WIPI1 (17q24.2) , ATG18, ATG18A, WPI49 tarjoaa beeta-propellialustaa proteiini-interaktioille.

https://www.ncbi.nlm.nih.gov/gene/55062

Official Symbol

WIPI1provided by HGNC

Official Full Name

WD repeat domain, phosphoinositide interacting 1provided by HGNC

Also known as

ATG18; ATG18A; WIPI49

Summary

This gene encodes a WD40 repeat protein. Members of the WD40 repeat family are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

Expression Ubiquitous expression in placenta (RPKM 11.9), heart (RPKM 11.3) and 25 other tissues See moreOrthologs mouse all

 

Preferred Names

WD repeat domain phosphoinositide-interacting protein 1

Names

WIPI-1 alpha

atg18 protein homolog

 

           ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..364
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q24.2"
     Protein         1..364
                     /product="WD repeat domain phosphoinositide-interacting
                     protein 1 isoform b"
                     /note="WD repeat domain phosphoinositide-interacting
                     protein 1; WIPI-1 alpha; atg18 protein homolog"
                     /calculated_mol_wt=39811
     Region          <6 ..180="" class="feature" feature_np_001307701.1_region_0="" note="WD40 domain,</span><span id=" region_name="WD40"> found in a number of eukaryotic proteins that cover a
 wide variety of functions including adaptor/regulatory modules in 
signal transduction, pre-mRNA processing and cytoskeleton assembly; 
typically contains a GH dipeptide 11-24 residues from its N-terminus and
 the WD dipeptide at its C-terminus and is 40 residues long, hence the 
name WD40; between GH and WD lies a conserved core; serves as a stable 
propeller-like platform to which proteins can bind either stably or 
reversibly; forms a propeller-like structure with several blades where 
each blade is composed of a four-stranded anti-parallel b-sheet; 
instances with few detectable copies are hypothesized to form larger 
structures by dimerization; each WD40 sequence repeat forms the first 
three strands of one blade and the last strand in the next blade; the 
last C-terminal WD40 repeat completes the blade structure of the first 
WD40 repeat to create the closed ring propeller-structure; residues on 
the top and bottom surface of the propeller are proposed to coordinate 
interactions with other proteins and/or small ligands; 7 copies of the 
repeat are present in this alignment.; cl25539"
                     /db_xref="CDD:330360"

      Region          63..102
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Region          107..144
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Region          154..186
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Region          192..230
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     Region          238..276
                     /region_name="WD40 repeat"
                     /note="WD40 repeat [structural motif]"
                     /db_xref="CDD:293791"
     CDS             1..364
                     /gene="WIPI1"
                     /gene_synonym="ATG18; ATG18A; WIPI49"
                     /coded_by="NM_001320772.1:267..1361"
                     /note="isoform b is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS82193.1"
                     /db_xref="GeneID:55062"
                     /db_xref="HGNC:HGNC:25471"
                     /db_xref="MIM:609224"
ORIGIN      
        1 mnvyhfkkgt eicnysyssn ilsirlnrqr llvcleesiy ihnikdmkll ktlldipanp
       61 tglcalsinh snsylaypgs ltsgeivlyd gnslktvcti aahegtlaai tfnasgskla
      121 sasekgtvir vfsvpdgqkl yefrrgmkry vtisslvfsm dsqflcassn tetvhifkle
      181 qvtnsrpeep stwsgymgkm fmaatnylpt qvsdmmhqdr afatarlnfs gqrnictlst
      241 iqklprllva sssghlymyn ldpqdggecv likthsllgs gtteenkend lrpslpqsya
      301 atvarpsass astvpgysed ggalrgevip ehefatgpvc lddenefppi ilcrgnqkgk
      361 tkqs
//

Conserved Domains (2) summary

sd00039
Location:63 → 102

7WD40; WD40 repeat [structural motif]

cl25539
Location:6 → 180

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from .

Related articles in PubMed

1. Detection of WIPI1 mRNA as an indicator of autophagosome formation. Tsuyuki S, et al. Autophagy, 2014 Mar. PMID 24384561, Free PMC Article
2. Fluorescence-based imaging of autophagy progression by human WIPI protein detection. Thost AK, et al. Methods, 2015 Mar. PMID 25462558
3. WIPI β-propellers at the crossroads of autophagosome and lipid droplet dynamics. Pfisterer SG, et al. Biochem Soc Trans, 2014 Oct. PMID 25233424
4. WIPI-dependent autophagy during neutrophil differentiation of NB4 acute promyelocytic leukemia cells. Brigger D, et al. Cell Death Dis, 2014 Jul 3. PMID 24991767, Free PMC ArticleAbstract
   Members of the WD-repeat protein interacting with phosphoinositides (WIPI) family are phosphatidylinositol 3-phosphate (PI3P) effectors that are essential for the formation of autophagosomes. Autophagosomes, unique double-membraned organelles, are characteristic for autophagy, a bulk degradation mechanism with cytoprotective and homeostatic function. Both, WIPI-1 and WIPI-2 are aberrantly expressed in several solid tumors, linking these genes to carcinogenesis. We now found that the expression of WIPI-1 was significantly reduced in a large cohort of 98 primary acute myeloid leukemia (AML) patient samples (complex karyotypes; t(8;21); t(15,17); inv(16)). In contrast, the expression of WIPI-2 was only reduced in acute promyelocytic leukemia (APL), a distinct subtype of AML (t(15,17)). As AML cells are blocked in their differentiation, we tested if the expression levels of WIPI-1 and WIPI-2 increase during all-trans retinoic acid (ATRA)-induced neutrophil differentiation of APL. According to the higher WIPI-1 expression in granulocytes compared with immature blast cells, WIPI-1 but not WIPI-2 expression was significantly induced during neutrophil differentiation of NB4 APL cells. Interestingly, the induction of WIPI-1 expression was dependent on the transcription factor PU.1, a master regulator of myelopoiesis, supporting our notion that WIPI-1 expression is reduced in AML patients lacking proper PU-1 activity. Further, knocking down WIPI-1 in NB4 cells markedly attenuated the autophagic flux and significantly reduced neutrophil differentiation. This result was also achieved by knocking down WIPI-2, suggesting that both WIPI-1 and WIPI-2 are functionally required and not redundant in mediating the PI3P signal at the onset of autophagy in NB4 cells. In line with these data, downregulation of PI3KC3 (hVPS34), which generates PI3P upstream of WIPIs, also inhibited neutrophil differentiation. In conclusion, we demonstrate that both WIPI-1 and WIPI-2 are required for the PI3P-dependent autophagic activity during neutrophil differentiation, and that PU.1-dependent WIPI-1 expression is significantly repressed in primary AML patient samples and that the induction of autophagic flux is associated with neutrophil differentiation of APL cells.
5. Freeze-fracture replica immunolabelling reveals human WIPI-1 and WIPI-2 as membrane proteins of autophagosomes. Proikas-Cezanne T, et al. J Cell Mol Med, 2011 Sep. PMID 21564513, Free PMC Article

See all (22) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. BAG1, CHMP2B, PEX3, and WIPI1 confirmed a strong differential gene expression, in 355 melanoma samples.
2. The specific autophagosomal localization of both WIPI1 and WIPI2 (refered to as WIPI puncta) has been employed to assess autophagy using fluorescence microscopy methods, such as confocal and live-cell video microscopy
3. Data suggest WIPI1/WIPI2 co-localize with microtubule-associated light chain 3 and autophagy related proteins 2/14L, participate in biogenesis of phagosomes, autophagy, and mobilization of lipids to/from intracellular droplets. [review-like article]
4. WIPI-1 and WIPI-2 are functionally required in mediating the PI3P signal at the onset of autophagy in NB4 cells.
5. the detection of WIPI1 mRNA is likely to be a convenient method of monitoring autophagosome formation in a wide range of cell types
6. Freeze-fracture replica immunolabelling reveals WD-repeat protein interacting with phosphoinositides 1 and 2 (WIPI-1 and WIPI-2) as membrane components of autophagosomes and the plasma membrane (PM).The notion that autophagosomal membranes are profoundly enriched in phosphatidylinositol 3‐phosphate (PtdIns(3)P) [8] is of key interest because autophagy is positively regulated by the activation of the phosphatidylinositol 3‐kinase class III complex 1, also including the tumour suppressor protein Beclin 1, that generates PtdIns(3)P [9]. Previously, we identified the human WIPI gene family that is aberrantly expressed in a variety of human cancer types [10]. We found that the WIPI protein family represents an ancient PtdIns(3)P/PtdIns(3,5)P₂‐binding β‐propeller protein family that includes WIPI‐1 and WIPI‐2 [10], both of which evolved from the yeast ancestral autophagy protein Atg18 [10, 11]. We characterized WIPI‐1 as a PtdIns(3)P‐effector protein functioning in the process of autophagy in human cancer cells [10, 12, 13]. Upon the induction of autophagy and the generation of PtdIns(3)P, both WIPI‐1 and WIPI‐2 specifically bind PtdIns(3)P and localize at initial autophagosomal membranes (phagophore) that are positive for further autophagy proteins, such as microtubule‐associated protein 1 light chain 3 (LC3) and Atg16 [10-14]. To clarify the precise localization of WIPI‐1 and WIPI‐2 upon the induction of autophagy we conducted freeze‐fracture immuno‐electron microscopy (immuno‐EM) because this method allows the employment of native, unfixed cells and, depending on the fracture, either of the two monolayers of a bilayer membrane is preserved [15].
   
7. Studies define a distinct role for WIPI1 and TORC1 signaling in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy.
8. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
9. Quantification of WIPI-1 puncta should be suitable to assay mammalian autophagy
10. share an evolutionary conserved function in autophagy and that autophagic capacity may be compromised in human cancers

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