Q63HK5 (TSH3_HUMAN) 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, ZNF537

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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.5
Subunit structure	Interacts (via homeobox domain) with APBB1 (via PID domain 1). 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. Ref.5
Subcellular location	Nucleus. Cell projection › growth cone By similarity. Note: Colocalizes with APBB1 in axonal growth cone By similarity. Colocalizes with APBB1 in the nucleus. Ref.5
Tissue specificity	Expressed in brain; strongly reduced in post-mortem elderly subjects with Alzheimer disease. Ref.4 Ref.5
Developmental stage	Expressed in peri-urothelial cells of the proximal ureter and renal pelvis at 9 weeks of gestation. Ref.8
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 CAB66739.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cell projection Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil Homeobox Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Developmental protein Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	in utero embryonic development Inferred from electronic annotation. Source: Compara kidney morphogenesis Inferred from electronic annotation. Source: Compara kidney smooth muscle cell differentiation Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara metanephros development Inferred from electronic annotation. Source: Compara musculoskeletal movement Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.5. Source: UniProtKB positive regulation of smooth muscle cell differentiation Inferred from electronic annotation. Source: Compara regulation of respiratory gaseous exchange by neurological system process Inferred from sequence or structural similarity. Source: UniProtKB sensory perception of touch Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ureter smooth muscle cell differentiation Inferred from electronic annotation. Source: Compara ureteric bud development Inferred from electronic annotation. Source: Compara ureteric peristalsis Inferred from electronic annotation. Source: Compara
Cellular_component	growth cone Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	chromatin binding Inferred from direct assay Ref.5. 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_0000047066

Regions

Zinc finger

214 – 238

25

C2H2-type 1

Zinc finger

275 – 299

25

C2H2-type 2

Zinc finger

386 – 404

19

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 Ref.7

Natural variations

Natural variant

469

1

E → G. Ref.1 Ref.8

VAR_063635

Natural variant

687

1

P → L.
Corresponds to variant rs4805664 [ dbSNP | Ensembl ].

VAR_052708

Experimental info

Mutagenesis

953 – 955

3

VKY → ATA: Does not inhibit interaction with APBB1. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

1081

Helix Strand Turn

Details...

Beta strand

213 – 220

8

Beta strand

222 – 225

4

Helix

226 – 235

10

Beta strand

278 – 280

3

Helix

287 – 296

10

Turn

297 – 301

5

Sequences

	Sequence		Length	Mass (Da)
	Q63HK5 [UniParc]. Last modified January 10, 2006. Version 2. Checksum: B4E0A4347B04E74A	FASTA	1,081	118,566
	10 20 30 40 50 60 MPRRKQQAPR RAAAYVSEEL KAAALVDEGL DPEEHTADGE PSAKYMCPEK ELARACPSYQ 70 80 90 100 110 120 NSPAAEFSCH EMDSESHISE TSDRMADFES GSIKNEEETK EVTVPLEDTT VSDSLEQMKA 130 140 150 160 170 180 VYNNFLSNSY WSNLNLNLHQ PSSEKNNGSS SSSSSSSSSC GSGSFDWHQS AMAKTLQQVS 190 200 210 220 230 240 QSRMLPEPSL FSTVQLYRQS SKLYGSIFTG ASKFRCKDCS AAYDTLVELT VHMNETGHYR 250 260 270 280 290 300 DDNHETDNNN PKRWSKPRKR SLLEMEGKED AQKVLKCMYC GHSFESLQDL SVHMIKTKHY 310 320 330 340 350 360 QKVPLKEPVT PVAAKIIPAT RKKASLELEL PSSPDSTGGT PKATISDTND ALQKNSNPYI 370 380 390 400 410 420 TPNNRYGHQN GASYAWHFEA RKSQILKCME CGSSHDTLQE LTAHMMVTGH FIKVTNSAMK 430 440 450 460 470 480 KGKPIVETPV TPTITTLLDE KVQSVPLAAT TFTSPSNTPA SISPKLNVEV KKEVDKEKAV 490 500 510 520 530 540 TDEKPKQKDK PGEEEEKCDI SSKYHYLTEN DLEESPKGGL DILKSLENTV TSAINKAQNG 550 560 570 580 590 600 TPSWGGYPSI HAAYQLPNMM KLSLGSSGKS TPLKPMFGNS EIVSPTKNQT LVSPPSSQTS 610 620 630 640 650 660 PMPKTNFHAM EELVKKVTEK VAKVEEKMKE PDGKLSPPKR ATPSPCSSEV GEPIKMEASS 670 680 690 700 710 720 DGGFRSQENS PSPPRDGCKD GSPLAEPVEN GKELVKPLAS SLSGSTAIIT DHPPEQPFVN 730 740 750 760 770 780 PLSALQSVMN IHLGKAAKPS LPALDPMSML FKMSNSLAEK AAVATPPPLQ SKKADHLDRY 790 800 810 820 830 840 FYHVNNDQPI DLTKGKSDKG CSLGSVLLSP TSTAPATSSS 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 TEQINSQIAQ 1030 1040 1050 1060 1070 1080 TKSPSEKMVT SSPEEDLGTS YQCKLCNRTF ASKHAVKLHL SKTHGKSPED HLLYVSELEK Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-469. Tissue: Endometrial tumor.
[2]	"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:143-150(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-1081. Tissue: Brain.
[3]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 176-1081. Tissue: Testis.
[4]	"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: TISSUE SPECIFICITY.
[5]	"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: FUNCTION, INTERACTION WITH APBB1; HDAC1 AND HDAC2, IDENTIFICATION IN A TRIMERIC COMPLEX WITH APBB1 AND HDAC1, CHROMATIN-BINDING, MUTAGENESIS OF 953-VAL--TYR-955, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[7]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-682, MASS SPECTROMETRY.
[8]	"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: VARIANT GLY-469, DEVELOPMENTAL STAGE.
[9]	"Solution structure of the first and the second ZF-C2H2-like domains of human teashirt homolog 3." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 200-303.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Life's first breath - Issue 122 of October 2010

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX648745 mRNA. Translation: CAH56184.1.
AB040907 mRNA. Translation: BAA95998.1.
AL136805 mRNA. Translation: CAB66739.1. Different initiation.

IPI

IPI00001743.

RefSeq

NP_065907.2. NM_020856.2.

UniGene

Hs.278436.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DMI	NMR	-	A	202-303	[»]

ProteinModelPortal

Q63HK5.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000240587.

PTM databases

PhosphoSite

Q63HK5.

Polymorphism databases

DMDM

85541971.

Proteomic databases

PaxDb

Q63HK5.

PRIDE

Q63HK5.

Protocols and materials databases

DNASU

57616.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000240587; ENSP00000240587; ENSG00000121297.

GeneID

57616.

KEGG

hsa:57616.

UCSC

uc002nsy.4. human.

Organism-specific databases

CTD

57616.

GeneCards

GC19M031765.

HGNC

HGNC:30700. TSHZ3.

HPA

HPA008834.

MIM

614119. gene.

neXtProt

NX_Q63HK5.

PharmGKB

PA134887020.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG83709.

HOGENOM

HOG000231480.

HOVERGEN

HBG079626.

InParanoid

Q63HK5.

KO

K09236.

OMA

DPMSMLF.

OrthoDB

EOG48GW2H.

Gene expression databases

ArrayExpress

Q63HK5.

Bgee

Q63HK5.

CleanEx

HS_TSHZ3.

Genevestigator

Q63HK5.

GermOnline

ENSG00000121297. Homo sapiens.

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

ChiTaRS

TSHZ3. human.

EvolutionaryTrace

Q63HK5.

GenomeRNAi

57616.

NextBio

64282.

SOURCE

Search...

Entry information

Entry name

TSH3_HUMAN

Accession

Primary (citable) accession number: Q63HK5
Secondary accession number(s): Q9H0G6, Q9P254

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2006
Last sequence update:	January 10, 2006
Last modified:	May 1, 2013
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.