Mitochondrial import inner membrane translocase subunit TIM16 also known as presequence translocated-associated motor subunit PAM16, mitochondria-associated granulocyte macrophage CSF-signaling molecule, or presequence translocated-associated motor subunit PAM16 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the PAM16

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Structure

The ''PAM16'' gene is located on the

p arm In genetics, a locus (: loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total numb ...

chromosome 16 Chromosome 16 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 16 spans about 90 million base pairs (the building material of DNA) and represents just under 3% of the total DNA in cel ...

at position 13.3 and it spans 11,150 base pairs. The ''PAM16'' gene produces a 15.1 kDa protein composed of 137

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

. The structure has been found to contain a 21-residue mitochondrial targeting leader sequence.

Function

The ''PAM16'' gene encodes for a mitochondrial

with multiple functions. It is responsible for the regulation of ATP-dependent

protein translocation Protein targeting or protein sorting is the Mechanism (biology), biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, diffe ...

into the

mitochondrial matrix In the mitochondrion, the matrix is the space within the inner membrane. It can also be referred as the mitochondrial fluid. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitoc ...

, inhibition of DNAJC19 stimulation of

HSPA9 Mitochondrial 70kDa heat shock protein (mtHsp70), also known as mortalin, is a protein that in humans is encoded by the ''HSPA9'' gene. Function The product encoded by this gene belongs to the heat shock protein 70 family which contains both ...

/ Mortalin

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...

activity, and granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. Furthermore, PAM16 plays a role in the import of nuclear-encoded mitochondrial proteins into the

and may be important in

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

(ROS)

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

Clinical Significance

Mutations in the ''PAM16'' gene has been shown to cause mitochondrial deficiencies and associated disorders. It is mainly associated with Megarbane-Dagher-Melike type spondylometaphyseal dysplasia, which is an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

disease characterized by pre- and

postnatal The postpartum (or postnatal) period begins after childbirth and is typically considered to last for six to eight weeks. There are three distinct phases of the postnatal period; the acute phase, lasting for six to twelve hours after birth; the ...

short stature Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ...

developmental delay The term developmental delay can refer to: *Global developmental delay, an umbrella term used when children are significantly delayed in two or more areas of development *Specific developmental disorder, a classification of disorders characterize ...

dysmorphic A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, genetic syndrome or birth defect. Dysmorphology is the study of dysm ...

facial appearance, narrow

chest The thorax (: thoraces or thoraxes) or chest is a part of the anatomy of mammals and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main di ...

, prominent

abdomen The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...

platyspondyly Congenital vertebral anomalies are a collection of malformations of the spine. Most, around 85%, are not clinically significant, but they can cause compression of the spinal cord by deforming the vertebral canal or causing instability. This condit ...

, short limbs, and other abnormalities of the

skeleton A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fra ...

Interactions

''PAM16'' has been known to interact with PAM18, DNAJC19,

TIMM17A Mitochondrial import inner membrane translocase subunit Tim17-A is an enzyme that in humans is encoded by the ''TIMM17A'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is ...

FEZ1 Fasciculation and elongation protein zeta-1 is a protein that in humans is encoded by the ''FEZ1'' gene. This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Exp ...

TRIM25 Tripartite motif-containing protein 25 is a protein that in humans is encoded by the ''TRIM25'' gene. The protein encoded by this gene is a member of the tripartite motif (TRIM) family grouping more than 70 TRIMs. TRIM proteins primarily functio ...

, MARC1, and other proteins.

Structure

Function

Clinical Significance

Interactions

References

Further reading