DAZ1_HUMAN
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 03-AUG-2022, entry version 180.
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 iPTMnet; Q9NQZ3; -.
DR PhosphoSitePlus; Q9NQZ3; -.
DR BioMuta; DAZ1; -.
DR DMDM; 44887841; -.
DR MassIVE; Q9NQZ3; -.
DR PaxDb; Q9NQZ3; -.
DR PRIDE; Q9NQZ3; -.
DR Antibodypedia; 21891; 179 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 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 PhylomeDB; Q9NQZ3; -.
DR TreeFam; TF324396; -.
DR PathwayCommons; Q9NQZ3; -.
DR SignaLink; Q9NQZ3; -.
DR BioGRID-ORCS; 1617; 9 hits in 212 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 right testis and 28 other tissues.
DR ExpressionAtlas; Q9NQZ3; baseline and differential.
DR Genevisible; Q9NQZ3; HS.
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; IPR037366; BOULE/DAZ.
DR InterPro; IPR034778; DAZ1-4.
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; PTHR11176; 8.
DR PANTHER; PTHR11176:SF8; PTHR11176:SF8; 8.
DR Pfam; PF18872; Daz; 9.
DR Pfam; PF00076; RRM_1; 3.
DR SMART; SM00360; RRM; 3.
DR SUPFAM; SSF54928; SSF54928; 3.
DR PROSITE; PS51890; DAZ; 9.
DR PROSITE; PS50102; RRM; 3.
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
