Anti-DLK-1/DLK1 Antibody Picoband® fluoro488 Vervoeging

Protein delta homolog 1 is a protein that in humans is encoded by the DLK1 gene. This gene encodes a transmembrane protein that contains multiple epidermal growth factor repeats that functions as a regulator of cell growth. The encoded protein is involved in the differentiation of several cell types including adipocytes. This gene is located in a region of chromosome 14 frequently showing unparental disomy, and is imprinted and expressed from the paternal allele. A single nucleotide variant in this gene is associated with child and adolescent obesity and shows polar overdominance, where heterozygotes carrying an active paternal allele express the phenotype, while mutant homozygotes are normal.

Cyclin-dependent-like kinase 5; Cell division protein kinase 5; Serine/threonine-protein kinase PSSALRE; Tau protein kinase II catalytic subunit; TPKII catalytic subunit; CDK5; CDKN5

DLK1

8788

P80370

Human

No cross-reactivity with other proteins.

E.coli-derived human DLK-1/DLK1 recombinant protein (Position: A24-I383) .

Isoform 1 is ubiquitously expressed. Accumulates in cortical neurons (at protein level) . Isoform 2 has only been detected in testis, skeletal muscle, colon, bone marrow and ovary.

Flow Cytometry

Cofactors, Vitamins/Minerals, Hematopoietic Progenitors, Metabolism, Myeloid, Pathways and Processes, Signal Transduction, Stem Cells, Vitamins/Minerals

Immunogen affinity purified.

Liquid

Proline-ed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in post-mitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution.

1. Cleaton, M. A. M., Dent, C. L., Howard, M., Corish, J. A., Gutteridge, I., Sovio, U., Gaccioli, F., Takahashi, N., Bauer, S. R., Charnock-Jones, D. S., Powell, T. L., Smith, G. C. S., Ferguson-Smith, A. C., Charalambous, M. Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction. Nature Genet. 48: 1473-1480, 2016. 2. Cockett, N. E., Jackson, S. P., Shay, T. L., Farnir, F., Berghmans, S., Snowder, G. D., Nielsen, D. M., Georges, M. Polar overdominance at the ovine callipyge locus. Science 273: 236-238, 1996. 3. Dauber, A., Cunha-Silva, M., Macedo, D. B., Brito, V. N., Abreu, A. P., Roberts, S. A., Montenegro, L. R., Andrew, M., Kirby, A., Weirauch, M. T., Labilloy, G., Bessa, D. S., Carroll, R. S., Jacobs, D. C., Chappell, P. E., Mendonca, B. B., Haig, D., Kaiser, U. B., Latronico, A. C. Paternally inherited DLK1 deletion associated with familial central precocious puberty. J. Clin. Endocr. Metab. 102: 1557-1567, 2017.

At -20 ̊C for one year from date of receipt. Avoid repeated freezing and thawing. Protect from light.

40108 MW

6

Cyclin-dependent kinase 5

Cell membrane. Peripheral membrane protein. Postsynaptic density. Cytoplasm. Perikaryon. Lamellipodium. Growth cone.

Hereditary hemochromatosis protein

Rabbit IgG

Each vial contains 50% glycerol, 0.9% NaCl, 0.2% Na2HPO4, 0.02% NaN3.