NHLRC2

NHL Repeat Containing Protein 2, or NHLRC2, is a protein encoded by the NHLRC2 gene . ^[1]

Nomenclature

NHLRC2 has also been referred to as Novel NHL Repeat Domain Containing Protein and 1200003F01Rik. ^[1]

Gene

NHLRC2 is located on the positive strand of chromosome 10, at position 10q25.3. ^[2] The full gene spans 62,533 base pairs (bp). ^[1] Eleven exons are transcribed in the protein-coding mRNA. ^{[3] [ failed verification ]} There is a second, less prevalent transcript variant of NHLRC2; this non-coding isoform is 522 bp of retained intron. ^{[4] [ failed verification ]}

Protein

General

The translated NHLRC2 protein is 726 amino acids long in humans and has a molecular weight of 79,442.59 g/mol. ^[1] It has been found in the cytosol, mitochondria, and/or peroxisomes of cells in which it is expressed. ^{[1] [5]}

NHL-Repeat

NHLRC2 is a part of the NHL-repeat superfamily of n-bladed beta-propellers. ^[1] Specifically, NHLRC2 is a 6-bladed beta-propeller. The NHL repeat is found in many eukaryotic and prokaryotic proteins, and is associated with growth factor regulators. ^{[6] [7]}

Function

The function of NHLRC2 is not yet fully understood. Using bioinformatic analysis, a "YVAD" motif was found to be conserved in eukaryotes, bacteria, and archaea. ^[8] "YVAD" shows up three times alone in the human NHLRC2 protein. ^[8] This motif is potentially involved in inhibiting caspases 1, 2, 3, 4 & 5, thus possibly having anti-apoptotic properties. ^{[9] [10]}

Expression

Normal Expression

According to NCBI GEO microarray expression patterns, as well as UniGene's Expressed Sequence Tag (EST) profiles, NHLRC2 is expressed at low levels throughout most human tissues. ^{[11] [12]}

Conditional Expression

NCBI GEO Profiles detailed several conditions under which NHLRC2 expression is increased in comparison to base expression levels. Many, but not all, conditional cases involved an increase of NHLRC2 expression in various cancer types, including—but not limited to—the following: leukemia, lymphomas, breast & mammary gland cancer, colorectal cancer, Wilms' tumor, and lung cancer. ^[11]

Homology

NHLRC2 has no human paralogs. Extensive orthologs were identified, however, using NCBI's BLAST and BLAT programs. ^{[13] [14]} A select group of orthologs are detailed in the table below. This is not an exhaustive list of orthologs; rather, it shows the diversity of NHLRC2 orthologs.

Predicted Post-Translational Modification

PSORT II predicted one possible cleavage site within NHLRC2 in humans: between amino aids 32Q and 33E. ^[5] PSORT II also predicted two possible vacuolar signaling motifs—KLPK and TLPK—in humans that were also conserved in close orthologs such as vertebrates and amphibians, but not in distant orthologs like insects or plants. ^[5]

References

1. GeneCards Database: NHLRC2
2. Grupe, A.; et al. (January 2006). "A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease". Am. J. Hum. Genet. 78 (1): 78–88. doi:10.1086/498851. PMC   1380225 . PMID   16385451.
3. "Transcript: NHLRC2_001". Ensembl Database. Retrieved March 3, 2015.
4. "Transcript: NHLRC2_002". Ensembl Database. Retrieved March 3, 2015.
5. Nakai, K (1999). "PSORT II Program". University of Tokyo, Japan.
6. "NHL Repeat Family". Superfamily HMM Library and Genome Server. Retrieved 5 February 2015.
7. Marchler-Bauer, A; et al. (2015). "CDD: NCBI's Conserved Domain Database". Nucleic Acids Res. 43 (Database issue): D222-6. doi:10.1093/nar/gku1221. PMC   4383992 . PMID   25414356.
8. Brendel, V; Bucher, P; Nourbakhsh, I.R.; Karlin, S (1992). "Methods and algorithms for statistical analysis of protein sequences". Proc. Natl. Acad. Sci. U.S.A. 89 (6): 2002–2006. Bibcode:1992PNAS...89.2002B. doi: 10.1073/pnas.89.6.2002 . PMC   48584 . PMID   1549558.
9. Ruffolo, R.R. Jr.; Feuerstein, G.Z.; Hunter, A.J.; Poste, George; Metcalf, B.W. (2004). Inflammatory Cells and Mediators in CNS Diseases. Harwood Academic Publishers. ISBN   0-203-30424-1.
10. Kumar, S (1998). Apoptosis: Mechanisms and Role in Disease. Results and Problems in Cell Differentiation. Vol. 24. Springer-Verlag. doi:10.1007/978-3-540-69185-3. ISBN   978-3-662-21625-5. S2CID   32549295.
11. "NHLRC2". Gene Expression Omnibus. Retrieved 4 Apr 2015.
12. "NHLRC2". UniGene EST Profiles. Retrieved 4 Apr 2015.
13. "BLAST". NCBI BLAST.
14. "BLAT". UCSC Genome Bioinformatics. Retrieved 4 February 2015.