UniProtKB - Q63HK5 (TSH3_HUMAN)
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Protein
Teashirt homolog 3
Gene
TSHZ3
Organism
Homo sapiens (Human)
Status
Functioni
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) (PubMed:19343227). 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 (By similarity). Involved in the modulation of glutamatergic synaptic transmission and long-term synaptic potentiation (By similarity).By similarity1 Publication
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Zinc fingeri | 214 – 238 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 25 | |
| Zinc fingeri | 275 – 299 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 25 | |
| Zinc fingeri | 386 – 404 | C2H2-type 3; atypicalPROSITE-ProRule annotationAdd BLAST | 19 | |
| DNA bindingi | 891 – 961 | Homeobox; atypicalPROSITE-ProRule annotationAdd BLAST | 71 | |
| Zinc fingeri | 976 – 998 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 | |
| Zinc fingeri | 1041 – 1064 | C2H2-type 5PROSITE-ProRule annotationAdd BLAST | 24 |
GO - Molecular functioni
- chromatin binding Source: UniProtKB
- DNA binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: GO_Central
GO - Biological processi
- long-term synaptic potentiation Source: UniProtKB
- multicellular organism development Source: GO_Central
- negative regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of synaptic transmission, glutamatergic Source: UniProtKB
- regulation of respiratory gaseous exchange by neurological system process Source: UniProtKB
- regulation of transcription from RNA polymerase II promoter Source: GO_Central
- transcription, DNA-templated Source: UniProtKB-KW
Keywordsi
| Molecular function | Developmental protein, DNA-binding, Repressor |
| Biological process | Transcription, Transcription regulation |
| Ligand | Metal-binding, Zinc |
Names & Taxonomyi
| Protein namesi | Recommended name: Teashirt homolog 3Alternative name(s): Zinc finger protein 537 |
| Gene namesi | Name:TSHZ3 Synonyms:KIAA1474, TSH3, ZNF537 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:30700. TSHZ3. |
Subcellular locationi
- Nucleus PROSITE-ProRule annotation1 Publication
- Cell projection › growth cone By similarity
Note: Colocalizes with APBB1 in axonal growth cone (By similarity). Colocalizes with APBB1 in the nucleus.By similarity
GO - Cellular componenti
- growth cone Source: UniProtKB-SubCell
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Keywords - Cellular componenti
Cell projection, NucleusPathology & Biotechi
Involvement in diseasei
TSHZ3 haploinsufficiency due to proximal chromosome 19q13.11 deletions causes a neurodevelopmental disorder characterized by developmental delay, absent or delayed speech, intellectual disability, and autistic features. Some patients may have reanal tract abnormalities.1 Publication
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 953 – 955 | VKY → ATA: Does not inhibit interaction with APBB1. 1 Publication | 3 |
Organism-specific databases
| DisGeNETi | 57616. |
| OpenTargetsi | ENSG00000121297. |
| PharmGKBi | PA134887020. |
Polymorphism and mutation databases
| BioMutai | TSHZ3. |
| DMDMi | 85541971. |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000047066 | 1 – 1081 | Teashirt homolog 3Add BLAST | 1081 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 682 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
| EPDi | Q63HK5. |
| MaxQBi | Q63HK5. |
| PaxDbi | Q63HK5. |
| PeptideAtlasi | Q63HK5. |
| PRIDEi | Q63HK5. |
PTM databases
| iPTMneti | Q63HK5. |
| PhosphoSitePlusi | Q63HK5. |
Expressioni
Tissue specificityi
Expressed in brain; strongly reduced in post-mortem elderly subjects with Alzheimer disease (PubMed:18776146, PubMed:19343227). Expressed in the fetal neocortex (PubMed:27668656).3 Publications
Developmental stagei
Expressed in peri-urothelial cells of the proximal ureter and renal pelvis at 9 weeks of gestation.1 Publication
Gene expression databases
| Bgeei | ENSG00000121297. |
| CleanExi | HS_TSHZ3. |
| ExpressionAtlasi | Q63HK5. baseline and differential. |
| Genevisiblei | Q63HK5. HS. |
Organism-specific databases
| HPAi | HPA008834. |
Interactioni
Subunit structurei
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 TSHZ3.1 Publication
Protein-protein interaction databases
| BioGridi | 121663. 21 interactors. |
| IntActi | Q63HK5. 16 interactors. |
| MINTi | MINT-4725267. |
| STRINGi | 9606.ENSP00000240587. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Beta strandi | 213 – 220 | Combined sources | 8 | |
| Beta strandi | 222 – 225 | Combined sources | 4 | |
| Helixi | 226 – 235 | Combined sources | 10 | |
| Beta strandi | 278 – 280 | Combined sources | 3 | |
| Helixi | 287 – 296 | Combined sources | 10 | |
| Turni | 297 – 301 | Combined sources | 5 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 2DMI | NMR | - | A | 202-303 | [»] | |
| ProteinModelPortali | Q63HK5. | |||||
| SMRi | Q63HK5. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Miscellaneous databases
| EvolutionaryTracei | Q63HK5. |
Family & Domainsi
Coiled coil
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Coiled coili | 606 – 630 | Sequence analysisAdd BLAST | 25 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 142 – 164 | Ser-richAdd BLAST | 23 | |
| Compositional biasi | 493 – 496 | Poly-Glu | 4 |
Sequence similaritiesi
Belongs to the teashirt C2H2-type zinc-finger protein family.Curated
Zinc finger
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Zinc fingeri | 214 – 238 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 25 | |
| Zinc fingeri | 275 – 299 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 25 | |
| Zinc fingeri | 386 – 404 | C2H2-type 3; atypicalPROSITE-ProRule annotationAdd BLAST | 19 | |
| Zinc fingeri | 976 – 998 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 | |
| Zinc fingeri | 1041 – 1064 | C2H2-type 5PROSITE-ProRule annotationAdd BLAST | 24 |
Keywords - Domaini
Coiled coil, Homeobox, Repeat, Zinc-fingerPhylogenomic databases
| eggNOGi | ENOG410IFDT. Eukaryota. ENOG410XQQR. LUCA. |
| GeneTreei | ENSGT00390000014977. |
| HOGENOMi | HOG000231480. |
| HOVERGENi | HBG079626. |
| InParanoidi | Q63HK5. |
| KOi | K09236. |
| OMAi | DHPPEQP. |
| OrthoDBi | EOG091G01GX. |
| PhylomeDBi | Q63HK5. |
| TreeFami | TF328447. |
Family and domain databases
| Gene3Di | 3.30.40.10. 1 hit. |
| InterProi | View protein in InterPro IPR001356. Homeobox_dom. IPR027008. Teashirt_fam. IPR026810. Tshz3. IPR013087. Znf_C2H2_type. IPR013083. Znf_RING/FYVE/PHD. |
| PANTHERi | PTHR12487. PTHR12487. 1 hit. PTHR12487:SF9. PTHR12487:SF9. 1 hit. |
| SMARTi | View protein in SMART SM00389. HOX. 1 hit. SM00355. ZnF_C2H2. 5 hits. |
| PROSITEi | View protein in PROSITE PS50071. HOMEOBOX_2. 1 hit. PS00028. ZINC_FINGER_C2H2_1. 4 hits. PS50157. ZINC_FINGER_C2H2_2. 2 hits. |
Sequencei
Sequence statusi: Complete.
Q63HK5-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPRRKQQAPR RAAAYVSEEL KAAALVDEGL DPEEHTADGE PSAKYMCPEK
60 70 80 90 100
ELARACPSYQ NSPAAEFSCH EMDSESHISE TSDRMADFES GSIKNEEETK
110 120 130 140 150
EVTVPLEDTT VSDSLEQMKA VYNNFLSNSY WSNLNLNLHQ PSSEKNNGSS
160 170 180 190 200
SSSSSSSSSC GSGSFDWHQS AMAKTLQQVS QSRMLPEPSL FSTVQLYRQS
210 220 230 240 250
SKLYGSIFTG ASKFRCKDCS AAYDTLVELT VHMNETGHYR DDNHETDNNN
260 270 280 290 300
PKRWSKPRKR SLLEMEGKED AQKVLKCMYC GHSFESLQDL SVHMIKTKHY
310 320 330 340 350
QKVPLKEPVT PVAAKIIPAT RKKASLELEL PSSPDSTGGT PKATISDTND
360 370 380 390 400
ALQKNSNPYI TPNNRYGHQN GASYAWHFEA RKSQILKCME CGSSHDTLQE
410 420 430 440 450
LTAHMMVTGH FIKVTNSAMK KGKPIVETPV TPTITTLLDE KVQSVPLAAT
460 470 480 490 500
TFTSPSNTPA SISPKLNVEV KKEVDKEKAV TDEKPKQKDK PGEEEEKCDI
510 520 530 540 550
SSKYHYLTEN DLEESPKGGL DILKSLENTV TSAINKAQNG TPSWGGYPSI
560 570 580 590 600
HAAYQLPNMM KLSLGSSGKS TPLKPMFGNS EIVSPTKNQT LVSPPSSQTS
610 620 630 640 650
PMPKTNFHAM EELVKKVTEK VAKVEEKMKE PDGKLSPPKR ATPSPCSSEV
660 670 680 690 700
GEPIKMEASS DGGFRSQENS PSPPRDGCKD GSPLAEPVEN GKELVKPLAS
710 720 730 740 750
SLSGSTAIIT DHPPEQPFVN PLSALQSVMN IHLGKAAKPS LPALDPMSML
760 770 780 790 800
FKMSNSLAEK AAVATPPPLQ SKKADHLDRY FYHVNNDQPI DLTKGKSDKG
810 820 830 840 850
CSLGSVLLSP TSTAPATSSS TVTTAKTSAV VSFMSNSPLR ENALSDISDM
860 870 880 890 900
LKNLTESHTS KSSTPSSISE KSDIDGATLE EAEESTPAQK RKGRQSNWNP
910 920 930 940 950
QHLLILQAQF AASLRQTSEG KYIMSDLSPQ ERMHISRFTG LSMTTISHWL
960 970 980 990 1000
ANVKYQLRRT GGTKFLKNLD TGHPVFFCND CASQIRTPST YISHLESHLG
1010 1020 1030 1040 1050
FRLRDLSKLS TEQINSQIAQ TKSPSEKMVT SSPEEDLGTS YQCKLCNRTF
1060 1070 1080
ASKHAVKLHL SKTHGKSPED HLLYVSELEK Q
Sequence cautioni
The sequence AAI27096 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI27097 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAB66739 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 176 | L → V in AAI27096 (PubMed:15489334).Curated | 1 | |
| Sequence conflicti | 176 | L → V in AAI27097 (PubMed:15489334).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_063635 | 469 | E → G2 PublicationsCorresponds to variant dbSNP:rs143453460Ensembl. | 1 | |
| Natural variantiVAR_052708 | 687 | P → L. Corresponds to variant dbSNP:rs4805664Ensembl. | 1 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BX648745 mRNA. Translation: CAH56184.1. AB040907 mRNA. Translation: BAA95998.1. AL136805 mRNA. Translation: CAB66739.1. Different initiation. BC127095 mRNA. Translation: AAI27096.1. Different initiation. BC127096 mRNA. Translation: AAI27097.1. Different initiation. |
| CCDSi | CCDS12421.2. |
| RefSeqi | NP_065907.2. NM_020856.3. |
| UniGenei | Hs.278436. |
Genome annotation databases
| Ensembli | ENST00000240587; ENSP00000240587; ENSG00000121297. |
| GeneIDi | 57616. |
| KEGGi | hsa:57616. |
| UCSCi | uc002nsy.5. human. |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:| 100% | UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry. |
| 90% | UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence). |
| 50% | UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster. |
Entry informationi
| Entry namei | TSH3_HUMAN | |
| Accessioni | Q63HK5Primary (citable) accession number: Q63HK5 Secondary accession number(s): A1L0U7, Q9H0G6, Q9P254 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 10, 2006 |
| Last sequence update: | January 10, 2006 | |
| Last modified: | June 7, 2017 | |
| This is version 135 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | 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. | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries - SIMILARITY comments
Index of protein domains and families
