ID   DAZ1_HUMAN              Reviewed;         744 AA.
AC   Q9NQZ3; Q1RMF9; Q9NQZ4;
DT   01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2004, sequence version 2.
DT   24-JAN-2024, entry version 187.
DE   RecName: Full=Deleted in azoospermia protein 1;
GN   Name=DAZ1; Synonyms=DAZ, SPGY;
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=12815422; DOI=10.1038/nature01722;
RA   Skaletsky H., Kuroda-Kawaguchi T., Minx P.J., Cordum H.S., Hillier L.W.,
RA   Brown L.G., Repping S., Pyntikova T., Ali J., Bieri T., Chinwalla A.,
RA   Delehaunty A., Delehaunty K., Du H., Fewell G., Fulton L., Fulton R.,
RA   Graves T.A., Hou S.-F., Latrielle P., Leonard S., Mardis E., Maupin R.,
RA   McPherson J., Miner T., Nash W., Nguyen C., Ozersky P., Pepin K., Rock S.,
RA   Rohlfing T., Scott K., Schultz B., Strong C., Tin-Wollam A., Yang S.-P.,
RA   Waterston R.H., Wilson R.K., Rozen S., Page D.C.;
RT   "The male-specific region of the human Y chromosome is a mosaic of discrete
RT   sequence classes.";
RL   Nature 423:825-837(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 244-744 (ISOFORM 1), GENE STRUCTURE, GENE
RP   NOMENCLATURE, AND TISSUE SPECIFICITY.
RX   PubMed=10936047; DOI=10.1006/geno.2000.6260;
RA   Saxena R., de Vries J.W.A., Repping S., Alagappan R.K., Skaletsky H.,
RA   Brown L.G., Ma P., Chen E., Hoovers J.M.N., Page D.C.;
RT   "Four DAZ genes in two clusters found in the AZFc region of the human Y
RT   chromosome.";
RL   Genomics 67:256-267(2000).
RN   [4]
RP   INTERACTION WITH DAZAP1 AND DAZAP2.
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   [5]
RP   SUBCELLULAR LOCATION.
RX   PubMed=11058556; DOI=10.1095/biolreprod63.5.1490;
RA   Reijo R.A., Dorfman D.M., Slee R., Renshaw A.A., Loughlin K.R., Cooke H.,
RA   Page D.C.;
RT   "DAZ family proteins exist throughout male germ cell development and
RT   transit from nucleus to cytoplasm at meiosis in humans and mice.";
RL   Biol. Reprod. 63:1490-1496(2000).
RN   [6]
RP   INTERACTION WITH DAZL.
RX   PubMed=10903443; DOI=10.1016/s0378-1119(00)00219-5;
RA   Ruggiu M., Cooke H.J.;
RT   "In vivo and in vitro analysis of homodimerisation activity of the mouse
RT   Dazl1 protein.";
RL   Gene 252:119-126(2000).
RN   [7]
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   [8]
RP   INTERACTION WITH PUM2; DZIP1 AND DZIP3.
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   [9]
RP   REVIEW.
RX   PubMed=12752250; DOI=10.1034/j.1600-0463.2003.11101161.x;
RA   Vogt P.H., Fernandes S.;
RT   "Polymorphic DAZ gene family in polymorphic structure of AZFc locus:
RT   artwork or functional for human spermatogenesis?";
RL   APMIS 111:115-127(2003).
RN   [10]
RP   INVOLVEMENT IN SPGFY2.
RX   PubMed=11095434; DOI=10.1210/jcem.85.11.6929;
RA   Moro E., Ferlin A., Yen P.H., Franchi P.G., Palka G., Foresta C.;
RT   "Male infertility caused by a de novo partial deletion of the DAZ cluster
RT   on the Y chromosome.";
RL   J. Clin. Endocrinol. Metab. 85:4069-4073(2000).
RN   [11]
RP   INVOLVEMENT IN SPGFY2.
RX   PubMed=11870237; DOI=10.1093/molehr/8.3.286;
RA   Fernandes S., Huellen K., Goncalves J., Dukal H., Zeisler J.,
RA   Rajpert De Meyts E., Skakkebaek N.E., Habermann B., Krause W., Sousa M.,
RA   Barros A., Vogt P.H.;
RT   "High frequency of DAZ1/DAZ2 gene deletions in patients with severe
RT   oligozoospermia.";
RL   Mol. Hum. Reprod. 8:286-298(2002).
RN   [12]
RP   INVOLVEMENT IN SPGFY2.
RX   PubMed=12801575; DOI=10.1016/s0015-0282(03)00338-8;
RA   Gianotten J., Hoffer M.J.V., De Vries J.W.A., Leschot N.J., Gerris J.,
RA   van der Veen F.;
RT   "Partial DAZ deletions in a family with five infertile brothers.";
RL   Fertil. Steril. 79:1652-1655(2003).
RN   [13]
RP   GENE DUPLICATION.
RX   PubMed=16275261; DOI=10.1016/j.fertnstert.2005.06.021;
RA   Writzl K., Zorn B., Peterlin B.;
RT   "Copy number of DAZ genes in infertile men.";
RL   Fertil. Steril. 84:1522-1525(2005).
RN   [14]
RP   TISSUE SPECIFICITY.
RX   PubMed=18385127; DOI=10.1093/humrep/den099;
RA   Huang W.J., Lin Y.W., Hsiao K.N., Eilber K.S., Salido E.C., Yen P.H.;
RT   "Restricted expression of the human DAZ protein in premeiotic germ cells.";
RL   Hum. Reprod. 23:1280-1289(2008).
RN   [15]
RP   TISSUE SPECIFICITY.
RX   PubMed=19223287; DOI=10.1093/humrep/dep032;
RA   Kim B., Lee Y., Kim Y., Lee K.H., Chun S., Rhee K., Seo J.T., Kim S.W.,
RA   Paick J.S.;
RT   "Polymorphic expression of DAZ proteins in the human testis.";
RL   Hum. Reprod. 24:1507-1515(2009).
RN   [16]
RP   FUNCTION.
RX   PubMed=19865085; DOI=10.1038/nature08562;
RA   Kee K., Angeles V.T., Flores M., Nguyen H.N., Reijo Pera R.A.;
RT   "Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid
RT   gamete formation.";
RL   Nature 462:222-225(2009).
CC   -!- FUNCTION: RNA-binding protein that plays an essential role in
CC       spermatogenesis. May act by binding to the 3'-UTR of mRNAs and
CC       regulating their translation. Promotes germ-cell progression to meiosis
CC       and formation of haploid germ cells. {ECO:0000269|PubMed:19865085}.
CC   -!- SUBUNIT: Forms a heterodimer with BOLL and DAZL. Interacts with PUM2,
CC       DAZAP1, DAZAP2, DZIP1 and DZIP3. {ECO:0000269|PubMed:10857750,
CC       ECO:0000269|PubMed:10903443, ECO:0000269|PubMed:11390979,
CC       ECO:0000269|PubMed:12511597}.
CC   -!- INTERACTION:
CC       Q9NQZ3; Q96EP5: DAZAP1; NbExp=3; IntAct=EBI-997955, EBI-2133162;
CC       Q9NQZ3; Q15038: DAZAP2; NbExp=3; IntAct=EBI-997955, EBI-724310;
CC       Q9NQZ3; Q92904: DAZL; NbExp=2; IntAct=EBI-997955, EBI-998153;
CC       Q9NQZ3; Q8TB72: PUM2; NbExp=5; IntAct=EBI-997955, EBI-311190;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11058556}. Nucleus
CC       {ECO:0000269|PubMed:11058556}. Note=Predominantly cytoplasmic. Nuclear
CC       at some stages of spermatozoide development. Localizes both to the
CC       nuclei and cytoplasm of spermatozoide differentiation. Nuclear in fetal
CC       gonocytes and in spermatogonial nuclei. It then relocates to the
CC       cytoplasm during male meiosis.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NQZ3-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NQZ3-2; Sequence=VSP_056239, VSP_056240;
CC   -!- TISSUE SPECIFICITY: Testis-specific. Expression restricted to
CC       premeiotic germ cells, particularly in spermatogonia (at protein
CC       level). {ECO:0000269|PubMed:10936047, ECO:0000269|PubMed:18385127,
CC       ECO:0000269|PubMed:19223287}.
CC   -!- DOMAIN: The DAZ domains are essential and mediate the interaction with
CC       DAZAP1 and DAZAP2.
CC   -!- POLYMORPHISM: The number as well as the precise structure of the DAZ
CC       proteins probably differs within the population.
CC       {ECO:0000305|PubMed:12752250}.
CC   -!- DISEASE: Spermatogenic failure Y-linked 2 (SPGFY2) [MIM:415000]: A
CC       disorder resulting in the absence (azoospermia) or reduction
CC       (oligozoospermia) of sperm in the semen, leading to male infertility.
CC       {ECO:0000269|PubMed:11095434, ECO:0000269|PubMed:11870237,
CC       ECO:0000269|PubMed:12801575}. Note=The disease may be caused by
CC       variants affecting the gene represented in this entry. AZFc deletions
CC       in the Yq11.23 region including the DAZ genes are the most common known
CC       genetic cause of human male infertility.
CC   -!- MISCELLANEOUS: DAZ genes are prone to deletions but also to
CC       duplications. In a population of infertile men, DAZ genes deletions are
CC       associated with oligozoospermia but an increased number of DAZ genes is
CC       not a significant risk factor for spermatogenic failure.
CC   -!- MISCELLANEOUS: The DAZ proteins (DAZ, DAZ2, DAZ4 and DAZ4) are all
CC       encoded by a strongly repeated region of the Y chromosome, in two
CC       clusters each comprising an inverted pair of DAZ genes. They are very
CC       similar, which gives their indidual characterization difficult. Thus,
CC       most experiments do not discriminate between the different members. One
CC       can therefore suppose that reported interactions with a DAZ protein
CC       involve all the 4 proteins.
CC   -!- SIMILARITY: Belongs to the RRM DAZ family. {ECO:0000255|PROSITE-
CC       ProRule:PRU01238}.
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DR   EMBL; AC010088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC053490; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC006338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC114927; AAI14928.1; -; mRNA.
DR   EMBL; AF271087; AAF91405.1; -; Transcribed_RNA.
DR   EMBL; AF271088; AAF91406.1; -; mRNA.
DR   CCDS; CCDS48209.1; -. [Q9NQZ3-1]
DR   RefSeq; NP_004072.3; NM_004081.5. [Q9NQZ3-1]
DR   AlphaFoldDB; Q9NQZ3; -.
DR   BioGRID; 107986; 10.
DR   IntAct; Q9NQZ3; 10.
DR   STRING; 9606.ENSP00000384573; -.
DR   iPTMnet; Q9NQZ3; -.
DR   PhosphoSitePlus; Q9NQZ3; -.
DR   BioMuta; DAZ1; -.
DR   DMDM; 44887841; -.
DR   MassIVE; Q9NQZ3; -.
DR   ProteomicsDB; 61241; -.
DR   Antibodypedia; 21891; 193 antibodies from 25 providers.
DR   DNASU; 1617; -.
DR   Ensembl; ENST00000405239.6; ENSP00000384573.1; ENSG00000188120.16. [Q9NQZ3-1]
DR   GeneID; 1617; -.
DR   KEGG; hsa:1617; -.
DR   MANE-Select; ENST00000405239.6; ENSP00000384573.1; NM_004081.7; NP_004072.3.
DR   UCSC; uc004fvl.4; human. [Q9NQZ3-1]
DR   AGR; HGNC:2682; -.
DR   CTD; 1617; -.
DR   DisGeNET; 1617; -.
DR   GeneCards; DAZ1; -.
DR   GeneReviews; DAZ1; -.
DR   HGNC; HGNC:2682; DAZ1.
DR   HPA; ENSG00000188120; Tissue enriched (testis).
DR   MalaCards; DAZ1; -.
DR   MIM; 400003; gene.
DR   MIM; 415000; phenotype.
DR   neXtProt; NX_Q9NQZ3; -.
DR   OpenTargets; ENSG00000188120; -.
DR   Orphanet; 1646; Partial chromosome Y deletion.
DR   PharmGKB; PA27149; -.
DR   VEuPathDB; HostDB:ENSG00000188120; -.
DR   GeneTree; ENSGT00530000063480; -.
DR   HOGENOM; CLU_022076_0_0_1; -.
DR   InParanoid; Q9NQZ3; -.
DR   OrthoDB; 4705505at2759; -.
DR   PhylomeDB; Q9NQZ3; -.
DR   TreeFam; TF324396; -.
DR   PathwayCommons; Q9NQZ3; -.
DR   SignaLink; Q9NQZ3; -.
DR   BioGRID-ORCS; 1617; 11 hits in 263 CRISPR screens.
DR   ChiTaRS; DAZ1; human.
DR   GeneWiki; DAZ1; -.
DR   GenomeRNAi; 1617; -.
DR   Pharos; Q9NQZ3; Tbio.
DR   PRO; PR:Q9NQZ3; -.
DR   Proteomes; UP000005640; Chromosome Y.
DR   RNAct; Q9NQZ3; Protein.
DR   Bgee; ENSG00000188120; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 30 other cell types or tissues.
DR   ExpressionAtlas; Q9NQZ3; baseline.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR   GO; GO:0003730; F:mRNA 3'-UTR binding; IBA:GO_Central.
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:0030154; P:cell differentiation; IEA:UniProtKB-KW.
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; 3.
DR   Gene3D; 3.30.70.330; -; 3.
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:SF8; DELETED IN AZOOSPERMIA PROTEIN 1-RELATED; 1.
DR   Pfam; PF18872; Daz; 9.
DR   Pfam; PF00076; RRM_1; 3.
DR   SMART; SM00360; RRM; 3.
DR   SUPFAM; SSF54928; RNA-binding domain, RBD; 3.
DR   PROSITE; PS51890; DAZ; 9.
DR   PROSITE; PS50102; RRM; 3.
DR   Genevisible; Q9NQZ3; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Developmental protein; Differentiation;
KW   Nucleus; Reference proteome; Repeat; RNA-binding; Spermatogenesis.
FT   CHAIN           1..744
FT                   /note="Deleted in azoospermia protein 1"
FT                   /id="PRO_0000081554"
FT   DOMAIN          40..115
FT                   /note="RRM 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT   DOMAIN          205..280
FT                   /note="RRM 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT   DOMAIN          370..445
FT                   /note="RRM 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT   DOMAIN          497..520
FT                   /note="DAZ 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT   DOMAIN          521..544
FT                   /note="DAZ 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT   DOMAIN          545..568
FT                   /note="DAZ 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT   DOMAIN          569..592
FT                   /note="DAZ 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT   DOMAIN          593..616
FT                   /note="DAZ 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT   DOMAIN          617..640
FT                   /note="DAZ 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT   DOMAIN          641..664
FT                   /note="DAZ 7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT   DOMAIN          665..688
FT                   /note="DAZ 8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT   DOMAIN          689..712
FT                   /note="DAZ 9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT   REGION          1..27
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          163..192
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          328..357
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         589..613
FT                   /note="YNYQPFPAYPSSPFQVTAGYQLPVY -> CEICKILVLKNAAAFLCHSKVNR
FT                   SI (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_056239"
FT   VAR_SEQ         614..744
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_056240"
FT   CONFLICT        287
FT                   /note="R -> G (in Ref. 3; AAF91405)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   744 AA;  82764 MW;  341CB19EFC82F757 CRC64;
     MSAANPETPN STISREASTQ SSSAAASQGW VLPEGKIVPN TVFVGGIDAR MDETEIGSCF
     GRYGSVKEVK IITNRTGVSK GYGFVSFVND VDVQKIVGSQ IHFHGKKLKL GPAIRKQKLC
     ARHVQPRPLV VNPPPPPQFQ NVWRNPNTET YLQPQITPNP VTQHVQSAAN PETPNSTISR
     EASTQSSSAA ASQGWVLPEG KIVPNTVFVG GIDARMDETE IGSCFGRYGS VKEVKIITNR
     TGVSKGYGFV SFVNDVDVQK IVGSQIHFHG KKLKLGPAIR KQKLCARHVQ PRPLVVNPPP
     PPQFQNVWRN PNTETYLQPQ ITPNPVTQHV QSAANPETPN STISREASTQ SSSAAASQGW
     VLPEGKIVPN TVFVGGIDAR MDETEIGSCF GRYGSVKEVK IITNRTGVSK GYGFVSFVND
     VDVQKIVGSQ IHFHGKKLKL GPAIRKQKLC ARHVQPRPLV VNPPPPPQFQ NVWRNPNTET
     YLQPQITPNP VTQHVQAYSA YPHSPGQVIT GCQLLVYNYQ EYPTYPDSAF QVTTGYQLPV
     YNYQPFPAYP RSPFQVTAGY QLPVYNYQAF PAYPNSPFQV ATGYQFPVYN YQPFPAYPSS
     PFQVTAGYQL PVYNYQAFPA YPNSPFQVAT GYQFPVYNYQ AFPAYPNSPV QVTTGYQLPV
     YNYQAFPAYP SSPFQVTTGY QLPVYNYQAF PAYPNSAVQV TTGYQFHVYN YQMPPQCPVG
     EQRRNLWTEA YKWWYLVCLI QRRD
//