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Protein

WD repeat domain phosphoinositide-interacting protein 1

Gene

WIPI1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an important role in autophagy and in particular starvation- and calcium-mediated autophagy, as well as in mitophagy. Functions upstream of the ATG12-ATG5-ATG16L1 complex and LC3, and downstream of the ULK1 and PI3-kinase complexes. Involved in xenophagy of Staphylococcus aureus. Invading S.aureus cells become entrapped in autophagosome-like WIPI1 positive vesicles targeted for lysosomal degradation. Plays also a distinct role in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy. May also regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway.8 Publications

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • estrogen receptor binding Source: UniProtKB
  • phosphatidylinositol-3,5-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol-3-phosphate binding Source: UniProtKB
  • receptor binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Autophagy

Enzyme and pathway databases

ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-381038. XBP1(S) activates chaperone genes.
SignaLinkiQ5MNZ9.
SIGNORiQ5MNZ9.

Names & Taxonomyi

Protein namesi
Recommended name:
WD repeat domain phosphoinositide-interacting protein 1
Short name:
WIPI-1
Alternative name(s):
Atg18 protein homolog
WD40 repeat protein interacting with phosphoinositides of 49 kDa
Short name:
WIPI 49 kDa
Gene namesi
Name:WIPI1
Synonyms:WIPI49
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:25471. WIPI1.

Subcellular locationi

GO - Cellular componenti

  • autophagosome membrane Source: UniProtKB
  • clathrin-coated vesicle Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
  • cytosol Source: GO_Central
  • endosome membrane Source: UniProtKB
  • extrinsic component of membrane Source: GO_Central
  • Golgi membrane Source: Reactome
  • pre-autophagosomal structure Source: MGI
  • pre-autophagosomal structure membrane Source: UniProtKB
  • trans-Golgi network Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi203S → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi205S → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi208G → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi209T → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi212R → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi226 – 227RR → AA: Loss of binding to phosphoinositides, does not disrupt the MPR pathway. 1 Publication2
Mutagenesisi226R → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi227R → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi228G → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi251S → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi255T → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1
Mutagenesisi257H → A: Loss of binding to phosphoinositides and abolishes puncta formation. 1 Publication1

Organism-specific databases

DisGeNETi55062.
OpenTargetsiENSG00000070540.
PharmGKBiPA142670575.

Polymorphism and mutation databases

BioMutaiWIPI1.
DMDMi146291100.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000514371 – 446WD repeat domain phosphoinositide-interacting protein 1Add BLAST446

Proteomic databases

MaxQBiQ5MNZ9.
PaxDbiQ5MNZ9.
PeptideAtlasiQ5MNZ9.
PRIDEiQ5MNZ9.

PTM databases

iPTMnetiQ5MNZ9.
PhosphoSitePlusiQ5MNZ9.

Expressioni

Tissue specificityi

Ubiquitously expressed. Highly expressed in skeletal muscle, heart, testis, pancreas and placenta. Highly expressed in G361, Sk-mel-28, Sk-mel-13, WM852 and WM451 cells. Up-regulated in a variety of tumor tissues.1 Publication

Gene expression databases

BgeeiENSG00000070540.
CleanExiHS_WIPI1.
ExpressionAtlasiQ5MNZ9. baseline and differential.
GenevisibleiQ5MNZ9. HS.

Organism-specific databases

HPAiCAB037230.
HPA007493.

Interactioni

Subunit structurei

Interacts with androgen receptor (AR) and the estrogen receptors ESR1 and ESR2. Binds PtdIns3P and to a lesser extent, PtdIns3,5P2 and PtdIns5P in vitro. Interaction with PtdIns3P is required for recruitment to membranes.1 Publication

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • estrogen receptor binding Source: UniProtKB
  • receptor binding Source: MGI

Protein-protein interaction databases

BioGridi120380. 12 interactors.
IntActiQ5MNZ9. 7 interactors.
MINTiMINT-1392030.
STRINGi9606.ENSP00000262139.

Structurei

3D structure databases

ProteinModelPortaliQ5MNZ9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati3 – 42WD 1Add BLAST40
Repeati47 – 88WD 2Add BLAST42
Repeati92 – 126WD 3Add BLAST35
Repeati131 – 173WD 4Add BLAST43
Repeati177 – 216WD 5Add BLAST40
Repeati222 – 261WD 6Add BLAST40
Repeati304 – 343WD 7Add BLAST40

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi131 – 136Nuclear receptor interaction6

Domaini

The N-terminus might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P).1 Publication

Sequence similaritiesi

Belongs to the WD repeat SVP1 family.Curated
Contains 7 WD repeats.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG2110. Eukaryota.
ENOG410XP6Y. LUCA.
GeneTreeiENSGT00730000110845.
HOGENOMiHOG000217544.
HOVERGENiHBG056639.
InParanoidiQ5MNZ9.
KOiK17908.
OMAiSTWTGYM.
OrthoDBiEOG091G08ZS.
PhylomeDBiQ5MNZ9.
TreeFamiTF314879.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
IPR032909. WIPI1.
[Graphical view]
PANTHERiPTHR11227:SF23. PTHR11227:SF23. 2 hits.
SMARTiSM00320. WD40. 2 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5MNZ9-1) [UniParc]FASTAAdd to basket
Also known as: WIPI-1 alpha

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEAEAADAPP GGVESALSCF SFNQDCTSLA TGTKAGYKLF SLSSVEQLDQ
60 70 80 90 100
VHGSNEIPDV YIVERLFSSS LVVVVSHTKP RQMNVYHFKK GTEICNYSYS
110 120 130 140 150
SNILSIRLNR QRLLVCLEES IYIHNIKDMK LLKTLLDIPA NPTGLCALSI
160 170 180 190 200
NHSNSYLAYP GSLTSGEIVL YDGNSLKTVC TIAAHEGTLA AITFNASGSK
210 220 230 240 250
LASASEKGTV IRVFSVPDGQ KLYEFRRGMK RYVTISSLVF SMDSQFLCAS
260 270 280 290 300
SNTETVHIFK LEQVTNSRPE EPSTWSGYMG KMFMAATNYL PTQVSDMMHQ
310 320 330 340 350
DRAFATARLN FSGQRNICTL STIQKLPRLL VASSSGHLYM YNLDPQDGGE
360 370 380 390 400
CVLIKTHSLL GSGTTEENKE NDLRPSLPQS YAATVARPSA SSASTVPGYS
410 420 430 440
EDGGALRGEV IPEHEFATGP VCLDDENEFP PIILCRGNQK GKTKQS
Length:446
Mass (Da):48,673
Last modified:May 1, 2007 - v3
Checksum:i35B5650990B62E31
GO
Isoform 2 (identifier: Q5MNZ9-2) [UniParc]FASTAAdd to basket
Also known as: WIPI-1 beta

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MEAEAA → M

Show »
Length:441
Mass (Da):48,202
Checksum:i969C220C162DC7F6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti63V → A in AAV80760 (PubMed:15602573).Curated1
Sequence conflicti249A → AA in AAV80760 (PubMed:15602573).Curated1
Sequence conflicti358S → R in BAA91423 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02484831T → I.2 PublicationsCorresponds to variant rs883541dbSNPEnsembl.1
Natural variantiVAR_053439308R → H.Corresponds to variant rs36084378dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0169661 – 6MEAEAA → M in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY691424 mRNA. Translation: AAV80760.1.
AK000917 mRNA. Translation: BAA91423.1.
AC007780 Genomic DNA. No translation available.
BC039867 mRNA. Translation: AAH39867.1.
CCDSiCCDS11677.1. [Q5MNZ9-1]
RefSeqiNP_001307701.1. NM_001320772.1.
NP_060453.3. NM_017983.6. [Q5MNZ9-1]
UniGeneiHs.463964.

Genome annotation databases

EnsembliENST00000262139; ENSP00000262139; ENSG00000070540. [Q5MNZ9-1]
GeneIDi55062.
KEGGihsa:55062.
UCSCiuc010dey.4. human. [Q5MNZ9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY691424 mRNA. Translation: AAV80760.1.
AK000917 mRNA. Translation: BAA91423.1.
AC007780 Genomic DNA. No translation available.
BC039867 mRNA. Translation: AAH39867.1.
CCDSiCCDS11677.1. [Q5MNZ9-1]
RefSeqiNP_001307701.1. NM_001320772.1.
NP_060453.3. NM_017983.6. [Q5MNZ9-1]
UniGeneiHs.463964.

3D structure databases

ProteinModelPortaliQ5MNZ9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120380. 12 interactors.
IntActiQ5MNZ9. 7 interactors.
MINTiMINT-1392030.
STRINGi9606.ENSP00000262139.

PTM databases

iPTMnetiQ5MNZ9.
PhosphoSitePlusiQ5MNZ9.

Polymorphism and mutation databases

BioMutaiWIPI1.
DMDMi146291100.

Proteomic databases

MaxQBiQ5MNZ9.
PaxDbiQ5MNZ9.
PeptideAtlasiQ5MNZ9.
PRIDEiQ5MNZ9.

Protocols and materials databases

DNASUi55062.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262139; ENSP00000262139; ENSG00000070540. [Q5MNZ9-1]
GeneIDi55062.
KEGGihsa:55062.
UCSCiuc010dey.4. human. [Q5MNZ9-1]

Organism-specific databases

CTDi55062.
DisGeNETi55062.
GeneCardsiWIPI1.
H-InvDBHIX0014115.
HGNCiHGNC:25471. WIPI1.
HPAiCAB037230.
HPA007493.
MIMi609224. gene.
neXtProtiNX_Q5MNZ9.
OpenTargetsiENSG00000070540.
PharmGKBiPA142670575.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2110. Eukaryota.
ENOG410XP6Y. LUCA.
GeneTreeiENSGT00730000110845.
HOGENOMiHOG000217544.
HOVERGENiHBG056639.
InParanoidiQ5MNZ9.
KOiK17908.
OMAiSTWTGYM.
OrthoDBiEOG091G08ZS.
PhylomeDBiQ5MNZ9.
TreeFamiTF314879.

Enzyme and pathway databases

ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-381038. XBP1(S) activates chaperone genes.
SignaLinkiQ5MNZ9.
SIGNORiQ5MNZ9.

Miscellaneous databases

ChiTaRSiWIPI1. human.
GeneWikiiWIPI1.
GenomeRNAii55062.
PROiQ5MNZ9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000070540.
CleanExiHS_WIPI1.
ExpressionAtlasiQ5MNZ9. baseline and differential.
GenevisibleiQ5MNZ9. HS.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
IPR032909. WIPI1.
[Graphical view]
PANTHERiPTHR11227:SF23. PTHR11227:SF23. 2 hits.
SMARTiSM00320. WD40. 2 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiWIPI1_HUMAN
AccessioniPrimary (citable) accession number: Q5MNZ9
Secondary accession number(s): Q8IXM5, Q9NWF8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: May 1, 2007
Last modified: November 2, 2016
This is version 123 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.