DEAF1_HUMAN
ID DEAF1_HUMAN Reviewed; 565 AA.
AC O75398; A8K1F8; A8K5R8; C7T5V5; O15152; O75399; O75510; O75511; O75512;
AC O75513; Q9UET1;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Deformed epidermal autoregulatory factor 1 homolog;
DE AltName: Full=Nuclear DEAF-1-related transcriptional regulator;
DE Short=NUDR;
DE AltName: Full=Suppressin;
DE AltName: Full=Zinc finger MYND domain-containing protein 5;
GN Name=DEAF1; Synonyms=SPN, ZMYND5;
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] (ISOFORMS 1 AND 2), AND MUTAGENESIS OF ARG-302
RP AND LYS-304.
RC TISSUE=Choriocarcinoma;
RX PubMed=9773984; DOI=10.1210/mend.12.10.0181;
RA Huggenvik J.I., Michelson R.J., Collard M.W., Ziemba A.J., Gurley P.,
RA Mowen K.A.;
RT "Characterization of a nuclear deformed epidermal autoregulatory factor-1
RT (DEAF-1)-related (NUDR) transcriptional regulator protein.";
RL Mol. Endocrinol. 12:1619-1639(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANTS VAL-186; ASN-191; ILE-191;
RP 199-CYS-ASP-ASN-ASP-202; ASP-202; LYS-218; 350-GLY-GLN-THR-352; HIS-356;
RP ASN-364; HIS-367; LEU-370; PHE-397; ALA-442; LYS-449; 451-GLY-ILE-452;
RP HIS-468; LEU-479; LYS-498; ASN-526; LEU-530; 537-HIS-LEU-538; HIS-542;
RP GLY-545 AND VAL-545, AND ROLE IN NEOPLASIA.
RC TISSUE=Colon, and Colon adenocarcinoma;
RX PubMed=11705868;
RA Manne U., Gary B.D., Oelschlager D.K., Weiss H.L., Frost A.R.,
RA Grizzle W.E.;
RT "Altered subcellular localization of suppressin, a novel inhibitor of cell-
RT cycle entry, is an independent prognostic factor in colorectal
RT adenocarcinomas.";
RL Clin. Cancer Res. 7:3495-3503(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Pancreas;
RX PubMed=19668219; DOI=10.1038/ni.1773;
RA Yip L., Su L., Sheng D., Chang P., Atkinson M., Czesak M., Albert P.R.,
RA Collier A.R., Turley S.J., Fathman C.G., Creusot R.J.;
RT "Deaf1 isoforms control the expression of genes encoding peripheral tissue
RT antigens in the pancreatic lymph nodes during type 1 diabetes.";
RL Nat. Immunol. 10:1026-1033(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Mammary gland;
RA LeBoeuf R.D., Blalock J.E., Tauber J.D.;
RT "Cloning and sequence analysis of the cDNA for human suppressin (spn).";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, and Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
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 [7]
RP FUNCTION.
RX PubMed=10521432; DOI=10.1074/jbc.274.43.30510;
RA Michelson R.J., Collard M.W., Ziemba A.J., Persinger J., Bartholomew B.,
RA Huggenvik J.I.;
RT "Nuclear DEAF-1-related (NUDR) protein contains a novel DNA binding domain
RT and represses transcription of the heterogeneous nuclear ribonucleoprotein
RT A2/B1 promoter.";
RL J. Biol. Chem. 274:30510-30519(1999).
RN [8]
RP FUNCTION OF SAND DOMAIN, AND MUTAGENESIS OF TYR-215; ARG-226; ARG-246;
RP LYS-250; TRP-252 AND LYS-253.
RX PubMed=11427895; DOI=10.1038/89675;
RA Bottomley M.J., Collard M.W., Huggenvik J.I., Liu Z., Gibson T.J.,
RA Sattler M.;
RT "The SAND domain structure defines a novel DNA-binding fold in
RT transcriptional regulation.";
RL Nat. Struct. Biol. 8:626-633(2001).
RN [9]
RP FUNCTION.
RX PubMed=18826651; DOI=10.1186/1471-213x-8-94;
RA Barker H.E., Smyth G.K., Wettenhall J., Ward T.A., Bath M.L.,
RA Lindeman G.J., Visvader J.E.;
RT "Deaf-1 regulates epithelial cell proliferation and side-branching in the
RT mammary gland.";
RL BMC Dev. Biol. 8:94-94(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP DNA-BINDING, IDENTIFICATION IN A COMPLEX WITH XRCC5 AND XRCC6, SUBCELLULAR
RP LOCATION, AND PHOSPHORYLATION BY DNA-PK COMPLEX.
RX PubMed=22442688; DOI=10.1371/journal.pone.0033404;
RA Jensik P.J., Huggenvik J.I., Collard M.W.;
RT "Deformed epidermal autoregulatory factor-1 (DEAF1) interacts with the Ku70
RT subunit of the DNA-dependent protein kinase complex.";
RL PLoS ONE 7:E33404-E33404(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176 AND THR-432, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION, INTERACTION WITH XRCC6, DNA-BINDING, TISSUE SPECIFICITY,
RP INVOLVEMENT IN VSVS, VARIANTS VSVS TRP-224; SER-228; SER-254 AND PRO-264,
RP CHARACTERIZATION OF VARIANTS VSVS TRP-224; SER-228; SER-254 AND PRO-264,
RP AND MUTAGENESIS OF LYS-250 AND LYS-253.
RX PubMed=24726472; DOI=10.1016/j.ajhg.2014.03.013;
RA Vulto-van Silfhout A.T., Rajamanickam S., Jensik P.J., Vergult S.,
RA de Rocker N., Newhall K.J., Raghavan R., Reardon S.N., Jarrett K.,
RA McIntyre T., Bulinski J., Ownby S.L., Huggenvik J.I., McKnight G.S.,
RA Rose G.M., Cai X., Willaert A., Zweier C., Endele S., de Ligt J.,
RA van Bon B.W., Lugtenberg D., de Vries P.F., Veltman J.A., van Bokhoven H.,
RA Brunner H.G., Rauch A., de Brouwer A.P., Carvill G.L., Hoischen A.,
RA Mefford H.C., Eichler E.E., Vissers L.E., Menten B., Collard M.W.,
RA de Vries B.B.;
RT "Mutations affecting the SAND domain of DEAF1 cause intellectual disability
RT with severe speech impairment and behavioral problems.";
RL Am. J. Hum. Genet. 94:649-661(2014).
RN [14]
RP STRUCTURE BY NMR OF 496-544 IN COMPLEX WITH ZINC IONS.
RX PubMed=16527309; DOI=10.1016/j.jmb.2006.01.087;
RA Spadaccini R., Perrin H., Bottomley M.J., Ansieau S., Sattler M.;
RT "Structure and functional analysis of the MYND domain.";
RL J. Mol. Biol. 358:498-508(2006).
RN [15]
RP RETRACTION NOTICE OF PUBMED:16527309: STRUCTURE BY NMR OF 496-544 IN
RP COMPLEX WITH ZINC IONS.
RX PubMed=18286714; DOI=10.1016/j.jmb.2008.01.071;
RA Spadaccini R., Perrin H., Bottomley M.J., Ansieau S., Sattler M.;
RT "Retraction notice to 'Structure and functional analysis of the MYND
RT domain' [J. Mol. Biol. (2006) 358, 498-508].";
RL J. Mol. Biol. 376:1523-1523(2008).
RN [16]
RP STRUCTURE BY NMR OF 501-544 IN COMPLEX WITH ZINC IONS, SUBUNIT, INTERACTION
RP WITH NCOR1 AND NCOR2, AND MUTAGENESIS OF HIS-538.
RX PubMed=23372760; DOI=10.1371/journal.pone.0054715;
RA Kateb F., Perrin H., Tripsianes K., Zou P., Spadaccini R., Bottomley M.,
RA Franzmann T.M., Buchner J., Ansieau S., Sattler M.;
RT "Structural and functional analysis of the DEAF-1 and BS69 MYND domains.";
RL PLoS ONE 8:E54715-E54715(2013).
RN [17]
RP INVOLVEMENT IN VSVS, AND VARIANT SER-228.
RX PubMed=21076407; DOI=10.1038/ng.712;
RA Vissers L.E., de Ligt J., Gilissen C., Janssen I., Steehouwer M.,
RA de Vries P., van Lier B., Arts P., Wieskamp N., del Rosario M.,
RA van Bon B.W., Hoischen A., de Vries B.B., Brunner H.G., Veltman J.A.;
RT "A de novo paradigm for mental retardation.";
RL Nat. Genet. 42:1109-1112(2010).
RN [18]
RP INVOLVEMENT IN NEDHELS.
RX PubMed=26048982; DOI=10.1136/jmedgenet-2015-103083;
RA Rajab A., Schuelke M., Gill E., Zwirner A., Seifert F.,
RA Morales Gonzalez S., Knierim E.;
RT "Recessive DEAF1 mutation associates with autism, intellectual disability,
RT basal ganglia dysfunction and epilepsy.";
RL J. Med. Genet. 52:607-611(2015).
RN [19]
RP VARIANT TRP-226.
RX PubMed=24668509; DOI=10.1002/ajmg.a.36482;
RA Faqeih E.A., Al-Owain M., Colak D., Kenana R., Al-Yafee Y., Al-Dosary M.,
RA Al-Saman A., Albalawi F., Al-Sarar D., Domiaty D., Daghestani M., Kaya N.;
RT "Novel homozygous DEAF1 variant suspected in causing white matter disease,
RT intellectual disability, and microcephaly.";
RL Am. J. Med. Genet. A 164A:1565-1570(2014).
CC -!- FUNCTION: Transcription factor that binds to sequence with multiple
CC copies of 5'-TTC[CG]G-3' present in its own promoter and that of the
CC HNRPA2B1 gene. Down-regulates transcription of these genes. Binds to
CC the retinoic acid response element (RARE) 5'-AGGGTTCACCGAAAGTTCA-3'.
CC Activates the proenkephalin gene independently of promoter binding,
CC probably through protein-protein interaction. When secreted, behaves as
CC an inhibitor of cell proliferation, by arresting cells in the G0 or G1
CC phase. Required for neural tube closure and skeletal patterning.
CC Regulates epithelial cell proliferation and side-branching in the
CC mammary gland. Controls the expression of peripheral tissue antigens in
CC pancreatic lymph nodes. Isoform 1 displays greater transcriptional
CC activity than isoform 4. Isoform 4 may inhibit transcriptional activity
CC of isoform 1 by interacting with isoform 1 and retaining it in the
CC cytoplasm. Transcriptional activator of EIF4G3.
CC {ECO:0000269|PubMed:10521432, ECO:0000269|PubMed:11427895,
CC ECO:0000269|PubMed:11705868, ECO:0000269|PubMed:18826651,
CC ECO:0000269|PubMed:19668219, ECO:0000269|PubMed:24726472}.
CC -!- SUBUNIT: Homodimer. Isoform 1 and isoform 4 may form a heterodimer.
CC Interacts with LMO2 and CLIM2 (By similarity). Interacts with LMO4;
CC LMO4 blocks export from nucleus (By similarity). May interact with the
CC corepressors NCOR1 and NCRO2. Identified in a complex with the XRCC5
CC and XRCC6 heterodimer. Interacts (via the SAND domain) with the DNA-PK
CC complex subunit XRCC6; the interaction is direct and may be inhibited
CC by DNA-binding. {ECO:0000250, ECO:0000269|PubMed:16527309,
CC ECO:0000269|PubMed:22442688, ECO:0000269|PubMed:23372760,
CC ECO:0000269|PubMed:24726472}.
CC -!- INTERACTION:
CC O75398; P42771: CDKN2A; NbExp=2; IntAct=EBI-718185, EBI-375053;
CC O75398; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-718185, EBI-742887;
CC O75398; Q14192: FHL2; NbExp=3; IntAct=EBI-718185, EBI-701903;
CC O75398; P49840: GSK3A; NbExp=3; IntAct=EBI-718185, EBI-1044067;
CC O75398; P49841: GSK3B; NbExp=2; IntAct=EBI-718185, EBI-373586;
CC O75398; P51608: MECP2; NbExp=3; IntAct=EBI-718185, EBI-1189067;
CC O75398; P37840: SNCA; NbExp=3; IntAct=EBI-718185, EBI-985879;
CC O75398; Q13148: TARDBP; NbExp=3; IntAct=EBI-718185, EBI-372899;
CC O75398; P12956: XRCC6; NbExp=7; IntAct=EBI-718185, EBI-353208;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus. Cytoplasm. Note=Cytoplasmic
CC in non-mucinous colorectal carcinoma. When expressed alone, localized
CC almost exclusively in the nucleus but, when expressed with isoform 4,
CC nuclear expression decreases to 32% and cytoplasmic expression
CC increases by 270%.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted. Note=Secreted in some cell
CC types.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted. Note=Secreted in some cell
CC types.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm. Nucleus. Note=When
CC expressed alone, localizes mainly in the cytoplasm but, when expressed
CC with isoform 1, nuclear localization is enhanced.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Hu-DF1;
CC IsoId=O75398-1; Sequence=Displayed;
CC Name=2; Synonyms=NUDR8;
CC IsoId=O75398-3; Sequence=VSP_005967;
CC Name=3; Synonyms=Suppressin;
CC IsoId=O75398-4; Sequence=VSP_005966;
CC Name=4; Synonyms=Hu-DF1-VAR;
CC IsoId=O75398-5; Sequence=VSP_038701, VSP_038702;
CC -!- TISSUE SPECIFICITY: Expressed in various tissues and cells such as in
CC peripheral mononuclear cells and hormone-secreting pituitary cells.
CC Expression in pancreatic lymph nodes of patients with type 1 diabetes
CC is 20 times higher than in healthy controls. Highly expressed in fetal
CC and adult brain. {ECO:0000269|PubMed:19668219,
CC ECO:0000269|PubMed:24726472}.
CC -!- PTM: May be phosphorylated by DNA-PK complex in a DNA independent
CC manner (in vitro). {ECO:0000269|PubMed:22442688}.
CC -!- DISEASE: Vulto-van Silfout-de Vries syndrome (VSVS) [MIM:615828]: An
CC autosomal dominant disorder characterized by intellectual disability,
CC poor speech, motor delay, and autistic features. Most patients have
CC additional non-specific features, including hypotonia and gait
CC abnormalities, seizures, which may be refractory, high pain threshold,
CC and sleep disturbances. {ECO:0000269|PubMed:21076407,
CC ECO:0000269|PubMed:24726472}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neurodevelopmental disorder with hypotonia, impaired
CC expressive language, and with or without seizures (NEDHELS)
CC [MIM:617171]: An autosomal recessive disorder characterized by
CC psychomotor delay, epilepsy, intellectual disability, speech impairment
CC and dyskinesia of the limbs. Patients also manifest autistic features
CC and other behavioral abnormalities. {ECO:0000269|PubMed:26048982}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Defective DEAF1 could confer a growth advantage to the
CC mutated cells influencing the development and progression of neoplasia,
CC e.g. in the case of colorectal carcinomas. Subcellular location in
CC colorectal carcinomas (cytoplasmic or nuclear) is a prognostic factor
CC that identifies a subgroup of patients with reduced survival. In
CC addition, changes in the subcellular location correlates with the
CC proliferative status of the cells.
CC -!- MISCELLANEOUS: [Isoform 3]: Has no predictable signal peptide.
CC {ECO:0000305}.
CC -!- CAUTION: This protein was first known as suppressin (characterized in
CC bovine neuroendocrine and immune cells). However, according to
CC PubMed:9773984, it is uncertain whether it corresponds really to the
CC suppressin also described in Ref.4. DEAF1 has been described as a
CC nuclear dimeric protein and suppressin as a secreted monomeric protein.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC25718.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors.; Evidence={ECO:0000305};
CC Sequence=AAC25719.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- SEQUENCE CAUTION: [Isoform 3]:
CC Sequence=AAC25718.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAC25719.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF049459; AAC79676.1; -; mRNA.
DR EMBL; AF049460; AAC79677.1; -; mRNA.
DR EMBL; AF068893; AAC25715.1; -; mRNA.
DR EMBL; AF068894; AAC25716.1; -; mRNA.
DR EMBL; AF068895; AAC25717.1; -; mRNA.
DR EMBL; AF068896; AAC25718.1; ALT_SEQ; mRNA.
DR EMBL; AF068897; AAC25719.1; ALT_FRAME; mRNA.
DR EMBL; FJ985253; ACU88060.1; -; mRNA.
DR EMBL; AF007165; AAB62704.1; -; mRNA.
DR EMBL; AK291383; BAF84072.1; -; mRNA.
DR EMBL; AK289873; BAF82562.1; -; mRNA.
DR EMBL; BC053322; AAH53322.1; -; mRNA.
DR CCDS; CCDS31327.1; -. [O75398-1]
DR RefSeq; NP_001280563.1; NM_001293634.1. [O75398-5]
DR RefSeq; NP_066288.2; NM_021008.3. [O75398-1]
DR PDB; 2JW6; NMR; -; A=496-544.
DR PDB; 4A24; NMR; -; A=501-544.
DR PDB; 5UWW; X-ray; 2.15 A; D=452-469.
DR PDBsum; 2JW6; -.
DR PDBsum; 4A24; -.
DR PDBsum; 5UWW; -.
DR AlphaFoldDB; O75398; -.
DR BMRB; O75398; -.
DR SMR; O75398; -.
DR BioGRID; 115777; 39.
DR CORUM; O75398; -.
DR ELM; O75398; -.
DR IntAct; O75398; 32.
DR MINT; O75398; -.
DR STRING; 9606.ENSP00000371846; -.
DR iPTMnet; O75398; -.
DR PhosphoSitePlus; O75398; -.
DR BioMuta; DEAF1; -.
DR EPD; O75398; -.
DR jPOST; O75398; -.
DR MassIVE; O75398; -.
DR MaxQB; O75398; -.
DR PaxDb; O75398; -.
DR PeptideAtlas; O75398; -.
DR PRIDE; O75398; -.
DR ProteomicsDB; 49968; -. [O75398-1]
DR ProteomicsDB; 49969; -. [O75398-3]
DR ProteomicsDB; 49970; -. [O75398-4]
DR ProteomicsDB; 49971; -. [O75398-5]
DR Antibodypedia; 9854; 339 antibodies from 30 providers.
DR DNASU; 10522; -.
DR Ensembl; ENST00000382409.4; ENSP00000371846.3; ENSG00000177030.19. [O75398-1]
DR GeneID; 10522; -.
DR KEGG; hsa:10522; -.
DR MANE-Select; ENST00000382409.4; ENSP00000371846.3; NM_021008.4; NP_066288.2.
DR UCSC; uc001lqq.2; human. [O75398-1]
DR CTD; 10522; -.
DR DisGeNET; 10522; -.
DR GeneCards; DEAF1; -.
DR HGNC; HGNC:14677; DEAF1.
DR HPA; ENSG00000177030; Tissue enhanced (brain).
DR MalaCards; DEAF1; -.
DR MIM; 602635; gene.
DR MIM; 615828; phenotype.
DR MIM; 617171; phenotype.
DR neXtProt; NX_O75398; -.
DR OpenTargets; ENSG00000177030; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR Orphanet; 468620; Intellectual disability-epilepsy-extrapyramidal syndrome.
DR Orphanet; 819; Smith-Magenis syndrome.
DR PharmGKB; PA27234; -.
DR VEuPathDB; HostDB:ENSG00000177030; -.
DR eggNOG; KOG4333; Eukaryota.
DR GeneTree; ENSGT00940000159701; -.
DR HOGENOM; CLU_039056_1_0_1; -.
DR InParanoid; O75398; -.
DR OMA; KDHQHSC; -.
DR OrthoDB; 662933at2759; -.
DR PhylomeDB; O75398; -.
DR TreeFam; TF325664; -.
DR PathwayCommons; O75398; -.
DR SignaLink; O75398; -.
DR SIGNOR; O75398; -.
DR BioGRID-ORCS; 10522; 13 hits in 1099 CRISPR screens.
DR ChiTaRS; DEAF1; human.
DR EvolutionaryTrace; O75398; -.
DR GenomeRNAi; 10522; -.
DR Pharos; O75398; Tbio.
DR PRO; PR:O75398; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O75398; protein.
DR Bgee; ENSG00000177030; Expressed in amygdala and 96 other tissues.
DR ExpressionAtlas; O75398; baseline and differential.
DR Genevisible; O75398; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0048706; P:embryonic skeletal system development; ISS:UniProtKB.
DR GO; GO:0007281; P:germ cell development; TAS:ProtInc.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0033599; P:regulation of mammary gland epithelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR Gene3D; 3.10.390.10; -; 1.
DR InterPro; IPR010919; SAND-like_dom_sf.
DR InterPro; IPR000770; SAND_dom.
DR InterPro; IPR024119; TF_DEAF-1.
DR InterPro; IPR002893; Znf_MYND.
DR PANTHER; PTHR10237; PTHR10237; 1.
DR Pfam; PF01342; SAND; 1.
DR Pfam; PF01753; zf-MYND; 1.
DR SMART; SM00258; SAND; 1.
DR SUPFAM; SSF63763; SSF63763; 1.
DR PROSITE; PS50864; SAND; 1.
DR PROSITE; PS01360; ZF_MYND_1; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Developmental protein;
KW Disease variant; DNA-binding; Epilepsy; Intellectual disability;
KW Metal-binding; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
KW Secreted; Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..565
FT /note="Deformed epidermal autoregulatory factor 1 homolog"
FT /id="PRO_0000074084"
FT DOMAIN 193..273
FT /note="SAND"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00185"
FT ZN_FING 504..540
FT /note="MYND-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT REGION 34..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 162..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..478
FT /note="Interaction with LMO4"
FT /evidence="ECO:0000250"
FT MOTIF 301..316
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT BINDING 504
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 507
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 515
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 518
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 524
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 528
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 536
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 540
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT MOD_RES 171
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1T5"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 179
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1T5"
FT MOD_RES 432
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88450"
FT VAR_SEQ 1..68
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11705868,
FT ECO:0000303|PubMed:14702039, ECO:0000303|Ref.4"
FT /id="VSP_005966"
FT VAR_SEQ 15..29
FT /note="EAAAVAAAAAVAAAA -> D (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9773984"
FT /id="VSP_005967"
FT VAR_SEQ 223..333
FT /note="GRGRCIKQGENWYSPTEFEAMAGRASSKDWKRSIRYAGRPLQCLIQDGILNP
FT HAASCTCAACCDDMTLSGPVRLFVPYKRRKKENELPTTPVKKDSPKNITLLPATAATTF
FT -> WDLKPSRCLLHLCCLLRRHDLI (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:19668219"
FT /id="VSP_038701"
FT VAR_SEQ 501
FT /note="E -> EVIHPPRLPKVLGLQ (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:19668219"
FT /id="VSP_038702"
FT VARIANT 186
FT /note="E -> V (in a primary colorectal cancer;
FT dbSNP:rs751727919)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013725"
FT VARIANT 191
FT /note="K -> I (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013726"
FT VARIANT 191
FT /note="K -> N (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013727"
FT VARIANT 199..202
FT /note="YDSE -> CDND (in a primary colorectal cancer)"
FT /id="VAR_013728"
FT VARIANT 202
FT /note="E -> D (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013729"
FT VARIANT 218
FT /note="R -> K (in a primary colorectal cancer;
FT dbSNP:rs1127312)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013730"
FT VARIANT 224
FT /note="R -> W (in VSVS; loss of DEAF1-promoter repression;
FT loss of transcriptional activation of EIF4G3; loss of DNA
FT binding; decreased interaction with XRCC6;
FT dbSNP:rs587777408)"
FT /evidence="ECO:0000269|PubMed:24726472"
FT /id="VAR_071371"
FT VARIANT 226
FT /note="R -> W (in dbSNP:rs587777623)"
FT /evidence="ECO:0000269|PubMed:24668509"
FT /id="VAR_071372"
FT VARIANT 228
FT /note="I -> S (in VSVS; loss of DEAF1-promoter repression;
FT loss of transcriptional activation of EIF4G3; loss of DNA
FT binding; loss of interaction with XRCC6;
FT dbSNP:rs587777406)"
FT /evidence="ECO:0000269|PubMed:21076407,
FT ECO:0000269|PubMed:24726472"
FT /id="VAR_065089"
FT VARIANT 254
FT /note="R -> S (in VSVS; loss of DEAF1-promoter repression;
FT gain of transcriptional activation of EIF4G3; a 9-fold
FT reduction in DNA binding; dbSNP:rs587777409)"
FT /evidence="ECO:0000269|PubMed:24726472"
FT /id="VAR_071373"
FT VARIANT 264
FT /note="Q -> P (in VSVS; loss of DEAF1-promoter repression;
FT loss of transcriptional activation of EIF4G3; loss of DNA
FT binding; loss of interaction with XRCC6;
FT dbSNP:rs587777407)"
FT /evidence="ECO:0000269|PubMed:24726472"
FT /id="VAR_071374"
FT VARIANT 350..352
FT /note="DRA -> GQT (in a primary colorectal cancer)"
FT /id="VAR_013731"
FT VARIANT 356
FT /note="E -> H (in a primary colorectal cancer; requires 2
FT nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013732"
FT VARIANT 364
FT /note="S -> N (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013733"
FT VARIANT 367
FT /note="Q -> H (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013734"
FT VARIANT 370
FT /note="V -> L (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013735"
FT VARIANT 397
FT /note="Y -> F (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013736"
FT VARIANT 442
FT /note="V -> A (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013737"
FT VARIANT 449
FT /note="E -> K (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013738"
FT VARIANT 451..452
FT /note="RS -> GI (in a primary colorectal cancer)"
FT /id="VAR_013739"
FT VARIANT 468
FT /note="Q -> H (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013740"
FT VARIANT 479
FT /note="H -> L (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013741"
FT VARIANT 498
FT /note="E -> K (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013742"
FT VARIANT 526
FT /note="T -> N (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013743"
FT VARIANT 530
FT /note="R -> L (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013744"
FT VARIANT 537..538
FT /note="QH -> HL (in a primary colorectal cancer)"
FT /id="VAR_013745"
FT VARIANT 542
FT /note="Q -> H (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013746"
FT VARIANT 545
FT /note="A -> G (in a primary colorectal cancer;
FT dbSNP:rs34114147)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013747"
FT VARIANT 545
FT /note="A -> V (in a primary colorectal cancer)"
FT /evidence="ECO:0000269|PubMed:11705868"
FT /id="VAR_013748"
FT MUTAGEN 215
FT /note="Y->Q: Reduces transcription activation."
FT /evidence="ECO:0000269|PubMed:11427895"
FT MUTAGEN 226
FT /note="R->A: Reduces transcription activation."
FT /evidence="ECO:0000269|PubMed:11427895"
FT MUTAGEN 246
FT /note="R->A: Reduces transcription activation."
FT /evidence="ECO:0000269|PubMed:11427895"
FT MUTAGEN 250
FT /note="K->A: Abolishes DNA-binding. Loss of DEAF1-promoter
FT repression; when associated with A-253. Loss of
FT transcriptional activation of EIF4G3; when associated with
FT A-253. Loss of interaction with XRCC6; when associated with
FT A-253. Loss of DNA binding; when associated with A-253."
FT /evidence="ECO:0000269|PubMed:11427895,
FT ECO:0000269|PubMed:24726472"
FT MUTAGEN 252
FT /note="W->Q: Abolishes DNA-binding."
FT /evidence="ECO:0000269|PubMed:11427895"
FT MUTAGEN 253
FT /note="K->A: Abolishes DNA-binding. oss of DEAF1-promoter
FT repression; when associated with A-250. Loss of
FT transcriptional activation of EIF4G3; when associated with
FT A-250. Loss of interaction with XRCC6; when associated with
FT A-250. Loss of DNA binding; when associated with A-250."
FT /evidence="ECO:0000269|PubMed:11427895,
FT ECO:0000269|PubMed:24726472"
FT MUTAGEN 302
FT /note="R->T: Abolishes nuclear localization."
FT /evidence="ECO:0000269|PubMed:9773984"
FT MUTAGEN 304
FT /note="K->T: Abolishes nuclear localization."
FT /evidence="ECO:0000269|PubMed:9773984"
FT MUTAGEN 538
FT /note="H->S: No effect on folding of MYND-type zinc
FT finger."
FT /evidence="ECO:0000269|PubMed:23372760"
FT CONFLICT 65
FT /note="A -> E (in Ref. 3; ACU88060)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="E -> D (in Ref. 4; AAB62704)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="P -> Q (in Ref. 3; ACU88060)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="A -> T (in Ref. 4; AAB62704)"
FT /evidence="ECO:0000305"
FT CONFLICT 294
FT /note="V -> L (in Ref. 4; AAB62704)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="D -> G (in Ref. 3; ACU88060)"
FT /evidence="ECO:0000305"
FT CONFLICT 522
FT /note="N -> K (in Ref. 4; AAB62704)"
FT /evidence="ECO:0000305"
FT HELIX 456..463
FT /evidence="ECO:0007829|PDB:5UWW"
FT STRAND 505..510
FT /evidence="ECO:0007829|PDB:2JW6"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:2JW6"
FT TURN 516..518
FT /evidence="ECO:0007829|PDB:2JW6"
FT STRAND 520..525
FT /evidence="ECO:0007829|PDB:2JW6"
FT HELIX 526..532
FT /evidence="ECO:0007829|PDB:2JW6"
FT TURN 533..535
FT /evidence="ECO:0007829|PDB:2JW6"
FT HELIX 536..538
FT /evidence="ECO:0007829|PDB:2JW6"
FT TURN 539..541
FT /evidence="ECO:0007829|PDB:2JW6"
SQ SEQUENCE 565 AA; 59327 MW; 3BDFEDBF6AD4BDDE CRC64;
MEDSDSAAKQ LGLAEAAAVA AAAAVAAAAA AAAGGEAEEP VLSRDEDSEE DADSEAERET
PRVTAVAVMA AEPGHMDMGA EALPGPDEAA AAAAFAEVTT VTVANVGAAA DNVFTTSVAN
AASISGHVLS GRTALQIGDS LNTEKATLIV VHTDGSIVET TGLKGPAAPL TPGPQSPPTP
LAPGQEKGGT KYNWDPSVYD SELPVRCRNI SGTLYKNRLG SGGRGRCIKQ GENWYSPTEF
EAMAGRASSK DWKRSIRYAG RPLQCLIQDG ILNPHAASCT CAACCDDMTL SGPVRLFVPY
KRRKKENELP TTPVKKDSPK NITLLPATAA TTFTVTPSGQ ITTSGALTFD RASTVEATAV
ISESPAQGDV FAGATVQEAS VQPPCRASHP EPHYPGYQDS CQIAPFPEAA LPTSHPKIVL
TSLPALAVPP PTPTKAAPPA LVNGLELSEP RSWLYLEEMV NSLLNTAQQL KTLFEQAKHA
STYREAATNQ AKIHADAERK EQSCVNCGRE AMSECTGCHK VNYCSTFCQR KDWKDHQHIC
GQSAAVTVQA DEVHVAESVM EKVTV
