Summary
Application
ELISA, WB, IHC-P, IF, ICC, FC
Basic Information
Immunogen
Purified recombinant fragment of mouse PKHD1
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Format
PBS with 0.05% sodium azide
Storage
Store at 4°C short term (1-2 weeks). Aliquot and store at-20°C long term. Avoid repeated freeze/thaw cycles.
Target
Full Name
PKHD1, Fibrocystin/Polyductin
Introduction
PKHD1 is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1.
Alternative Names
AI118496; AI182499; FPC; Tigm1
Function
Promotes ciliogenesis in renal epithelial cells and therefore participates in the tubules formation and/ or ensures the maintenance of the architecture of the lumen of the kidney (By similarity).
Has an impact on cellular symmetry by ensuring correct bipolar cell division through the regulation of centrosome duplication and mitotic spindle assembly and by maintaining oriented cell division (OCD) during tubular elongation through planar cell polarity (PCP) pathway (PubMed:20554582).
During epithelial cell morphogenesis regulates also cell-cell and cell-matrix adhesion and participates in cell motility (By similarity).
Promotes cell-cell contact through the positive regulation of PTK2 kinase activity leading to either positive regulation of epithelial cell proliferation through the HRAS/RAF1 pathways, or negative regulation of apoptosis through the PDK1/AKT1 pathway (By similarity).
May act in collecting-duct and biliary differentiation (PubMed:11919560).
May participate in the regulation of the cholangiocytes proliferation and the CCN2 production in an CXCL8-dependent manner (PubMed:30898581).
Biological Process
Branching morphogenesis of an epithelial tubeISS:UniProtKB
Cell-cell adhesionISS:UniProtKB
Cell-cell junction organizationISS:UniProtKB
Cellular calcium ion homeostasisManual Assertion Based On ExperimentIMP:UniProtKB
Cilium assemblyIEA:Ensembl
Epithelial cell morphogenesisISS:UniProtKB
Establishment of centrosome localizationISS:UniProtKB
Establishment of mitotic spindle orientationISS:UniProtKB
Homeostatic process1 PublicationNAS:UniProtKB
Kidney developmentIEA:Ensembl
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of cellular component movementISS:UniProtKB
Negative regulation of epithelial cell apoptotic processISS:UniProtKB
Negative regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of protein kinase B signalingManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of epithelial cell proliferationISS:UniProtKB
Regulation of cell adhesionISS:UniProtKB
Regulation of cell-cell adhesionISS:UniProtKB
Regulation of cell-matrix adhesionISS:UniProtKB
Regulation of centrosome duplicationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cholangiocyte proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of establishment of planar polarityISS:UniProtKB
Regulation of TOR signalingManual Assertion Based On ExperimentIMP:UniProtKB
Cellular Location
Cell membrane
Cytoplasm
Cell projection, cilium
Cytoplasm, cytoskeleton, cilium basal body
Cytoplasm, cytoskeleton, spindle
Chromosome, centromere
Apical cell membrane
Nucleus
Secreted, extracellular exosome
Secreted
Endoplasmic reticulum
Golgi apparatus
The intracellular C-terminal fragment (ICD) translocates to the nucleus and is not detected in primary cilia (PubMed:17470460, PubMed:16956880).
The extracellular domain (PECD) traffics beyond the mid-Golgi and localizes on exosome like vesicles (ELVs) attached to the primary cilium (By similarity).
In the urine, the extracellular domain (PECD) exists as an highly abundant secreted form and a less abundant PECD form that is either tethered to or shed with the C-terminal fragment (PTM) in ELVs (By similarity).
The majority of full length PKHD1 protein resides at the endoplasmic reticulum and cannot pass beyond the mid-Golgi apparatus and is not detected in primary cilia (By similarity).
The intra-cellular C-terminal fragment of 21-kDa translocates to the nucleus. The extracellular domain traffics beyond the mid-Golgi and localizes on exosome like vesicles (ELVs) attached to the primary cilium (By similarity).
Involvement in disease
Polycystic kidney disease 4, with or without polycystic liver disease (PKD4):
A severe form of polycystic kidney disease affecting the kidneys and, in some cases, the hepatic biliary tract. The clinical spectrum is widely variable, with most cases presenting during infancy. The fetal phenotypic features classically include enlarged and echogenic kidneys, as well as oligohydramnios secondary to a poor urine output. Up to 50% of the affected neonates die shortly after birth, as a result of severe pulmonary hypoplasia and secondary respiratory insufficiency. In the subset that survives the perinatal period, morbidity and mortality are mainly related to severe systemic hypertension, renal insufficiency, and portal hypertension due to portal-tract fibrosis. PKD4 inheritance is autosomal recessive.
Topology
Extracellular: 24-3858
Helical: 3859-3879
Cytoplasmic: 3880-4074
PTM
Several proteolytic cleavages occur within the extracellular domain, whereas at least one cleavage occurs within the cytoplasmic domain (PubMed:16956880).
Cleaved by a probable proprotein convertase which produces an extracellular domain (polyductin extracellular domain, (PECD)) and a C-terminal fragment (polyductin transmembrane fragment (PTM)) which are tethered together by disulfide bonds (PubMed:17470460).
This extracellular domain (PECD) is then shed from the primary cilium by activation of a member of the ADAM metalloproteinase disintegrins family, resulting in concomitant release of an intra-cellular C-terminal fragment (ICD) via a gamma-secretase-dependent process (PubMed:17470460).
The proteolytic cleavage of the C-terminal intracellular fragment (ICD) is controlled by cytosolic calcium concentration and activation of PKC (PubMed:16956880).
Palmitoylated. Palmitoylation facilitates membrane targeting and the trafficking to the cilia.
N-glycosylated.
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