Ankyrin repeat and kinase domain containing 1 (ANKK1) also known as protein kinase PKK2 or sugen kinase 288 (SgK288) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that in humans is encoded by the ''ANKK1''

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 ...

. The ANKK1 is a member of an extensive family of the Ser/Thr protein kinase family, and

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...

superfamily involved in

signal transduction pathways Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

Clinical significance

This gene contains a

single nucleotide polymorphism In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...

that causes an amino acid substitution within the 11th of 12

ankyrin repeat The ankyrin repeat is a 33-residue motif in proteins consisting of two alpha helices separated by loops, first discovered in signaling proteins in yeast Cdc10 and ''Drosophila'' Notch. Domains consisting of ankyrin tandem repeats mediate prot ...

s of ANKK1 (Glu713Lys of 765 residues). This polymorphism, which is commonly referred to Taq1A, was previously believed to be located in the

promoter region In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of ...

of the

DRD2 Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, i ...

gene, since the polymorphism is proximal to the DRD2 gene and can influence DRD2 receptor expression. It is now known to be located in the coding region of the ANKK1 gene which controls the synthesis of

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

in the brain. The A1 allele is associated with increased activity of striatal L-amino acid decarboxylase.

A1+ allele

* Hepatitis C infection *

Antisocial personality disorder Antisocial personality disorder (ASPD or infrequently APD) is a personality disorder characterized by a long-term pattern of disregard of, or violation of, the rights of others as well as a difficulty sustaining long-term relationships. Lack ...

* Borderline personality traits * Schizoid/avoidant behavior Given that the A1+ allele is associated with antisocial personality disorder, one may infer that the allele is also associated with

narcissistic personality disorder Narcissistic personality disorder (NPD) is a personality disorder characterized by a life-long pattern of exaggerated feelings of self-importance, an excessive need for admiration, a diminished ability or unwillingness to empathize with other ...

and

histrionic personality disorder Histrionic personality disorder (HPD) is defined by the American Psychiatric Association as a personality disorder characterized by a pattern of excessive attention-seeking behaviors, usually beginning in early childhood, including inappropriate ...

. However, these predictions have not yet been empirically verified.

A1+ genotype frequencies

European population estimates for A1+ genotype frequencies range from 20.8 to 43.4% (National Center of Biotechnology Information (NCBI), identification number rs1800497).

Addictive behaviors

The ANKK1 gene is closely linked to dopamine receptor D2 (

) on chromosome band 11q23.1. The A1

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

of the Taq1A polymorphism (rs1800497T), is located ≈10kb downstream of the

dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...

DRD2 gene.

Dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

(DA) is a

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

in the brain, which controls feelings of wellbeing. This sensation results from the interaction of dopamine and other neurotransmitters such as

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

, the

opioids Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

, and other brain chemicals. Dopamine increases the motivation for food cravings and appetite mediation. The

Reward Deficiency Syndrome Kenneth Blum (born August 8, 1939) is an American scientist who has studied neuropsychopharmacology and genetics. Until 1995 he was a professor of Pharmacology at the University of Texas Health Science Center at San Antonio. Blum originated the t ...

(RDS) involves the pleasures or reward mechanisms that rely on dopamine. The result of this deficiency is based on the genetic makeup; this helps explain how certain simple genetic anomalies can give rise to complex aberrant behaviours as the ones mentioned previously. The A1 allelic prevalence has been reported to be significantly higher in

obese Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

individuals than in lean subjects, moreover, individuals with increased body mass index (BMI) (BMI ≥ 30 kg/m²) have fewer DRD2 dopamine receptors. Investigators have also suggested that hormonal mechanism may underline a gender difference in the ability to suppress hunger in relation to this SNP, which may contribute to the greater incidence of obesity in women compared to men. However, authors have pointed out that A1 carriers have difficulty in learning from

negative feedback Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by ...

in a reinforcement-learning task and are less efficient at learning to avoid actions that have negative consequences.

References

External links

*For more related information on the SNP:
SNPedia
*Dopamine receptor D2; DRD2
OMNI Entry
*The Human Gene Compendium DRD2
GeneCards
* {{Addiction Signal transduction Protein kinases