PDCD6IP

Programmed cell death 6-interacting protein also known as ALIX is a protein that in humans is encoded by the PDCD6IP gene.[5][6]

PDCD6IP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2OEV, 2OEW, 2OEX, 2OJQ, 2R02, 2R03, 2R05, 2XS1, 2XS8, 2ZNE, 3C3O, 3C3Q, 3C3R, 3E1R, 3WUV, 4JJY
Identifiers
Aliases	PDCD6IP, AIP1, ALIX, DRIP4, HP95, programmed cell death 6 interacting protein
External IDs	OMIM: 608074 MGI: 1333753 HomoloGene: 22614 GeneCards: PDCD6IP
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p22.3 Start 33,798,571 bp[1] End 33,869,707 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 F3 Start 113,651,744 bp[2] End 113,708,259 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein homodimerization activity • GO:0001948 protein binding • protein dimerization activity • proteinase activated receptor binding • calcium-dependent protein binding Cellular component • immunological synapse • focal adhesion • microtubule organizing center • extracellular vesicle • endoplasmic reticulum exit site • extracellular region • myelin • cytoskeleton • melanosome • membrane • extracellular exosome • cytoplasm • cytosol • actomyosin • bicellular tight junction • cell junction • Flemming body Biological process • cell cycle • mitotic metaphase plate congression • protein transport • positive regulation of exosomal secretion • GO:0019067 viral life cycle • regulation of mitotic spindle assembly • ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway • positive regulation of extracellular exosome assembly • cell separation after cytokinesis • regulation of centrosome duplication • nucleus organization • multivesicular body assembly • regulation of extracellular exosome assembly • apoptotic process • cell division • viral budding via host ESCRT complex • GO:0022415 viral process • actomyosin contractile ring assembly • maintenance of epithelial cell apical/basal polarity • bicellular tight junction assembly • regulation of membrane permeability • mitotic cytokinesis • viral budding • protein homooligomerization • transport • midbody abscission Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10015	18571
Ensembl	ENSG00000170248	ENSMUSG00000032504
UniProt	Q8WUM4	Q9WU78
RefSeq (mRNA)	NM_001162429 NM_001256192 NM_013374	NM_001164677 NM_001164678 NM_011052
RefSeq (protein)	NP_001155901 NP_001243121 NP_037506	NP_001158149 NP_001158150 NP_035182
Location (UCSC)	Chr 3: 33.8 – 33.87 Mb	Chr 9: 113.65 – 113.71 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

This gene encodes a protein thought to participate in programmed cell death. 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.[6]

Function

PDCD6IP protein is part of ESCRT pathway. It participates in the membrane scission of the revers topology budding and participates in multivesicular body formation.[7] It is also vital at the later stages and for successful completion of cytokinesis.[8]

Interactions

PDCD6IP has been shown to interact with PDCD6.[5][9] The V domain of PDCD6IP recognises Short linear motif LYPxLxxL and this motif is mimicked by p6 late domain of HIV and related viruses which facilitates viral hijacking of ESCRT pathway and consequential budding of viral particles.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000170248 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032504 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Vito P, Pellegrini L, Guiet C, D'Adamio L (Feb 1999). "Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction". J Biol Chem. 274 (3): 1533–40. doi:10.1074/jbc.274.3.1533. PMID 9880530.
6. "Entrez Gene: PDCD6IP programmed cell death 6 interacting protein".
7. Vietri, Marina; Radulovic, Maja; Stenmark, Harald (January 2020). "The many functions of ESCRTs". Nature Reviews Molecular Cell Biology. 21 (1): 25–42. doi:10.1038/s41580-019-0177-4. PMID 31705132. S2CID 207939465.
8. Carlton, Jez G.; Martin-Serrano, Juan (29 June 2007). "Parallels Between Cytokinesis and Retroviral Budding: A Role for the ESCRT Machinery". Science. 316 (5833): 1908–1912. Bibcode:2007Sci...316.1908C. doi:10.1126/science.1143422. PMID 17556548. S2CID 29191843.
9. Satoh, Hirokazu; Shibata Hideki; Nakano Yoshimi; Kitaura Yasuyuki; Maki Masatoshi (Mar 2002). "ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner". Biochem. Biophys. Res. Commun. United States. 291 (5): 1166–72. doi:10.1006/bbrc.2002.6600. ISSN 0006-291X. PMID 11883939.
10. Votteler, Jörg; Sundquist, Wesley I. (September 2013). "Virus Budding and the ESCRT Pathway". Cell Host & Microbe. 14 (3): 232–241. doi:10.1016/j.chom.2013.08.012. PMC 3819203. PMID 24034610.

Further reading

• Wood JD, Yuan J, Margolis RL, et al. (1998). "Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins". Mol. Cell. Neurosci. 11 (3): 149–60. doi:10.1006/mcne.1998.0677. PMID 9647693. S2CID 20003277.
• Missotten M, Nichols A, Rieger K, Sadoul R (1999). "Alix, a novel mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene 2 (ALG-2) protein". Cell Death Differ. 6 (2): 124–9. doi:10.1038/sj.cdd.4400456. PMID 10200558.
• Nagase T, Kikuno R, Ishikawa KI, et al. (2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
• Wu Y, Pan S, Che S, et al. (2002). "Overexpression of Hp95 induces G1 phase arrest in confluent HeLa cells". Differentiation. 67 (4–5): 139–53. doi:10.1046/j.1432-0436.2001.670406.x. PMID 11683497.
• Satoh H, Shibata H, Nakano Y, et al. (2002). "ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner". Biochem. Biophys. Res. Commun. 291 (5): 1166–72. doi:10.1006/bbrc.2002.6600. PMID 11883939.
• Chatellard-Causse C, Blot B, Cristina N, et al. (2002). "Alix (ALG-2-interacting protein X), a protein involved in apoptosis, binds to endophilins and induces cytoplasmic vacuolization". J. Biol. Chem. 277 (32): 29108–15. doi:10.1074/jbc.M204019200. PMID 12034747.
• Wu Y, Pan S, Luo W, et al. (2002). "Hp95 promotes anoikis and inhibits tumorigenicity of HeLa cells". Oncogene. 21 (44): 6801–8. doi:10.1038/sj.onc.1205849. PMID 12360406.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Vincent O, Rainbow L, Tilburn J, et al. (2003). "YPXL/I is a protein interaction motif recognized by aspergillus PalA and its human homologue, AIP1/Alix". Mol. Cell. Biol. 23 (5): 1647–55. doi:10.1128/MCB.23.5.1647-1655.2003. PMC 151718. PMID 12588984.
• Schmidt MH, Chen B, Randazzo LM, Bogler O (2004). "SETA/CIN85/Ruk and its binding partner AIP1 associate with diverse cytoskeletal elements, including FAKs, and modulate cell adhesion". J. Cell Sci. 116 (Pt 14): 2845–55. doi:10.1242/jcs.00522. PMID 12771190.
• Katoh K, Shibata H, Suzuki H, et al. (2003). "The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting". J. Biol. Chem. 278 (40): 39104–13. doi:10.1074/jbc.M301604200. PMID 12860994.
• Leonard D, Ajuh P, Lamond AI, Legerski RJ (2003). "hLodestar/HuF2 interacts with CDC5L and is involved in pre-mRNA splicing". Biochem. Biophys. Res. Commun. 308 (4): 793–801. doi:10.1016/S0006-291X(03)01486-4. PMID 12927788.
• Strack B, Calistri A, Craig S, et al. (2003). "AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding". Cell. 114 (6): 689–99. doi:10.1016/S0092-8674(03)00653-6. PMID 14505569. S2CID 10733770.
• von Schwedler UK, Stuchell M, Müller B, et al. (2003). "The protein network of HIV budding". Cell. 114 (6): 701–13. doi:10.1016/S0092-8674(03)00714-1. PMID 14505570. S2CID 16894972.
• Martin-Serrano J, Yarovoy A, Perez-Caballero D, et al. (2003). "Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins". Proc. Natl. Acad. Sci. U.S.A. 100 (21): 12414–9. Bibcode:2003PNAS..10012414M. doi:10.1073/pnas.2133846100. PMC 218772. PMID 14519844.
• Peck JW, Bowden ET, Burbelo PD (2004). "Structure and function of human Vps20 and Snf7 proteins". Biochem. J. 377 (Pt 3): 693–700. doi:10.1042/BJ20031347. PMC 1223912. PMID 14583093.
• Katoh K, Shibata H, Hatta K, Maki M (2004). "CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms". Arch. Biochem. Biophys. 421 (1): 159–65. doi:10.1016/j.abb.2003.09.038. PMID 14678797.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Matsuo H, Chevallier J, Mayran N, et al. (2004). "Role of LBPA and Alix in multivesicular liposome formation and endosome organization". Science. 303 (5657): 531–4. Bibcode:2004Sci...303..531M. doi:10.1126/science.1092425. PMID 14739459. S2CID 36353407.

External links

• PDCD6IP human gene location in the UCSC Genome Browser.
• PDCD6IP human gene details in the UCSC Genome Browser.