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FLASH GENE
Symbol PDCD6IP contributors: mct/ - updated : 29-01-2014
HGNC name programmed cell death 6 interacting protein
HGNC id 8766
Location 3p22.3      Physical location : 33.840.065 - 33.911.194
Synonym name
  • ALG-2 interacting protein X
  • ALG-2-interacting protein 1
  • dopamine receptor interacting protein 4
  • apoptosis-linked gene 2-interacting protein X
  • Synonym symbol(s) Alix, AIP1, HP95, KIAA1375, MGC17003, DRIP4
    DNA
    TYPE functioning gene
    STRUCTURE 71.64 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC344787 3p22.3 similar to KIAA2033 protein KIAA0089 3p22.3 similar to KIAA2033 protein LOC391525 3 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) CKLFSF8 3p22.3 chemokine-like factor super family 8 CKLFSF7 3p22.3 chemokine-like factor super family 7 CKLFSF6 3p22.3 chemokine-like factor super family 6 LOC285260 3p22.3 similar to ribosomal protein L31 DNCLI1 3p22.2 dynein, cytoplasmic, light intermediate polypeptide 1 LOC391526 3 similar to Immunoglobulin-binding protein 1 (CD79a-binding protein 1) (B cell signal transduction molecule alpha 4) (Alpha 4 protein) CNOT10 3p22.3 CCR4-NOT transcription complex, subunit 10 LOC389101 3 similar to 60S ribosomal protein L23a LOC389102 3 similar to YPLR6490 LOC131405 3p22.3 similar to abnormal cell LINeage LIN-41, heterochronic gene; Drosophila dappled/ vertebrate TRipartite Motif protein related; B-box zinc finger, Filamin and NHL repeat containing protein (123.8 kD) (lin-41) CCR4 3p24 chemokine (C-C motif) receptor 4 LOC389103 3 LOC389103 GLB1 3p21.33 galactosidase, beta 1 CRTAP 3p22 cartilage associated protein KIAA0527 3p22.3 KIAA0527 protein FBXL2 3p24.3 F-box and leucine-rich repeat protein 2 UBP1 3p22.2 upstream binding protein 1 (LBP-1a) CLASP2 3p24.2-p21.33 cytoplasmic linker associated protein 2 LOC389104 3 similar to CLIP-associating protein 1; multiple asters 1 PDCD6IP 3p22.3 programmed cell death 6 interacting protein LOC285307 3p22.2 hypothetical LOC285307 FECHP 3p23-p22 ferrochelatase pseudogene LOC389105 3 LOC389105 ARPP-21 3p22.1 LOC389105
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 5957 - 868 - -
    18 - 5972 - 873 - -
    6 - 1569 - 271 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvesselsaorta   
    digestivemouthgingiva   
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunespleen   lowly
    Nervousbrain   moderately
    Respiratorydiaphragm     Homo sapiensAdult
     respiratory tracttrachea  highly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Muscularstriatumcardiac   Homo sapiensAdult
    Muscularstriatum    Homo sapiensAdult
    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, with Phe105 loop playing a key role in HIV-1 release, interacting 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-AA 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
  • a middle region called the V-domain and containing a coiled-coil motif , binding directly and selectively to K63-linked polyUb chains (
  • 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
    homolog to yeast Bro1
    Homologene
    FAMILY SOCS (suppressor of cytokine signaling) family of proteins
    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
  • in myotubes, a specific pool of PDCD6IP colocalizes with NEURL2
  • 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 ALIX protein functions within the ESCRT pathway to facilitate intralumenal endosomal vesicle formation, the abscission stage of cytokinesis, and enveloped virus budding
  • multifunctional adaptor protein that participates in basic cellular processes, including membrane trafficking and actin cytoskeleton assembly
  • negatively modulates muscle cell migration and adhesion to substrate
  • 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
  • key role for syndecan-syntenin-PDCD6IP in membrane transport and signalling processes
  • 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)
  • associate with F-actin in epithelial cells and fibroblasts, where it participates in the organization of actin fibers
  • 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
  • directly interacts with alpha-actinin and promotes its association with F-actin in fibroblast
  • PDCD6IP is a bona fide interacting partner of NEURL2 and interaction between the two native proteins occurs in the differentiated muscle fibers
  • SDCBP interacts directly with PDCD6IP through LYPX(n)L motifs, similarly to retroviral proteins
  • important role for K63 polyUb binding by PDCD6 in retroviral release
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS