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PDCD6IP programmed cell death 6 interacting protein [ Homo sapiens (human) ]

Gene ID: 10015, updated on 4-Nov-2018

Summary

Official Symbol
PDCD6IPprovided by HGNC
Official Full Name
programmed cell death 6 interacting proteinprovided by HGNC
Primary source
HGNC:HGNC:8766
See related
Ensembl:ENSG00000170248 MIM:608074; Vega:OTTHUMG00000130751
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AIP1; ALIX; HP95; DRIP4
Summary
This gene encodes a protein that functions within the ESCRT pathway in the abscission stage of cytokinesis, in intralumenal endosomal vesicle formation, and in enveloped virus budding. Studies using mouse cells have shown that overexpression of this protein can block apoptosis. In addition, the product of this gene binds to the product of the PDCD6 gene, a protein required for apoptosis, in a calcium-dependent manner. This gene product also binds to endophilins, proteins that regulate membrane shape during endocytosis. Overexpression of this gene product and endophilins results in cytoplasmic vacuolization, which may be partly responsible for the protection against cell death. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. Related pseudogenes have been identified on chromosome 15. [provided by RefSeq, Jan 2012]
Expression
Ubiquitous expression in colon (RPKM 28.2), esophagus (RPKM 23.0) and 25 other tissues See more
Orthologs

Genomic context

See PDCD6IP in Genome Data Viewer
Location:
3p22.3
Exon count:
20
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 3 NC_000003.12 (33798571..33869707)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (33840063..33911199)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377023 Neighboring gene SDA1 domain containing 1 pseudogene 3 Neighboring gene uncharacterized LOC105377024 Neighboring gene long intergenic non-protein coding RNA 1811

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
NHGRI GWA Catalog
Genome-wide association study of chronic periodontitis in a general German population.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 incorporates PDCD6IP (ALIX) and TSG101 into virions, which is sensitive to mutations in YP and PTAP domains respectively PubMed
HIV-1 replication, specifically budding, requires PDCD6IP (ALIX) as shown through shRNA knockdown in HEK293T cells PubMed
Knockdown of programmed cell death 6 interacting protein (AIP1, ALIX) by siRNA inhibits HIV-1 release and infectivity PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env In the absence of Vpu, Env accumulates extensively within clathrin-coated endosomal structures, including the viral proteins Gag and MA; the tetraspanins CD63 and CD81; the adaptor protein complex AP-3; and AIP1/ALIX, a cellular cofactor for viral budding PubMed
Nef nef HIV-1 Nef-mediated CD4 degradation requires ALIX and interaction of Nef with ALIX in endosomes that contain CD4 PubMed
nef HIV-1 Nef interacts with ALIX in late endosomes, and Bro1 (residues 1-360) and V (residues 360-717) domains of ALIX are required for this interaction with Nef PubMed
nef Residues 135-138 of HIV-1 Nef bind to AIP1 in vitro and in cells; the binding between Nef and AIP1 is required for formation of multivesicular bodies (MVBs) and contributes to the egress of viral particles from infected cells PubMed
nef HIV-1 Nef increases the production of exosomes and co-localizes with exosomal proteins CD63, AIP/Alix, AChE, Hsc70, LAMP2, and annexin A2 in HeLa cells PubMed
Pr55(Gag) gag HIV-1 NC-mediated incorporation of ALIX into virions requires the zinc fingers of NC and the Bro1 domain of ALIX PubMed
gag Superresolution imaging of HIV-1 Gag and ESCRT proteins (TSG101, ALIX, CHMP4B, and CHMP4C) demonstrates in HeLa cells that Gag assemblages often has ESCRT proteins in their direct vicinity PubMed
gag Galectin-3 co-localizes with HIV-1 Gag and Alix, and facilitates the association of Gag with Alix in cells PubMed
gag Incorporation of ALIX into HIV-1 virus-like particles is dependent on the Gag late domains PubMed
gag ALIX recruitment to both HIV-1 and EIAV Gag is transient at the end of Gag polymerization and the HIV-1 and EIAV profiles are only different in terms of the retention level of ALIX within the virus-like particles PubMed
gag The Bro1 domain of Alix inhibits HIV budding by targeting both PTAP/TSG101 and LYPXnL/Alix pathways. The NC domain of Gag is the primary target for Bro1 inhibition by Gag-mediated recruitment of Bro1 to the plasma membrane PubMed
gag The S40F mutation in HIV-1 p6 enhances ALIX binding to HIV-1 Gag in the yeast two-hybrid assay. The Y36S mutation introduced into the S40F mutant disrupts ALIX interaction with Gag and restores spherical particle formation in cells PubMed
gag Fusion protein Dub-Alix, the catalytic domain of the Herpes Simplex UL36 deubiquitinating enzyme (DUb) fused onto Alix, inhibits HIV-1 release, which involves the interaction between HIV-1 Gag and Alix PubMed
gag In the absence of Vpu, Env accumulates extensively within clathrin-coated endosomal structures, including the viral proteins Gag and MA; the tetraspanins CD63 and CD81; the adaptor protein complex AP-3; and AIP1/ALIX, a cellular cofactor for viral budding PubMed
gag Alix-mediated rescue of HIV-1 PTAP(-) release requires interaction with Nedd4-1. Ubiquitinated Alix is incorporated into HIV-1 PTAP(-) rescued particles PubMed
gag Phe105 loop (residues 99-112) in the Bro1 domain of Alix is required for efficient Alix-mediated HIV-1 release. The disruption of the Phe105 loop interferes with its ability to interact with HIV-1 Gag PubMed
gag Recruitment of CHMP4B by ALIX to HIV-1 Gag puncta is observed in in-vitro membrane model PubMed
gag ALIX proteins with point mutations (Val498Asp, Phe676Asp, and Ile683Asp) that inhibit the p6 36YPLASL41 binding fail to rescue HIV-1 deltaPTAP release or infectivity PubMed
gag Overexpression of AIP1(364-716) severely disrupts Gag processing, resulting in an increase in the ratio of Gag to p25/p24 PubMed
gag A single amino acid Phe676 of Alix is at the center of a large hydrophobic pocket and is crucial for binding to HIV-1 p6 PubMed
gag Overexpression of AIP1(364-716) leads to a reduction in the cell-associated levels of HIV-1 Gag PubMed
matrix gag In the absence of Vpu, Env accumulates extensively within clathrin-coated endosomal structures, including the viral proteins Gag and MA; the tetraspanins CD63 and CD81; the adaptor protein complex AP-3; and AIP1/ALIX, a cellular cofactor for viral budding PubMed
nucleocapsid gag HIV-1 NC-mediated incorporation of ALIX into virions requires the zinc fingers of NC and the Bro1 domain of ALIX PubMed
gag The N-terminal Bro1 domain (Brox) of ALIX bind to HIV-1 NC. Unexpectedly, Brox retains significant activity even if its CHMP4 binding site is disrupted PubMed
gag Residues Q8, K11, K48, R51, R56, and K60 are part of the Bro1 domain of ALIX binding to HIV-1 NC, which involves RNA. Disruption of the Bro1-NC binding inhibits ALIX function in virus release PubMed
gag The Bro1 domain of Alix inhibits HIV budding by targeting both PTAP/TSG101 and LYPXnL/Alix pathways. The NC domain of Gag is the primary target for Bro1 inhibition by Gag-mediated recruitment of Bro1 to the plasma membrane PubMed
p6 gag Knockdown of Alix by shRNA reduces the association of HIV-1 p6 with galectin-3 in cells PubMed
gag A novel tetra-peptide insertion (PYXE), identified in Gag-p6 ALIX-binding region in protease inhibitor failure Indian HIV-1C sequences, may be predicted to restore ALIX-mediated virus release pathway PubMed
gag The S40F mutation in HIV-1 p6 enhances ALIX binding to HIV-1 Gag in the yeast two-hybrid assay. The Y36S mutation introduced into the S40F mutant disrupts ALIX interaction with Gag and restores spherical particle formation in cells PubMed
gag The phenolic hydroxyl of the tyrosine residue in the 36YPXnL domain of HIV-1 p6 is essential for ALIX-mediated HIV-1 budding. Y36F mutant blocks ALIX recruitment PubMed
gag Mutations (Y36A, Y36S/L44H, Y36S/L44R, L41A, and L41R) between p6 residues 36 and 44 inhibit the Alix-p6 interaction PubMed
gag AIP1 is incorporated into HIV-1 virions through its interaction with HIV-1 p6 PubMed
gag AIP1 binds to the LXXLF motif in HIV-1 p6 (amino acids 41-44) and along with TSG101 acts as a component of the viral budding machinery PubMed
gag Natural loss of L35Y36 residues in p6 of HIV-1 subtype C prevents p6 from ALIX interaction PubMed
gag ALIX proteins with point mutations (Val498Asp, Phe676Asp, and Ile683Asp) that inhibit the p6 36YPLASL41 binding fail to rescue HIV-1 deltaPTAP release or infectivity PubMed
gag An ALIX fragment encompassing residues 391-510 is a minimal p6deltaSQKQ binding site within the middle region of ALIX PubMed
gag The Bro1 domain of Alix inhibits HIV budding by targeting both PTAP/TSG101 and LYPXnL/Alix pathways PubMed
gag The ability of ALIX to rescue an HIV p6 PTAP mutant depends on its C-terminal proline-rich domain (PRD), but not on its binding sites for Tsg101 PubMed
gag Overexpression of the Alix V domain inhibits HIV-1 release from cells; this inhibition of release is reversed by mutations that block binding of the Alix V domain to p6 PubMed
gag Residues 360-702 of Alix spans the shape of the letter 'V' and is termed the V domain, which has a topologically complex arrangement of 11 alpha-helices; Phe676 is at the center of a large hydrophobic pocket and is crucial for binding to HIV-1 p6 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Budding and maturation of HIV virion, organism-specific biosystem (from REACTOME)
    Budding and maturation of HIV virion, organism-specific biosystemWith the virus components precariously assembled on the inner leaflet of the plasma membrane, the host cell machinery is required for viral budding. The virus takes advantage of the host ESCRT pathwa...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Endocytosis, organism-specific biosystem (from KEGG)
    Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • Endocytosis, conserved biosystem (from KEGG)
    Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • HIV Infection, organism-specific biosystem (from REACTOME)
    HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
  • HIV Life Cycle, organism-specific biosystem (from REACTOME)
    HIV Life Cycle, organism-specific biosystemThe life cycle of HIV-1 is divided into early and late phases, shown schematically in the figure. In the early phase, an HIV-1 virion binds to receptors and co-receptors on the human host cell surfac...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • Late Phase of HIV Life Cycle, organism-specific biosystem (from REACTOME)
    Late Phase of HIV Life Cycle, organism-specific biosystemThe late phase of the HIV-1 life cycle includes the regulated expression of the HIV gene products and the assembly of viral particles. The assembly of viral particles will be covered in a later relea...
  • Uptake and actions of bacterial toxins, organism-specific biosystem (from REACTOME)
    Uptake and actions of bacterial toxins, organism-specific biosystemThe toxic effects of many bacteria on their human hosts are mediated by proteins released from the bacteria that enter human cells and disrupt critical cellular functions (Henkel et al. 2010). All of...
  • Uptake and function of anthrax toxins, organism-specific biosystem (from REACTOME)
    Uptake and function of anthrax toxins, organism-specific biosystemBacillus anthracis bacteria target cells in an infected human through the action of three secreted bacterial proteins, LF, EF, and PA (reviews: Turk 2007; Young and Collier 2007). LF (lethal factor) ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC17003

Gene Ontology Provided by GOA

Function Evidence Code Pubs
calcium-dependent protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
proteinase activated receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
actomyosin contractile ring assembly ISS
Inferred from Sequence or Structural Similarity
more info
 
apoptotic process IEA
Inferred from Electronic Annotation
more info
 
bicellular tight junction assembly ISS
Inferred from Sequence or Structural Similarity
more info
 
maintenance of epithelial cell apical/basal polarity ISS
Inferred from Sequence or Structural Similarity
more info
 
midbody abscission IMP
Inferred from Mutant Phenotype
more info
PubMed 
mitotic cytokinesis IDA
Inferred from Direct Assay
more info
PubMed 
NOT mitotic metaphase plate congression IMP
Inferred from Mutant Phenotype
more info
PubMed 
multivesicular body assembly NAS
Non-traceable Author Statement
more info
PubMed 
NOT nucleus organization IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of exosomal secretion IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of extracellular exosome assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein homooligomerization IDA
Inferred from Direct Assay
more info
PubMed 
protein transport IEA
Inferred from Electronic Annotation
more info
 
regulation of centrosome duplication IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of extracellular exosome assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of membrane permeability ISS
Inferred from Sequence or Structural Similarity
more info
 
NOT regulation of mitotic spindle assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
viral budding IDA
Inferred from Direct Assay
more info
PubMed 
viral budding via host ESCRT complex IGI
Inferred from Genetic Interaction
more info
PubMed 
viral budding via host ESCRT complex NAS
Non-traceable Author Statement
more info
PubMed 
viral life cycle TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
Flemming body IDA
Inferred from Direct Assay
more info
PubMed 
actomyosin ISS
Inferred from Sequence or Structural Similarity
more info
 
bicellular tight junction IEA
Inferred from Electronic Annotation
more info
 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
endoplasmic reticulum exit site IMP
Inferred from Mutant Phenotype
more info
PubMed 
extracellular exosome HDA PubMed 
extracellular exosome IDA
Inferred from Direct Assay
more info
PubMed 
extracellular vesicle HDA PubMed 
focal adhesion HDA PubMed 
immunological synapse IDA
Inferred from Direct Assay
more info
PubMed 
melanosome IEA
Inferred from Electronic Annotation
more info
 
membrane HDA PubMed 
microtubule organizing center IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
programmed cell death 6-interacting protein
Names
ALG-2 interacting protein 1
ALG-2-interacting protein X
PDCD6-interacting protein
apoptosis-linked gene 2-interacting protein X
dopamine receptor interacting protein 4

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_033961.1 RefSeqGene

    Range
    5001..76137
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001162429.2NP_001155901.1  programmed cell death 6-interacting protein isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2).
    Source sequence(s)
    AB037796, AL695629, BC068454, BI492166, CR739098, DA149360, DA652213
    Consensus CDS
    CCDS54561.1
    UniProtKB/Swiss-Prot
    Q8WUM4
    Related
    ENSP00000411825.2, ENST00000457054.6
    Conserved Domains (4) summary
    cd09235
    Location:365703
    V_Alix; Middle V-domain of mammalian Alix and related domains are dimerization and protein interaction modules
    cd09240
    Location:2350
    BRO1_Alix; Protein-interacting, N-terminal, Bro1-like domain of mammalian Alix and related domains
    pfam12273
    Location:820873
    RCR; Chitin synthesis regulation, resistance to Congo red
    pfam13949
    Location:417706
    ALIX_LYPXL_bnd; ALIX V-shaped domain binding to HIV
  2. NM_001256192.1NP_001243121.1  programmed cell death 6-interacting protein isoform 3

    See identical proteins and their annotated locations for NP_001243121.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks several 3' exons but contains an alternate 3' exon, and it thus differs in the 3' coding region and 3' UTR, compared to variant 2. The encoded isoform (3) has a distinct and significantly shorter C-terminus, compared to isoform 2.
    Source sequence(s)
    AI346371, DA652213, GQ131806
    UniProtKB/Swiss-Prot
    Q8WUM4
    Conserved Domains (1) summary
    cl14649
    Location:2239
    BRO1_Alix_like; Protein-interacting Bro1-like domain of mammalian Alix and related domains
  3. NM_013374.5NP_037506.2  programmed cell death 6-interacting protein isoform 1

    See identical proteins and their annotated locations for NP_037506.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) uses an alternate in-frame splice site in the central coding region, compared to variant 2, resulting in an isoform (1) that is shorter than isoform 2.
    Source sequence(s)
    AB037796, AF349951, AL695629, BC020066, BI492166, CR739098, DA149360, DA652213
    Consensus CDS
    CCDS2660.1
    UniProtKB/Swiss-Prot
    Q8WUM4
    Related
    ENSP00000307387.3, OTTHUMP00000161316, ENST00000307296.7, OTTHUMT00000253251
    Conserved Domains (4) summary
    cd09235
    Location:360698
    V_Alix; Middle V-domain of mammalian Alix and related domains are dimerization and protein interaction modules
    cd09240
    Location:2345
    BRO1_Alix; Protein-interacting, N-terminal, Bro1-like domain of mammalian Alix and related domains
    cl25716
    Location:814868
    Amelogenin; Amelogenin
    cl26464
    Location:712866
    Atrophin-1; Atrophin-1 family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p12 Primary Assembly

    Range
    33798571..33869707
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011533252.1XP_011531554.1  programmed cell death 6-interacting protein isoform X1

    See identical proteins and their annotated locations for XP_011531554.1

    Conserved Domains (4) summary
    cd09235
    Location:175513
    V_Alix; Middle V-domain of mammalian Alix and related domains are dimerization and protein interaction modules
    pfam13949
    Location:227516
    ALIX_LYPXL_bnd; ALIX V-shaped domain binding to HIV
    cl14649
    Location:1160
    BRO1_Alix_like; Protein-interacting Bro1-like domain of mammalian Alix and related domains
    cl23782
    Location:630683
    RCR; Chitin synthesis regulation, resistance to Congo red
  2. XM_011533253.1XP_011531555.1  programmed cell death 6-interacting protein isoform X1

    See identical proteins and their annotated locations for XP_011531555.1

    Conserved Domains (4) summary
    cd09235
    Location:175513
    V_Alix; Middle V-domain of mammalian Alix and related domains are dimerization and protein interaction modules
    pfam13949
    Location:227516
    ALIX_LYPXL_bnd; ALIX V-shaped domain binding to HIV
    cl14649
    Location:1160
    BRO1_Alix_like; Protein-interacting Bro1-like domain of mammalian Alix and related domains
    cl23782
    Location:630683
    RCR; Chitin synthesis regulation, resistance to Congo red
  3. XM_017005488.1XP_016860977.1  programmed cell death 6-interacting protein isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NR_027867.1: Suppressed sequence

    Description
    NR_027867.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript, which appears to be incompletely processed at its 5'' end.
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