NBEAL1

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.[5] The translated protein is a total 56 exons that constitute a final length of 2694 amino acids.[6] There are currently 9 known isoforms within humans.[3]

Neurobeachin-like1 contains five domains: DUF4704, DUF4800, PH_BEACH, Beach, and WD40 repeats.[6]

DUF4704 is a domain of unknown function. While the function of this domain is unknown, it is conserved within neurobeachin proteins in eukaryotes.[4] It begins at amino acid 859 and spans until number 1115.[3]

DUF4800 is a domain of unknown function. It begins at amino acid 1580, spanning until 1833.[3] While it is uncharacterized in function, it is found within eukaryotes.[7]

Spanning from amino acid 1886 until amino acid 1983, this domain is referred to as a Pleckstrin Homology domain in the BEACH domain.[8] 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.[9]

The Beige and Chediak-Higashi (BEACH) 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.[10] 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.[10] 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.[2] In NBEAL1, this follows the PH_BEACH domain, beginning at amino acid 2005 and ending at amino acid 2284.[3]

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.[3]

• Molecular weight of 307.3 kilo Daltons[11]
• Predicted to be localized to the mitochondria[12]

The secondary structure of NBEAL1 is predicted to be a combination of alpha helices, beta sheets and random coils.[13]

I-TASSER predicted this 3D structure for amino acids 1-1500 of NBEAL1.

Predicted structure via I-TASSER of NBEAL1, amino acids 1501-2694.

I-TASSER was used to predict a 3D structure of NBEAL1.[14] 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.

The following document illustrates the different post-translational modifications.

The different post-translational modifications are illustrated in this conceptually annotated transcript.

According to GeneCards, NBEAL1 has a few paralogs: NBEAL2, WDFY3, NBEA, LRBA, Lysosomal trafficking regulator (LYST), and WDFY3.[19] The table below summarizes the paralogs of NBEAL1.

Using Biology Workbench, a Multiple Sequence Alignment was done to illustrate the highly conserved aspects of NBEAL1 in close orthologs to the homo sapiens gene.