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Protein

WD repeat domain phosphoinositide-interacting protein 1

Gene

WIPI1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Biological processAutophagy

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

EuPathDBiHostDB:ENSG00000070540.12
HGNCiHGNC:25471 WIPI1
MIMi609224 gene
neXtProtiNX_Q5MNZ9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

EPDiQ5MNZ9
MaxQBiQ5MNZ9
PaxDbiQ5MNZ9
PeptideAtlasiQ5MNZ9
PRIDEiQ5MNZ9
ProteomicsDBi63590
63591 [Q5MNZ9-2]

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 Expressed in 228 organ(s), highest expression level in sperm
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

Protein-protein interaction databases

BioGridi120380, 12 interactors
IntActiQ5MNZ9, 7 interactors
STRINGi9606.ENSP00000262139

Structurei

3D structure databases

ProteinModelPortaliQ5MNZ9
SMRiQ5MNZ9
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

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR036322 WD40_repeat_dom_sf
IPR032909 WIPI1
PANTHERiPTHR11227:SF23 PTHR11227:SF23, 1 hit
SMARTiView protein in SMART
SM00320 WD40, 2 hits
SUPFAMiSSF50978 SSF50978, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G5EA37G5EA37_HUMAN
WD repeat domain phosphoinositide-i...
WIPI1 hCG_28468
364Annotation score:
K7EK57K7EK57_HUMAN
WD repeat domain phosphoinositide-i...
WIPI1
369Annotation score:
K7ELY0K7ELY0_HUMAN
WD repeat domain phosphoinositide-i...
WIPI1
205Annotation score:
K7EKN0K7EKN0_HUMAN
WD repeat domain phosphoinositide-i...
WIPI1
82Annotation score:
K7EKC5K7EKC5_HUMAN
WD repeat domain phosphoinositide-i...
WIPI1
54Annotation score:

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 → I2 PublicationsCorresponds to variant dbSNP:rs883541Ensembl.1
Natural variantiVAR_053439308R → H. Corresponds to variant dbSNP:rs36084378Ensembl.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

Similar proteinsi

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
SMRiQ5MNZ9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120380, 12 interactors
IntActiQ5MNZ9, 7 interactors
STRINGi9606.ENSP00000262139

PTM databases

iPTMnetiQ5MNZ9
PhosphoSitePlusiQ5MNZ9

Polymorphism and mutation databases

BioMutaiWIPI1
DMDMi146291100

Proteomic databases

EPDiQ5MNZ9
MaxQBiQ5MNZ9
PaxDbiQ5MNZ9
PeptideAtlasiQ5MNZ9
PRIDEiQ5MNZ9
ProteomicsDBi63590
63591 [Q5MNZ9-2]

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
EuPathDBiHostDB:ENSG00000070540.12
GeneCardsiWIPI1
H-InvDBiHIX0014115
HGNCiHGNC:25471 WIPI1
HPAiCAB037230
HPA007493
MIMi609224 gene
neXtProtiNX_Q5MNZ9
OpenTargetsiENSG00000070540
PharmGKBiPA142670575
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2110 Eukaryota
ENOG410XP6Y LUCA
GeneTreeiENSGT00730000110845
HOGENOMiHOG000217544
HOVERGENiHBG056639
InParanoidiQ5MNZ9
KOiK17908
OMAiKMFMAAS
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
PROiPR:Q5MNZ9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000070540 Expressed in 228 organ(s), highest expression level in sperm
CleanExiHS_WIPI1
ExpressionAtlasiQ5MNZ9 baseline and differential
GenevisibleiQ5MNZ9 HS

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR036322 WD40_repeat_dom_sf
IPR032909 WIPI1
PANTHERiPTHR11227:SF23 PTHR11227:SF23, 1 hit
SMARTiView protein in SMART
SM00320 WD40, 2 hits
SUPFAMiSSF50978 SSF50978, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiWIPI1_HUMAN
AccessioniPrimary (citable) accession number: Q5MNZ9
Secondary accession number(s): Q8IXM5, Q9NWF8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: May 1, 2007
Last modified: November 7, 2018
This is version 139 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
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