# THAP3

THAP domain-containing protein 3 (THAP3) is a protein that, in Homo sapiens (humans), is encoded by the THAP3 gene. The THAP3 protein is as known as MGC33488, LOC90326, and THAP domain-containing, apoptosis associated protein 3. This protein contains the Thanatos-associated protein (THAP) domain and a host-cell factor 1C binding motif. These domains allow THAP3 to influence a variety of processes, including transcription and neuronal development. THAP3 is ubiquitously expressed in H. sapiens, though expression is highest in the kidneys.

## Gene

The H. sapiens THAP3 gene is a protein-encoding gene that is located on the plus strand of chromosome 1 at cytogenetic location 1p36.31. It is 10,727 base pairs long, spanning from genomic coordinates 6,624,868-6,635,595. It contains 6 exons.

### Expression

In H. sapiens, THAP3 gene is expressed ubiquitously throughout different tissues, and expression is greatest in the kidneys. It has also been determined that expression of THAP3 tends to be slightly higher in organs located in the abdomen and male and female sexual organs, such as the ovaries, testes, prostate, adrenal gland, spleen, liver, and colon, though expression in the kidneys is 1.4-1.5x higher than those organs. THAP3 mRNA is 1.3x. more abundant in H. sapiens fetal brain tissue than in H. sapiens adult kidney tissue.

## mRNA

Transcription of the THAP3 gene can result in 11 different mRNA variants, of which 8 are alternatively spliced and 3 are unspliced. Variant 1 is the predominant variant and encodes THAP3 protein isoform 1.
Alternatively spliced Homo sapiens THAP3 mRNA transcript variants :
| Variant | Sequence length (nucleotides) | Accession number |
| 1 | 1358 | NM_001195752.2 |
| 2 | 2071 | NM_138350.4 |
| 3 | 1361 | NM_001195753.2 |
| 4 | 1262 | NM_001394496.1 |
| 5 | 2050 | NM_001394497.1 |
| 6 | 2047 | NM_001394498.1 |
| 7 | 1123 | NM_001394499.1 |
| 8 | 1120 | NM_001394500.1 |

## Protein

The H. sapiens THAP3 protein is predicted to have a molecular weight of 26.9 kilodaltons and a pI of 10.26. The amino acid sequence is isoleucine and tyrosine rich and arginine poor. Characteristics domains of H. sapiens are the THAP domain (THAP) and the hell-cell factor 1C binding motif (HCM).

### Isoforms

Due to having 8 alternatively spliced variants, there are 8 THAP3 isoforms.
Isoforms of Homo sapiens THAP3 :
| Isoform | Sequence length (amino acids) | Accession number | Encoded by |
| 1 | 238 | NP_001182681.1 | Variant 1 |
| 2 | 175 | NP_612359.2 | Variant 2 |
| 3 | 239 | NP_001182682.1 | Variant 3 |
| 4 | 236 | NP_001381425.1 | Variant 4 |
| 5 | 168 | NP_001381426.1 | Variant 5 |
| 6 | 167 | NP_001381427.1 | Variant 6 |
| 7 | 148 | NP_001381428.1 | Variant 7 |
| 8 | 147 | NP_001381429.1 | Variant 8 |

### Structure

The predicted H. sapiens THAP3 tertiary structure contains a globular region and an alpha helix. The globular region is located near the N-terminus of the sequence and is the structure of the THAP domain. It spans amino acids 4-82. The alpha helix is located from amino acids 186-230 and contains the host-cell factor 1C binding motif.

### Regulation
#### Localization

THAP3 can be localized in the nucleus or mitochondria of H. sapiens cells.

#### Post-translation modifications

The H. sapiens the THAP3 protein has 30 predicted phosphorylation sites, 28 predicted O-β-glycosylation sites, and 11 predicted Yin-Yang sites. Many proteins involved in transcription regulation are influenced by phosphorylation and glycosylation sites, which corroborates THAP3's function.

## Homology and evolution
### Paralogs

The H. sapiens THAP3 protein, along with several other proteins, is part of the THAP family of proteins. All of these proteins contain the THAP domain and are, thus, paralogs of H. sapiens THAP3.
Paralogs of Homo sapiens THAP3 protein :
| Protein Name | E-Value! | Percent Identity to THAP3 |
| THAP1 | 8×10$^{−23}$ | 48.00 |
| THAP2 | 6×10$^{−17}$ | 45.24 |
| THAP5 | 4×10$^{−13}$ | 31.96 |
| THAP6 | 6×10$^{−6}$ | 34.44 |
| THAP7 | 1×10$^{−7}$ | 33.33 |
| THAP8 | 8×10$^{−11}$ | 31.96 |
| THAP9 | 2×10$^{−8}$ | 32.99 |

### Orthologs

There are approximately 206 orthlologs of H. sapiens THAP3. Orthologs can be found in a variety of taxomonic classes, including mammals, reptiles, amphibians, bony fishes, and cartilaginous fishes. However, there are no orthologs in bacteria, fungi, protists, archaea, plants, invertebrates, or birds. Additionally, not all orders are represented with in a class. For example, in reptiles, orthologs to H. sapiens THAP3 are found in testudines (turtles or tortoises) and not found in crocodilia (crocodiles and alligators) or squamata (lizards and snakes). Similarly, there are only orthologs in apoda within amphibians. There are no orthologs in anura (frogs) or urodela (salamanders).
In closely related organisms, those diverged 0-160 million years ago (MYA), percent similarity of orthologs ranges from 36-82.9%. THAP3 sequences in rodents are the least conserved compared to H. sapiens. Sequences that diverged 319-353 MYA, those moderately related, have 47.2-68.9% similarity to H. sapiens THAP3, and 41.3-54.1% similarity in organisms that are distantly related, diverged 431-464 MYA.
Orthologs of Homo sapiens THAP3 :
| Taxonomic Class | Scientific Name | Common Name | Taxonomic Order | Date of Divergence | Accession Number | Percent Identity to THAP3 | Percent Similarity to THAP3 |
| Mammals | Marmota flaviventris | Yellow-bellied marmot | Rodentia | 87 | XP_027803226.1 | 29.9 | 36 |
| | Lontra canadensis | North American river otter | Carnivora | 94 | XP_032719186.1 | 59.5 | 65.8 |
| | Eptesicus fuscus | Big brown bat | Chiroptera | 94 | XP_028016747.1 | 65.0 | 69.6 |
| | Balaenoptera musculus | Blue whale | Cetacea | 94 | XP_036686252.1 | 77.5 | 82.9 |
| | Dromiciops gliroides | Colocolo opossum | Microbiotheria | 160 | XP_043850206.1 | 64.6 | 74.5 |
| | Phascolarctos cinereus | Koala | Diprotodontia | 160 | XP_020830574.1 | 65.7 | 76.4 |
| Reptiles | Caretta caretta | Loggerhead turtle | Testudines | 319 | XP_048680971.1 | 36.9 | 47.2 |
| | Gopherus evgoodei | Goode's thornscrub tortoise | Testudines | 319 | XP_030393185.1 | 48.9 | 58.1 |
| | Chelonoidis abingdonii | Abingdon Island giant tortoise | Testudines | 319 | XP_032619750.1 | 48.9 | 61.4 |
| | Mauremys mutica | Yellow pond turtle | Testudines | 319 | XP_044852367.1 | 49.0 | 60.9 |
| Amphibians | Microcaecilia unicolor | Microcaecilia unicolor | Gymnophiona | 353 | XP_030041702.1 | 41.2 | 56.8 |
| | Geotrypetes seraphini | Gaboon caecilian | Gymnophiona | 353 | XP_033777236.1 | 44.2 | 57.8 |
| Bony Fishes | Electrophorus electricus | Electric eel | Gymnotiformes | 431 | XP_026873261.2 | 31.9 | 41.3 |
| | Coregonus clupeaformis | Lake whitefish | Salmoniformes | 431 | XP_041712304.2 | 32.9 | 47.7 |
| | Brienomyrus brachyistius | Baby whale | Osteoglossiformes | 431 | XP_048872538.1 | 33.5 | 46.3 |
| | Puntigrus tetrazona | Sumatra barb | Cypriniformes | 431 | XP_043081346.1 | 34.0 | 48.1 |
| Cartilaginous Fishes | Rhincodon typus | Whale shark | Orectolobiformes | 464 | XP_020386430.1 | 39.0 | 53.4 |
| | Chiloscyllium plagiosum | White-spotted bamboo shark | Orectolobiformes | 464 | XP_043531920.1 | 39.0 | 53.0 |
| | Amblyraja radiata | Thorny skate | Rajiformes | 464 | XP_032904038.1 | 40.2 | 54.1 |

### Evolution

H. sapiens THAP3 has evolved at a rate similar to H. sapiens fibrinogen alpha, which is involved in the immune system.

## Protein interactions

H. sapiens THAP3 interacts with proteins involved in various cellular processes, like transcription regulation and neuronal development. It is also interacts with molecular chaperones during its translation.
Homo sapiens THAP3 Protein Interactions :
| Process | Protein Name | Identified By! | Interaction Type |
| Transcription Regulation | CHAT | two hybrid assay | Functional |
| | FGFR3 | two hybrid assay | Functional |
| | HCF1C | affinity capture - mass spectrometry | Functional |
| | OGT | affinity capture - mass spectrometry | Functional |
| | PKN1 | two hybrid assay | Functional |
| | POLR2A | two hybrid assay | Functional |
| | TARDBP | two hybrid assay | Functional |
| Neuronal Development | LSAMP | two hybrid assay | Functional |
| | DNAJB6 | two hybrid assay | Functional |
| Protein Folding | BAG6 | two hybrid assay | Developmental |

## Clinical significance

THAP3 contributes to the presentation of X-linked Dystonia-Parkinsonism, also known as Lubag Syndrome. This disease is a neurodegenerative movement disorder that predominantly affects males of Filipino descent. Symptoms include tremors, bradykinesia, rigidity, postural instability, shuffling gait and dystonia, which typically develops later in life.