Dickkopf (DKK) is a family of proteins consisting of five members as of 2020. That is,

vertebrates Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

usually contain five genes that are members of the family. The most well-studied is Dickkopf-related protein 1 (DKK1). DKK proteins inhibit the

Wnt signaling pathway In cellular biology, the Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt, pronounced "wint", is a portmanteau created from the ...

coreceptors LRP5 and LRP6. They bind with high affinity as

ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...

to KREMEN1 and KREMEN2, which are

transmembrane proteins A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...

. DKK proteins have important roles in the development of vertebrates.

Etymology

is a German word meaning "stubborn person", or literally, "thick head". It was coined as the name for these proteins in a 1998 ''

Nature Nature is an inherent character or constitution, particularly of the Ecosphere (planetary), ecosphere or the universe as a whole. In this general sense nature refers to the Scientific law, laws, elements and phenomenon, phenomena of the physic ...

'' paper by Glinka ''et al.'' in reference to the discovery that DKK1 induces head formation in the

embryogenesis An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...

of ''

Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos'' = strange, πους, ''pous'' = foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described with ...

''.

Structure

DKK proteins are

glycoproteins Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

consisting of 255–350

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 ...

. DKK1, DKK2, and DKK4 have similar molecular weights, at 24–29 k Da (kilodaltons). DKK3 is heaviest, at 38 kDa. In addition to having similar weights, DKK1, -2, and -4 have high structural similarity, with two shared

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

-rich domains. DKK3 differs from -1, -2, and -4 by the presence of a Soggy domain at its

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

Proteins

Four DKK proteins and one DKK-like protein occur in humans and other vertebrates, with five proteins in the family in total: * DKK1 * DKK2 * DKK3 * DKK4 * DKKL1 (soggy-1, Cancer/testis antigen 34)

Human disease

DKK proteins are believed to be involved with several human diseases, including bone cancer and neurodegenerative disease. Evidence also indicates DKK1 and DKK3 are involved in the

pathophysiology Pathophysiology (or physiopathology) is a branch of study, at the intersection of pathology and physiology, concerning disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is ...

of the

artery An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...

, where they could contribute to

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

References

{{Wiktionary Protein families