NBEAL1


NBEAL1 is a protein that in humans is encoded by the NBEAL1 gene. It is found on chromosome 2q33.2 of Homo sapiens.
Through the different domains of this protein, the function of NBEAL1 is predicted to be involved in the following cellular mechanisms: vesicle trafficking, membrane dynamics, receptor signaling, pre-mRNA processing, signal transduction and cytoskeleton assembly. NBEAL1 is also known as Amytorophic Lateral Sclerosis 2 Chromosomal Region, ALS2CR16 and ALS2CR17.

Protein Properties

Transcript

The mRNA for this protein consists of 9058 base pairs in a linear sequence with the coding sequence begins at base pair number 334 and extends until base pair number 8418. The translated protein is a total 56 exons that constitute a final length of 2694 amino acids. There are currently 9 known isoforms within humans.

Domains

Neurobeachin-like1 contains five domains: DUF4704, DUF4800, PH_BEACH, Beach, and WD40 repeats.
DUF4704
DUF4704 is a domain of unknown function. While the function of this domain is unknown, it is conserved within neurobeachin proteins in eukaryotes. It begins at amino acid 859 and spans until number 1115.
DUF4800
DUF4800 is a domain of unknown function. It begins at amino acid 1580, spanning until 1833. While it is uncharacterized in function, it is found within eukaryotes.
PH_BEACH
Spanning from amino acid 1886 until amino acid 1983, this domain is referred to as a Pleckstrin Homology domain in the BEACH domain. It has a PH because the fold of this domain is similar to the PH domain, but is not identical in the sequence of the canonical PH domains. The PH_BEACH domain is not able to bind phospholipids.
Beach
The Beige and Chediak-Higashi domain is one of the most significant domains within this protein. This domain is highly conserved roughly 280 amino acid domain, present in nine different human BEACH domains. It located after the PH_BEACH domain in the sequence. While not much is understood on the exact function of BDCP proteins within the BEACH domain, it is known that they serve many purposes within cellular mechanisms: vesicular transport, apoptosis, membrane dynamics and receptor signaling. This protein family is of great clinical importance currently because mutations in this domain have been identified in multiple human disorders. For example, neurobeachin-like1 is upregulated in glioma: as the pathological grade of the glioma increases, the expression of neurobeachin-like1 is decreased. In NBEAL1, this follows the PH_BEACH domain, beginning at amino acid 2005 and ending at amino acid 2284.
WD40
NBEAL1 has one WD40 domain within NBEAL1. From amino acid 2409 to 2682 is the entire WD40 domain. Within the domain, from 2406 to 2439, there is a structural motif WD40 repeat. The WD40 domain is found in a number of eukaryotic proteins that have multiple functions. These include, but are not limited to, adaptor/regulatory modules in signal transduction, pre-mRNA processing, and cytoskeleton assembly.

Properties

Secondary

The secondary structure of NBEAL1 is predicted to be a combination of alpha helices, beta sheets and random coils.

Tertiary

I-TASSER was used to predict a 3D structure of NBEAL1. Since NBEAL1 is longer in amino acid length than allowed for input, it was split in half to predict the structure of the whole protein.

Post-Translational Modifications

The following document illustrates the different post-translational modifications.

Expression

Using the EST abundance profile through Unigene, NBEAL1 expression was discovered based on both body sites and health states. NBEAL1 shows expression in the brain, embryonic tissue, eye, intestine, kidney, liver, lung, mammary glands, ovaries, pancreas, pharynx, placenta, prostate, skin, stomach, testis, thyroid, and trachea. Based on transcripts per million, expression is highest in the stomach at 62 transcripts per million, with pancreas and trachea being next with their transcripts per million being 37 and 38, respectively. The lowest transcripts per million in the brain, eye, placenta and testis, all at 4 per million. When looking at the breakdown by different health states, NBEAL1 is highly expressed in multiple tumors. Again, the abundance was highest in gastrointestinal tumors, correlating to the high expression of NBEAL1 within the stomach. However, NBEAL1 expression is not seen in pancreatic tumors, which may signify something about its function within the pancreas. The abundance also differs in developmental stages, the highest being the fetal stage with 21 transcripts per million and the adult at 14 transcripts per million.

Function

The function of NBEAL1 is not yet well understood by the scientific community. However, given the function of the different domains and disease associations, it is predicted that the NBEAL1 protein may be involved in a variety of functions. As of now they include, but are not limited to, protein-protein interactions, vesicle trafficking, membrane dynamics, receptor signaling, apoptosis, adaptor/regulatory modules in signal transduction, pre-mRNA processing, and cytoskeleton assembly.

Clinical Significance

This protein has been associated with NBEAL1 are Amyotrophic Lateral Sclerosis, Juvenile and Adenocarcinoma, although the function in these diseases has not yet been identified.

Homology

Neurobeachin-like1 is a highly conserved protein. It has orthologs found in many life forms, including but not limited to: reptiles, birds, amphibians, mammals, fish, and a few invertebrates. The following table presents some of the orthologs found using searches in BLAST and BLAT.
Scientific NameCommon NameAccession NumberSequence LengthPercent Identity
Homo sapiensHumanNP_001107604.12694-
Pan troglodytesChimpanzeeXP_525997.3269499
Gorilla gorilla gorillaWestern Lowland GorillaXP_018878299.1269499
Mus musculusMouseNP_77560268898
Cerocebus taysSooty angabeyXP_011903312267897
Canis lupus familiarisDogXP_545603.3269393
Ailuropoda melanoleucaGiant PandaXP_019655126.1269393
Trichechus manatus latirostrisWest Indian ManateeXP_004378299268293
Tursiops truncatusCommon Bottlenose DolphinXP_019794654.1268292.7
Eptesicus cuscusBig Brown BatXP_008144758.1272292
Zonotrichia albicollisWhite Throated SparrowXP_014120514.1270780
Gallus gallusChickenXP_004942730.1272578.7
Python bivattatusBurmese PythonXP_007422078.1268779
Xenopus tropicalisWestern Clawed FrogXP_012826463.1268774
Callorhinchus miliiAustralian GhostsharkXP_007888887.1274970.2
Danio rerioZebrafishXP_009300392272366.3
Octopus bimaculoidesCalifornia two-spot octopusXP_014777916.1258441.2
Daphnia magnaPlanktonic crustaceanKZS037292734
34.4
Drosophila busckiiFruit flyXP_017842328.1272234

Paralogs

According to GeneCards, NBEAL1 has a few paralogs: NBEAL2, WDFY3, NBEA, LRBA, Lysosomal trafficking regulator, and WDFY3. The table below summarizes the paralogs of NBEAL1.
Gene NameSpeciesAccession NumberSequence LengthPercent Identity
NBEAL2Homo sapiensNP_055990275446
NBEAHomo sapiensNP_056483.3294622.8
LRBAHomo sapiensNP_996717.2286322.5
WDFY3Homo sapiensXP_016863397.1354421.8
LYSTHomo sapiensNP_001288294.1380119.3