SP4_HUMAN
ID SP4_HUMAN Reviewed; 784 AA.
AC Q02446; O60402; Q32M52;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Transcription factor Sp4;
DE AltName: Full=SPR-1;
GN Name=SP4;
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], AND VARIANT LYS-197.
RC TISSUE=Uterus;
RX PubMed=1454515; DOI=10.1093/nar/20.21.5519;
RA Hagen G., Mueller S., Beato M., Suske G.;
RT "Cloning by recognition site screening of two novel GT box binding
RT proteins: a family of Sp1 related genes.";
RL Nucleic Acids Res. 20:5519-5525(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [9]
RP INACTIVATION OF 9AATAD MOTIF.
RX PubMed=31375868; DOI=10.1007/s00018-019-03251-w;
RA Piskacek M., Havelka M., Jendruchova K., Knight A., Keegan L.P.;
RT "The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with
RT valines and intron reservoirs.";
RL Cell. Mol. Life Sci. 77:1793-1810(2020).
CC -!- FUNCTION: Binds to GT and GC boxes promoters elements. Probable
CC transcriptional activator.
CC -!- INTERACTION:
CC Q02446; Q13444: ADAM15; NbExp=3; IntAct=EBI-10198587, EBI-77818;
CC Q02446; Q9BXS5: AP1M1; NbExp=3; IntAct=EBI-10198587, EBI-541426;
CC Q02446; Q9BTQ8: ATXN7L1; NbExp=3; IntAct=EBI-10198587, EBI-10298510;
CC Q02446; A0A0S2Z5G4: BANP; NbExp=3; IntAct=EBI-10198587, EBI-16429704;
CC Q02446; B4DE54: BANP; NbExp=3; IntAct=EBI-10198587, EBI-16429313;
CC Q02446; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-10198587, EBI-11524452;
CC Q02446; Q8N9N5-7: BANP; NbExp=3; IntAct=EBI-10198587, EBI-16429296;
CC Q02446; Q96Q77: CIB3; NbExp=6; IntAct=EBI-10198587, EBI-10292696;
CC Q02446; P27658: COL8A1; NbExp=3; IntAct=EBI-10198587, EBI-747133;
CC Q02446; P41970: ELK3; NbExp=3; IntAct=EBI-10198587, EBI-1758534;
CC Q02446; Q75MZ5: FOXP2; NbExp=4; IntAct=EBI-10198587, EBI-10255915;
CC Q02446; P52655: GTF2A1; NbExp=3; IntAct=EBI-10198587, EBI-389518;
CC Q02446; A0A024R5S0: hCG_2003792; NbExp=6; IntAct=EBI-10198587, EBI-10188461;
CC Q02446; Q8TAP4: LMO3; NbExp=3; IntAct=EBI-10198587, EBI-742259;
CC Q02446; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-10198587, EBI-739832;
CC Q02446; Q4G0S1: LOC730441; NbExp=3; IntAct=EBI-10198587, EBI-10241801;
CC Q02446; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-10198587, EBI-348259;
CC Q02446; Q13952-2: NFYC; NbExp=3; IntAct=EBI-10198587, EBI-11956831;
CC Q02446; Q16656: NRF1; NbExp=3; IntAct=EBI-10198587, EBI-2547810;
CC Q02446; Q16656-4: NRF1; NbExp=3; IntAct=EBI-10198587, EBI-11742836;
CC Q02446; Q9HAT8: PELI2; NbExp=3; IntAct=EBI-10198587, EBI-448407;
CC Q02446; Q96T60: PNKP; NbExp=3; IntAct=EBI-10198587, EBI-1045072;
CC Q02446; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-10198587, EBI-1389308;
CC Q02446; P14859: POU2F1; NbExp=5; IntAct=EBI-10198587, EBI-624770;
CC Q02446; P14859-6: POU2F1; NbExp=3; IntAct=EBI-10198587, EBI-11526590;
CC Q02446; P86479: PRR20C; NbExp=5; IntAct=EBI-10198587, EBI-10172814;
CC Q02446; P86480: PRR20D; NbExp=3; IntAct=EBI-10198587, EBI-12754095;
CC Q02446; Q02446: SP4; NbExp=3; IntAct=EBI-10198587, EBI-10198587;
CC Q02446; Q5MJ10: SPANXN2; NbExp=3; IntAct=EBI-10198587, EBI-12023934;
CC Q02446; Q5MJ09: SPANXN3; NbExp=3; IntAct=EBI-10198587, EBI-12037215;
CC Q02446; Q14119: VEZF1; NbExp=3; IntAct=EBI-10198587, EBI-11980193;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Abundant in brain.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors. In SP4, the motif is
CC inactive. {ECO:0000269|PubMed:31375868}.
CC -!- SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; X68561; CAA48563.1; -; mRNA.
DR EMBL; AK289728; BAF82417.1; -; mRNA.
DR EMBL; AC004595; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471073; EAW93733.1; -; Genomic_DNA.
DR EMBL; BC109300; AAI09301.1; -; mRNA.
DR CCDS; CCDS5373.1; -.
DR PIR; S26638; S26638.
DR RefSeq; NP_001313472.1; NM_001326543.1.
DR RefSeq; NP_003103.2; NM_003112.4.
DR AlphaFoldDB; Q02446; -.
DR SMR; Q02446; -.
DR BioGRID; 112554; 61.
DR IntAct; Q02446; 31.
DR STRING; 9606.ENSP00000222584; -.
DR GlyGen; Q02446; 22 sites, 2 O-linked glycans (22 sites).
DR iPTMnet; Q02446; -.
DR PhosphoSitePlus; Q02446; -.
DR BioMuta; SP4; -.
DR DMDM; 218511800; -.
DR EPD; Q02446; -.
DR jPOST; Q02446; -.
DR MassIVE; Q02446; -.
DR MaxQB; Q02446; -.
DR PaxDb; Q02446; -.
DR PeptideAtlas; Q02446; -.
DR PRIDE; Q02446; -.
DR ProteomicsDB; 58090; -.
DR Antibodypedia; 4135; 70 antibodies from 21 providers.
DR DNASU; 6671; -.
DR Ensembl; ENST00000222584.8; ENSP00000222584.3; ENSG00000105866.15.
DR GeneID; 6671; -.
DR KEGG; hsa:6671; -.
DR MANE-Select; ENST00000222584.8; ENSP00000222584.3; NM_003112.5; NP_003103.2.
DR UCSC; uc003sva.4; human.
DR CTD; 6671; -.
DR DisGeNET; 6671; -.
DR GeneCards; SP4; -.
DR HGNC; HGNC:11209; SP4.
DR HPA; ENSG00000105866; Low tissue specificity.
DR MIM; 600540; gene.
DR neXtProt; NX_Q02446; -.
DR OpenTargets; ENSG00000105866; -.
DR PharmGKB; PA36046; -.
DR VEuPathDB; HostDB:ENSG00000105866; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000157827; -.
DR HOGENOM; CLU_019688_2_0_1; -.
DR InParanoid; Q02446; -.
DR OMA; NQQAILP; -.
DR OrthoDB; 1085860at2759; -.
DR PhylomeDB; Q02446; -.
DR TreeFam; TF350150; -.
DR PathwayCommons; Q02446; -.
DR SignaLink; Q02446; -.
DR SIGNOR; Q02446; -.
DR BioGRID-ORCS; 6671; 10 hits in 1103 CRISPR screens.
DR ChiTaRS; SP4; human.
DR GeneWiki; Sp4_transcription_factor; -.
DR GenomeRNAi; 6671; -.
DR Pharos; Q02446; Tbio.
DR PRO; PR:Q02446; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q02446; protein.
DR Bgee; ENSG00000105866; Expressed in cerebellar vermis and 183 other tissues.
DR ExpressionAtlas; Q02446; baseline and differential.
DR Genevisible; Q02446; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR InterPro; IPR030453; SP4.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR23235:SF17; PTHR23235:SF17; 2.
DR Pfam; PF00096; zf-C2H2; 2.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
PE 1: Evidence at protein level;
KW Activator; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..784
FT /note="Transcription factor Sp4"
FT /id="PRO_0000047144"
FT ZN_FING 647..671
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 677..701
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 707..729
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 109..150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 467..475
FT /note="9aaTAD; inactive"
FT /evidence="ECO:0000269|PubMed:31375868"
FT COMPBIAS 32..50
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 285..390
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 197
FT /note="Q -> K (in dbSNP:rs1042848)"
FT /evidence="ECO:0000269|PubMed:1454515"
FT /id="VAR_047975"
FT CONFLICT 379..380
FT /note="QP -> HA (in Ref. 1; CAA48563)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="A -> Q (in Ref. 1; CAA48563)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 784 AA; 81985 MW; 5B0B03EC03657993 CRC64;
MSDQKKEEEE EAAAAAAMAT EGGKTSEPEN NNKKPKTSGS QDSQPSPLAL LAATCSKIGT
PGENQATGQQ QIIIDPSQGL VQLQNQPQQL ELVTTQLAGN AWQLVASTPP ASKENNVSQP
ASSSSSSSSS NNGSASPTKT KSGNSSTPGQ FQVIQVQNPS GSVQYQVIPQ LQTVEGQQIQ
INPTSSSSLQ DLQGQIQLIS AGNNQAILTA ANRTASGNIL AQNLANQTVP VQIRPGVSIP
LQLQTLPGTQ AQVVTTLPIN IGGVTLALPV INNVAAGGGT GQVGQPAATA DSGTSNGNQL
VSTPTNTTTS ASTMPESPSS STTCTTTAST SLTSSDTLVS SADTGQYAST SASSSERTIE
ESQTPAATES EAQSSSQLQP NGMQNAQDQS NSLQQVQIVG QPILQQIQIQ QPQQQIIQAI
PPQSFQLQSG QTIQTIQQQP LQNVQLQAVN PTQVLIRAPT LTPSGQISWQ TVQVQNIQSL
SNLQVQNAGL SQQLTITPVS SSGGTTLAQI APVAVAGAPI TLNTAQLASV PNLQTVSVAN
LGAAGVQVQG VPVTITSVAG QQQGQDGVKV QQATIAPVTV AVGGIANATI GAVSPDQLTQ
VHLQQGQQTS DQEVQPGKRL RRVACSCPNC REGEGRGSNE PGKKKQHICH IEGCGKVYGK
TSHLRAHLRW HTGERPFICN WMFCGKRFTR SDELQRHRRT HTGEKRFECP ECSKRFMRSD
HLSKHVKTHQ NKKGGGTALA IVTSGELDSS VTEVLGSPRI VTVAAISQDS NPATPNVSTN
MEEF