C12orf40, also known as Chromosome 12 Open Reading Frame 40, HEL-206, and Epididymis Luminal Protein 206 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in

humans Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

is encoded by the ''C12orf40''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Gene

Human gene

In humans, the gene for ''C12orf40'' is located on

chromosome 12 Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the to ...

. There are 13 exons in the canonical isoform that is transcribed into an

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

of 2797 base pairs. Three other isoforms have been isolated.

Evolution

Homologs exist as distant as the

green sea turtle The green sea turtle (''Chelonia mydas''), also known as the green turtle, black (sea) turtle or Pacific green turtle, is a species of large sea turtle of the family Cheloniidae. It is the only species in the genus ''Chelonia''. Its range exten ...

and

chickens The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adult m ...

at approximately 60% sequence identity, suggesting that the gene may have arisen in the

amniotes Amniotes are a clade of tetrapod vertebrates that comprises sauropsids (including all reptiles and birds, and extinct parareptiles and non-avian dinosaurs) and synapsids (including pelycosaurs and therapsids such as mammals). They are distingu ...

after their divergence from other

tetrapods Tetrapods (; ) are four-limbed vertebrate animals constituting the superclass Tetrapoda (). It includes extant and extinct amphibians, sauropsids (reptiles, including dinosaurs and therefore birds) and synapsids (pelycosaurs, extinct therapsids ...

; the first 4 exons are conserved with 36% identity as distantly as the

anemone ''Anemone'' () is a genus of flowering plants in the buttercup family Ranunculaceae. Plants of the genus are commonly called windflowers. They are native to the temperate and subtropical regions of all continents except Australia, New Zealand an ...

Protein

Properties

The human ''C12orf40'' protein is 652 amino acids in length. Its molecular weight is predicted to be 74.52 kDa, and its isoelectric point 7.822. Amino acids 229-652 contain a domain of unknown function (''DUF4552'') which is conserved in

vertebrates Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

. ''C12orf40'' is predicted to be a soluble protein with no transmembrane segments. Its secondary and tertiary structures are not currently known.

Interactions

Experimental evidence shows that C12orf40 has a physical interaction with dynein light chain 2 (

DYNLL2 Dynein light chain 2, cytoplasmic is a protein that in humans is encoded by the ''DYNLL2'' gene. Interactions DYNLL2 has been shown to interact with DLG4, C12orf40, DLGAP1, MYO5A Unconventional myosin-Va is a motor protein in charge of the in ...

). This protein is part of a complex that regulates the function of the motor protein dynein.

Expression

Within the cell, ''C12orf40'' is predicted to be present in the nucleus based on signals within its sequence. An analysis of normal human tissues shows that ''C12orf40'' expression occurs primarily in the

testis A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testostero ...

, suggesting importance to the male reproductive system.

Clinical significance

The function of ''C12orf40'' is not yet well understood. However, the

three prime untranslated region In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...

(3' UTR) of ''C12orf40'' is highly similar to the 3' UTR of the

cystic fibrosis transmembrane conductance regulator Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the ''CFTR'' gene. Geneticist Lap-Chee Tsui and his team identified the CFTR gene in 1989 as the gene linked wi ...

(CFTR), which may mean that the two genes share certain expression patterns. In the

fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...

of hypertrophic scars, exposure to the immunosuppressant

Tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

causes ''C12orf40'' up-regulation. In pigs, a region homologous to human ''C12orf40'' plays a role in

arthrogryposis Arthrogryposis (AMC) describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning "curving of joints" (', "joint"; ', late Latin form of late Greek ', "hooking"). Children born with one ...

, a disease characterized by congenital fibrosis. The common thread of these studies suggests that ''C12orf40'' may have a connection to the formation of healthy connective tissue.

References

{{reflist Chromosomes Protein families