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The gene at chromosome 11 open reading frame 21 is known as c11orf21.

Location
C11orf21 is also known as Chromosome 11 Open Reading Frame 21 and Uncharacterized Protein C11orf21.

It is a 2831 base pair gene which has two isoforms. It is located on the reverse strand of chromosome 11 at positions 2295645 - 2302060, or equivalently at15.5 on the short arm of human chromosome 11 (c11p15.5).

Paralogs and Orthologs
There are no paralogs associated with c11orf21. Orthologs associated with c11orf21 all belong to the family of primates.

Evolution
According to the Encyclopedia Britannica primates can be regarded as Old World monkeys, New World Monkeys and Apes. Old World monkeys are more closely related to the apes than New World monkeys; the distinction between Old World and New World monkeys is based on the shape of the nose.[./Applewebdata://FA7D133A-6AB8-405C-A995-A24255923D0F#%20ftn1 [1] ]

The following list of primates with c11orf21 orthologs is taken from the NIH:[./Applewebdata://FA7D133A-6AB8-405C-A995-A24255923D0F#%20ftn2 [2] ]

Old World monkeys


 * Colobus angolensis palliatus
 * Chlorocebus sabaeus
 * Cercocebus atys
 * Macaca fascicularis
 * Macaca mulatta
 * Macaca nemestrina
 * Papio Anubis
 * Theropithecus gelada
 * Mandrillus leucophaeus
 * Rhinopithecus roxellana
 * Piliocolobus tephrosceles

Apes


 * Gorilla gorilla
 * Pan paniscus
 * Pan troglodytes
 * Homo sapiens
 * Pongo abelii
 * Nomascus leucogenys

New World monkeys


 * Cebus capucinus imitator,
 * Callithrix jacchus,
 * Aotus nancymaae

From the genetic evolution of the various primates in figure XXXXX and the ortholog map associated with c11orf21 it seems to be the case that the genetic diversity of c11orf21 tracks the general genetic diversity of primates. It also appears to be the case that c11orf21 as a functional gene first appeared right after the split indicated by the red arrow in figure XXXXX and that additional genetic changes occurred throughout, with another major split as indicated by the blue arrow of figure XXXXX.

Tissue Expression


Based on the above gene expression map from adult homo sapien tissues this gene appears to be most highly expressed in the bone marrow, spleen and lymph nodes as well as, to a lesser degree, the appendix. This appears to indicate that c11orf21 plays a role in immunology.

Also, this gene is expressed in the heart and lungs, potentially indicating a function in the cardiovascular system.

Disease Expression
Disease associated with the expression of c11orf21 is present in blood by far more than any other tissue. The spleen is the second most affected tissue, although the number of times it is present is approximately 1/4 that of disease number is blood. Due to the fact that other tissue types are significantly less affected than blood and the spleen, it is difficult to assess the relevance of how significantly disease affects other tissue types.

The type of disease that is significantly most correlated with the c11orf21 gene is leukemia.

Immunochemistry
Immunochemistry associated with c11orf21 indicates that there is an apparent association between this gene and heart tissue and also with cervical cancer. These associations appear to agree with the observed tissue and disease expressions shown above.

Isoforms
There are two isoforms associated with c11orf21, NM_001142946.3 (uncharacterized protein C11orf21 isoform 1) which translates to protein NP_001136418.1 and NM_001329958.2 (uncharacterized protein C11orf21 isoform 2) which translates to protein NP_001316887.1. Besides these two variants there is a third variant, an RNA sequence called NR_138249.2. This potential function of this third variant is unknown; it is considered a non-coding sequence because it does not meet the RefSeq criteria.

Stem Loop Structures
A stem-loop is located between 83-99 from the 5' end and consists of the sequence 5'-gcccaagacaccagggc-3'.

The hairpin turn (or stem loop, as indicated by the red arrows in Figures 11, 12 and 13) is the area where an important role in RNA functionality may be found. According to Svoboda, et. al., the stem loop, "can guide RNA folding, determine interactions in a ribozyme, protect messenger RNA (mRNA) from degradation, serve as a recognition motif for RNA binding proteins or act as a substrate for enzymatic reactions." [./Applewebdata://4120A969-FF2B-4648-BA95-D19C8F7B68CF#%20ftn1 [1] ]

It is unclear which of these key functions this stem loop supports; this is an area that warrants additional research. [./Applewebdata://4120A969-FF2B-4648-BA95-D19C8F7B68CF#%20ftnref1 [1] ]Svoboda, P., & Cara, A. (2006). Hairpin RNA: A secondary structure of primary importance. Cellular and Molecular Life Sciences, 63(7), 901-908.

Composition
MASFLVWPLRTALRGGKSWA    1

GPGVGCGGDGARGGGELSLS   21

NLDLPGAGEAGLEHHPLLGH   41

LFISAVPRWPHLSSQSGVEP   61

PDRWTGTPGWPSRDQEAPGS   81

MMPPAAAQPSAHGALVPPAT  101

AHEPVDHPALHWLACCCCLS  121

LPGQLPLAIRLGWDLDLEAG  141

PSSGKLCPRARRWQPLPS    161[./Applewebdata://53F111EE-BFBD-4686-949C-181A09F8A713#%20ftnref1 [1] ][./Applewebdata://53F111EE-BFBD-4686-949C-181A09F8A713#%20ftnref2 [2] ] [./Applewebdata://53F111EE-BFBD-4686-949C-181A09F8A713#%20ftnref1 [1] ]Technical University of Denmark, http://www.cbs.dtu.dk/cgibin/webface2.fcgi?jobid=5D4754250000546815834634&wait=20

[./Applewebdata://53F111EE-BFBD-4686-949C-181A09F8A713#%20ftnref2 [2] ]Underlined text indicates highly conserved domain DUF4620

Distant and Strict Ortholog Alignment
The most interesting feature of the conserved amino acids is the fact that there is an extremely conserved region at the beginning of the gene but in all cases the last fifty amino acids are radically divergent, with divergence beginning about 110 amino acids into the gene. This indicates that the most important functionality associated with c11orf21 is associated with the first 100-110 amino acid residues.

Secondary Structure
c11orf21 appears to be a simple protein that does not display any exotic secondary structure. The interesting things about the conformation is that fact that it is rather linear without many alpha helices. This may help to explain why c11orf21 is so prevalent in the extracellular spaces, the lack of polarity and charge and the apparently simple nature of this protein may help to make it more easily transportable across the cellular membrane.

Post-Translational Modifications
MASFLVWPLRTALRGGKSWAGPGVGCGGDGARGGGELSLSNLDLPGAGEAGLEHHPLLGH    1

LFISAVPRWPHLSSQSGVEPPDRWTGTPGWPSRDQEAPGSMMPPAAAQPSAHGALVPPAT   61

AHEPVDHPALHWLACCCCLSLPGQLPLAIRLGWDLDLEAGPSSGKLCPRARRWQPLPS   121

Locations of potential Post-Translational Modifications include:

Serines at 38, 40, 63, 74, 76, 100, 140 and 163.

Threonines at 84, 86 and 120.[./Applewebdata://9D6B4D76-51A8-4EAA-B277-CEC3A38B9F20#%20ftn1 [1] ] [./Applewebdata://9D6B4D76-51A8-4EAA-B277-CEC3A38B9F20#%20ftnref1 [1] ]Technical University of Denmark

http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5D4754250000546815834634&wait=20

Typical Locations Within the Cell
The most likely locations for the protein associated with the gene c11orf21 are the cell nucleus, followed by the extracellular space and then within the cytosol and mitochondrion.[1]

[1] Jensen Lab at Cal Tech, https://compartments.jensenlab.org/Entity?figures=subcell_cell_%%&knowledge=10&textmining=10&predictions=10&type1=9606&type2=-22&id1=ENSP00000406541

Additional References