DLK1

DLK1
Identifiers
Aliases	DLK1, DLK, DLK-1, Delta1, FA1, PREF1, Pref-1, ZOG, pG2, AW742678, DlkI, Ly107, Peg9, SCP1, delta like non-canonical Notch ligand 1
External IDs	OMIM: 176290; MGI: 94900; HomoloGene: 2846; GeneCards: DLK1; OMA:DLK1 - orthologs
Gene location (Human)
Chr.	Chromosome 14 (human)
End	100,738,224 bp
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)
End	109,429,262 bp
RNA expression pattern
	Top expressed in
	right adrenal cortex; ; left adrenal cortex; ; anterior pituitary; ; cartilage tissue; ; beta cell; ; glutes; ; left ovary; ; placenta; ; parotid gland; ; body of tongue;
	Top expressed in
	yolk sac; ; adrenal gland; ; hypothalamus; ; placenta; ; neural tube; ; mesencephalon; ; genital tubercle; ; limb; ; rhombencephalon; ; tail of embryo;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	calcium ion binding; molecular function;
Cellular component	integral component of membrane; membrane; extracellular space; cytoplasm;
Biological process	cell differentiation; negative regulation of Notch signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	8788
	13386
	ENSG00000185559
	ENSMUSG00000040856
	P80370
	Q09163
	NM_001032997; NM_003836; NM_001317172
	NM_001190703; NM_001190704; NM_001190705; NM_010052
	NP_001304101; NP_003827; NP_003827.3
	NP_001177632; NP_001177633; NP_001177634; NP_034182
	Wikidata
View/Edit Human	View/Edit Mouse

Protein delta homolog 1, delta like non-canonical Notch ligand 1, fetal antigen 1⁵ or preadipocyte factor 1⁶ is a protein that in humans is encoded by the DLK1 gene.⁷⁸⁹

It is expressed as a transmembrane protein, but a soluble form cleaved off by ADAM17 is active in inhibiting adipogenesis,¹⁰ the differentiation of pre-adipocytes into adipocytes.¹¹

It is a member of the EGF-like family of homeotic proteins.¹²

Part of the Dlk1-DIO3 imprinting control region, this gene is one involved in the epigenetic process that causes a subset of genes to be regulated based on their parental origin.¹³

Such imprinted genes are required for the formation of the placenta as well as the development of cellular lineages such as those derived from the mesoderm and ectoderm.¹⁴

References

GRCh38: Ensembl release 89: ENSG00000185559 – Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000040856 – Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Jensen C, Teisner B, Højrup P, Rasmussen H, Madsen O, Nielsen B, Skjødt K (1993). "Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2". Human Reproduction. 8 (4): 635–641. doi:10.1093/oxfordjournals.humrep.a138110. PMID 8501199.
Smas CM, Sul HS (1993). "Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation". Cell. 73 (4): 725–734. doi:10.1016/0092-8674(93)90252-L. PMID 8500166. S2CID 23634189.
Laborda J, Sausville EA, Hoffman T, Notario V (1993). "dlk, a Putative Mammalian Homeotic Gene Differentially Expressed in Small Cell Lung Carcinoma and Neuroendocrine Tumor Cell Line". The Journal of Biological Chemistry. 268 (6): 3817–20. doi:10.1016/S0021-9258(18)53544-4. PMID 8095043.
Jensen CH, Krogh TN, Højrup P, Clausen PP, Skjødt K, Larsson LI, Enghild JJ, Teisner B (1994). "Protein Structure of Fetal Antigen 1 (FA1). A Novel Circulating Human Epidermal-Growth-Factor-Like Protein Expressed in Neuroendocrine Tumors and its Relation to the Gene Products of Dlk and pG2". European Journal of Biochemistry. 225 (1): 83–92. doi:10.1111/j.1432-1033.1994.00083.x. PMID 7925474.
EntrezGene 8788
Wang Y, Sul HS (2009). "Pref-1 Regulates Mesenchymal Cell Commitment and Differentiation through Sox9". Cell Metabolism. 9 (3): 287–302. doi:10.1016/j.cmet.2009.01.013. PMC 2673480. PMID 19254573.
Adipogenesis at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Laborda J (2000). "The role of the epidermal growth factor-like protein dlk in cell differentiation". Histology and Histopathology. 15 (1): 119–29. PMID 10668203.
Lin SP, Coan P, da Rocha ST, Seitz H, Cavaille J, Teng PW, Takada S, Ferguson-Smith AC (Jan 2007). "Differential regulation of imprinting in the murine embryo and placenta by the Dlk1-Dio3 imprinting control region". Development. 134 (2): 417–426. doi:10.1242/dev.02726. PMID 17166925.
Hernandez A, Fiering S, Martinez E, Galton VA, St Germain D (Nov 2002). "The gene locus encoding iodothyronine deiodinase type 3 (Dio3) is imprinted in the fetus and expresses antisense transcripts". Endocrinology. 143 (11): 4483–4486. doi:10.1210/en.2002-220800. PMID 12399446.

Further reading

Helamn LJ, Sack N, Plon SE, Israel MA (1990). "The sequence of an adrenal specific human cDNA, pG2". Nucleic Acids Research. 18 (3): 685. doi:10.1093/nar/18.3.685. PMC 333507. PMID 2308864.
Helman LJ (1987). "Molecular Markers of Neuroendocrine Development and Evidence of Environmental Regulation". Proceedings of the National Academy of Sciences. 84 (8): 2336–9. Bibcode:1987PNAS...84.2336H. doi:10.1073/pnas.84.8.2336. PMC 304645. PMID 3470797.
Lee YL, Helman L, Hoffman T, Laborda J (1995). "Dlk, pG2 and Pref-1 mRNAs encode similar proteins belonging to the EGF-like superfamily. Identification of polymorphic variants of this RNA". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1261 (2): 223–32. doi:10.1016/0167-4781(95)00007-4. PMID 7711066.
Smas CM, Sul HS (1993). "Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation". Cell. 73 (4): 725–34. doi:10.1016/0092-8674(93)90252-L. PMID 8500166. S2CID 23634189.
Jensen CH, Teisner B, Højrup P, Rasmussen HB, Madsen OD, Nielsen B, Skjødt K (1993). "Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2". Human Reproduction. 8 (4): 635–41. doi:10.1093/oxfordjournals.humrep.a138110. PMID 8501199.
Tornehave D, Jensen CH, Teisner B, Larsson LI (1996). "FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression". Histochemistry and Cell Biology. 106 (6): 535–42. doi:10.1007/BF02473268. PMID 8985741. S2CID 19673701.
Jensen CH, Schroder HD, Teisner B, Laursen I, Brandrup F, Rasmussen HB (1999). "Fetal antigen 1, a member of the epidermal growth factor superfamily, in neurofibromas and serum from patients with neurofibromatosis type 1". British Journal of Dermatology. 140 (6): 1054–9. doi:10.1046/j.1365-2133.1999.02906.x. PMID 10354070. S2CID 25598902.
Gubina E, Ruiz-Hidalgo M, Baladrón V, Laborda J (1999). "Assignment of DLK1 to human chromosome band 14q32 by in situ hybridization". Cytogenetic and Genome Research. 84 (3–4): 206–7. doi:10.1159/000015259. hdl:10578/47987. PMID 10393432. S2CID 491728.
Jensen CH, Erb K, Westergaard LG, Kliem A, Teisner B (1999). "Fetal antigen 1, an EGF multidomain protein in the sex hormone-producing cells of the gonads and the microenvironment of germ cells". Molecular Human Reproduction. 5 (10): 908–13. doi:10.1093/molehr/5.10.908. PMID 10508217.
Aguan K, Carvajal JA, Thompson LP, Weiner CP (2000). "Application of a functional genomics approach to identify differentially expressed genes in human myometrium during pregnancy and labour". Molecular Human Reproduction. 6 (12): 1141–5. doi:10.1093/molehr/6.12.1141. PMID 11101697.
Andersen M (2001). "Fetal Antigen 1 in Healthy Adults and Patients with Pituitary Disease: Relation to Physiological, Pathological, and Pharmacological GH Levels". Journal of Clinical Endocrinology & Metabolism. 86 (11): 5465–70. doi:10.1210/jcem.86.11.7990. PMID 11701723. S2CID 24831931.
Jensen CH, Meyer M, Schroder HD, Kliem A, Zimmer J, Teisner B (2001). "Neurons in the monoaminergic nuclei of the rat and human central nervous system express FA1/dlk". NeuroReport. 12 (18): 3959–63. doi:10.1097/00001756-200112210-00021. PMID 11742219. S2CID 30021418.
Baladrón V, Ruiz-Hidalgo MJ, Bonvini E, Gubina E, Notario V, Laborda J (2002). "The EGF-like Homeotic Protein dlk Affects Cell Growth and Interacts with Growth-Modulating Molecules in the Yeast Two-Hybrid System". Biochemical and Biophysical Research Communications. 291 (2): 193–204. doi:10.1006/bbrc.2002.6431. hdl:10578/47986. PMID 11846389.
Panin VM, Shao L, Lei L, Moloney DJ, Irvine KD, Haltiwanger RS (2002). "Notch Ligands Are Substrates for Protein O-Fucosyltransferase-1 and Fringe". Journal of Biological Chemistry. 277 (33): 29945–52. doi:10.1074/jbc.M204445200. PMID 12036964.
Doggett KL, Briggs JA, Linton MF, Fazio S, Head DR, Xie J, Hashimoto Y, Laborda J, Briggs RC (2002). "Retroviral mediated expression of the human myeloid nuclear antigen in a null cell line upregulatesDlk1 expression". Journal of Cellular Biochemistry. 86 (1): 56–66. doi:10.1002/jcb.10190. PMID 12112016. S2CID 30240885.
Van Limpt VA, Chan AJ, Van Sluis PG, Caron HN, Van Noesel CJ, Versteeg R (2003). "High delta-like 1 expression in a subset of neuroblastoma cell lines corresponds to a differentiated chromaffin cell type". International Journal of Cancer. 105 (1): 61–9. doi:10.1002/ijc.11047. PMID 12672031.
Abdallah BM, Jensen CH, Gutierrez G, Leslie RG, Jensen TG, Kassem M (2004). "Regulation of Human Skeletal Stem Cells Differentiation by Dlk1/Pref-1". Journal of Bone and Mineral Research. 19 (5): 841–52. doi:10.1359/JBMR.040118. PMID 15068508. S2CID 23774562.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000185559 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000040856 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Jensen C, Teisner B, Højrup P, Rasmussen H, Madsen O, Nielsen B, Skjødt K (1993). "Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2". Human Reproduction. 8 (4): 635–641. doi:10.1093/oxfordjournals.humrep.a138110. PMID 8501199.

[6] Smas CM, Sul HS (1993). "Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation". Cell. 73 (4): 725–734. doi:10.1016/0092-8674(93)90252-L. PMID 8500166. S2CID 23634189.

[pmid8095043-7] Laborda J, Sausville EA, Hoffman T, Notario V (1993). "dlk, a Putative Mammalian Homeotic Gene Differentially Expressed in Small Cell Lung Carcinoma and Neuroendocrine Tumor Cell Line". The Journal of Biological Chemistry. 268 (6): 3817–20. doi:10.1016/S0021-9258(18)53544-4. PMID 8095043.

[pmid7925474-8] Jensen CH, Krogh TN, Højrup P, Clausen PP, Skjødt K, Larsson LI, Enghild JJ, Teisner B (1994). "Protein Structure of Fetal Antigen 1 (FA1). A Novel Circulating Human Epidermal-Growth-Factor-Like Protein Expressed in Neuroendocrine Tumors and its Relation to the Gene Products of Dlk and pG2". European Journal of Biochemistry. 225 (1): 83–92. doi:10.1111/j.1432-1033.1994.00083.x. PMID 7925474.

[entrez-9] EntrezGene 8788

[10] Wang Y, Sul HS (2009). "Pref-1 Regulates Mesenchymal Cell Commitment and Differentiation through Sox9". Cell Metabolism. 9 (3): 287–302. doi:10.1016/j.cmet.2009.01.013. PMC 2673480. PMID 19254573.

[11] Adipogenesis at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[12] Laborda J (2000). "The role of the epidermal growth factor-like protein dlk in cell differentiation". Histology and Histopathology. 15 (1): 119–29. PMID 10668203.

[ShauPingLin-13] Lin SP, Coan P, da Rocha ST, Seitz H, Cavaille J, Teng PW, Takada S, Ferguson-Smith AC (Jan 2007). "Differential regulation of imprinting in the murine embryo and placenta by the Dlk1-Dio3 imprinting control region". Development. 134 (2): 417–426. doi:10.1242/dev.02726. PMID 17166925.

[ArturoHernandez-14] Hernandez A, Fiering S, Martinez E, Galton VA, St Germain D (Nov 2002). "The gene locus encoding iodothyronine deiodinase type 3 (Dio3) is imprinted in the fetus and expresses antisense transcripts". Endocrinology. 143 (11): 4483–4486. doi:10.1210/en.2002-220800. PMID 12399446.

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