Q86SG3 (DAZ4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Deleted in azoospermia protein 4

Gene names

Name:

DAZ4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	579 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	RNA-binding protein that plays an essential role in spermatogenesis. May act by binding to the 3'-UTR of mRNAs and regulating their translation.
Subunit structure	Forms a heterodimer with BOLL and DAZL. Interacts with PUM2, DAZAP1, DAZAP2, DZIP1 and DZIP3. Ref.4 Ref.6 Ref.7 Ref.8
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Nuclear at some stages of spermatozoide development. Localizes both to the nuclei and cytoplasm of spermatozoide differentiation. Nuclear in fetal gonocytes and in spermatogonial nuclei. It then relocates to the cytoplasm during male meiosis. Ref.5
Tissue specificity	Testis-specific. Expression restricted to premeiotic germ cells, particularly in spermatogonia (at protein level). Ref.1 Ref.13 Ref.14
Domain	The DAZ-like repeats are essential and mediate the interaction with DAZAP1 and DAZAP2.
Polymorphism	The number as well as the precise structure of the DAZ proteins probably differs within the population.
Involvement in disease	Spermatogenic failure Y-linked 2 (SPGFY2) [MIM:415000]: A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility. Note: The disease may be caused by mutations affecting the gene represented in this entry. AZFc deletions in the Yq11.23 region including the DAZ genes are the most common known genetic cause of human male infertility. Ref.10 Ref.11
Miscellaneous	DAZ genes are prone to deletions but also to duplications. In a population of infertile men, DAZ genes deletions are associated with oligozoospermia but an increased number of DAZ genes is not a significant risk factor for spermatogenic failure. The DAZ proteins (DAZ, DAZ2, DAZ4 and DAZ4) are all encoded by a strongly repeated region of the Y chromosome, in two clusters each comprising an inverted pair of DAZ genes. They are very similar, which gives their indidual characterization difficult. Thus, most experiments do not discriminate between the different members. One can therefore suppose that reported interactions with a DAZ protein involve all the 4 proteins.
Sequence similarities	Belongs to the RRM DAZ family. Contains 9 DAZ-like domains. Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Biological process	Differentiation Spermatogenesis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	RNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q86SG3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q86SG3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-165: Missing.
     166-166: Q → M
     486-509: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 579	579	Deleted in azoospermia protein 4		PRO_0000081557
Regions
	Domain	40 – 115	76	RRM 1
	Domain	205 – 280	76	RRM 2
	Domain	335 – 355	21	DAZ-like 1
	Domain	359 – 379	21	DAZ-like 2
	Domain	384 – 404	21	DAZ-like 3
	Domain	407 – 427	21	DAZ-like 4
	Domain	431 – 451	21	DAZ-like 5
	Domain	455 – 475	21	DAZ-like 6
	Domain	479 – 499	21	DAZ-like 7
	Domain	503 – 523	21	DAZ-like 8
	Domain	527 – 547	21	DAZ-like 9
Natural variations
	Alternative sequence	1 – 165	165	Missing in isoform 2.		VSP_009454
	Alternative sequence	166	1	Q → M in isoform 2.		VSP_009455
	Alternative sequence	486 – 509	24	Missing in isoform 2.		VSP_009456
Experimental info
	Sequence conflict	238	1	T → S in AAF91332. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2004. Version 2. Checksum: BE0537C8DD4E9174	FASTA	579	64,785
	10 20 30 40 50 60 MSAANPETPN STISREASTQ SSSAAASQGW VLPEGKIVPN TVFVGGIDAR MDETEIGSCF 70 80 90 100 110 120 GRYGSVKEVK IITNRTGVSK GYGFVSFVND VDVQKIVGSQ IHFHGKKLKL GPAIRKQKLC 130 140 150 160 170 180 ARHVQPRPLV VNPPPPPQFQ NVWRNPNTET YLQPQITPNP VTQHVQSAAN PETPNSTISR 190 200 210 220 230 240 EASTQSSSAA ASQGWVLPEG KIVPNTVFVG GIDARMDETE IGSCFGRYGS VKEVKIITNR 250 260 270 280 290 300 TGVSKGYGFV SFVNDVDVQK IVGSQIHFHG KKLKLGPAIR KQKLCARHVQ PRPLVVNPPP 310 320 330 340 350 360 PPQFQNVWRN PNTETYLQPQ ITPNPVTQHV QAYSAYPHSP GQVITGCQLL VYNYQEYPTY 370 380 390 400 410 420 PDSAFQVTTG YQLPVYNYQP FPAYPRSPFQ VTAGYQLPVY NYQAFPAYPN SPFQVATGYQ 430 440 450 460 470 480 FPVYNYQPFP AYPSSPFQVT AGYQLPVYNY QAFPAYPNSP FQVATGYQFP VYNYQAFPAY 490 500 510 520 530 540 PNSPVQVTTG YQLPVYNYQA FPAYPSSPFQ VTTGYQLPVY NYQAFPAYPN SAVQVTTGYQ 550 560 570 FHVYNYQMPP QCPVGEQRRN LWTEAYKWWY LVCLIQRRD
	Isoform 2 [UniParc]. Checksum: A9567AFD5659A9D5	FASTA	390	44,085
	10 20 30 40 50 60 MSAANPETPN STISREASTQ SSSAAASQGW VLPEGKIVPN TVFVGGIDAR MDETEIGSCF 70 80 90 100 110 120 GRYGSVKEVK IITNRTGVSK GYGFVSFVND VDVQKIVGSQ IHFHGKKLKL GPAIRKQKLC 130 140 150 160 170 180 ARHVQPRPLV VNPPPPPQFQ NVWRNPNTET YLQPQITPNP VTQHVQAYSA YPHSPGQVIT 190 200 210 220 230 240 GCQLLVYNYQ EYPTYPDSAF QVTTGYQLPV YNYQPFPAYP RSPFQVTAGY QLPVYNYQAF 250 260 270 280 290 300 PAYPNSPFQV ATGYQFPVYN YQPFPAYPSS PFQVTAGYQL PVYNYQAFPA YPNSPFQVAT 310 320 330 340 350 360 GYQFPVYNYQ AFPAYPNSPV QVTTGYQLPV YNYQAFPAYP NSAVQVTTGY QFHVYNYQMP 370 380 390 PQCPVGEQRR NLWTEAYKWW YLVCLIQRRD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Four DAZ genes in two clusters found in the AZFc region of the human Y chromosome." Saxena R., de Vries J.W.A., Repping S., Alagappan R.K., Skaletsky H., Brown L.G., Ma P., Chen E., Hoovers J.M.N., Page D.C. Genomics 67:256-267(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GENE STRUCTURE, GENE NOMENCLATURE, TISSUE SPECIFICITY. Tissue: Testis.
[2]	"The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes." Skaletsky H., Kuroda-Kawaguchi T., Minx P.J., Cordum H.S., Hillier L.W., Brown L.G., Repping S., Pyntikova T., Ali J., Bieri T., Chinwalla A., Delehaunty A., Delehaunty K., Du H., Fewell G., Fulton L., Fulton R., Graves T.A. , Hou S.-F., Latrielle P., Leonard S., Mardis E., Maupin R., McPherson J., Miner T., Nash W., Nguyen C., Ozersky P., Pepin K., Rock S., Rohlfing T., Scott K., Schultz B., Strong C., Tin-Wollam A., Yang S.-P., Waterston R.H., Wilson R.K., Rozen S., Page D.C. Nature 423:825-837(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[4]	"Identification of two novel proteins that interact with germ-cell-specific RNA-binding proteins DAZ and DAZL1." Tsui S., Dai T., Roettger S., Schempp W., Salido E.C., Yen P.H. Genomics 65:266-273(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DAZAP1 AND DAZAP2.
[5]	"DAZ family proteins exist throughout male germ cell development and transit from nucleus to cytoplasm at meiosis in humans and mice." Reijo R.A., Dorfman D.M., Slee R., Renshaw A.A., Loughlin K.R., Cooke H., Page D.C. Biol. Reprod. 63:1490-1496(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"In vivo and in vitro analysis of homodimerisation activity of the mouse Dazl1 protein." Ruggiu M., Cooke H.J. Gene 252:119-126(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DAZL.
[7]	"A gene family required for human germ cell development evolved from an ancient meiotic gene conserved in metazoans." Xu E.Y., Moore F.L., Reijo Pera R.A. Proc. Natl. Acad. Sci. U.S.A. 98:7414-7419(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BOLL.
[8]	"Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-like proteins." Moore F.L., Jaruzelska J., Fox M.S., Urano J., Firpo M.T., Turek P.J., Dorfman D.M., Reijo Pera R.A. Proc. Natl. Acad. Sci. U.S.A. 100:538-543(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PUM2; DZIP1 AND DZIP3.
[9]	"Polymorphic DAZ gene family in polymorphic structure of AZFc locus: artwork or functional for human spermatogenesis?" Vogt P.H., Fernandes S. APMIS 111:115-127(2003) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[10]	"Male infertility caused by a de novo partial deletion of the DAZ cluster on the Y chromosome." Moro E., Ferlin A., Yen P.H., Franchi P.G., Palka G., Foresta C. J. Clin. Endocrinol. Metab. 85:4069-4073(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SPGFY2.
[11]	"Partial DAZ deletions in a family with five infertile brothers." Gianotten J., Hoffer M.J.V., De Vries J.W.A., Leschot N.J., Gerris J., van der Veen F. Fertil. Steril. 79:1652-1655(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SPGFY2.
[12]	"Copy number of DAZ genes in infertile men." Writzl K., Zorn B., Peterlin B. Fertil. Steril. 84:1522-1525(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GENE DUPLICATION.
[13]	"Restricted expression of the human DAZ protein in premeiotic germ cells." Huang W.J., Lin Y.W., Hsiao K.N., Eilber K.S., Salido E.C., Yen P.H. Hum. Reprod. 23:1280-1289(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[14]	"Polymorphic expression of DAZ proteins in the human testis." Kim B., Lee Y., Kim Y., Lee K.H., Chun S., Rhee K., Seo J.T., Kim S.W., Paick J.S. Hum. Reprod. 24:1507-1515(2009) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF248482 mRNA. Translation: AAF91331.1. AF248483 mRNA. Translation: AAF91332.1. AC006338 Genomic DNA. No translation available. BC047480 mRNA. Translation: AAH47480.1. BC047617 mRNA. Translation: AAH47617.1.
IPI	IPI00160336. IPI00401506.
RefSeq	NP_001005375.1. NM_001005375.2. NP_065153.1. NM_020420.3.
UniGene	Hs.522868. Hs.70936.
3D structure databases
ProteinModelPortal	Q86SG3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000371742.
PTM databases
PhosphoSite	Q86SG3.
Polymorphism databases
DMDM	44887840.
Proteomic databases
PRIDE	Q86SG3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000440066; ENSP00000401363; ENSG00000205916. ENST00000449750; ENSP00000389300; ENSG00000205916.
GeneID	57135.
KEGG	hsa:57135.
UCSC	uc004fvm.3. human. uc004fvn.3. human.
Organism-specific databases
CTD	57135.
GeneCards	GC0YP026979.
HGNC	HGNC:15966. DAZ4.
HPA	HPA047113.
MIM	400003. gene. 415000. phenotype.
neXtProt	NX_Q86SG3.
Orphanet	1646. Partial chromosome Y deletion.
PharmGKB	PA27152.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG048860.
InParanoid	Q86SG3.
Gene expression databases
ArrayExpress	Q86SG3.
Bgee	Q86SG3.
CleanEx	HS_DAZ4.
Genevestigator	Q86SG3.
GermOnline	ENSG00000188120. Homo sapiens.
Family and domain databases
Gene3D	3.30.70.330. 3 hits.
InterPro	IPR012677. Nucleotide-bd_a/b_plait. IPR000504. RRM_dom. [Graphical view]
Pfam	PF00076. RRM_1. 2 hits. [Graphical view]
SMART	SM00360. RRM. 2 hits. [Graphical view]
PROSITE	PS50102. RRM. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	DAZ4. human.
GenomeRNAi	57135.
NextBio	63055.
SOURCE	Search...

Entry information

Entry name

DAZ4_HUMAN

Accession

Primary (citable) accession number: Q86SG3
Secondary accession number(s): Q9NR88, Q9NR89

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	March 1, 2004
Last modified:	May 1, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.