SOX5_MOUSE
ID SOX5_MOUSE Reviewed; 763 AA.
AC P35710; O88184; O89018;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Transcription factor SOX-5 {ECO:0000305};
GN Name=Sox5 {ECO:0000303|PubMed:9714725, ECO:0000312|MGI:MGI:98367};
GN Synonyms=Sox-5 {ECO:0000303|PubMed:1396566};
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] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Brain, and Testis;
RX PubMed=1396566; DOI=10.1002/j.1460-2075.1992.tb05455.x;
RA Denny P., Swift S., Connor F., Ashworth A.;
RT "An SRY-related gene expressed during spermatogenesis in the mouse encodes
RT a sequence-specific DNA-binding protein.";
RL EMBO J. 11:3705-3712(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=9714725; DOI=10.1016/s0167-4781(98)00086-4;
RA Hiraoka Y., Ogawa M., Sakai Y., Kido S., Aiso S.;
RT "The mouse Sox5 gene encodes a protein containing the leucine zipper and
RT the Q box.";
RL Biochim. Biophys. Acta 1399:40-46(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION,
RP SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=9755172; DOI=10.1093/emboj/17.19.5718;
RA Lefebvre V., Li P., de Crombrugghe B.;
RT "A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in
RT chondrogenesis and cooperatively activate the type II collagen gene.";
RL EMBO J. 17:5718-5733(1998).
RN [4]
RP FUNCTION.
RX PubMed=8078769; DOI=10.1093/nar/22.16.3339;
RA Connor F., O'Cary P.D., Read C.M., Preston N.S., Driscoll P.C., Denny P.,
RA Crane-Robinson C., Ashworth A.;
RT "DNA binding and bending properties of the post-meiotically expressed Sry-
RT related protein Sox-5.";
RL Nucleic Acids Res. 22:3339-3346(1994).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11702786; DOI=10.1016/s1534-5807(01)00003-x;
RA Smits P., Li P., Mandel J., Zhang Z., Deng J.M., Behringer R.R.,
RA de Crombrugghe B., Lefebvre V.;
RT "The transcription factors L-Sox5 and Sox6 are essential for cartilage
RT formation.";
RL Dev. Cell 1:277-290(2001).
RN [6]
RP INDUCTION.
RX PubMed=12414734; DOI=10.1101/gad.1017802;
RA Akiyama H., Chaboissier M.C., Martin J.F., Schedl A., de Crombrugghe B.;
RT "The transcription factor Sox9 has essential roles in successive steps of
RT the chondrocyte differentiation pathway and is required for expression of
RT Sox5 and Sox6.";
RL Genes Dev. 16:2813-2828(2002).
RN [7]
RP FUNCTION.
RX PubMed=15529345; DOI=10.1002/art.20611;
RA Ikeda T., Kamekura S., Mabuchi A., Kou I., Seki S., Takato T., Nakamura K.,
RA Kawaguchi H., Ikegawa S., Chung U.I.;
RT "The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals
RT sufficient for induction of permanent cartilage.";
RL Arthritis Rheum. 50:3561-3573(2004).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14993235; DOI=10.1083/jcb.200312045;
RA Smits P., Dy P., Mitra S., Lefebvre V.;
RT "Sox5 and Sox6 are needed to develop and maintain source, columnar, and
RT hypertrophic chondrocytes in the cartilage growth plate.";
RL J. Cell Biol. 164:747-758(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=26150426; DOI=10.1093/nar/gkv688;
RA Liu C.F., Lefebvre V.;
RT "The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through
RT super-enhancers to drive chondrogenesis.";
RL Nucleic Acids Res. 43:8183-8203(2015).
RN [11]
RP FUNCTION.
RX PubMed=26525805; DOI=10.1111/jnc.13414;
RA Baroti T., Schillinger A., Wegner M., Stolt C.C.;
RT "Sox13 functionally complements the related Sox5 and Sox6 as important
RT developmental modulators in mouse spinal cord oligodendrocytes.";
RL J. Neurochem. 136:316-328(2016).
RN [12]
RP DEVELOPMENTAL STAGE.
RX PubMed=27923061; DOI=10.1371/journal.pgen.1006474;
RA Brunmeir R., Wu J., Peng X., Kim S.Y., Julien S.G., Zhang Q., Xie W.,
RA Xu F.;
RT "Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators
RT of Murine Brown Adipogenesis.";
RL PLoS Genet. 12:E1006474-E1006474(2016).
RN [13]
RP STRUCTURE BY NMR OF 554-632.
RX PubMed=11266597; DOI=10.1110/ps.32801;
RA Cary P.D., Read C.M., Davis B., Driscoll P.C., Crane-Robinson C.;
RT "Solution structure and backbone dynamics of the DNA-binding domain of
RT mouse Sox-5.";
RL Protein Sci. 10:83-98(2001).
CC -!- FUNCTION: Transcription factor involved in chondrocytes differentiation
CC and cartilage formation (PubMed:1396566, PubMed:11702786,
CC PubMed:8078769, PubMed:15529345, PubMed:14993235). Specifically binds
CC the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and
CC promotes expression of genes important for chondrogenesis, including
CC cartilage matrix protein-coding genes, such as COL2A1 and AGC1
CC (PubMed:9755172, PubMed:11702786, PubMed:26150426). Required for overt
CC chondrogenesis when condensed prechondrocytes differentiate into early
CC stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on
CC active enhancers and super-enhancers associated with cartilage-specific
CC genes, and thereby potentiate SOX9's ability to transactivate
CC (PubMed:11702786, PubMed:15529345, PubMed:14993235, PubMed:26150426).
CC Not involved in precartilaginous condensation, the first step in
CC chondrogenesis, during which skeletal progenitors differentiate into
CC prechondrocytes (PubMed:14993235). Together with SOX6, required to form
CC and maintain a pool of highly proliferating chondroblasts between
CC epiphyses and metaphyses, to form columnar chondroblasts, delay
CC chondrocyte prehypertrophy but promote hypertrophy, and to delay
CC terminal differentiation of chondrocytes on contact with ossification
CC fronts (PubMed:14993235). Binds to the proximal promoter region of the
CC myelin protein MPZ gene (PubMed:26525805).
CC {ECO:0000269|PubMed:11702786, ECO:0000269|PubMed:1396566,
CC ECO:0000269|PubMed:14993235, ECO:0000269|PubMed:15529345,
CC ECO:0000269|PubMed:26150426, ECO:0000269|PubMed:26525805,
CC ECO:0000269|PubMed:8078769, ECO:0000269|PubMed:9755172}.
CC -!- SUBUNIT: Forms homodimers and heterodimers with SOX6.
CC {ECO:0000269|PubMed:9755172}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9755172}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P35710-1; Sequence=Displayed;
CC Name=2; Synonyms=L-Sox5 {ECO:0000303|PubMed:11702786,
CC ECO:0000303|PubMed:9755172};
CC IsoId=P35710-2; Sequence=VSP_007266, VSP_007267;
CC Name=3;
CC IsoId=P35710-3; Sequence=VSP_007265, VSP_007267;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in the embryo and in adult
CC testis. {ECO:0000269|PubMed:9714725}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in chondrocytes and, to a
CC lesser extent, in brain. {ECO:0000269|PubMed:9755172}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Testis-specific.
CC {ECO:0000269|PubMed:1396566}.
CC -!- DEVELOPMENTAL STAGE: Expression is transiently increased during brown
CC adipocyte differentiation. {ECO:0000269|PubMed:27923061}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 3]: Expressed during spermatogenesis.
CC {ECO:0000269|PubMed:1396566}.
CC -!- INDUCTION: Expression is dependent on SOX9.
CC {ECO:0000269|PubMed:12414734}.
CC -!- DISRUPTION PHENOTYPE: Newborn mice display mild skeletal abnormalities
CC (PubMed:11702786). Mice lacking both Sox5 and Sox6 develop a severe
CC chondrodysplasia characterized by the virtual absence of cartilage:
CC chondrogenic cells are largely arrested at the stage of chondrogenic
CC mesenchymal condensations (PubMed:11702786). Embryos lacking Sox5
CC (homozygous knockout) and heterozygous for Sox6 live until birth and
CC show severe growth plate chondrocyte defects (PubMed:14993235). Embryos
CC lacking Sox6 (homozygous knockout) and heterozygous for Sox5 live until
CC birth and show severe growth plate chondrocyte defects
CC (PubMed:14993235). {ECO:0000269|PubMed:11702786,
CC ECO:0000269|PubMed:14993235}.
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DR EMBL; X65657; CAA46608.1; -; mRNA.
DR EMBL; X65658; CAA46609.1; -; mRNA.
DR EMBL; AB006330; BAA32567.1; -; mRNA.
DR EMBL; AJ010604; CAA09269.1; -; mRNA.
DR CCDS; CCDS39702.1; -. [P35710-1]
DR CCDS; CCDS57469.1; -. [P35710-2]
DR CCDS; CCDS85183.1; -. [P35710-3]
DR PIR; S25195; S25195.
DR RefSeq; NP_001230092.1; NM_001243163.1.
DR PDB; 1I11; NMR; -; A=554-632.
DR PDBsum; 1I11; -.
DR AlphaFoldDB; P35710; -.
DR BMRB; P35710; -.
DR SMR; P35710; -.
DR BioGRID; 203409; 2.
DR IntAct; P35710; 1.
DR STRING; 10090.ENSMUSP00000047567; -.
DR ChEMBL; CHEMBL2176780; -.
DR iPTMnet; P35710; -.
DR PhosphoSitePlus; P35710; -.
DR jPOST; P35710; -.
DR MaxQB; P35710; -.
DR PaxDb; P35710; -.
DR PeptideAtlas; P35710; -.
DR PRIDE; P35710; -.
DR ProteomicsDB; 261481; -. [P35710-1]
DR ProteomicsDB; 261482; -. [P35710-2]
DR ProteomicsDB; 261483; -. [P35710-3]
DR Antibodypedia; 12481; 248 antibodies from 30 providers.
DR DNASU; 20678; -.
DR Ensembl; ENSMUST00000111748; ENSMUSP00000107377; ENSMUSG00000041540. [P35710-3]
DR GeneID; 20678; -.
DR KEGG; mmu:20678; -.
DR CTD; 6660; -.
DR MGI; MGI:98367; Sox5.
DR VEuPathDB; HostDB:ENSMUSG00000041540; -.
DR eggNOG; KOG0528; Eukaryota.
DR GeneTree; ENSGT00940000156122; -.
DR HOGENOM; CLU_018522_0_1_1; -.
DR InParanoid; P35710; -.
DR OrthoDB; 465521at2759; -.
DR PhylomeDB; P35710; -.
DR BioGRID-ORCS; 20678; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Sox5; mouse.
DR EvolutionaryTrace; P35710; -.
DR PRO; PR:P35710; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P35710; protein.
DR Bgee; ENSMUSG00000041540; Expressed in cortical plate and 215 other tissues.
DR ExpressionAtlas; P35710; baseline and differential.
DR Genevisible; P35710; MM.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:MGI.
DR GO; GO:0055059; P:asymmetric neuroblast division; ISO:MGI.
DR GO; GO:0001502; P:cartilage condensation; IMP:UniProtKB.
DR GO; GO:0051216; P:cartilage development; IDA:UniProtKB.
DR GO; GO:0045165; P:cell fate commitment; IGI:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:MGI.
DR GO; GO:0021953; P:central nervous system neuron differentiation; IGI:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:0061036; P:positive regulation of cartilage development; ISO:MGI.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IDA:UniProtKB.
DR GO; GO:2000741; P:positive regulation of mesenchymal stem cell differentiation; ISO:MGI.
DR GO; GO:0060164; P:regulation of timing of neuron differentiation; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.30.10; -; 1.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR Pfam; PF00505; HMG_box; 1.
DR SMART; SM00398; HMG; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR PROSITE; PS50118; HMG_BOX_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Coiled coil;
KW Differentiation; DNA-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..763
FT /note="Transcription factor SOX-5"
FT /id="PRO_0000048727"
FT DNA_BIND 556..624
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 76..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..426
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 708..763
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 193..274
FT /evidence="ECO:0000255"
FT COILED 448..515
FT /evidence="ECO:0000255"
FT COMPBIAS 76..127
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..387
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..411
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 731..750
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35711"
FT MOD_RES 131
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35711"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35711"
FT MOD_RES 372
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35711"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35711"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35711"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35711"
FT VAR_SEQ 1..322
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1396566"
FT /id="VSP_007265"
FT VAR_SEQ 56..90
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9755172"
FT /id="VSP_007266"
FT VAR_SEQ 340..388
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:1396566,
FT ECO:0000303|PubMed:9755172"
FT /id="VSP_007267"
FT CONFLICT 102
FT /note="S -> A (in Ref. 3; CAA09269)"
FT /evidence="ECO:0000305"
FT CONFLICT 679
FT /note="S -> G (in Ref. 1; CAA46608)"
FT /evidence="ECO:0000305"
FT HELIX 562..575
FT /evidence="ECO:0007829|PDB:1I11"
FT HELIX 583..594
FT /evidence="ECO:0007829|PDB:1I11"
FT HELIX 600..602
FT /evidence="ECO:0007829|PDB:1I11"
FT HELIX 603..617
FT /evidence="ECO:0007829|PDB:1I11"
SQ SEQUENCE 763 AA; 84090 MW; E38B1470ECCB1DE7 CRC64;
MLTDPDLPQE FERMSSKRPA SPYGETDGEV AMVTSRQKVE EEESERLPAF HLPLHVSFPN
KPHSEEFQPV SLLTQETCGP RTPTVQHNTM EVDGNKVMSS LSPYNSSTSP QKAEEGGRQS
GESVSSAALG TPERRKGSLA DVVDTLKQRK MEELIKNEPE DTPSIEKLLS KDWKDKLLAM
GSGNFGEIKG TPESLAEKER QLMGMINQLT SLREQLLAAH DEQKKLAASQ IEKQRQQMEL
AKQQQEQIAR QQQQLLQQQH KINLLQQQIQ VQGQLPPLMI PVFPPDQRTL AAAAQQGFLL
PPGFSYKAGC SDPYPVQLIP TTMAAAAAAT PGLGPLQLQQ FYAAQLAAMQ VSPGGKLLGL
PQGNLGAAVS PTSIHTDKST NSPPPKSKDE VAQPLNLSAK PKTSDGKSPA SPTSPHMPAL
RINSGAGPLK ASVPAALASP SARVSTIGYL NDHDAVTKAI QEARQMKEQL RREQQALDGK
VAVVNSIGLS NCRTEKEKTT LESLTQQLAV KQNEEGKFSH GMMDFNMSGD SDGSAGVSES
RIYRESRGRG SNEPHIKRPM NAFMVWAKDE RRKILQAFPD MHNSNISKIL GSRWKAMTNL
EKQPYYEEQA RLSKQHLEKY PDYKYKPRPK RTCLVDGKKL RIGEYKAIMR NRRQEMRQYF
NVGQQAQIPI ATAGVVYPSA IAMAGMPSPH LPSEHSSVSS SPEPGMPVIQ STYGAKGEEP
HIKEEIQAED INGEIYEEYD EEEEDPDVDY GSDSENHIAG QAN
