zong Y.,
RA Song J., Zhang S., Dai C., Gong F., Lu G., Zheng W., Lin G.;
RT "Homozygous pathogenic variants in ACTL9 cause fertilization failure and
RT male infertility in humans and mice.";
RL Am. J. Hum. Genet. 108:469-481(2021).
CC -!- FUNCTION: Testis-specic protein that plays an important role in fusion
CC of proacrosomal vesicles and perinuclear theca formation.
CC {ECO:0000269|PubMed:33626338}.
CC -!- SUBUNIT: Interacts with ACTL7A. {ECO:0000269|PubMed:33626338}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome
CC {ECO:0000269|PubMed:33626338}. Cytoplasm, cytoskeleton, perinuclear
CC theca {ECO:0000269|PubMed:33626338}. Note=Localizes predominantly in
CC the equatorial segment of the sperm head and neck regions, with some
CC localization in the acrosomal segment of the head. Colocalizes in the
CC acrosomal and equatorial segments of sperm with ACTL7A. Colocalizes
CC with PLCZ1 in the equatorial segment of the head of capacitated sperm.
CC {ECO:0000269|PubMed:33626338}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:33626338}.
CC -!- DISEASE: Spermatogenic failure 53 (SPGF53) [MIM:619258]: An autosomal
CC recessive infertility disorder characterized by impaired oocyte
CC fertilization due to oocyte activation failure, in association with
CC structural anomalies in sperm heads. {ECO:0000269|PubMed:33626338}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the actin family. {ECO:0000305}.
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DR EMBL; AY248901; AAP20052.1; -; mRNA.
DR EMBL; AK292258; BAF84947.1; -; mRNA.
DR EMBL; AC093230; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024028; AAH24028.1; -; mRNA.
DR EMBL; BC045752; AAH45752.1; -; mRNA.
DR CCDS; CCDS12207.1; -.
DR RefSeq; NP_848620.3; NM_178525.4.
DR AlphaFoldDB; Q8TC94; -.
DR BioGRID; 129853; 1.
DR STRING; 9606.ENSP00000316674; -.
DR iPTMnet; Q8TC94; -.
DR PhosphoSitePlus; Q8TC94; -.
DR BioMuta; ACTL9; -.
DR DMDM; 308153636; -.
DR MassIVE; Q8TC94; -.
DR PaxDb; Q8TC94; -.
DR PeptideAtlas; Q8TC94; -.
DR PRIDE; Q8TC94; -.
DR ProteomicsDB; 74103; -.
DR Antibodypedia; 12540; 119 antibodies from 19 providers.
DR DNASU; 284382; -.
DR Ensembl; ENST00000324436.5; ENSP00000316674.3; ENSG00000181786.5.
DR Ensembl; ENST00000612068.1; ENSP00000482603.1; ENSG00000181786.5.
DR GeneID; 284382; -.
DR KEGG; hsa:284382; -.
DR MANE-Select; ENST00000324436.5; ENSP00000316674.3; NM_178525.5; NP_848620.3.
DR UCSC; uc032hly.2; human.
DR CTD; 284382; -.
DR DisGeNET; 284382; -.
DR GeneCards; ACTL9; -.
DR HGNC; HGNC:28494; ACTL9.
DR HPA; ENSG00000181786; Tissue enriched (testis).
DR MIM; 619251; gene.
DR MIM; 619258; phenotype.
DR neXtProt; NX_Q8TC94; -.
DR OpenTargets; ENSG00000181786; -.
DR Orphanet; 276234; Non-syndromic male infertility due to sperm motility disorder.
DR PharmGKB; PA165392996; -.
DR VEuPathDB; HostDB:ENSG00000181786; -.
DR eggNOG; KOG0676; Eukaryota.
DR GeneTree; ENSGT00940000163012; -.
DR HOGENOM; CLU_027965_0_2_1; -.
DR InParanoid; Q8TC94; -.
DR OrthoDB; 649708at2759; -.
DR PhylomeDB; Q8TC94; -.
DR TreeFam; TF354237; -.
DR PathwayCommons; Q8TC94; -.
DR SignaLink; Q8TC94; -.
DR BioGRID-ORCS; 284382; 14 hits in 1060 CRISPR screens.
DR GenomeRNAi; 284382; -.
DR Pharos; Q8TC94; Tdark.
DR PRO; PR:Q8TC94; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8TC94; protein.
DR Bgee; ENSG00000181786; Expressed in sperm and 35 other tissues.
DR Genevisible; Q8TC94; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR GO; GO:0005869; C:dynactin complex; IBA:GO_Central.
DR GO; GO:0033011; C:perinuclear theca; IDA:UniProtKB.
DR GO; GO:0061827; C:sperm head; IDA:UniProtKB.
DR GO; GO:0001675; P:acrosome assembly; IMP:UniProtKB.
DR GO; GO:0009566; P:fertilization; IDA:UniProtKB.
DR GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW.
DR InterPro; IPR004000; Actin.
DR InterPro; IPR030074; ACTL9.
DR InterPro; IPR043129; ATPase_NBD.
DR PANTHER; PTHR11937; PTHR11937; 1.
DR PANTHER; PTHR11937:SF194; PTHR11937:SF194; 1.
DR Pfam; PF00022; Actin; 1.
DR PRINTS; PR00190; ACTIN.
DR SMART; SM00268; ACTIN; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Disease variant;
KW Fertilization; Reference proteome.
FT CHAIN 1..416
FT /note="Actin-like protein 9"
FT /id="PRO_0000332297"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 37
FT /note="S -> F (in dbSNP:rs2340550)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_043000"
FT VARIANT 42
FT /note="A -> D (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_043001"
FT VARIANT 51
FT /note="A -> V (in dbSNP:rs10410943)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_043002"
FT VARIANT 227
FT /note="N -> H (in dbSNP:rs4804079)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.1"
FT /id="VAR_043003"
FT VARIANT 332
FT /note="A -> T (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs782721280)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_043004"
FT VARIANT 345
FT /note="S -> L (in SPGF53; unknown pathological
FT significance; reduces interaction with ACTL7A)"
FT /evidence="ECO:0000269|PubMed:33626338"
FT /id="VAR_085431"
FT VARIANT 380
FT /note="V -> L (in SPGF53; unknown pathological
FT significance; reduces interaction with ACTL7A)"
FT /evidence="ECO:0000269|PubMed:33626338"
FT /id="VAR_085432"
FT VARIANT 403..416
FT /note="Missing (in SPGF53; unknown pathological
FT significance; abolishes interaction with ACTL7A)"
FT /evidence="ECO:0000269|PubMed:33626338"
FT /id="VAR_085433"
FT CONFLICT 148
FT /note="F -> S (in Ref. 1; AAP20052)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 416 AA; 45516 MW; B4CE3043F99E2195 CRC64;
MDASRPKSSE SQSSLEAPRP GPNPSPNVVN KPLQRDSPGM VADRLPPKTG AVVIDMGTGT
CKVGFAGQAS PTYTVATILG CQPKKPATSG QSGLQTFIGE AARVLPELTL VQPLRSGIVV
DWDAAELIWR HLLEHDLRVA THDHPLLFSD PPFSPATNRE KLVEVAFESL RSPAMYVASQ
SVLSVYAHGR VSGLVVDTGH GVTYTVPVFQ GYNLLHATER LDLAGNNLTA FLAEMLLQAG
LPLGQQDLDL VENIKHHYCY VASDFQKEQA RPEQEYKRTL KLPDGRTVTL GKELFQCPEL
LFNPPEVPGL SPVGLSTMAK QSLRKLSLEM RADLAQNVLL CGGSSLFTGF EGRFRAELLR
ALPAETHVVV AAQPTRNFSV WIGGSILASL RAFQSCWVLR EQYEEQGPYI VYRKCY
