ID   SP7_MOUSE               Reviewed;         428 AA.
AC   Q8VI67; Q8C5R3; Q8C6A7;
DT   16-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   27-MAR-2024, entry version 156.
DE   RecName: Full=Transcription factor Sp7;
DE   AltName: Full=C22;
DE   AltName: Full=Zinc finger protein osterix;
GN   Name=Sp7; Synonyms=Osx;
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=11792318; DOI=10.1016/s0092-8674(01)00622-5;
RA   Nakashima K., Zhou X., Kunkel G., Zhang Z., Deng J.M., Behringer R.R.,
RA   de Crombrugghe B.;
RT   "The novel zinc finger-containing transcription factor osterix is required
RT   for osteoblast differentiation and bone formation.";
RL   Cell 108:17-29(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Head, and Olfactory neuron;
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   FUNCTION, AND INDUCTION.
RX   PubMed=17510056; DOI=10.1074/jbc.m702614200;
RA   Xing W., Singgih A., Kapoor A., Alarcon C.M., Baylink D.J., Mohan S.;
RT   "Nuclear factor-E2-related factor-1 mediates ascorbic acid induction of
RT   osterix expression via interaction with antioxidant-responsive element in
RT   bone cells.";
RL   J. Biol. Chem. 282:22052-22061(2007).
RN   [4]
RP   INTERACTION WITH RIOX1.
RX   PubMed=19927124; DOI=10.1038/emboj.2009.332;
RA   Sinha K.M., Yasuda H., Coombes M.M., Dent S.Y., de Crombrugghe B.;
RT   "Regulation of the osteoblast-specific transcription factor Osterix by
RT   NO66, a Jumonji family histone demethylase.";
RL   EMBO J. 29:68-79(2010).
RN   [5]
RP   FUNCTION, PROPIONYLATION AT LYS-41; LYS-45; LYS-358 AND LYS-368,
RP   DEPROPIONYLATION BY SIRT7, AND MUTAGENESIS OF 41-LYS--LYS-46 AND LYS-368.
RX   PubMed=30026585; DOI=10.1038/s41467-018-05187-4;
RA   Fukuda M., Yoshizawa T., Karim M.F., Sobuz S.U., Korogi W., Kobayasi D.,
RA   Okanishi H., Tasaki M., Ono K., Sawa T., Sato Y., Chirifu M., Masuda T.,
RA   Nakamura T., Tanoue H., Nakashima K., Kobashigawa Y., Morioka H., Bober E.,
RA   Ohtsuki S., Yamagata Y., Ando Y., Oike Y., Araki N., Takeda S., Mizuta H.,
RA   Yamagata K.;
RT   "SIRT7 has a critical role in bone formation by regulating lysine acylation
RT   of SP7/Osterix.";
RL   Nat. Commun. 9:2833-2833(2018).
CC   -!- FUNCTION: Transcriptional activator essential for osteoblast
CC       differentiation (PubMed:11792318, PubMed:17510056, PubMed:30026585).
CC       Binds to SP1 and EKLF consensus sequences and to other G/C-rich
CC       sequences (PubMed:11792318, PubMed:17510056).
CC       {ECO:0000269|PubMed:11792318, ECO:0000269|PubMed:17510056,
CC       ECO:0000269|PubMed:30026585}.
CC   -!- SUBUNIT: Interacts with RIOX1; the interaction is direct and inhibits
CC       transcription activator activity. {ECO:0000269|PubMed:19927124}.
CC   -!- INTERACTION:
CC       Q8VI67; Q9JJF3: Riox1; NbExp=3; IntAct=EBI-7608836, EBI-7608809;
CC       Q8VI67; Q9H6W3: RIOX1; Xeno; NbExp=6; IntAct=EBI-7608836, EBI-2513645;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11792318}.
CC   -!- TISSUE SPECIFICITY: Osteoblast/chondrocyte specific.
CC       {ECO:0000269|PubMed:11792318}.
CC   -!- INDUCTION: In response to ascorbic acid induction, expression is
CC       activated by NFE2L1 in osteoblasts. {ECO:0000269|PubMed:17510056}.
CC   -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC       number of yeast and animal transcription factors.
CC       {ECO:0000250|UniProtKB:Q8TDD2}.
CC   -!- PTM: Propionylated (PubMed:30026585). Depropionylation at Lys-368 by
CC       SIRT7 activates transcription factor activity and positively regulates
CC       bone formation by osteoblasts (PubMed:30026585).
CC       {ECO:0000269|PubMed:30026585}.
CC   -!- PTM: Ubiquitination at leads to proteasomal degradation. SP7 is a
CC       short-live protein with an endogenous half-life of approximately 12
CC       hours (By similarity). {ECO:0000250|UniProtKB:Q8TDD2}.
CC   -!- DISRUPTION PHENOTYPE: Death in the immediate postnatal period due to
CC       difficulty in breathing. Mice rapidly become cyanotic and die within 15
CC       min of birth. New-born homozygous show severe inward bending of
CC       forelimbs and hindlimbs. They develop a normal cartilage skeleton but
CC       fail to form bone and to express osteoblast-specific marker genes. In
CC       endochondral skeletal elements, mesenchymal cells together with
CC       osteoclasts and blood vessels, invade the mineralized cartilage matrix.
CC       {ECO:0000269|PubMed:11792318}.
CC   -!- SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein family.
CC       {ECO:0000305}.
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DR   EMBL; AF184902; AAL60067.1; -; mRNA.
DR   EMBL; AK032521; BAC27908.1; -; mRNA.
DR   EMBL; AK076229; BAC36263.1; -; mRNA.
DR   EMBL; AK077375; BAC36774.1; -; mRNA.
DR   CCDS; CCDS37228.1; -.
DR   RefSeq; NP_001335134.1; NM_001348205.1.
DR   RefSeq; NP_569725.1; NM_130458.4.
DR   RefSeq; XP_006520582.1; XM_006520519.3.
DR   AlphaFoldDB; Q8VI67; -.
DR   SMR; Q8VI67; -.
DR   BioGRID; 228354; 7.
DR   DIP; DIP-46090N; -.
DR   IntAct; Q8VI67; 12.
DR   MINT; Q8VI67; -.
DR   STRING; 10090.ENSMUSP00000077596; -.
DR   GlyGen; Q8VI67; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8VI67; -.
DR   PhosphoSitePlus; Q8VI67; -.
DR   PaxDb; 10090-ENSMUSP00000077596; -.
DR   ProteomicsDB; 257291; -.
DR   Antibodypedia; 3133; 201 antibodies from 33 providers.
DR   DNASU; 170574; -.
DR   Ensembl; ENSMUST00000078508.7; ENSMUSP00000077596.6; ENSMUSG00000060284.8.
DR   GeneID; 170574; -.
DR   KEGG; mmu:170574; -.
DR   UCSC; uc007xvm.1; mouse.
DR   AGR; MGI:2153568; -.
DR   CTD; 121340; -.
DR   MGI; MGI:2153568; Sp7.
DR   VEuPathDB; HostDB:ENSMUSG00000060284; -.
DR   eggNOG; KOG1721; Eukaryota.
DR   GeneTree; ENSGT00940000161293; -.
DR   HOGENOM; CLU_019484_4_2_1; -.
DR   InParanoid; Q8VI67; -.
DR   OMA; NTPSPWW; -.
DR   OrthoDB; 5359201at2759; -.
DR   PhylomeDB; Q8VI67; -.
DR   TreeFam; TF350150; -.
DR   BioGRID-ORCS; 170574; 2 hits in 77 CRISPR screens.
DR   PRO; PR:Q8VI67; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; Q8VI67; Protein.
DR   Bgee; ENSMUSG00000060284; Expressed in dental pulp and 100 other cell types or tissues.
DR   ExpressionAtlas; Q8VI67; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:BHF-UCL.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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; IDA:NTNU_SB.
DR   GO; GO:0034224; P:cellular response to zinc ion starvation; IEA:Ensembl.
DR   GO; GO:0071529; P:cementum mineralization; IDA:MGI.
DR   GO; GO:0071344; P:diphosphate metabolic process; IMP:MGI.
DR   GO; GO:0010467; P:gene expression; IDA:MGI.
DR   GO; GO:0060218; P:hematopoietic stem cell differentiation; ISO:MGI.
DR   GO; GO:0001649; P:osteoblast differentiation; IMP:MGI.
DR   GO; GO:2000738; P:positive regulation of stem cell differentiation; ISO:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 3.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   PANTHER; PTHR23235; KRUEPPEL-LIKE TRANSCRIPTION FACTOR; 1.
DR   PANTHER; PTHR23235:SF19; TRANSCRIPTION FACTOR SP7; 1.
DR   Pfam; PF00096; zf-C2H2; 3.
DR   SMART; SM00355; ZnF_C2H2; 3.
DR   SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 2.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
DR   Genevisible; Q8VI67; MM.
PE   1: Evidence at protein level;
KW   Activator; DNA-binding; Isopeptide bond; Metal-binding; Nucleus;
KW   Reference proteome; Repeat; Transcription; Transcription regulation;
KW   Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..428
FT                   /note="Transcription factor Sp7"
FT                   /id="PRO_0000047151"
FT   ZN_FING         291..315
FT                   /note="C2H2-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         321..345
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         351..373
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          30..84
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          229..257
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          364..428
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           153..161
FT                   /note="9aaTAD"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TDD2"
FT   MOD_RES         41
FT                   /note="N6-propionyllysine"
FT                   /evidence="ECO:0000305|PubMed:30026585"
FT   MOD_RES         45
FT                   /note="N6-propionyllysine"
FT                   /evidence="ECO:0000305|PubMed:30026585"
FT   MOD_RES         358
FT                   /note="N6-propionyllysine"
FT                   /evidence="ECO:0000305|PubMed:30026585"
FT   MOD_RES         368
FT                   /note="N6-propionyllysine"
FT                   /evidence="ECO:0000269|PubMed:30026585"
FT   CROSSLNK        55
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TDD2"
FT   CROSSLNK        227
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TDD2"
FT   MUTAGEN         41..46
FT                   /note="KGGTKK->RGGTRR: Decreased propionylation."
FT                   /evidence="ECO:0000269|PubMed:30026585"
FT   MUTAGEN         368
FT                   /note="K->R: Decreased propionylation, leading to increased
FT                   transcription activator activity."
FT                   /evidence="ECO:0000269|PubMed:30026585"
FT   CONFLICT        64
FT                   /note="P -> L (in Ref. 2; BAC36263)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        130
FT                   /note="H -> Y (in Ref. 2; BAC36774)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   428 AA;  44718 MW;  B794988958743586 CRC64;
     MASSLLEEEA HYGSSPLAML TAACSKFGGS SPLRDSTTLG KGGTKKPYAD LSAPKTMGDA
     YPAPFSSTNG LLSPAGSPPA PASGYANDYP PFPHSFPGPT GAQDPGLLVP KGHSSSDCLP
     SVYTSLDMTH PYGSWYKAGI HAGISPGPGN TPTPWWDMHP GGNWLGGGQG QGDGLQGTLS
     TGPAQPPLNP QLPTYPSDFA PLNPAPYPAP HLLQPGPQHV LPQDVYKPKA VGNSGQLEGS
     GAAKPPRGAG TGGSGGYAGS GAGRSTCDCP NCQELERLGA AAAGLRKKPI HSCHIPGCGK
     VYGKASHLKA HLRWHTGERP FVCNWLFCGK RFTRSDELER HVRTHTREKK FTCLLCSKRF
     TRSDHLSKHQ RTHGEPGPGP PPSGPKELGE GRSVGEEEAN QPPRSSTSPA PPEKAHGGSP
     EQSNLLEI
//