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FLASH GENE

Symbol

PDCD6IP

contributors: mct/ - updated : 21-09-2010

HGNC name	programmed cell death 6 interacting protein
HGNC id	8766

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_013374 18 - 5957 NP_037506 - 868 - - NM_001162429 - - 5972 NP_001155901 - 873 - -

EXPRESSION

Type	ubiquitous

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 Cardiovascular vessels aorta       Digestive liver         digestive mouth gingiva       Hearing/Equilibrium ear inner cochlea   highly Lymphoid/Immune spleen       lowly Nervous brain       moderately Respiratory respiratory tract trachea     highly Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text	placenta, lowly in fetal brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal BRO1 domain interacts with CHMP4 proteins that function in multivesicular endosome biogenesis, and N-terminal PRR (proline-rich region) that is unfolded, at least before HCK-SH3 recognition
	12-amino acid PXY repeat of the C-terminal proline-rich domain necessary for binding PDCD6, which are homology domain-3 (SH3)-binding domains
	a tyrosine autophosphorylation consensus sequence
	several additional conserved tyrosines
	pro-rich regions that are bound by PDCD6 Ca2+-dependently
	C-terminal half blocked apoptosis depending on its capacity to bind PDCD6

HOMOLOGY

interspecies

homolog to murine Pdcd6ip

Homologene

FAMILY

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
text	concentrated in phagosomes and exosomes
	concentrate at centrosomes and are then recruited to the midbodies of dividing cells

basic FUNCTION	participating in programmed cell death
	can block apoptosis
	regulator of the endo-lysosomal system
	plays important roles in targeting the pathway to function in retrovirus budding by binding directly to viral Gag proteins, and may play widespread roles in the release of highly divergent enveloped viruses
	function at the endosome to help sort membrane proteins into vesicles that bud into the lumen to create multivesicular bodies
	cytosolic protein which interacts with proteins involved in deforming membranes during various processes including endocytosis, endosomal sorting, virus budding and cytokinesis
	can serve as an adaptor that recruits CHMP4/ESCRT-III complexes to function at distinct biological membranes
	modulator of caspase-dependent and caspase-independent cell death, including neuronal cell death, that is also part of the endosomal transport system
	involved in cell death through mechanisms which remain unclear but require its binding partner PDCD6
	critical component of caspase 9 activation and apoptosis triggered by calcium

CELLULAR PROCESS	cell life, antiapoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

	glycosylation with ALG2, are new actors of the TNFRSF1A pathway
	ESCRT-III (CHMP) proteins pathhway

a component	PDCD6IP/PDCD6 complex as a regulator of cell death controlling both caspase-dependent and -independent pathways
	functions as a subunit of the heterotetrameric ESCRT-I complex (endosomal sorting complex required for transport-I), together with two other MVB (multivesicular body) pathway proteins: VPS28, VPS37B
	forms a complex with the TNFRSF1A depending on its capacity to bind ESCRT proteins

INTERACTION

DNA

RNA

small molecule

protein	binds to endophilins and induces cytoplasmic vacuolization
	regulates cell death in a way involving interactions with the calcium-binding protein PDCD6 and with proteins of ESCRT (endosomal sorting complex required for transport)
	binds to HIV-1 p6 and is incorporated in HIV-1 virions
	target protein for PDCD6, participating in multiple functions, including apoptosis, endocytic membrane trafficking, and cytoskeletal remodeling
	interacts with a series of different proteins, including CEP55, CD2AP, with three other proteins involved in cytokinesis, ROCK1, and IQGAP, and viral late domains of the YPXL class
	interacting with TSG101 and PDCD6 (Ca2+-loaded PDCD6 bridges PDCD6IP and TSG101 as an adaptor protein)
	HCK (haemopoietic cell kinase) SH3 domain interactor(
	crucial mediator of Ca(2+) induced caspase 9 activation
	PDCD6 and PDCD6IP cooperate in transducing Ca2+-regulated signals during cell death
	is a novel HCK (haemopoietic cell kinase) SH3 domain interactor

cell & other

REGULATION

ASSOCIATED DISORDERS

ANIMAL & CELL MODELS