ID   DAZP2_MOUSE             Reviewed;         168 AA.
AC   Q9DCP9; O88675; Q3UVI4;
DT   01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   27-MAR-2024, entry version 133.
DE   RecName: Full=DAZ-associated protein 2;
DE   AltName: Full=Deleted in azoospermia-associated protein 2;
DE   AltName: Full=Proline-rich protein expressed in brain {ECO:0000303|PubMed:10373015};
DE   AltName: Full=Proline-rich transcript in brain protein {ECO:0000250|UniProtKB:Q15038};
GN   Name=Dazap2; Synonyms=Prtb {ECO:0000303|PubMed:10373015};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   STRAIN=CD-1; TISSUE=Brain;
RX   PubMed=10373015;
RX   DOI=10.1002/(sici)1097-0177(199906)215:2<108::aid-dvdy3>3.0.co;2-i;
RA   Yang W., Mansour S.L.;
RT   "Expression and genetic analysis of prtb, a gene that encodes a highly
RT   conserved proline-rich protein expressed in the brain.";
RL   Dev. Dyn. 215:108-116(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and NOD;
RC   TISSUE=Head, Heart, Kidney, Liver, Thymus, and Urinary bladder;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain, and Eye;
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   INDUCTION.
RX   PubMed=11787059; DOI=10.1002/jcb.10018;
RA   Sommerfeldt D.W., Zhi J., Rubin C.T., Hadjiargyrou M.;
RT   "Proline-rich transcript of the brain (prtb) is a serum-responsive gene in
RT   osteoblasts and upregulated during adhesion.";
RL   J. Cell. Biochem. 84:301-308(2002).
RN   [5]
RP   TISSUE SPECIFICITY, AND INTERACTION WITH SOX6.
RX   PubMed=14530442; DOI=10.1093/nar/gkg807;
RA   Cohen-Barak O., Yi Z., Hagiwara N., Monzen K., Komuro I., Brilliant M.H.;
RT   "Sox6 regulation of cardiac myocyte development.";
RL   Nucleic Acids Res. 31:5941-5948(2003).
RN   [6]
RP   FUNCTION, INTERACTION WITH LEF1, AND TISSUE SPECIFICITY.
RX   PubMed=19304756; DOI=10.1093/nar/gkp179;
RA   Lukas J., Mazna P., Valenta T., Doubravska L., Pospichalova V.,
RA   Vojtechova M., Fafilek B., Ivanek R., Plachy J., Novak J., Korinek V.;
RT   "Dazap2 modulates transcription driven by the Wnt effector TCF-4.";
RL   Nucleic Acids Res. 37:3007-3020(2009).
CC   -!- FUNCTION: In unstressed cells, promotes SIAH1-mediated
CC       polyubiquitination and degradation of the serine/threonine-protein
CC       kinase HIPK2, probably by acting as a loading factor that potentiates
CC       complex formation between HIPK2 and ubiquitin ligase SIAH1 (By
CC       similarity). In response to DNA damage, localizes to the nucleus
CC       following phosphorylation by HIPK2 and modulates the expression of a
CC       subset of TP53/p53 target genes by binding to TP53 at target gene
CC       promoters (By similarity). This limits the expression of a number of
CC       cell death-mediating TP53 target genes, reducing DNA damage-induced
CC       cell death (By similarity). Enhances the binding of transcription
CC       factor TCF7L2/TCF4, a Wnt signaling pathway effector, to the promoters
CC       of target genes (PubMed:19304756). Plays a role in stress granule
CC       formation (By similarity). {ECO:0000250|UniProtKB:Q15038,
CC       ECO:0000269|PubMed:19304756}.
CC   -!- SUBUNIT: Interacts with SOX6 (PubMed:14530442). Interacts with DAZ1 and
CC       DAZL (By similarity). Interacts with IL17RB (By similarity). May
CC       interact with FAM168B (By similarity). Interacts with INCA1 (By
CC       similarity). Interacts with EIF4G1 and EIF4G2 (By similarity).
CC       Interacts (via PPAY motif) with NEDD4 (via WW domains) (By similarity).
CC       Interacts with transcription factor TCF4; the interaction results in
CC       localization of DAZAP2 to the nucleus (By similarity). Interacts with
CC       transcription factors TCF7 and TCF7L1 (By similarity). Interacts with
CC       transcription factor LEF1 (PubMed:19304756). Interacts with
CC       serine/threonine-protein kinase HIPK2; the interaction results in
CC       phosphorylation of DAZAP2 which causes localization of DAZAP2 to the
CC       nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-
CC       dependent degradation of HIPK2 (By similarity). Interacts with
CC       ubiquitin ligase SIAH1; the interaction is decreased following
CC       phosphorylation of DAZAP2 by HIPK2 (By similarity). Interacts with
CC       TP53; the interaction is triggered by DNA damage (By similarity).
CC       {ECO:0000250|UniProtKB:Q15038, ECO:0000269|PubMed:14530442,
CC       ECO:0000269|PubMed:19304756}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q15038}. Nucleus
CC       {ECO:0000250|UniProtKB:Q15038}. Nucleus speckle
CC       {ECO:0000250|UniProtKB:Q15038}. Nucleus, nuclear body
CC       {ECO:0000250|UniProtKB:Q15038}. Cytoplasm, Stress granule
CC       {ECO:0000250|UniProtKB:Q15038}. Note=Predominantly nuclear in
CC       macrophages, stimulation of IL17RB with its ligand IL17E induces
CC       accumulation in the cytoplasm (By similarity). Predominantly
CC       cytoplasmic when unphosphorylated and localizes to the nucleus
CC       following phosphorylation by HIPK2 (By similarity). Localizes to stress
CC       granules under cellular stress conditions (By similarity).
CC       {ECO:0000250|UniProtKB:Q15038}.
CC   -!- TISSUE SPECIFICITY: Widely expressed (PubMed:14530442,
CC       PubMed:19304756). Highly expressed in brain (PubMed:10373015).
CC       {ECO:0000269|PubMed:10373015, ECO:0000269|PubMed:14530442,
CC       ECO:0000269|PubMed:19304756}.
CC   -!- DEVELOPMENTAL STAGE: Between 11.5 dpc and 12.5 dpc it is specifically
CC       expressed in the developing heart. From 13.5 dpc, expression in the
CC       heart disappears, while it becomes strongly expressed in the brain. Up-
CC       regulated during adhesion and differentiation to beating
CC       cardiomyocytes. {ECO:0000269|PubMed:10373015}.
CC   -!- INDUCTION: By serum stimulation. {ECO:0000269|PubMed:11787059}.
CC   -!- PTM: Ubiquitinated by SMURF2, leading to proteasomal degradation.
CC       Ubiquitinated by NEDD4, leading to proteasomal degradation.
CC       {ECO:0000250|UniProtKB:Q15038}.
CC   -!- PTM: Following DNA damage, phosphorylated by HIPK2 which promotes
CC       DAZAP2 localization to the nucleus, reduces interaction of DAZAP2 with
CC       HIPK2 and SIAH1, and prevents DAZAP2-dependent ubiquitination of HIPK2
CC       by E3 ubiquitin-protein ligase SIAH1 and subsequent HIPK2 proteasomal
CC       degradation. {ECO:0000250|UniProtKB:Q15038}.
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DR   EMBL; AF085348; AAC34594.1; -; mRNA.
DR   EMBL; AK002595; BAB22216.1; -; mRNA.
DR   EMBL; AK050159; BAC34100.1; -; mRNA.
DR   EMBL; AK088916; BAC40651.1; -; mRNA.
DR   EMBL; AK132139; BAE20995.1; -; mRNA.
DR   EMBL; AK137246; BAE23285.1; -; mRNA.
DR   EMBL; AK146970; BAE27575.1; -; mRNA.
DR   EMBL; BC014808; AAH14808.1; -; mRNA.
DR   EMBL; BC083347; AAH83347.1; -; mRNA.
DR   CCDS; CCDS27841.1; -.
DR   RefSeq; NP_036003.2; NM_011873.2.
DR   AlphaFoldDB; Q9DCP9; -.
DR   BioGRID; 204844; 4.
DR   IntAct; Q9DCP9; 1.
DR   STRING; 10090.ENSMUSP00000000356; -.
DR   iPTMnet; Q9DCP9; -.
DR   PhosphoSitePlus; Q9DCP9; -.
DR   PaxDb; 10090-ENSMUSP00000000356; -.
DR   ProteomicsDB; 277953; -.
DR   Pumba; Q9DCP9; -.
DR   Antibodypedia; 26360; 127 antibodies from 22 providers.
DR   DNASU; 23994; -.
DR   Ensembl; ENSMUST00000000356.10; ENSMUSP00000000356.9; ENSMUSG00000000346.10.
DR   GeneID; 23994; -.
DR   KEGG; mmu:23994; -.
DR   UCSC; uc007xrt.1; mouse.
DR   AGR; MGI:1344344; -.
DR   CTD; 9802; -.
DR   MGI; MGI:1344344; Dazap2.
DR   VEuPathDB; HostDB:ENSMUSG00000000346; -.
DR   eggNOG; ENOG502QTNQ; Eukaryota.
DR   GeneTree; ENSGT00390000000685; -.
DR   HOGENOM; CLU_135110_0_0_1; -.
DR   InParanoid; Q9DCP9; -.
DR   OMA; YPQTMPL; -.
DR   OrthoDB; 5405485at2759; -.
DR   PhylomeDB; Q9DCP9; -.
DR   TreeFam; TF329672; -.
DR   BioGRID-ORCS; 23994; 2 hits in 77 CRISPR screens.
DR   ChiTaRS; Dazap2; mouse.
DR   PRO; PR:Q9DCP9; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; Q9DCP9; Protein.
DR   Bgee; ENSMUSG00000000346; Expressed in blood and 286 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR   GO; GO:0016604; C:nuclear body; ISS:UniProtKB.
DR   GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0005667; C:transcription regulator complex; IC:MGI.
DR   GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:WormBase.
DR   GO; GO:0002039; F:p53 binding; ISS:UniProtKB.
DR   GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:WormBase.
DR   GO; GO:0120283; F:protein serine/threonine kinase binding; ISS:UniProtKB.
DR   GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:WormBase.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:UniProtKB.
DR   GO; GO:0050699; F:WW domain binding; ISO:MGI.
DR   GO; GO:1905636; P:positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding; IMP:UniProtKB.
DR   GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR   GO; GO:0034063; P:stress granule assembly; ISS:UniProtKB.
DR   InterPro; IPR022730; DAZ_assoc-2.
DR   PANTHER; PTHR31638; DAZ-ASSOCIATED PROTEIN 2; 1.
DR   PANTHER; PTHR31638:SF3; DAZ-ASSOCIATED PROTEIN 2; 1.
DR   Pfam; PF11029; DAZAP2; 1.
DR   Genevisible; Q9DCP9; MM.
PE   1: Evidence at protein level;
KW   Cytoplasm; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT   CHAIN           1..168
FT                   /note="DAZ-associated protein 2"
FT                   /id="PRO_0000079789"
FT   REGION          1..25
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           39..42
FT                   /note="PPAY"
FT                   /evidence="ECO:0000250|UniProtKB:Q15038"
FT   COMPBIAS        11..25
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         77
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q15038"
FT   CONFLICT        162
FT                   /note="D -> N (in Ref. 1; AAC34594)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   168 AA;  17289 MW;  49EDDAA29D8E3AAC CRC64;
     MNSKGQYPTQ PTYPVQPPGN PVYPQTLHLP QAPPYTDAPP AYSELYRPSF VHPGAATVPT
     MSAAFPGASL YLPMAQSVAV GPLGSTIPMA YYPVGPIYPP GSAVLVEGGY DAGARFGAGA
     TAGNIPPPPP GCPPNAAQLA VMQGANVLVT QRKGNFFMGG SDGGYTIW
//