| Dickkopf-related protein 1 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | DKK1 | ||||||
| NCBI gene | 22943 | ||||||
| HGNC | 2891 | ||||||
| OMIM | 605189 | ||||||
| RefSeq | NP_036374 | ||||||
| UniProt | O94907 | ||||||
| Other data | |||||||
| Locus | Chr. 10 q21.1 | ||||||
| |||||||
| Dickkopf-related protein 2 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | DKK2 | ||||||
| NCBI gene | 27123 | ||||||
| HGNC | 2892 | ||||||
| OMIM | 605415 | ||||||
| RefSeq | NP_055236 | ||||||
| UniProt | Q9UBU2 | ||||||
| Other data | |||||||
| Locus | Chr. 4 q25 | ||||||
| |||||||
| Dickkopf-related protein 3 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | DKK3 | ||||||
| NCBI gene | 27122 | ||||||
| HGNC | 2893 | ||||||
| OMIM | 605416 | ||||||
| RefSeq | NP_037385 | ||||||
| UniProt | Q9QUN9 | ||||||
| Other data | |||||||
| Locus | Chr. 11 p15.3 | ||||||
| |||||||
| Dickkopf-related protein 4 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | DKK4 | ||||||
| NCBI gene | 27121 | ||||||
| HGNC | 2894 | ||||||
| OMIM | 605417 | ||||||
| RefSeq | NP_055235 | ||||||
| UniProt | Q9UBT3 | ||||||
| Other data | |||||||
| Locus | Chr. 8 p11.21 | ||||||
| |||||||
Dickkopf (DKK) is a family of proteins consisting of five members as of 2020. That is, vertebrates usually contain five genes that are members of the family. The most well-studied is Dickkopf-related protein 1 (DKK1). [1] DKK proteins inhibit the Wnt signaling pathway coreceptors LRP5 and LRP6. They bind with high affinity as ligands to KREMEN1 and KREMEN2, which are transmembrane proteins. [2] DKK proteins have important roles in the development of vertebrates. [2]
Etymology
Dickkopf is a German word meaning "stubborn person", or literally, "thick head". It was coined as the name for these proteins in a 1998 Nature paper by Glinka et al. [3] in reference to the discovery that DKK1 induces head formation in the embryogenesis of Xenopus. [4]
Structure
DKK proteins are glycoproteins consisting of 255–350 amino acids. DKK1, DKK2, and DKK4 have similar molecular weights, at 24–29 k Da (kilodaltons). DKK3 is heaviest, at 38 kDa. [2] In addition to having similar weights, DKK1, -2, and -4 have high structural similarity, with two shared cysteine-rich domains. DKK3 differs from -1, -2, and -4 by the presence of a Soggy domain at its N-terminus. [5]
Proteins
Four DKK proteins and one DKK-like protein occur in humans and other vertebrates, [6] with five proteins in the family in total: [7]
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 of the artery, where they could contribute to atherosclerosis. [5]
References
- ^ Jackstadt R, Hodder MC, Sansom OJ (2020-03-09). "WNT and β-Catenin in Cancer: Genes and Therapy". Annual Review of Cancer Biology. 4 (1): 177–196. doi: 10.1146/annurev-cancerbio-030419-033628. ISSN 2472-3428.
- ^ a b c d Niehrs C (December 2006). "Function and biological roles of the Dickkopf family of Wnt modulators". Oncogene. 25 (57): 7469–81. doi: 10.1038/sj.onc.1210054. PMID 17143291. S2CID 27082767.
- ^ Glinka A, et al. (22 January 1998). "Dickkopf-1 is a Member of a New Family of Secreted Proteins and Functions in Head Induction". Nature. 391 (6665): 357–362. Bibcode: 1998Natur.391..357G. doi: 10.1038/34848. ISSN 0028-0836. OCLC 918993798. PMID 9450748. S2CID 29306691.
- ^ Kagey MH, He X (December 2017). "Rationale for Targeting the Wnt Signalling Modulator Dickkopf-1 for Oncology". British Journal of Pharmacology. 174 (24): 4637–4650. doi: 10.1111/bph.13894. ISSN 0007-1188. OCLC 1167996437. PMC 5727329. PMID 28574171.
- ^ a b Baetta R, Banfi C (July 2019). "Dkk (Dickkopf) Proteins". Arteriosclerosis, Thrombosis, and Vascular Biology. 39 (7): 1330–1342. doi: 10.1161/ATVBAHA.119.312612. PMID 31092014.
- ^ Patel S, Barkell AM, Gupta D, Strong SL, Bruton S, Muskett FW, et al. (August 2018). "Structural and functional analysis of Dickkopf 4 (Dkk4): New insights into Dkk evolution and regulation of Wnt signaling by Dkk and Kremen proteins". The Journal of Biological Chemistry. 293 (31): 12149–12166. doi: 10.1074/jbc.RA118.002918. PMC 6078440. PMID 29925589.
- ^ Shao YC, Wei Y, Liu JF, Xu XY (2017). "The role of Dickkopf family in cancers: from Bench to Bedside". American Journal of Cancer Research. 7 (9): 1754–1768. PMC 5622213. PMID 28979801.
| Dickkopf-related protein 1 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | DKK1 | ||||||
| NCBI gene | 22943 | ||||||
| HGNC | 2891 | ||||||
| OMIM | 605189 | ||||||
| RefSeq | NP_036374 | ||||||
| UniProt | O94907 | ||||||
| Other data | |||||||
| Locus | Chr. 10 q21.1 | ||||||
| |||||||
| Dickkopf-related protein 2 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | DKK2 | ||||||
| NCBI gene | 27123 | ||||||
| HGNC | 2892 | ||||||
| OMIM | 605415 | ||||||
| RefSeq | NP_055236 | ||||||
| UniProt | Q9UBU2 | ||||||
| Other data | |||||||
| Locus | Chr. 4 q25 | ||||||
| |||||||
| Dickkopf-related protein 3 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | DKK3 | ||||||
| NCBI gene | 27122 | ||||||
| HGNC | 2893 | ||||||
| OMIM | 605416 | ||||||
| RefSeq | NP_037385 | ||||||
| UniProt | Q9QUN9 | ||||||
| Other data | |||||||
| Locus | Chr. 11 p15.3 | ||||||
| |||||||
| Dickkopf-related protein 4 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | DKK4 | ||||||
| NCBI gene | 27121 | ||||||
| HGNC | 2894 | ||||||
| OMIM | 605417 | ||||||
| RefSeq | NP_055235 | ||||||
| UniProt | Q9UBT3 | ||||||
| Other data | |||||||
| Locus | Chr. 8 p11.21 | ||||||
| |||||||
Dickkopf (DKK) is a family of proteins consisting of five members as of 2020. That is, vertebrates usually contain five genes that are members of the family. The most well-studied is Dickkopf-related protein 1 (DKK1). [1] DKK proteins inhibit the Wnt signaling pathway coreceptors LRP5 and LRP6. They bind with high affinity as ligands to KREMEN1 and KREMEN2, which are transmembrane proteins. [2] DKK proteins have important roles in the development of vertebrates. [2]
Etymology
Dickkopf is a German word meaning "stubborn person", or literally, "thick head". It was coined as the name for these proteins in a 1998 Nature paper by Glinka et al. [3] in reference to the discovery that DKK1 induces head formation in the embryogenesis of Xenopus. [4]
Structure
DKK proteins are glycoproteins consisting of 255–350 amino acids. DKK1, DKK2, and DKK4 have similar molecular weights, at 24–29 k Da (kilodaltons). DKK3 is heaviest, at 38 kDa. [2] In addition to having similar weights, DKK1, -2, and -4 have high structural similarity, with two shared cysteine-rich domains. DKK3 differs from -1, -2, and -4 by the presence of a Soggy domain at its N-terminus. [5]
Proteins
Four DKK proteins and one DKK-like protein occur in humans and other vertebrates, [6] with five proteins in the family in total: [7]
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 of the artery, where they could contribute to atherosclerosis. [5]
References
- ^ Jackstadt R, Hodder MC, Sansom OJ (2020-03-09). "WNT and β-Catenin in Cancer: Genes and Therapy". Annual Review of Cancer Biology. 4 (1): 177–196. doi: 10.1146/annurev-cancerbio-030419-033628. ISSN 2472-3428.
- ^ a b c d Niehrs C (December 2006). "Function and biological roles of the Dickkopf family of Wnt modulators". Oncogene. 25 (57): 7469–81. doi: 10.1038/sj.onc.1210054. PMID 17143291. S2CID 27082767.
- ^ Glinka A, et al. (22 January 1998). "Dickkopf-1 is a Member of a New Family of Secreted Proteins and Functions in Head Induction". Nature. 391 (6665): 357–362. Bibcode: 1998Natur.391..357G. doi: 10.1038/34848. ISSN 0028-0836. OCLC 918993798. PMID 9450748. S2CID 29306691.
- ^ Kagey MH, He X (December 2017). "Rationale for Targeting the Wnt Signalling Modulator Dickkopf-1 for Oncology". British Journal of Pharmacology. 174 (24): 4637–4650. doi: 10.1111/bph.13894. ISSN 0007-1188. OCLC 1167996437. PMC 5727329. PMID 28574171.
- ^ a b Baetta R, Banfi C (July 2019). "Dkk (Dickkopf) Proteins". Arteriosclerosis, Thrombosis, and Vascular Biology. 39 (7): 1330–1342. doi: 10.1161/ATVBAHA.119.312612. PMID 31092014.
- ^ Patel S, Barkell AM, Gupta D, Strong SL, Bruton S, Muskett FW, et al. (August 2018). "Structural and functional analysis of Dickkopf 4 (Dkk4): New insights into Dkk evolution and regulation of Wnt signaling by Dkk and Kremen proteins". The Journal of Biological Chemistry. 293 (31): 12149–12166. doi: 10.1074/jbc.RA118.002918. PMC 6078440. PMID 29925589.
- ^ Shao YC, Wei Y, Liu JF, Xu XY (2017). "The role of Dickkopf family in cancers: from Bench to Bedside". American Journal of Cancer Research. 7 (9): 1754–1768. PMC 5622213. PMID 28979801.