# LUZP2

Leucine zipper protein 2 is a protein that in humans is encoded by the LUZP2 gene. There are no orthologs in invertebrates, but many in vertebrates. It is a transcription factor found in eukaryotes.

## Gene

The LUZP2 gene is found on the short arm of chromosome 11 at position 11p14.3. It is located on the plus strand.
The gene contains 23 introns, and can produce 11 alternatively spliced mRNAs.

## Protein structure

LUZP2 encodes a leucine zipper protein that is 346 amino acids in length, and has a molecular weight of ~39 kDa. This protein is secreted, and is found mostly expressed within the brain and spinal cord.
The protein contains a signal peptide, 3 glycosylation sites, a leucine zipper region, and a disordered region. It also contains 3 highly conserved "QLKE" amino acid repeats.

### Leucine zipper

The leucine zipper motif is located on positions 164-192 of the protein, and contains 4 conserved lysine and 4 conserved leucine residues. Leucine zippers usually facilitate protein-protein interactions and contain many amphipathic helices that form a left-handed dimeric coiled-coil structure. They also often contain leucine residues spaced 7 amino acids apart.

## Abundance
### Protein Abundance

LUZP2 protein is present in higher amounts than most proteins, but is more abundant in the cerebral cortex and brain. Immunohistochemical staining using anti-LUZP2 rabbit antibodies shows it to be present in low levels in the pancreas and high in the cerebral cortex. Interestingly, it is present in high levels in neuronal projections, suggesting it could have some role in the development of the vertebral nervous system.

### In situ hybridization

Based on in situ hybridization studies, LUZP2 mRNA is expressed at low levels throughout the brain, but more highly concentrated in the regions of the forebrain, the thalamus, and the hypothalamus. LUZP2 is also least expressed in the cerebellum compared to other structures.

## Clinical findings

Based on a data mining study investigating low-grade Gliomas, LUZP2 downregulation was found to be associated with higher-grade tumors, suggesting that LUZP2 expression decreased as tumors became more aggressive. Low LUZP2 expression was also associated with worse overall survival in patients with low-grade gliomas across multiple cohorts.
This gene has also been found deleted in some patients with Wilms tumor-aniridia-ganomalies-mental retardation (WAGR) syndrome.

## Evolution

LUZP2 has many orthologs in vertebrates. It is highly conserved in mammals, birds, and reptiles.
LUZP2 is expected to have first appeared in cartilaginous fish around 462 million years ago, and is evolving at an intermediate rate, slower than fibrinogen alpha, but faster than cytochrome c.
| LUZP2 | Genus and Species | Common Name | Taxonomic Order | Median Date of Divergence (MYA) | Accession # | Sequence Length (aa) | Sequence Identity to Human Protein (%) | Sequence Similarity to Human Protein (%) |
| Mammals | Homo sapiens | Human | Primates | 0 | NP_001009909.2 | 346 | 100.0 | 100.0 |
| | Mesocricetus auratus | Golden hamster | Rodentia | 87 | XP_040589238.1 | 345 | 83.2 | 89.6 |
| | Ursus arctos | Brown bear | Carnivora | 94 | XP_048073596.2 | 347 | 80.2 | 89.1 |
| | Dromiciops gliroides | Colocolo opossum | Marsupialia | 160 | XP_043829349.1 | 345 | 70.9 | 79.8 |
| | Ornithorhynchus anatinus | Platypus | Monotremata | 180 | XP_028914921.1 | 347 | 70.4 | 80.2 |
| Birds | Cygnus olor | Mute swan | Anseriformes | 319 | XP_040415405.1 | 343 | 67.1 | 76.6 |
| | Gallus gallus | Red junglefowl | Galliformes | 319 | NP_001186450.1 | 344 | 66.2 | 74.9 |
| | Falco cherrug | Saker falcon | Falconiformes | 319 | XP_027654513.1 | 314 | 66.2 | 74.3 |
| | Corvus brachyrhynchos | American crow | Passeriformes | 319 | XP_017581874.1 | 352 | 65.8 | 73.7 |
| Reptiles | Dermochelys coriacea | Leatherback sea turtle | Testudines | 319 | XP_038262088.1 | 343 | 66.6 | 75.2 |
| | Notechis scutatus | Mainland tiger snake | Squamta | 319 | XP_026520543.1 | 336 | 63.2 | 72.2 |
| | Varanus komodoensis | Komodo dragon | Squamata | 319 | XP_044282044.1 | 364 | 59.8 | 71.0 |
| | Alligator mississippiensis | American alligator | Crocodilia | 319 | XP_019332548.2 | 425 | 55.9 | 62.9 |
| Amphibians | Rhinatrema bivittatum | Two-lined caecilian | Gymnophiona | 352 | XP_029438260.1 | 342 | 62.2 | 74.9 |
| | Xenopus laevis | African clawed frog | Anura | 352 | XP_018113009.1 | 344 | 60.6 | 72.1 |
| | Pleurodeles waltl | Iberian ribbed newt | Urodela | 352 | XP_069078053.1 | 348 | 59.7 | 71.4 |
| Fishes | Protopterus annectens | West african lungfish | Ceratodontiformes | 408 | XP_043939274.1 | 349 | 54.7 | 67.6 |
| | Periophthalmus magnuspinnatus | Mudskipper | Gobiiformes | 429 | XP_033847668.1 | 347 | 46.6 | 59.6 |
| | Danio rerio | Zebrafish | Cypriniformes | 429 | NP_001108187.1 | 346 | 49.3 | 60.3 |
| | Amblyraja radiata | Thorny skate | Rajiformes | 462 | XP_032894536.1 | 306 | 43.0 | 57.9 |
| | Carcharodon carcharias | Great white shark | Lamniformes | 462 | XP_041052683.1 | 307 | 48.2 | 61.0 |

## Possible Interactions

LUZP2 mostly interacts with proteins found the nucleus. Proteins that showed the most promising interactions with LUZP2 include the serine/threonine kinase TNIK, GAS2, and CBX5.
| Protein | Function | Location | Method | Source |
| c-Src Tyrosine Kinase (CSK) | Regulation of embryonic development and cell growth | Many, including nucleus | Synthetic lethality | BioGRID |
| Heterogenous Ribonucleoprotein L (HBRNPL) | Nucelocytoplasmic export | Nucleus, extracellular | Affinity capture-RNA | BioGRID |
| Chromobox 5 (CBX5) | Formation of kinetochores and heterochromatin | Nucleus | Tandem affinity purification | IntAct |
| Estrogen-receptor 1 (ESR1) | Nuclear hormone receptor | Many, including nucleus | Affinity chromography technology | IntAct |
| TRAF2 and NCK Interacting Kinase (TNIK) | Ser/thr kinase that activates Wnt signaling pathway | Many, including nucleus | Two hybrid fragment pooling approaching | IntAct |
| Growth Arrest Specific 2 (GAS2) | Microfilament dynamics during cell cycle and apoptosis | Cytosol, cytoskeleton | Co-expression, Co-mentioned in Pubmed abstracts | STRING |
| Family With Sequence Similarity 81 Member A (FAM81A) | Enables protein binding | Cytosol, nucleus | Co-expression, Co-mentioned in Pubmed abstracts | STRING |
| Cyclic AMP-Responsive Element-Binding Protein 3 (CREB3) | Leucine-zipper protein, binds cAMP-response elements and regulates proliferation | Golgi, cytosol, endoplasmic reticulum, nucleus | Co-mentioned in Pubmed abstracts | STRING |
| Ankyrin Repeat Domain 55 (ANKRD55) | Enables protein binding | Nucleus | Co-mentioned in Pubmed abstracts | STRING |
| Clathrin Heavy Chain Linker Domain Containing 1 (CLHC1) | Enables protein binding | Cytosol, nucleus | Co-mentioned in Pubmed abstracts | STRING |
| Zinc Finger DHHC-Type Palmitoyltransferase 19 (ZDHHC19) | Mediates palmitoylation proteins such as RRAS and SQSTM1, positively regualtes autophagy | Golgi, endoplasmic reticulum, nucleus, plasma membrane | Co-mentioned in PubMed abstract | STRING |