SPDEF_HUMAN
ID SPDEF_HUMAN Reviewed; 335 AA.
AC O95238; B4DWH8; F5H778;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=SAM pointed domain-containing Ets transcription factor;
DE AltName: Full=Prostate epithelium-specific Ets transcription factor;
DE Short=Prostate-specific Ets;
DE AltName: Full=Prostate-derived Ets factor;
GN Name=SPDEF; Synonyms=PDEF, PSE;
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).
RC TISSUE=Prostatic carcinoma;
RX PubMed=10675039; DOI=10.1016/s0378-1119(99)00484-9;
RA Yamada N., Tamai Y., Miyamoto H., Nozaki M.;
RT "Cloning and expression of the mouse Pse gene encoding a novel Ets family
RT member.";
RL Gene 241:267-274(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH AR.
RC TISSUE=Prostate;
RX PubMed=10625666; DOI=10.1074/jbc.275.2.1216;
RA Oettgen P., Finger E., Sun Z., Akbarali Y., Thamrongsak U., Boltax J.,
RA Grall F., Dube A., Weiss A., Brown L., Quinn G., Kas K., Endress G.,
RA Kunsch C., Libermann T.A.;
RT "PDEF, a novel prostate epithelium-specific ets transcription factor,
RT interacts with the androgen receptor and activates prostate-specific
RT antigen gene expression.";
RL J. Biol. Chem. 275:1216-1225(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary gland;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [6]
RP INTERACTION WITH NKX3-1.
RX PubMed=11809674;
RA Chen H., Nandi A.K., Li X., Bieberich C.J.;
RT "NKX-3.1 interacts with prostate-derived Ets factor and regulates the
RT activity of the PSA promoter.";
RL Cancer Res. 62:338-340(2002).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 247-335 IN COMPLEX WITH DNA.
RX PubMed=15882048; DOI=10.1021/bi047352t;
RA Wang Y., Feng L., Said M., Balderman S., Fayazi Z., Liu Y., Ghosh D.,
RA Gulick A.M.;
RT "Analysis of the 2.0 A crystal structure of the protein-DNA complex of the
RT human PDEF Ets domain bound to the prostate specific antigen regulatory
RT site.";
RL Biochemistry 44:7095-7106(2005).
RN [8]
RP STRUCTURE BY NMR OF 131-213.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SAM_pnt-domain of ETS transcription factor PDEF
RT (prostate Ets).";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: May function as an androgen-independent transactivator of the
CC prostate-specific antigen (PSA) promoter. Binds to 5'-GGAT-3' DNA
CC sequences. May play a role in the regulation of the prostate gland
CC and/or prostate cancer development. Acts as a transcriptional activator
CC for SERPINB5 promoter. {ECO:0000269|PubMed:10625666}.
CC -!- SUBUNIT: Interacts with the DNA-binding domain of the androgen
CC receptor. Interacts with NKX3-1. {ECO:0000269|PubMed:10625666,
CC ECO:0000269|PubMed:11809674, ECO:0000269|PubMed:15882048}.
CC -!- INTERACTION:
CC O95238; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-12811275, EBI-2837444;
CC O95238; Q86XR8-3: CEP57; NbExp=3; IntAct=EBI-12811275, EBI-11752486;
CC O95238; P20674: COX5A; NbExp=3; IntAct=EBI-12811275, EBI-715032;
CC O95238; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-12811275, EBI-744099;
CC O95238; Q96MY7: FAM161B; NbExp=3; IntAct=EBI-12811275, EBI-7225287;
CC O95238; P25786: PSMA1; NbExp=3; IntAct=EBI-12811275, EBI-359352;
CC O95238; Q7Z614-3: SNX20; NbExp=3; IntAct=EBI-12811275, EBI-12336127;
CC O95238; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-12811275, EBI-9090990;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95238-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95238-2; Sequence=VSP_044722;
CC -!- TISSUE SPECIFICITY: Expressed in a very restricted set of primarily
CC hormone-regulated epithelial tissues with particularly high expression
CC in the prostate gland. Significantly lower expression is seen in other
CC hormone regulated tissues such as mammary gland, salivary gland, and
CC ovary. Expressed in prostate carcinoma cells.
CC {ECO:0000269|PubMed:10625666}.
CC -!- SIMILARITY: Belongs to the ETS family. {ECO:0000305}.
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DR EMBL; AB031549; BAA89543.1; -; mRNA.
DR EMBL; AF071538; AAC95296.1; -; mRNA.
DR EMBL; AK301543; BAG63040.1; -; mRNA.
DR EMBL; BX255971; CAI23605.1; -; Genomic_DNA.
DR EMBL; AL157372; CAI23605.1; JOINED; Genomic_DNA.
DR EMBL; BX255972; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX255973; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021299; AAH21299.1; -; mRNA.
DR CCDS; CCDS4794.1; -. [O95238-1]
DR CCDS; CCDS59013.1; -. [O95238-2]
DR RefSeq; NP_001239223.1; NM_001252294.1. [O95238-2]
DR RefSeq; NP_036523.1; NM_012391.2. [O95238-1]
DR PDB; 1YO5; X-ray; 2.00 A; C=247-335.
DR PDB; 2DKX; NMR; -; A=131-213.
DR PDBsum; 1YO5; -.
DR PDBsum; 2DKX; -.
DR AlphaFoldDB; O95238; -.
DR SMR; O95238; -.
DR BioGRID; 117335; 35.
DR IntAct; O95238; 19.
DR STRING; 9606.ENSP00000363149; -.
DR iPTMnet; O95238; -.
DR PhosphoSitePlus; O95238; -.
DR BioMuta; SPDEF; -.
DR EPD; O95238; -.
DR MassIVE; O95238; -.
DR MaxQB; O95238; -.
DR PaxDb; O95238; -.
DR PeptideAtlas; O95238; -.
DR PRIDE; O95238; -.
DR ProteomicsDB; 27406; -.
DR ProteomicsDB; 50737; -. [O95238-1]
DR Antibodypedia; 15077; 232 antibodies from 30 providers.
DR DNASU; 25803; -.
DR Ensembl; ENST00000374037.8; ENSP00000363149.3; ENSG00000124664.11. [O95238-1]
DR Ensembl; ENST00000544425.2; ENSP00000442715.1; ENSG00000124664.11. [O95238-2]
DR GeneID; 25803; -.
DR KEGG; hsa:25803; -.
DR MANE-Select; ENST00000374037.8; ENSP00000363149.3; NM_012391.3; NP_036523.1.
DR UCSC; uc003ojq.3; human. [O95238-1]
DR CTD; 25803; -.
DR DisGeNET; 25803; -.
DR GeneCards; SPDEF; -.
DR HGNC; HGNC:17257; SPDEF.
DR HPA; ENSG00000124664; Tissue enhanced (prostate, salivary gland).
DR MIM; 608144; gene.
DR neXtProt; NX_O95238; -.
DR OpenTargets; ENSG00000124664; -.
DR PharmGKB; PA134993886; -.
DR VEuPathDB; HostDB:ENSG00000124664; -.
DR eggNOG; KOG3805; Eukaryota.
DR GeneTree; ENSGT00940000157549; -.
DR HOGENOM; CLU_877059_0_0_1; -.
DR InParanoid; O95238; -.
DR OMA; TWVAKGP; -.
DR OrthoDB; 908495at2759; -.
DR PhylomeDB; O95238; -.
DR TreeFam; TF318679; -.
DR PathwayCommons; O95238; -.
DR SignaLink; O95238; -.
DR SIGNOR; O95238; -.
DR BioGRID-ORCS; 25803; 33 hits in 1091 CRISPR screens.
DR ChiTaRS; SPDEF; human.
DR EvolutionaryTrace; O95238; -.
DR GeneWiki; SPDEF; -.
DR GenomeRNAi; 25803; -.
DR Pharos; O95238; Tbio.
DR PRO; PR:O95238; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O95238; protein.
DR Bgee; ENSG00000124664; Expressed in parotid gland and 127 other tissues.
DR Genevisible; O95238; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0072148; P:epithelial cell fate commitment; IEA:Ensembl.
DR GO; GO:0002068; P:glandular epithelial cell development; IEA:Ensembl.
DR GO; GO:0060576; P:intestinal epithelial cell development; IEA:Ensembl.
DR GO; GO:0060480; P:lung goblet cell differentiation; IEA:Ensembl.
DR GO; GO:0010454; P:negative regulation of cell fate commitment; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:BHF-UCL.
DR GO; GO:0010455; P:positive regulation of cell fate commitment; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
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; IEA:Ensembl.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR000418; Ets_dom.
DR InterPro; IPR046328; ETS_fam.
DR InterPro; IPR003118; Pointed_dom.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11849; PTHR11849; 1.
DR Pfam; PF00178; Ets; 1.
DR Pfam; PF02198; SAM_PNT; 1.
DR PRINTS; PR00454; ETSDOMAIN.
DR SMART; SM00413; ETS; 1.
DR SMART; SM00251; SAM_PNT; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR PROSITE; PS00345; ETS_DOMAIN_1; 1.
DR PROSITE; PS00346; ETS_DOMAIN_2; 1.
DR PROSITE; PS50061; ETS_DOMAIN_3; 1.
DR PROSITE; PS51433; PNT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..335
FT /note="SAM pointed domain-containing Ets transcription
FT factor"
FT /id="PRO_0000223958"
FT DOMAIN 129..213
FT /note="PNT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00762"
FT DNA_BIND 249..332
FT /note="ETS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00237"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 75..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 212..227
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044722"
FT VARIANT 57
FT /note="A -> T (in dbSNP:rs2233639)"
FT /id="VAR_048955"
FT CONFLICT 49
FT /note="A -> G (in Ref. 3; BAG63040)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="K -> N (in Ref. 3; BAG63040)"
FT /evidence="ECO:0000305"
FT HELIX 132..139
FT /evidence="ECO:0007829|PDB:2DKX"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:2DKX"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:2DKX"
FT HELIX 155..165
FT /evidence="ECO:0007829|PDB:2DKX"
FT HELIX 172..175
FT /evidence="ECO:0007829|PDB:2DKX"
FT HELIX 180..185
FT /evidence="ECO:0007829|PDB:2DKX"
FT HELIX 188..194
FT /evidence="ECO:0007829|PDB:2DKX"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:2DKX"
FT HELIX 200..213
FT /evidence="ECO:0007829|PDB:2DKX"
FT HELIX 251..260
FT /evidence="ECO:0007829|PDB:1YO5"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:1YO5"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:1YO5"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:1YO5"
FT TURN 274..277
FT /evidence="ECO:0007829|PDB:1YO5"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:1YO5"
FT HELIX 284..295
FT /evidence="ECO:0007829|PDB:1YO5"
FT HELIX 302..311
FT /evidence="ECO:0007829|PDB:1YO5"
FT TURN 312..316
FT /evidence="ECO:0007829|PDB:1YO5"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:1YO5"
FT STRAND 328..332
FT /evidence="ECO:0007829|PDB:1YO5"
SQ SEQUENCE 335 AA; 37518 MW; D3117E1AEEBA95EC CRC64;
MGSASPGLSS VSPSHLLLPP DTVSRTGLEK AAAGAVGLER RDWSPSPPAT PEQGLSAFYL
SYFDMLYPED SSWAAKAPGA SSREEPPEEP EQCPVIDSQA PAGSLDLVPG GLTLEEHSLE
QVQSMVVGEV LKDIETACKL LNITADPMDW SPSNVQKWLL WTEHQYRLPP MGKAFQELAG
KELCAMSEEQ FRQRSPLGGD VLHAHLDIWK SAAWMKERTS PGAIHYCAST SEESWTDSEV
DSSCSGQPIH LWQFLKELLL KPHSYGRFIR WLNKEKGIFK IEDSAQVARL WGIRKNRPAM
NYDKLSRSIR QYYKKGIIRK PDISQRLVYQ FVHPI
