DAZ4_HUMAN
ID DAZ4_HUMAN Reviewed; 579 AA.
AC Q86SG3; Q9NR88; Q9NR89;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Deleted in azoospermia protein 4;
GN Name=DAZ4;
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), GENE STRUCTURE, GENE NOMENCLATURE,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [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=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 [12]
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 [13]
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 [14]
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).
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.
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 -!- 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=Q86SG3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86SG3-2; Sequence=VSP_009454, VSP_009455, VSP_009456;
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:12801575}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry. AZFc deletions in the Yq11.23 region including the DAZ
CC genes are the most common known genetic cause of human male
CC 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; AF248482; AAF91331.1; -; mRNA.
DR EMBL; AF248483; AAF91332.1; -; mRNA.
DR EMBL; AC006338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047480; AAH47480.1; -; mRNA.
DR EMBL; BC047617; AAH47617.1; -; mRNA.
DR CCDS; CCDS55557.1; -. [Q86SG3-2]
DR RefSeq; NP_001005375.1; NM_001005375.2. [Q86SG3-1]
DR RefSeq; NP_065153.1; NM_020420.3. [Q86SG3-2]
DR AlphaFoldDB; Q86SG3; -.
DR iPTMnet; Q86SG3; -.
DR PhosphoSitePlus; Q86SG3; -.
DR BioMuta; DAZ4; -.
DR DMDM; 44887840; -.
DR MassIVE; Q86SG3; -.
DR PaxDb; Q86SG3; -.
DR PeptideAtlas; Q86SG3; -.
DR PRIDE; Q86SG3; -.
DR Antibodypedia; 5164; 143 antibodies from 22 providers.
DR DNASU; 57135; -.
DR Ensembl; ENST00000449750.7; ENSP00000389300.2; ENSG00000205916.12. [Q86SG3-2]
DR Ensembl; ENST00000634662.1; ENSP00000489430.1; ENSG00000205916.12. [Q86SG3-1]
DR GeneID; 57135; -.
DR KEGG; hsa:57135; -.
DR UCSC; uc065cvv.1; human. [Q86SG3-1]
DR CTD; 57135; -.
DR DisGeNET; 57135; -.
DR GeneCards; DAZ4; -.
DR HGNC; HGNC:15966; DAZ4.
DR HPA; ENSG00000205916; Group enriched (stomach, testis).
DR MalaCards; DAZ4; -.
DR MIM; 400003; gene.
DR MIM; 400048; gene.
DR MIM; 415000; phenotype.
DR neXtProt; NX_Q86SG3; -.
DR OpenTargets; ENSG00000188120; -.
DR OpenTargets; ENSG00000205916; -.
DR Orphanet; 1646; Partial chromosome Y deletion.
DR PharmGKB; PA27152; -.
DR VEuPathDB; HostDB:ENSG00000205916; -.
DR GeneTree; ENSGT00530000063480; -.
DR HOGENOM; CLU_022076_0_0_1; -.
DR InParanoid; Q86SG3; -.
DR OrthoDB; 1610446at2759; -.
DR TreeFam; TF324396; -.
DR PathwayCommons; Q86SG3; -.
DR SignaLink; Q86SG3; -.
DR BioGRID-ORCS; 57135; 6 hits in 204 CRISPR screens.
DR ChiTaRS; DAZ4; human.
DR GenomeRNAi; 57135; -.
DR Pharos; Q86SG3; Tbio.
DR PRO; PR:Q86SG3; -.
DR Proteomes; UP000005640; Chromosome Y.
DR RNAct; Q86SG3; protein.
DR Bgee; ENSG00000205916; Expressed in right testis and 9 other tissues.
DR ExpressionAtlas; Q86SG3; baseline.
DR Genevisible; Q86SG3; HS.
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:0003730; F:mRNA 3'-UTR binding; IBA:GO_Central.
DR GO; GO:0008494; F:translation activator activity; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR CDD; cd12672; RRM_DAZL; 2.
DR Gene3D; 3.30.70.330; -; 2.
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; 7.
DR PANTHER; PTHR11176:SF8; PTHR11176:SF8; 7.
DR Pfam; PF18872; Daz; 9.
DR Pfam; PF00076; RRM_1; 2.
DR SMART; SM00360; RRM; 2.
DR SUPFAM; SSF54928; SSF54928; 2.
DR PROSITE; PS51890; DAZ; 9.
DR PROSITE; PS50102; RRM; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Developmental protein; Differentiation;
KW Nucleus; Reference proteome; Repeat; RNA-binding; Spermatogenesis.
FT CHAIN 1..579
FT /note="Deleted in azoospermia protein 4"
FT /id="PRO_0000081557"
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 332..355
FT /note="DAZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT DOMAIN 356..379
FT /note="DAZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT DOMAIN 380..403
FT /note="DAZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT DOMAIN 404..427
FT /note="DAZ 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT DOMAIN 428..451
FT /note="DAZ 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT DOMAIN 452..475
FT /note="DAZ 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT DOMAIN 476..499
FT /note="DAZ 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT DOMAIN 500..523
FT /note="DAZ 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01238"
FT DOMAIN 524..547
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 VAR_SEQ 1..165
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009454"
FT VAR_SEQ 166
FT /note="Q -> M (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009455"
FT VAR_SEQ 486..509
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009456"
FT CONFLICT 238
FT /note="T -> S (in Ref. 1; AAF91332)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 579 AA; 64785 MW; BE0537C8DD4E9174 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 QAYSAYPHSP GQVITGCQLL VYNYQEYPTY
PDSAFQVTTG YQLPVYNYQP FPAYPRSPFQ VTAGYQLPVY NYQAFPAYPN SPFQVATGYQ
FPVYNYQPFP AYPSSPFQVT AGYQLPVYNY QAFPAYPNSP FQVATGYQFP VYNYQAFPAY
PNSPVQVTTG YQLPVYNYQA FPAYPSSPFQ VTTGYQLPVY NYQAFPAYPN SAVQVTTGYQ
FHVYNYQMPP QCPVGEQRRN LWTEAYKWWY LVCLIQRRD
