ID DAZL_HUMAN Reviewed; 295 AA. AC Q92904; O15396; Q5HYB4; Q92909; DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 27-MAR-2024, entry version 198. DE RecName: Full=Deleted in azoospermia-like; DE AltName: Full=DAZ homolog; DE AltName: Full=DAZ-like autosomal; DE AltName: Full=Deleted in azoospermia-like 1; DE AltName: Full=SPGY-like-autosomal; GN Name=DAZL; Synonyms=DAZH, DAZL1, DAZLA, SPGYLA; 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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=8896558; DOI=10.1038/ng1196-292; RA Saxena R., Brown L.G., Hawkins T., Alagappan R.K., Skaletsky H., RA Reeve M.P., Reijo R.A., Rozen S., Dinulos M.B., Disteche C.M., Page D.C.; RT "The DAZ gene cluster on the human Y chromosome arose from an autosomal RT gene that was transposed, repeatedly amplified and pruned."; RL Nat. Genet. 14:292-299(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=8968755; DOI=10.1093/hmg/5.12.2005; RA Shan Z., Hirschmann P., Seebacher T., Edelmann A., Jauch A., Morell J., RA Urbitsch P., Vogt P.H.; RT "A SPGY copy homologous to the mouse gene Dazla and the Drosophila gene RT boule is autosomal and expressed only in the human male gonad."; RL Hum. Mol. Genet. 5:2005-2011(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=8968756; DOI=10.1093/hmg/5.12.2013; RA Yen P.H., Chai N.-N., Salido E.C.; RT "The human autosomal gene DAZLA: testis specificity and a candidate for RT male infertility."; RL Hum. Mol. Genet. 5:2013-2017(1996). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=9294855; DOI=10.1093/molehr/3.8.705; RA Chai N.-N., Phillips A., Fernandez A., Yen P.H.; RT "A putative human male infertility gene DAZLA: genomic structure and RT methylation status."; RL Mol. Hum. Reprod. 3:705-708(1997). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [10] RP DOMAIN, AND INTERACTION WITH DAZAP1 AND DAZAP2. RC TISSUE=Testis; RX PubMed=10857750; DOI=10.1006/geno.2000.6169; RA Tsui S., Dai T., Roettger S., Schempp W., Salido E.C., Yen P.H.; RT "Identification of two novel proteins that interact with germ-cell-specific RT RNA-binding proteins DAZ and DAZL1."; RL Genomics 65:266-273(2000). RN [11] RP INTERACTION WITH BOLL. RX PubMed=11390979; DOI=10.1073/pnas.131090498; RA Xu E.Y., Moore F.L., Reijo Pera R.A.; RT "A gene family required for human germ cell development evolved from an RT ancient meiotic gene conserved in metazoans."; RL Proc. Natl. Acad. Sci. U.S.A. 98:7414-7419(2001). RN [12] RP INTERACTION WITH PUM2. RX PubMed=12511597; DOI=10.1073/pnas.0234478100; RA Moore F.L., Jaruzelska J., Fox M.S., Urano J., Firpo M.T., Turek P.J., RA Dorfman D.M., Reijo Pera R.A.; RT "Human Pumilio-2 is expressed in embryonic stem cells and germ cells and RT interacts with DAZ (Deleted in AZoospermia) and DAZ-like proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 100:538-543(2003). RN [13] RP VARIANTS ALA-12 AND ALA-54. RX PubMed=12414900; DOI=10.1210/jc.2002-020016; RA Teng Y.-N., Lin Y.-M., Lin Y.-H., Tsao S.-Y., Hsu C.-C., Lin S.-J., RA Tsai W.-C., Kuo P.-L.; RT "Association of a single-nucleotide polymorphism of the deleted-in- RT azoospermia-like gene with susceptibility to spermatogenic failure."; RL J. Clin. Endocrinol. Metab. 87:5258-5264(2002). RN [14] RP VARIANT GLY-115. RX PubMed=22021443; DOI=10.1073/pnas.1105211108; RA Jenkins H.T., Malkova B., Edwards T.A.; RT "Kinked beta-strands mediate high-affinity recognition of mRNA targets by RT the germ-cell regulator DAZL."; RL Proc. Natl. Acad. Sci. U.S.A. 108:18266-18271(2011). CC -!- FUNCTION: RNA-binding protein, which is essential for gametogenesis in CC both males and females. Plays a central role during spermatogenesis. CC Acts by binding to the 3'-UTR of mRNA, specifically recognizing GUU CC triplets, and thereby regulating the translation of key transcripts (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: Homodimer and heterodimer. Multiple DAZL RRMs can bind to a CC single RNA containing multiple GUU triplets (By similarity). Forms a CC heterodimer with DAZ. Interacts with BOLL, DAZAP1 and DAZAP2. Interacts CC with PUM2. {ECO:0000250, ECO:0000269|PubMed:10857750, CC ECO:0000269|PubMed:11390979, ECO:0000269|PubMed:12511597}. CC -!- INTERACTION: CC Q92904; Q9NQZ3: DAZ1; NbExp=2; IntAct=EBI-998153, EBI-997955; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. CC Note=Predominantly cytoplasmic. Nuclear in spermatogonia until near the CC end of the meiotic prophase and cytoplasmic localization from then CC onward. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q92904-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92904-2; Sequence=VSP_043208; CC -!- TISSUE SPECIFICITY: Testis specific. {ECO:0000269|PubMed:8896558, CC ECO:0000269|PubMed:8968755, ECO:0000269|PubMed:8968756}. CC -!- DOMAIN: The DAZ domain mediates the interaction with DAZAP1 and DAZAP2. CC {ECO:0000269|PubMed:10857750}. CC -!- SIMILARITY: Belongs to the RRM DAZ family. {ECO:0000255|PROSITE- CC ProRule:PRU01238}. 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; U65918; AAC50813.1; -; mRNA. DR EMBL; U66726; AAB39935.1; -; mRNA. DR EMBL; U66078; AAB63596.1; -; mRNA. DR EMBL; U77476; AAB84361.1; -; Genomic_DNA. DR EMBL; U77467; AAB84361.1; JOINED; Genomic_DNA. DR EMBL; U77468; AAB84361.1; JOINED; Genomic_DNA. DR EMBL; U77469; AAB84361.1; JOINED; Genomic_DNA. DR EMBL; U77470; AAB84361.1; JOINED; Genomic_DNA. DR EMBL; U77471; AAB84361.1; JOINED; Genomic_DNA. DR EMBL; U77472; AAB84361.1; JOINED; Genomic_DNA. DR EMBL; U77473; AAB84361.1; JOINED; Genomic_DNA. DR EMBL; U77474; AAB84361.1; JOINED; Genomic_DNA. DR EMBL; U77475; AAB84361.1; JOINED; Genomic_DNA. DR EMBL; AK303026; BAG64152.1; -; mRNA. DR EMBL; BX648638; CAI45996.1; -; mRNA. DR EMBL; AC010139; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471055; EAW64279.1; -; Genomic_DNA. DR EMBL; BC027595; AAH27595.1; -; mRNA. DR CCDS; CCDS43059.1; -. [Q92904-1] DR CCDS; CCDS54556.1; -. [Q92904-2] DR RefSeq; NP_001177740.1; NM_001190811.1. [Q92904-2] DR RefSeq; NP_001342.2; NM_001351.3. [Q92904-1] DR AlphaFoldDB; Q92904; -. DR SMR; Q92904; -. DR BioGRID; 107987; 145. DR IntAct; Q92904; 5. DR STRING; 9606.ENSP00000250863; -. DR iPTMnet; Q92904; -. DR PhosphoSitePlus; Q92904; -. DR BioMuta; DAZL; -. DR DMDM; 27805453; -. DR EPD; Q92904; -. DR MassIVE; Q92904; -. DR PaxDb; 9606-ENSP00000250863; -. DR PeptideAtlas; Q92904; -. DR ProteomicsDB; 75589; -. [Q92904-1] DR ProteomicsDB; 75590; -. [Q92904-2] DR Antibodypedia; 6122; 381 antibodies from 38 providers. DR DNASU; 1618; -. DR Ensembl; ENST00000250863.12; ENSP00000250863.8; ENSG00000092345.14. [Q92904-2] DR Ensembl; ENST00000399444.7; ENSP00000382373.3; ENSG00000092345.14. [Q92904-1] DR GeneID; 1618; -. DR KEGG; hsa:1618; -. DR MANE-Select; ENST00000399444.7; ENSP00000382373.3; NM_001351.4; NP_001342.2. DR UCSC; uc003cba.4; human. [Q92904-1] DR AGR; HGNC:2685; -. DR CTD; 1618; -. DR DisGeNET; 1618; -. DR GeneCards; DAZL; -. DR HGNC; HGNC:2685; DAZL. DR HPA; ENSG00000092345; Tissue enriched (testis). DR MIM; 601486; gene. DR neXtProt; NX_Q92904; -. DR OpenTargets; ENSG00000092345; -. DR PharmGKB; PA27155; -. DR VEuPathDB; HostDB:ENSG00000092345; -. DR eggNOG; KOG0118; Eukaryota. DR GeneTree; ENSGT00530000063480; -. DR HOGENOM; CLU_084802_0_0_1; -. DR InParanoid; Q92904; -. DR OMA; SQEDYFK; -. DR OrthoDB; 3964771at2759; -. DR PhylomeDB; Q92904; -. DR TreeFam; TF324396; -. DR PathwayCommons; Q92904; -. DR SignaLink; Q92904; -. DR BioGRID-ORCS; 1618; 33 hits in 1143 CRISPR screens. DR ChiTaRS; DAZL; human. DR GeneWiki; DAZL; -. DR GenomeRNAi; 1618; -. DR Pharos; Q92904; Tbio. DR PRO; PR:Q92904; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q92904; Protein. DR Bgee; ENSG00000092345; Expressed in oocyte and 56 other cell types or tissues. DR ExpressionAtlas; Q92904; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0005840; C:ribosome; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0003730; F:mRNA 3'-UTR binding; IBA:GO_Central. DR GO; GO:0003723; F:RNA binding; TAS:ProtInc. DR GO; GO:0008494; F:translation activator activity; IDA:UniProtKB. DR GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; IBA:GO_Central. DR GO; GO:0007147; P:female meiosis II; IEA:Ensembl. DR GO; GO:0007281; P:germ cell development; TAS:ProtInc. DR GO; GO:0001556; P:oocyte maturation; IEA:Ensembl. DR GO; GO:0045836; P:positive regulation of meiotic nuclear division; IEA:Ensembl. DR GO; GO:0045948; P:positive regulation of translational initiation; IDA:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW. DR CDD; cd12672; RRM_DAZL; 1. DR Gene3D; 3.30.70.330; -; 1. DR InterPro; IPR043628; DAZ_dom. DR InterPro; IPR037551; DAZ_RRM_vert. DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf. DR InterPro; IPR035979; RBD_domain_sf. DR InterPro; IPR000504; RRM_dom. DR PANTHER; PTHR11176; BOULE-RELATED; 1. DR PANTHER; PTHR11176:SF4; DELETED IN AZOOSPERMIA-LIKE; 1. DR Pfam; PF18872; Daz; 1. DR Pfam; PF00076; RRM_1; 1. DR SMART; SM00360; RRM; 1. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 1. DR PROSITE; PS51890; DAZ; 1. DR PROSITE; PS50102; RRM; 1. DR Genevisible; Q92904; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Developmental protein; Differentiation; KW Nucleus; Phosphoprotein; Reference proteome; RNA-binding; Spermatogenesis; KW Translation regulation. FT CHAIN 1..295 FT /note="Deleted in azoospermia-like" FT /id="PRO_0000081559" FT DOMAIN 40..115 FT /note="RRM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT DOMAIN 167..190 FT /note="DAZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01238" FT REGION 1..25 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 80..132 FT /note="Homodimerization" FT /evidence="ECO:0000250" FT MOD_RES 276 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q64368" FT VAR_SEQ 1 FT /note="M -> MAAPSCGGDRKARLTPSLPHE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17974005" FT /id="VSP_043208" FT VARIANT 12 FT /note="T -> A (in dbSNP:rs11710967)" FT /evidence="ECO:0000269|PubMed:12414900" FT /id="VAR_017780" FT VARIANT 54 FT /note="T -> A (probable risk factor for spermatogenic FT failure; this substitution may lead to affect the DAZL FT transcript stability and prevent its translation; FT dbSNP:rs121918346)" FT /evidence="ECO:0000269|PubMed:12414900" FT /id="VAR_017781" FT VARIANT 115 FT /note="R -> G (severely impaired RNA-binding)" FT /evidence="ECO:0000269|PubMed:22021443" FT /id="VAR_069231" FT CONFLICT 3 FT /note="T -> I (in Ref. 3; AAB63596)" FT /evidence="ECO:0000305" FT CONFLICT 253 FT /note="Q -> R (in Ref. 4; AAB84361)" FT /evidence="ECO:0000305" SQ SEQUENCE 295 AA; 33178 MW; 21B360739B35B95F CRC64; MSTANPETPN STISREASTQ SSSAATSQGY ILPEGKIMPN TVFVGGIDVR MDETEIRSFF ARYGSVKEVK IITDRTGVSK GYGFVSFFND VDVQKIVESQ INFHGKKLKL GPAIRKQNLC AYHVQPRPLV FNHPPPPQFQ NVWTNPNTET YMQPTTTMNP ITQYVQAYPT YPNSPVQVIT GYQLPVYNYQ MPPQWPVGEQ RSYVVPPAYS AVNYHCNEVD PGAEVVPNEC SVHEATPPSG NGPQKKSVDR SIQTVVSCLF NPENRLRNSV VTQDDYFKDK RVHHFRRSRA MLKSV //