Q8CGV9 (TSH3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Teashirt homolog 3

Alternative name(s):
Zinc finger protein 537

Gene names

Name:	Tshz3
Synonyms:	Kiaa1474, Tsh3, Zfp537, Znf537

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1081 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional regulator involved in developmental processes. Function in association with APBB1, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. TSHZ3-mediated transcription repression involves the recruitment of histone deacetylases HDAC1 and HDAC2. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s). Regulates the development of neurons involved in both respiratory rhythm and airflow control. Promotes maintenance of nucleus ambiguus (nA) motoneurons, which govern upper airway function, and establishes a respiratory rhythm generator (RRG) activity compatible with survival at birth. Involved in the differentiation of the proximal uretic smooth muscle cells during developmental processes. Involved in the up-regulation of myocardin, that directs the expression of smooth muscle cells in the proximal ureter. Ref.1 Ref.3 Ref.5 Ref.6
Subunit structure	Interacts (via N-terminus) with HDAC1 and HDAC2; the interaction is direct. Found in a trimeric complex with APBB1 and HDAC1; the interaction between HDAC1 and APBB1 is mediated by TSHZ3 By similarity. Interacts (via homeobox domain) with APBB1 (via PID domain 1). Ref.4
Subcellular location	Nucleus By similarity. Cell projection › growth cone By similarity. Note: Colocalizes with APBB1 in the nucleus. Colocalizes with APBB1 in axonal growth cone By similarity.
Developmental stage	Expressed in branchio and viscero motoneurons at 10.5 dpc. Expressed in the nucleus ambiguus (nA) motoneurons at 15.5 dpc. Expressed in the brainstem respiratory rhythm generator (RRG), including two interacting neuronal networks constituting two oscillators: the pre-Boetzinger complex (preBoetC) at 15.5 dpc and the embryonic parafacial respiratory group (e-pF or pFRG) at 14.4 dpc, that contributes both to motor coordination of the respiratory apparatus and confers central chemosensitivity, as well as in cranial motoneurons targeting chest muscles that control the upper airway opening. Expressed in the developing urinary tract. Expressed in ureteric bud (UB) stalk at 11.5 dpc. Expressed in mesenchymal cells along and around the UB stalk, and absent from the UB epithelium and in scattered cells within the metanephric medullary stroma at 12.5 dpc. Expressed in mesenchymal cells in proximal ureters at 14 dpc, preceding the smooth muscle precursor cells differentiation and the expression of contractile proteins from 15 dpc. Expressed in mesenchymal cells of the ureter and renal pelvis, and in renal medullary stroma, in the mesenchymal cells adjacent to the epithelium and in the peripheral mesenchyme where smooth muscle (SM) starts to differentiate; the outer rim of nephrogenic mesenchyme was negative at 15.5. In the bladder, expressed in the submucosal loose connective tissue adjacent to the epithelium and in the detrusor SM layer at 18.5 dpc. Ref.3 Ref.5 Ref.6
Induction	Up-regulated by BMP4.
Disruption phenotype	Mice fail to breathe and die at birth. Display pronounced cell death of motoneurons in the nucleus ambiguus and induce strong alterations of rhythmogenesis in the embryonic parafacial respiratory group (e-pF or pFRG) oscillator and cranial motoneurons that control the upper airways. Mice also fail to form small smooth cells in the proximal ureter and urine flow is impaired because of functional obstruction caused by absent peristalsis in the proximal ureter that leads to hydronephrosis and hydroureter phenotypes. Ref.3 Ref.5
Sequence similarities	Belongs to the teashirt C2H2-type zinc-finger protein family. Contains 5 C2H2-type zinc fingers. Contains 1 homeobox DNA-binding domain.
Sequence caution	The sequence BAD90255.1 differs from that shown. Reason: Frameshift at position 78.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cell projection Nucleus
Domain	Coiled coil Homeobox Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Developmental protein Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	in utero embryonic development Inferred from mutant phenotype Ref.3. Source: MGI kidney morphogenesis Inferred from mutant phenotype Ref.3. Source: MGI kidney smooth muscle cell differentiation Inferred from mutant phenotype Ref.3. Source: UniProtKB lung development Inferred from mutant phenotype Ref.3. Source: UniProtKB metanephros development Inferred from expression pattern Ref.3. Source: UniProtKB musculoskeletal movement Inferred from mutant phenotype Ref.3. Source: MGI negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of smooth muscle cell differentiation Inferred from mutant phenotype Ref.3. Source: MGI regulation of respiratory gaseous exchange by neurological system process Inferred from mutant phenotype Ref.5. Source: UniProtKB sensory perception of touch Inferred from mutant phenotype Ref.3. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ureter smooth muscle cell differentiation Inferred from mutant phenotype Ref.3. Source: UniProtKB ureteric bud development Inferred from mutant phenotype Ref.3. Source: MGI ureteric peristalsis Inferred from mutant phenotype Ref.3. Source: UniProtKB
Cellular_component	growth cone Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay PubMed 18614015. Source: MGI nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	chromatin binding Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1081	1081	Teashirt homolog 3		PRO_0000047067
Regions
	Zinc finger	214 – 238	25	C2H2-type 1
	Zinc finger	275 – 299	25	C2H2-type 2
	Zinc finger	387 – 410	24	C2H2-type 3; atypical
	DNA binding	891 – 961	71	Homeobox; atypical
	Zinc finger	976 – 998	23	C2H2-type 4
	Zinc finger	1041 – 1064	24	C2H2-type 5
	Coiled coil	606 – 630	25	Potential
	Compositional bias	142 – 164	23	Ser-rich
	Compositional bias	493 – 496	4	Poly-Glu
Amino acid modifications
	Modified residue	682	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	110	1	T → I in AAL38978. Ref.1
	Sequence conflict	663	1	S → G in BAD90255. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8CGV9 [UniParc]. Last modified January 10, 2006. Version 2. Checksum: C69AD8A9A2816669	FASTA	1,081	118,626
	10 20 30 40 50 60 MPRRKQQAPR RAAAYVSDEL KAAALVEDDV EPEEQAADGE PSAKYMCPEK ELSKACPSYQ 70 80 90 100 110 120 NSPAAEFSSH EMDSESHISE TSDRMADFES SSIKNEEETK EVQVPLEDTT VSDSLEQMKA 130 140 150 160 170 180 VYNNFLSNSY WSNLNLNLHQ PSSENNGGSS SSSSSSSSSC GSGSFDWHQS AMAKTLQQVS 190 200 210 220 230 240 QNRMLPEPSL FSTVQLYRQS SKLYGSIFTG ASKFRCKDCS AAYDTLVELT VHMNETGHYR 250 260 270 280 290 300 DDNHETDNNN PKRWSKPRKR SLLEMEGKED AQKVLKCMYC GHSFESLQDL SVHMIKTKHY 310 320 330 340 350 360 QKVPLKEPVT PVAAKIIPAA RKKPSLELEL PSSPDSTGGT PKATLSDASD ALQKNSNPYI 370 380 390 400 410 420 TPNNRYGHQN GASYAWHFEA RKSQILKCME CGSSHDTLQE LTAHMMVTGH FIKVTNSAMK 430 440 450 460 470 480 KGKPIMETPV TPTITTLLDE KVQSVPLAAT TFTSPSNTPA SVSPKLAVEI KKEVDKEKAV 490 500 510 520 530 540 PDEKPKEREK PSEEEEKYDI SSKYHYLTEN DLEESPKGGL DILKSLENTV TSAINKAQNG 550 560 570 580 590 600 TPSWGGYPSI HAAYQLPNMM KLSLGSSGKS TPLKPMFGNS EIVSPTKTQT LVSPPSSQTS 610 620 630 640 650 660 PMPKTNFHAM EELVKKVTEK VAKVEEKMKE PEGKLSPPKR ATPSPCSSEQ SEPIKMEASS 670 680 690 700 710 720 DGSFKSQENS PSPPRDACKE ASPSAEPVEN GKELVKPLSG GLSGSTAIIT DHPPEQPFVN 730 740 750 760 770 780 PLSALQSVMN IHLGKAAKPS LPALDPMSML FKMSNSLAEK AAVATPPPLQ AKKAEHLDRY 790 800 810 820 830 840 FYHVNNDQPI DLTKGKSDKG CSLGSGLLSP TSTSPATSSS TVTTAKTSAV VSFMSNSPLR 850 860 870 880 890 900 ENALSDISDM LKNLTESHTS KSSTPSSISE KSDIDGATLE EAEESTPAQK RKGRQSNWNP 910 920 930 940 950 960 QHLLILQAQF AASLRQTSEG KYIMSDLSPQ ERMHISRFTG LSMTTISHWL ANVKYQLRRT 970 980 990 1000 1010 1020 GGTKFLKNLD TGHPVFFCND CASQIRTPST YISHLESHLG FRLRDLSKLS TEQINNQIAQ 1030 1040 1050 1060 1070 1080 TKSPSEKLVT SSPEEDLGTT YQCKLCNRTF ASKHAVKLHL SKTHGKSPED HLLFVSELEK Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Three putative murine Teashirt orthologues specify trunk structures in Drosophila in the same way as the Drosophila teashirt gene." Manfroid I., Caubit X., Kerridge S., Fasano L. Development 131:1065-1073(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], POSSIBLE FUNCTION.
[2]	"Prediction of the coding sequences of mouse homologues of KIAA gene. The complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., Koga H. Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Fetal brain.
[3]	"Teashirt 3 is necessary for ureteral smooth muscle differentiation downstream of SHH and BMP4." Caubit X., Lye C.M., Martin E., Core N., Long D.A., Vola C., Jenkins D., Garratt A.N., Skaer H., Woolf A.S., Fasano L. Development 135:3301-3310(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
[4]	"FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4." Kajiwara Y., Akram A., Katsel P., Haroutunian V., Schmeidler J., Beecham G., Haines J.L., Pericak-Vance M.A., Buxbaum J.D. PLoS ONE 4:E5071-E5071(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APBB1.
[5]	"Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control." Caubit X., Thoby-Brisson M., Voituron N., Filippi P., Bevengut M., Faralli H., Zanella S., Fortin G., Hilaire G., Fasano L. J. Neurosci. 30:9465-9476(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
[6]	"Analysis of TSHZ2 and TSHZ3 genes in congenital pelvi-ureteric junction obstruction." Jenkins D., Caubit X., Dimovski A., Matevska N., Lye C.M., Cabuk F., Gucev Z., Tasic V., Fasano L., Woolf A.S. Nephrol. Dial. Transplant. 25:54-60(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Life's first breath - Issue 122 of October 2010

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY063491 mRNA. Translation: AAL38978.1. AK220396 mRNA. Translation: BAD90255.1. Frameshift.
IPI	IPI00229585.
RefSeq	NP_758502.1. NM_172298.2.
UniGene	Mm.44141.
3D structure databases
ProteinModelPortal	Q8CGV9.
SMR	Q8CGV9. Positions 200-303.
ModBase	Search...
PTM databases
PhosphoSite	Q8CGV9.
Proteomic databases
PRIDE	Q8CGV9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021641; ENSMUSP00000021641; ENSMUSG00000021217.
GeneID	243931.
KEGG	mmu:243931.
UCSC	uc009gkj.1. mouse.
Organism-specific databases
CTD	57616.
MGI	MGI:2442819. Tshz3.
Rouge	Search...
Phylogenomic databases
eggNOG	NOG83709.
GeneTree	ENSGT00390000014977.
HOGENOM	HOG000231480.
HOVERGEN	HBG079626.
InParanoid	Q8CGV9.
KO	K09236.
OrthoDB	EOG48GW2H.
Gene expression databases
ArrayExpress	Q8CGV9.
Bgee	Q8CGV9.
CleanEx	MM_TSHZ3.
Genevestigator	Q8CGV9.
GermOnline	ENSMUSG00000021217. Mus musculus.
Family and domain databases
InterPro	IPR001356. Homeodomain. IPR009057. Homeodomain-like. IPR027008. Teashirt_fam. IPR026810. Tshz3. IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. [Graphical view]
PANTHER	PTHR12487. PTHR12487. 1 hit. PTHR12487:SF5. PTHR12487:SF5. 1 hit.
Pfam	PF00096. zf-C2H2. 1 hit. [Graphical view]
SMART	SM00389. HOX. 1 hit. SM00355. ZnF_C2H2. 5 hits. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. False negative. PS50071. HOMEOBOX_2. 1 hit. PS00028. ZINC_FINGER_C2H2_1. 4 hits. PS50157. ZINC_FINGER_C2H2_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	386042.
SOURCE	Search...

Entry information

Entry name

TSH3_MOUSE

Accession

Primary (citable) accession number: Q8CGV9
Secondary accession number(s): Q5DTX4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2006
Last sequence update:	January 10, 2006
Last modified:	April 3, 2013
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program