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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

Corresponding disease	ARPKD polycystic kidney disease, infantile type with hepatic fibrosis 1
Location	6p12.3      Physical location : 51.480.144 - 51.952.423
Synonym name	polyductin
	tigmin
	TIG multiple domains 1
	fibrocystin
Synonym symbol(s)	FCYT, TIGM1, FPC, FLJ46150, DKFZp686C01112, ARPKD, PKD4

DNA

TYPE	functioning gene
STRUCTURE	472.30 kb     67 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed variant 3 71 polyA site 14000 isoform 3 - 3858 - 2002 11898128 also called polyductin M NM_170724 61 splicing 11604 NP_733842 371 3396 - 2010 20554582 tigmin NM_138694 67 splicing 16235 NP_619639 447 4074 adult kidney, liver, and pancreas 2010 20554582 fibrocystin (polyductin S) a single transmembrane domain and an intracellular C-terminus involvement in cilia function cytoplasmic C-terminal region with 192 AAs receptor-like protein in addition, cleavage and release of its ectodomain into the renal tubular/duct lumen

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly   gallbladder       lowly Homo sapiens   mouth tongue       Endocrine pancreas       moderately Reproductive male system testis       Urinary kidney tubule collecting duct   predominantly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Digestive epithelial cell Homo sapiens Urinary duct cell Homo sapiens Urinary tubular cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text

kidney

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