ID   TSH3_MOUSE              Reviewed;        1081 AA.
AC   Q8CGV9; Q5DTX4;
DT   10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   10-JAN-2006, sequence version 2.
DT   08-NOV-2023, entry version 155.
DE   RecName: Full=Teashirt homolog 3;
DE   AltName: Full=Zinc finger protein 537;
GN   Name=Tshz3; Synonyms=Kiaa1474, Tsh3, Zfp537, Znf537;
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], AND POSSIBLE FUNCTION.
RX   PubMed=14973285; DOI=10.1242/dev.00977;
RA   Manfroid I., Caubit X., Kerridge S., Fasano L.;
RT   "Three putative murine Teashirt orthologues specify trunk structures in
RT   Drosophila in the same way as the Drosophila teashirt gene.";
RL   Development 131:1065-1073(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Fetal brain;
RA   Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA   Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT   complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT   screening of terminal sequences of cDNA clones randomly sampled from size-
RT   fractionated libraries.";
RL   Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=18776146; DOI=10.1242/dev.022442;
RA   Caubit X., Lye C.M., Martin E., Core N., Long D.A., Vola C., Jenkins D.,
RA   Garratt A.N., Skaer H., Woolf A.S., Fasano L.;
RT   "Teashirt 3 is necessary for ureteral smooth muscle differentiation
RT   downstream of SHH and BMP4.";
RL   Development 135:3301-3310(2008).
RN   [4]
RP   INTERACTION WITH APBB1.
RX   PubMed=19343227; DOI=10.1371/journal.pone.0005071;
RA   Kajiwara Y., Akram A., Katsel P., Haroutunian V., Schmeidler J.,
RA   Beecham G., Haines J.L., Pericak-Vance M.A., Buxbaum J.D.;
RT   "FE65 binds Teashirt, inhibiting expression of the primate-specific
RT   caspase-4.";
RL   PLoS ONE 4:E5071-E5071(2009).
RN   [5]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX   PubMed=20631175; DOI=10.1523/jneurosci.1765-10.2010;
RA   Caubit X., Thoby-Brisson M., Voituron N., Filippi P., Bevengut M.,
RA   Faralli H., Zanella S., Fortin G., Hilaire G., Fasano L.;
RT   "Teashirt 3 regulates development of neurons involved in both respiratory
RT   rhythm and airflow control.";
RL   J. Neurosci. 30:9465-9476(2010).
RN   [6]
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=19745106; DOI=10.1093/ndt/gfp453;
RA   Jenkins D., Caubit X., Dimovski A., Matevska N., Lye C.M., Cabuk F.,
RA   Gucev Z., Tasic V., Fasano L., Woolf A.S.;
RT   "Analysis of TSHZ2 and TSHZ3 genes in congenital pelvi-ureteric junction
RT   obstruction.";
RL   Nephrol. Dial. Transplant. 25:54-60(2010).
RN   [7]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=27668656; DOI=10.1038/ng.3681;
RA   Caubit X., Gubellini P., Andrieux J., Roubertoux P.L., Metwaly M., Jacq B.,
RA   Fatmi A., Had-Aissouni L., Kwan K.Y., Salin P., Carlier M., Lieden A.,
RA   Rudd E., Shinawi M., Vincent-Delorme C., Cuisset J.M., Lemaitre M.P.,
RA   Abderrehamane F., Duban B., Lemaitre J.F., Woolf A.S., Bockenhauer D.,
RA   Severac D., Dubois E., Zhu Y., Sestan N., Garratt A.N.,
RA   Kerkerian-Le Goff L., Fasano L.;
RT   "TSHZ3 deletion causes an autism syndrome and defects in cortical
RT   projection neurons.";
RL   Nat. Genet. 48:1359-1369(2016).
CC   -!- FUNCTION: Transcriptional regulator involved in developmental
CC       processes. Functions in association with APBB1, SET and HDAC factors as
CC       a transcriptional repressor, that inhibits the expression of CASP4.
CC       TSHZ3-mediated transcription repression involves the recruitment of
CC       histone deacetylases HDAC1 and HDAC2. Associates with chromatin in a
CC       region surrounding the CASP4 transcriptional start site(s). Regulates
CC       the development of neurons involved in both respiratory rhythm and
CC       airflow control. Promotes maintenance of nucleus ambiguus (nA)
CC       motoneurons, which govern upper airway function, and establishes a
CC       respiratory rhythm generator (RRG) activity compatible with survival at
CC       birth. Involved in the differentiation of the proximal uretic smooth
CC       muscle cells during developmental processes. Involved in the up-
CC       regulation of myocardin, that directs the expression of smooth muscle
CC       cells in the proximal ureter. Involved in the modulation of
CC       glutamatergic synaptic transmission and long-term synaptic potentiation
CC       (PubMed:27668656). {ECO:0000269|PubMed:18776146,
CC       ECO:0000269|PubMed:19745106, ECO:0000269|PubMed:20631175,
CC       ECO:0000269|PubMed:27668656}.
CC   -!- SUBUNIT: Interacts (via N-terminus) with HDAC1 and HDAC2; the
CC       interaction is direct. Found in a trimeric complex with APBB1 and
CC       HDAC1; the interaction between HDAC1 and APBB1 is mediated by TSHZ3 (By
CC       similarity). Interacts (via homeobox domain) with APBB1 (via PID domain
CC       1). {ECO:0000250, ECO:0000269|PubMed:19343227}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC       Cell projection, growth cone {ECO:0000250}. Note=Colocalizes with APBB1
CC       in the nucleus. Colocalizes with APBB1 in axonal growth cone (By
CC       similarity). {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in corticostriatal neurons.
CC       {ECO:0000269|PubMed:27668656}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in branchio and viscero motoneurons at
CC       10.5 dpc. Expressed in the nucleus ambiguus (nA) motoneurons at 15.5
CC       dpc. Expressed in the brainstem respiratory rhythm generator (RRG),
CC       including two interacting neuronal networks constituting two
CC       oscillators: the pre-Boetzinger complex (preBoetC) at 15.5 dpc and the
CC       embryonic parafacial respiratory group (e-pF or pFRG) at 14.4 dpc, that
CC       contributes both to motor coordination of the respiratory apparatus and
CC       confers central chemosensitivity, as well as in cranial motoneurons
CC       targeting chest muscles that control the upper airway opening.
CC       Expressed in the developing urinary tract. Expressed in ureteric bud
CC       (UB) stalk at 11.5 dpc. Expressed in mesenchymal cells along and around
CC       the UB stalk, and absent from the UB epithelium and in scattered cells
CC       within the metanephric medullary stroma at 12.5 dpc. Expressed in
CC       mesenchymal cells in proximal ureters at 14 dpc, preceding the smooth
CC       muscle precursor cells differentiation and the expression of
CC       contractile proteins from 15 dpc. Expressed in mesenchymal cells of the
CC       ureter and renal pelvis, and in renal medullary stroma, in the
CC       mesenchymal cells adjacent to the epithelium and in the peripheral
CC       mesenchyme where smooth muscle (SM) starts to differentiate; the outer
CC       rim of nephrogenic mesenchyme was negative at 15.5. In the bladder,
CC       expressed in the submucosal loose connective tissue adjacent to the
CC       epithelium and in the detrusor SM layer at 18.5 dpc.
CC       {ECO:0000269|PubMed:18776146, ECO:0000269|PubMed:19745106,
CC       ECO:0000269|PubMed:20631175}.
CC   -!- INDUCTION: Up-regulated by BMP4.
CC   -!- DISRUPTION PHENOTYPE: Mice fail to breathe and die at birth. Display
CC       pronounced cell death of motoneurons in the nucleus ambiguus and induce
CC       strong alterations of rhythmogenesis in the embryonic parafacial
CC       respiratory group (e-pF or pFRG) oscillator and cranial motoneurons
CC       that control the upper airways. Mice also fail to form small smooth
CC       cells in the proximal ureter and urine flow is impaired because of
CC       functional obstruction caused by absent peristalsis in the proximal
CC       ureter that leads to hydronephrosis and hydroureter phenotypes.
CC       {ECO:0000269|PubMed:18776146, ECO:0000269|PubMed:20631175}.
CC   -!- SIMILARITY: Belongs to the teashirt C2H2-type zinc-finger protein
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAD90255.1; Type=Frameshift; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Life's first breath - Issue
CC       122 of October 2010;
CC       URL="https://web.expasy.org/spotlight/back_issues/122";
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DR   EMBL; AY063491; AAL38978.1; -; mRNA.
DR   EMBL; AK220396; BAD90255.1; ALT_FRAME; mRNA.
DR   CCDS; CCDS39913.1; -.
DR   RefSeq; NP_758502.1; NM_172298.2.
DR   AlphaFoldDB; Q8CGV9; -.
DR   SMR; Q8CGV9; -.
DR   BioGRID; 232587; 1.
DR   STRING; 10090.ENSMUSP00000021641; -.
DR   iPTMnet; Q8CGV9; -.
DR   PhosphoSitePlus; Q8CGV9; -.
DR   MaxQB; Q8CGV9; -.
DR   PaxDb; 10090-ENSMUSP00000021641; -.
DR   ProteomicsDB; 298247; -.
DR   DNASU; 243931; -.
DR   GeneID; 243931; -.
DR   KEGG; mmu:243931; -.
DR   UCSC; uc009gkj.1; mouse.
DR   AGR; MGI:2442819; -.
DR   CTD; 57616; -.
DR   MGI; MGI:2442819; Tshz3.
DR   eggNOG; ENOG502RJS7; Eukaryota.
DR   InParanoid; Q8CGV9; -.
DR   OrthoDB; 5407068at2759; -.
DR   PhylomeDB; Q8CGV9; -.
DR   TreeFam; TF328447; -.
DR   BioGRID-ORCS; 243931; 4 hits in 77 CRISPR screens.
DR   ChiTaRS; Tshz3; mouse.
DR   PRO; PR:Q8CGV9; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q8CGV9; Protein.
DR   GO; GO:0030426; C:growth cone; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IBA:GO_Central.
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:0001701; P:in utero embryonic development; IMP:MGI.
DR   GO; GO:0060993; P:kidney morphogenesis; IMP:MGI.
DR   GO; GO:0072195; P:kidney smooth muscle cell differentiation; IMP:UniProtKB.
DR   GO; GO:0060291; P:long-term synaptic potentiation; IMP:UniProtKB.
DR   GO; GO:0030324; P:lung development; IMP:UniProtKB.
DR   GO; GO:0001656; P:metanephros development; IEP:UniProtKB.
DR   GO; GO:0050881; P:musculoskeletal movement; IMP:MGI.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; IMP:MGI.
DR   GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IMP:UniProtKB.
DR   GO; GO:0002087; P:regulation of respiratory gaseous exchange by nervous system process; IMP:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0050975; P:sensory perception of touch; IMP:MGI.
DR   GO; GO:0048745; P:smooth muscle tissue development; IMP:MGI.
DR   GO; GO:0072193; P:ureter smooth muscle cell differentiation; IMP:UniProtKB.
DR   GO; GO:0001657; P:ureteric bud development; IMP:MGI.
DR   GO; GO:0072105; P:ureteric peristalsis; IMP:UniProtKB.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 2.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR027008; Teashirt_fam.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   PANTHER; PTHR12487:SF5; TEASHIRT HOMOLOG 3; 1.
DR   PANTHER; PTHR12487; TEASHIRT-RELATED; 1.
DR   Pfam; PF13912; zf-C2H2_6; 1.
DR   SMART; SM00389; HOX; 1.
DR   SMART; SM00355; ZnF_C2H2; 5.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2.
PE   1: Evidence at protein level;
KW   Cell projection; Coiled coil; Developmental protein; DNA-binding; Homeobox;
KW   Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW   Repressor; Transcription; Transcription regulation; Zinc; Zinc-finger.
FT   CHAIN           1..1081
FT                   /note="Teashirt homolog 3"
FT                   /id="PRO_0000047067"
FT   ZN_FING         214..238
FT                   /note="C2H2-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         275..299
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         387..410
FT                   /note="C2H2-type 3; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   DNA_BIND        891..961
FT                   /note="Homeobox; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   ZN_FING         976..998
FT                   /note="C2H2-type 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         1041..1064
FT                   /note="C2H2-type 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          25..104
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          141..161
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          238..257
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          325..346
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          474..499
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          626..699
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          792..824
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          855..897
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          606..630
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        55..69
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        70..104
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        330..346
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        641..673
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        804..824
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        855..873
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        874..890
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         682
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63HK5"
FT   CONFLICT        110
FT                   /note="T -> I (in Ref. 1; AAL38978)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        663
FT                   /note="S -> G (in Ref. 2; BAD90255)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1081 AA;  118626 MW;  C69AD8A9A2816669 CRC64;
     MPRRKQQAPR RAAAYVSDEL KAAALVEDDV EPEEQAADGE PSAKYMCPEK ELSKACPSYQ
     NSPAAEFSSH EMDSESHISE TSDRMADFES SSIKNEEETK EVQVPLEDTT VSDSLEQMKA
     VYNNFLSNSY WSNLNLNLHQ PSSENNGGSS SSSSSSSSSC GSGSFDWHQS AMAKTLQQVS
     QNRMLPEPSL FSTVQLYRQS SKLYGSIFTG ASKFRCKDCS AAYDTLVELT VHMNETGHYR
     DDNHETDNNN PKRWSKPRKR SLLEMEGKED AQKVLKCMYC GHSFESLQDL SVHMIKTKHY
     QKVPLKEPVT PVAAKIIPAA RKKPSLELEL PSSPDSTGGT PKATLSDASD ALQKNSNPYI
     TPNNRYGHQN GASYAWHFEA RKSQILKCME CGSSHDTLQE LTAHMMVTGH FIKVTNSAMK
     KGKPIMETPV TPTITTLLDE KVQSVPLAAT TFTSPSNTPA SVSPKLAVEI KKEVDKEKAV
     PDEKPKEREK PSEEEEKYDI SSKYHYLTEN DLEESPKGGL DILKSLENTV TSAINKAQNG
     TPSWGGYPSI HAAYQLPNMM KLSLGSSGKS TPLKPMFGNS EIVSPTKTQT LVSPPSSQTS
     PMPKTNFHAM EELVKKVTEK VAKVEEKMKE PEGKLSPPKR ATPSPCSSEQ SEPIKMEASS
     DGSFKSQENS PSPPRDACKE ASPSAEPVEN GKELVKPLSG GLSGSTAIIT DHPPEQPFVN
     PLSALQSVMN IHLGKAAKPS LPALDPMSML FKMSNSLAEK AAVATPPPLQ AKKAEHLDRY
     FYHVNNDQPI DLTKGKSDKG CSLGSGLLSP TSTSPATSSS TVTTAKTSAV VSFMSNSPLR
     ENALSDISDM LKNLTESHTS KSSTPSSISE KSDIDGATLE EAEESTPAQK RKGRQSNWNP
     QHLLILQAQF AASLRQTSEG KYIMSDLSPQ ERMHISRFTG LSMTTISHWL ANVKYQLRRT
     GGTKFLKNLD TGHPVFFCND CASQIRTPST YISHLESHLG FRLRDLSKLS TEQINNQIAQ
     TKSPSEKLVT SSPEEDLGTT YQCKLCNRTF ASKHAVKLHL SKTHGKSPED HLLFVSELEK
     Q
//