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FLASH GENE

Symbol

PKHD1

contributors: mct - updated : 16-12-2020

HGNC name	polycystic kidney and hepatic disease 1 (autosomal recessive)
HGNC id	9016

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	signal peptide
	multiple copies (6 to 7) of a domain TIG/IPT (immunoglobulin-like fold shared by plexing and transcription factors)
	TMEM2 homology domain
	DKFZ homology domain
	transmembrane domain
	C terminal EF-hand domain (to associate with a calcium ion), and a large extracellular domain that is tethered to the C-terminal stalk by disulfide bridges, cleaved at a probable proprotein convertase site, and with a PKD2 -binding domain
	cytoplasmic tail, reported to include a ciliary targeting sequence, a nuclear localization signal, and a polycystin-2 binding domain, is thought to traffic to the nucleus after cleavage

HOMOLOGY

interspecies

ortholog to rattus Arpkd

Homologene

FAMILY

CATEGORY

receptor membrane

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,nuclear envelope
text	type I membrane protein, ciliary localization, in primary apical cilia
	localized in the primary cilia of kidney tubular epithelia cells and cholangiocytes of bile ducts
	endogenous form localizes to the centrosome and mitotic spindle in human renal epithelial cells

basic FUNCTION	may be a receptor protein that acts in collecting-duct and biliary differentiation
	functional and/or structural component of primary cilia in kidney tubular cells
	novel function in centrosome duplication and mitotic spindle assembly during cell division and mitotic defects due to its dysfunction contribute to cystogenesis in ARPKD
	may form a signaling complex at the spindle pole with other cystogenic proteins and modulate mitotic spindle orientation and bipolarity during mitosis, in addition to their role in primary cilia in fully differentiated cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	interacts with CAMLG, a protein with an intracellular distribution that is similar to that of PKD2
	interacting with PKD1, PKD2 (PKD1 locus could potentially be important modifiers of ARPKD disease severity)
	interaction with PI3K/Akt pathway which is involved in apoptotic function in PKHD1-silenced cells, and PI3K/Akt inhibition correlates with upregulation of NFKB activity
	PKHD1 regulates RHOA levels and function
	disruption of PKHD1 function results in dysregulated trafficking of both ubiquitin E3 ligases, SMURF1 and SMURF2
	ATMIN is a modulator of PKHD1

cell & other

REGULATION

Other

regulated by TCF2 (C-terminal domain of TCF2 is required for the activation of PKHD1)

ASSOCIATED DISORDERS

corresponding disease(s)

ARPKD

related resource

Autosomal Recessive Polycystic Kidney Disease

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   caused by mutation of TCF2 produce kidney cysts constitutional       loss of function disruption of PKHD1 activity results in altered trafficking of multiple proteins

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS