SP7_MOUSE
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 03-AUG-2022, entry version 147.
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 iPTMnet; Q8VI67; -.
DR PhosphoSitePlus; Q8VI67; -.
DR PaxDb; Q8VI67; -.
DR PRIDE; Q8VI67; -.
DR ProteomicsDB; 257291; -.
DR Antibodypedia; 3133; 181 antibodies from 33 providers.
DR DNASU; 170574; -.
DR Ensembl; ENSMUST00000078508; ENSMUSP00000077596; ENSMUSG00000060284.
DR GeneID; 170574; -.
DR KEGG; mmu:170574; -.
DR UCSC; uc007xvm.1; mouse.
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; PTRSSCD; -.
DR OrthoDB; 664813at2759; -.
DR PhylomeDB; Q8VI67; -.
DR TreeFam; TF350150; -.
DR BioGRID-ORCS; 170574; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q8VI67; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8VI67; protein.
DR Bgee; ENSMUSG00000060284; Expressed in dental pulp and 99 other tissues.
DR ExpressionAtlas; Q8VI67; baseline and differential.
DR Genevisible; Q8VI67; MM.
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: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:0051336; P:regulation of hydrolase activity; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 3.
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; 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
