DKKL1_MOUSE
ID DKKL1_MOUSE Reviewed; 230 AA.
AC Q9QZL9; Q9EQT4; Q9ERW0; Q9ERW1;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Dickkopf-like protein 1 {ECO:0000250|UniProtKB:Q9UK85};
DE AltName: Full=Protein soggy-1;
DE Short=SGY-1 {ECO:0000303|PubMed:10570958};
DE Flags: Precursor;
GN Name=Dkkl1 {ECO:0000312|MGI:MGI:1354963}; Synonyms=Sgy1;
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 [MRNA].
RX PubMed=10570958; DOI=10.1016/s0378-1119(99)00365-0;
RA Krupnik V.E., Sharp J.D., Jiang C., Robison K., Chickering T.W.,
RA Amaravadi L., Brown D.E., Guyot D., Mays G., Leiby K., Chang B., Duong T.,
RA Goodearl A.D.J., Gearing D.P., Sokol S.Y., McCarthy S.A.;
RT "Functional and structural diversity of the human Dickkopf gene family.";
RL Gene 238:301-313(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-128,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11024178; DOI=10.1093/nar/28.20.3982;
RA Kaneko K.J., DePamphilis M.L.;
RT "Soggy, a spermatocyte-specific gene, lies upstream of and antipodal to
RT TEAD-2, a transcription factor expressed at the beginning of mouse
RT development.";
RL Nucleic Acids Res. 28:3982-3990(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RA Tate G.;
RT "Genomic organization of the human and mouse Soggy.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 TISSUE SPECIFICITY, GLYCOSYLATION, DEVELOPMENTAL STAGE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15892050; DOI=10.1002/mrd.20314;
RA Kohn M.J., Kaneko K.J., DePamphilis M.L.;
RT "DkkL1 (Soggy), a Dickkopf family member, localizes to the acrosome during
RT mammalian spermatogenesis.";
RL Mol. Reprod. Dev. 71:516-522(2005).
RN [6]
RP INTERACTION WITH SLY, AND SUBCELLULAR LOCATION.
RX PubMed=19176879; DOI=10.1095/biolreprod.108.075382;
RA Reynard L.N., Cocquet J., Burgoyne P.S.;
RT "The multi-copy mouse gene Sycp3-like Y-linked (Sly) encodes an abundant
RT spermatid protein that interacts with a histone acetyltransferase and an
RT acrosomal protein.";
RL Biol. Reprod. 81:250-257(2009).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18818293; DOI=10.1210/en.2008-0673;
RA Dakhova O., O'Day D., Kinet N., Yucer N., Wiese M., Shetty G., Ducy P.;
RT "Dickkopf-like1 regulates postpubertal spermatocyte apoptosis and
RT testosterone production.";
RL Endocrinology 150:404-412(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, GLYCOSYLATION, AND FUNCTION.
RX PubMed=19596310; DOI=10.1016/j.fertnstert.2009.06.011;
RA Kaneko K.J., Kohn M.J., Liu C., DePamphilis M.L.;
RT "The acrosomal protein Dickkopf-like 1 (DKKL1) is not essential for
RT fertility.";
RL Fertil. Steril. 93:1526-1532(2010).
RN [10]
RP DEVELOPMENTAL STAGE, AND FUNCTION.
RX PubMed=19596312; DOI=10.1016/j.fertnstert.2009.06.010;
RA Kohn M.J., Sztein J., Yagi R., DePamphilis M.L., Kaneko K.J.;
RT "The acrosomal protein Dickkopf-like 1 (DKKL1) facilitates sperm
RT penetration of the zona pellucida.";
RL Fertil. Steril. 93:1533-1537(2010).
RN [11]
RP INTERACTION WITH SLXL1.
RX PubMed=21698294; DOI=10.1371/journal.pone.0020866;
RA Zhuang X.J., Hou X.J., Liao S.Y., Wang X.X., Cooke H.J., Zhang M., Han C.;
RT "SLXL1, a novel acrosomal protein, interacts with DKKL1 and is involved in
RT fertilization in mice.";
RL PLoS ONE 6:E20866-E20866(2011).
RN [12]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=22817830; DOI=10.1186/1477-7827-10-51;
RA Yan Q., Wu X., Chen C., Diao R., Lai Y., Huang J., Chen J., Yu Z., Gui Y.,
RA Tang A., Cai Z.;
RT "Developmental expression and function of DKKL1/Dkkl1 in humans and mice.";
RL Reprod. Biol. Endocrinol. 10:51-51(2012).
RN [13]
RP DEVELOPMENTAL STAGE.
RX PubMed=27550540; DOI=10.1038/srep31668;
RA Mulvaney J.F., Thompkins C., Noda T., Nishimura K., Sun W.W., Lin S.Y.,
RA Coffin A., Dabdoub A.;
RT "Kremen1 regulates mechanosensory hair cell development in the mammalian
RT cochlea and the zebrafish lateral line.";
RL Sci. Rep. 6:31668-31668(2016).
CC -!- FUNCTION: Involved in fertilization by facilitating sperm penetration
CC of the zona pellucida (PubMed:19596312, PubMed:22817830). May promote
CC spermatocyte apoptosis, thereby limiting sperm production. In adults,
CC may reduce testosterone synthesis in Leydig cells (PubMed:18818293). Is
CC not essential either for development or fertility (PubMed:19596310).
CC {ECO:0000269|PubMed:18818293, ECO:0000269|PubMed:19596310,
CC ECO:0000269|PubMed:19596312, ECO:0000269|PubMed:22817830}.
CC -!- SUBUNIT: Interacts with SLXL1; Co-localize in seminiferous tubules
CC (PubMed:21698294). Interacts with SLY (PubMed:19176879).
CC {ECO:0000269|PubMed:19176879, ECO:0000269|PubMed:21698294}.
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000269|PubMed:15892050, ECO:0000269|PubMed:19176879}.
CC Note=Localized specifically to the crescent shaped acrosome at the apex
CC of the sperm head. {ECO:0000269|PubMed:15892050}.
CC -!- TISSUE SPECIFICITY: Testis-specific. Abundant in the seminiferous
CC tubules where it is associated with developing spermatocytes. Expressed
CC only in testis (at protein level) (PubMed:15892050, PubMed:19596310).
CC Not detectable on postnatal days 4 and 9 but after day 18 it gradually
CC increased as the development of testes progressed. Expressed at high
CC levels in testis and at weak levels in epididymis (PubMed:22817830).
CC {ECO:0000269|PubMed:11024178, ECO:0000269|PubMed:15892050,
CC ECO:0000269|PubMed:19596310, ECO:0000269|PubMed:22817830}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the embryo only after day 15. In the
CC adult, expressed only in developing spermatocytes. Expressed in the
CC developing cochlea. Detected only in developing spermatocytes and
CC spermatids in seminiferous tubules. Moreover, first appears
CC specifically in zygotene/pachytene spermatocytes. Found in puddles in
CC the pachytene spermatocytes of all stage tubules and then in crescent
CC shaped structures characteristic of acrosomes in early step spermatids.
CC Detected in mature sperm (PubMed:15892050). Expressed strongly in
CC trophoblast stem cells and further up-regulated in trophoblast giant
CC cells. Expression is maintained in post-implantation placental tissues
CC in utero. Highly expressed from 7.5 dpc trophectoderm to 12.5 dpc
CC placenta. Expression remains baseline in postimplantation embryonic
CC tissues (PubMed:19596312). {ECO:0000269|PubMed:11024178,
CC ECO:0000269|PubMed:15892050, ECO:0000269|PubMed:19596312,
CC ECO:0000269|PubMed:27550540}.
CC -!- DOMAIN: Contains a N-terminal domain similar to that of the N-terminal
CC section of DKK3.
CC -!- PTM: N-glycosylated during spermatogenesis. Not N-glycosylated in
CC mature sperm. {ECO:0000269|PubMed:15892050,
CC ECO:0000269|PubMed:19596310}.
CC -!- DISRUPTION PHENOTYPE: Nullizygous embryos Dkkl1 mice develop into
CC viable, fertile adults. {ECO:0000269|PubMed:18818293,
CC ECO:0000269|PubMed:19596310}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF177399; AAF02679.1; -; mRNA.
DR EMBL; AF274312; AAG21340.1; -; mRNA.
DR EMBL; AF274313; AAG21341.1; -; Genomic_DNA.
DR EMBL; AB051203; BAB20027.1; -; Genomic_DNA.
DR EMBL; BC002215; AAH02215.1; -; mRNA.
DR CCDS; CCDS21235.1; -.
DR RefSeq; NP_056604.2; NM_015789.3.
DR AlphaFoldDB; Q9QZL9; -.
DR IntAct; Q9QZL9; 1.
DR STRING; 10090.ENSMUSP00000033057; -.
DR GlyGen; Q9QZL9; 3 sites.
DR PhosphoSitePlus; Q9QZL9; -.
DR PaxDb; Q9QZL9; -.
DR PRIDE; Q9QZL9; -.
DR ProteomicsDB; 279719; -.
DR Antibodypedia; 31990; 270 antibodies from 27 providers.
DR DNASU; 50722; -.
DR Ensembl; ENSMUST00000033057; ENSMUSP00000033057; ENSMUSG00000030792.
DR GeneID; 50722; -.
DR KEGG; mmu:50722; -.
DR UCSC; uc009guc.2; mouse.
DR CTD; 27120; -.
DR MGI; MGI:1354963; Dkkl1.
DR VEuPathDB; HostDB:ENSMUSG00000030792; -.
DR eggNOG; ENOG502SZ2Z; Eukaryota.
DR GeneTree; ENSGT00390000014026; -.
DR HOGENOM; CLU_100447_0_0_1; -.
DR InParanoid; Q9QZL9; -.
DR OMA; RRSHQDT; -.
DR OrthoDB; 1323997at2759; -.
DR PhylomeDB; Q9QZL9; -.
DR TreeFam; TF337340; -.
DR BioGRID-ORCS; 50722; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Dkkl1; mouse.
DR PRO; PR:Q9QZL9; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9QZL9; protein.
DR Bgee; ENSMUSG00000030792; Expressed in seminiferous tubule of testis and 77 other tissues.
DR ExpressionAtlas; Q9QZL9; baseline and differential.
DR Genevisible; Q9QZL9; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0039706; F:co-receptor binding; IBA:GO_Central.
DR GO; GO:0048019; F:receptor antagonist activity; IBA:GO_Central.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:2000225; P:negative regulation of testosterone biosynthetic process; IMP:UniProtKB.
DR GO; GO:0007341; P:penetration of zona pellucida; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IDA:MGI.
DR InterPro; IPR039863; DKK-like.
DR PANTHER; PTHR12113; PTHR12113; 1.
PE 1: Evidence at protein level;
KW Cytoplasmic vesicle; Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..230
FT /note="Dickkopf-like protein 1"
FT /id="PRO_0000007229"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 35
FT /note="F -> V (in Ref. 3; BAB20027)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="R -> S (in Ref. 3; BAB20027)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="L -> H (in Ref. 1; AAF02679)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 230 AA; 26639 MW; E50951F0975DDD8A CRC64;
MCRLRVLLLL LPLAFVSSSA LPIHDVDSQQ NTSGFLGLQR LLQSFSRLFL KNDLLRDLDN
FFSSPMDFRD LPRNFHQEEN QEHRMGNHTL SSHLQIDKVT DNQTGEVLIS EKVEASIEPE
RNPEGDWKVP KVEAKEPPVP VQKVTDSLHP EPRQVAFWIM KMPRRRTQPD VQDGGRWLIE
KRHRMQAIRD GLRGGAREDS LEDGVHIPQH AKLPVRKTHF LYILRPSQQL
