ID   ZHX3_RAT                Reviewed;         951 AA.
AC   Q80Z36; Q1I1B1;
DT   01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT   12-DEC-2006, sequence version 2.
DT   03-AUG-2022, entry version 138.
DE   RecName: Full=Zinc fingers and homeoboxes protein 3;
DE   AltName: Full=Zinc finger and homeodomain protein 3;
GN   Name=Zhx3;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116 {ECO:0000312|EMBL:BAC65210.1};
RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAY41072.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DNA-BINDING, TISSUE SPECIFICITY, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Kidney;
RX   PubMed=17056598; DOI=10.1074/jbc.m606664200;
RA   Liu G., Clement L.C., Kanwar Y.S., Avila-Casado C., Chugh S.S.;
RT   "ZHX proteins regulate podocyte gene expression during the development of
RT   nephrotic syndrome.";
RL   J. Biol. Chem. 281:39681-39692(2006).
RN   [2] {ECO:0000305, ECO:0000312|EMBL:BAC65210.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 114-635.
RC   TISSUE=Ovary {ECO:0000312|EMBL:BAC65210.1};
RX   PubMed=12659632; DOI=10.1042/bj20021866;
RA   Yamada K., Kawata H., Shou Z., Hirano S., Mizutani T., Yazawa T.,
RA   Sekiguchi T., Yoshino M., Kajitani T., Miyamoto K.;
RT   "Analysis of zinc-fingers and homeoboxes (ZHX)-1-interacting proteins:
RT   molecular cloning and characterization of a member of the ZHX family,
RT   ZHX3.";
RL   Biochem. J. 373:167-178(2003).
CC   -!- FUNCTION: Acts as a transcriptional repressor. Involved in the early
CC       stages of mesenchymal stem cell (MSC) osteogenic differentiation. Is a
CC       regulator of podocyte gene expression during primary glomerula disease.
CC       Binds to promoter DNA. {ECO:0000269|PubMed:17056598}.
CC   -!- SUBUNIT: Homodimer (via homeobox domain 1). Heterodimer with ZHX1 (via
CC       homeobox domain 1). Heterodimer with ZHX2 (via homeobox domain 1).
CC       Heterodimerization with ZHX1 is a prerequisite for repressor activity.
CC       Interacts with NFYA. {ECO:0000250|UniProtKB:Q9H4I2}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17056598}. Nucleus
CC       {ECO:0000255|PROSITE-ProRule:PRU00108, ECO:0000269|PubMed:17056598}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:17056598}.
CC   -!- SIMILARITY: Belongs to the ZHX family. {ECO:0000255}.
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DR   EMBL; DQ017884; AAY41072.1; -; mRNA.
DR   EMBL; AB081947; BAC65210.1; -; mRNA.
DR   RefSeq; NP_001040562.1; NM_001047097.1.
DR   RefSeq; XP_008760566.1; XM_008762344.2.
DR   AlphaFoldDB; Q80Z36; -.
DR   SMR; Q80Z36; -.
DR   STRING; 10116.ENSRNOP00000034076; -.
DR   jPOST; Q80Z36; -.
DR   PaxDb; Q80Z36; -.
DR   PRIDE; Q80Z36; -.
DR   Ensembl; ENSRNOT00000032588; ENSRNOP00000034076; ENSRNOG00000027988.
DR   GeneID; 311604; -.
DR   KEGG; rno:311604; -.
DR   UCSC; RGD:631431; rat.
DR   CTD; 23051; -.
DR   RGD; 631431; Zhx3.
DR   eggNOG; ENOG502RC6G; Eukaryota.
DR   GeneTree; ENSGT00950000182893; -.
DR   HOGENOM; CLU_009147_1_0_1; -.
DR   InParanoid; Q80Z36; -.
DR   OMA; ACEPEDD; -.
DR   OrthoDB; 518562at2759; -.
DR   PhylomeDB; Q80Z36; -.
DR   TreeFam; TF333363; -.
DR   PRO; PR:Q80Z36; -.
DR   Proteomes; UP000002494; Chromosome 3.
DR   Bgee; ENSRNOG00000027988; Expressed in testis and 18 other tissues.
DR   ExpressionAtlas; Q80Z36; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IDA:GO_Central.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:GO_Central.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IC:NTNU_SB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd00086; homeodomain; 5.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR024578; Homez_homeobox_dom.
DR   InterPro; IPR041057; ZHX_Znf_C2H2.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   Pfam; PF00046; Homeodomain; 2.
DR   Pfam; PF11569; Homez; 1.
DR   Pfam; PF18387; zf_C2H2_ZHX; 1.
DR   SMART; SM00389; HOX; 5.
DR   SMART; SM00355; ZnF_C2H2; 2.
DR   SUPFAM; SSF46689; SSF46689; 5.
DR   SUPFAM; SSF57667; SSF57667; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 4.
PE   1: Evidence at protein level;
KW   Cytoplasm; Differentiation; DNA-binding; Homeobox; Metal-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Repeat; Repressor; Transcription;
KW   Transcription regulation; Zinc; Zinc-finger.
FT   CHAIN           1..951
FT                   /note="Zinc fingers and homeoboxes protein 3"
FT                   /id="PRO_0000049397"
FT   ZN_FING         77..100
FT                   /note="C2H2-type 1"
FT                   /evidence="ECO:0000255"
FT   ZN_FING         109..132
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255"
FT   DNA_BIND        298..357
FT                   /note="Homeobox 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   DNA_BIND        487..546
FT                   /note="Homeobox 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   DNA_BIND        605..664
FT                   /note="Homeobox 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   DNA_BIND        759..818
FT                   /note="Homeobox 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   DNA_BIND        830..889
FT                   /note="Homeobox 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          1..66
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          198..249
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          237..481
FT                   /note="Required for homodimerization and interaction with
FT                   NFYA"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4I2"
FT   REGION          297..495
FT                   /note="Required for repressor activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4I2"
FT   REGION          490..548
FT                   /note="Required for nuclear localization"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4I2"
FT   REGION          621..642
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          661..702
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          885..951
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        50..65
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        229..248
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        661..678
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        934..951
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         597
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4I2"
FT   MOD_RES         701
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8C0Q2"
FT   MOD_RES         716
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4I2"
FT   MOD_RES         922
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4I2"
FT   MOD_RES         941
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4I2"
SQ   SEQUENCE   951 AA;  103783 MW;  BB9B27023233242B CRC64;
     MASKRKSTTP CMIPVKTMVL PGASTEAQPV EPLPEGPQQD LPSEAPEASS EAAPNPSSTD
     GSALANGHRG TLDGYVYSCK ECDFRSQDVT HFVGHMTSEH TDFNKDPHFV CTGCSFLAKT
     PEGLSLHNAK CHSGEASFLW NVTKPDNHVV VEQSVPENAS SSVLAGESTE GTEIIITKTP
     IMKIMKGKAE AKKIHMLKEN APTQPGGEAL PKPLAGETEG KEGDHTFING ATPVSQASAN
     STKPPHTANG PLIGTVPVLP AGIAQFLSLQ QPTVHPQHHP HQPLPTSKAL PKVMIPLSSI
     PTYNAAMDSN SFLKNSFHKF PYPTKAELCY LTVVTKYPEE QLKIWFTAQR LKQGISWSPE
     EIEDARKKMF NTVIQSVPQP TITVLNTPLV ASAGNVQHLI QAALPGHAVG QPEGTAGGLL
     VTQPLMANGL QASSSSLPLT TASVPKPTAA PINTVCSNTT SAVKVVNAAQ SLLTACPSIT
     SQAFLDANIY KNKKSHEQLS ALKGSFCRNQ FPGQSEVEHL TKVTGLSTRE VRKWFSDRRY
     HCRNLKGTRA MVPGEHGSVL IDSVPEVPFP LSSKVPEVPC VPTATSLVSH PATKRQSWHQ
     TPDFTPTKYK ERAPEQLRVL ESSFAQNPLP PEEELDRLRS ETKMTRREID GWFSERRKRV
     NAEETKKADG HAPQEEAEGA EEEGRDEELA SELRAPGENG SSEMFLSHTL AERKVSPIKI
     NLKNLRVTEA SGKSELPGMG MGVCEPEEDG LNKAVEQPPS RVSYKKTAQQ RHLLRQLFVQ
     TQWPSNQDYD SIMAQTGLPR PEVVRWFGDS RYALKNGQLK WYEDYKRGNF PPGLLVIAPG
     NRELLQDYYM THKMLCEEDL QTLCEKTQMS AQQVKQWFAE KMGEETRAVA DTSSEDQGPG
     HGEPVAVDKV LGDACAALSE NSEAWEPSAP EAGSEPFDTS SPQSGRQLET D