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Protein

WD repeat domain phosphoinositide-interacting protein 2

Gene

WIPI2

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

Functioni

Early component of the autophagy machinery being involved in formation of preautophagosomal structures and their maturation into mature phagosomes in response to phosphatidylinositol 3-phosphate (PtdIns3P). May bind PtdIns3P.1 Publication
Isoform 4: Recruits the ATG12-ATG5-ATG16L1 complex to omegasomes and preautophagosomal structures, resulting in ATG8 family proteins lipidation and starvation-induced autophagy. Isoform 4 is also required for autophagic clearance of pathogenic bacteria. Isoform 4 binds the membrane surrounding Salmonella and recruits the ATG12-5-16L1 complex, initiating LC3 conjugation, autophagosomal membrane formation, and engulfment of Salmonella.1 Publication

GO - Molecular functioni

GO - Biological processi

  • autophagosome assembly Source: UniProtKB
  • autophagy of mitochondrion Source: GO_Central
  • macroautophagy Source: Reactome
  • protein lipidation Source: GO_Central
  • protein lipidation involved in autophagosome assembly Source: Ensembl
  • protein localization to phagophore assembly site Source: GO_Central
  • xenophagy Source: Ensembl

Keywordsi

Biological processAutophagy

Enzyme and pathway databases

ReactomeiR-HSA-1632852 Macroautophagy
SignaLinkiQ9Y4P8
SIGNORiQ9Y4P8

Names & Taxonomyi

Protein namesi
Recommended name:
WD repeat domain phosphoinositide-interacting protein 2
Short name:
WIPI-2
Alternative name(s):
WIPI49-like protein 2
Gene namesi
Name:WIPI2
ORF Names:CGI-50
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000157954.14
HGNCiHGNC:32225 WIPI2
MIMi609225 gene
neXtProtiNX_Q9Y4P8

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

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi126R → E: Impairs interaction with ATG16L1. 1 Publication1
Mutagenesisi143R → E: Decreasess interaction with ATG16L1. 1 Publication1
Mutagenesisi242R → T: Impairs preautophagosomal localization; when associated with T-243. 1 Publication1
Mutagenesisi243R → T: Impairs preautophagosomal localization; when associated with T-242. 1 Publication1

Organism-specific databases

DisGeNETi26100
OpenTargetsiENSG00000157954
PharmGKBiPA142670576

Polymorphism and mutation databases

BioMutaiWIPI2
DMDMi74762063

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000514401 – 454WD repeat domain phosphoinositide-interacting protein 2Add BLAST454

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei413PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Y4P8
PaxDbiQ9Y4P8
PeptideAtlasiQ9Y4P8
PRIDEiQ9Y4P8
ProteomicsDBi86236
86237 [Q9Y4P8-2]
86238 [Q9Y4P8-3]
86239 [Q9Y4P8-4]
86240 [Q9Y4P8-5]
86241 [Q9Y4P8-6]

PTM databases

iPTMnetiQ9Y4P8
PhosphoSitePlusiQ9Y4P8

Expressioni

Tissue specificityi

Ubiquitously expressed (at protein level). Highly expressed in heart, skeletal muscle and pancreas. Expression is down-regulated in pancreatic and in kidney tumors.2 Publications

Inductioni

Expression is repressed by ZKSCAN3.1 Publication

Gene expression databases

BgeeiENSG00000157954 Expressed in 243 organ(s), highest expression level in middle temporal gyrus
CleanExiHS_WIPI2
ExpressionAtlasiQ9Y4P8 baseline and differential
GenevisibleiQ9Y4P8 HS

Organism-specific databases

HPAiHPA019852
HPA021488

Interactioni

Subunit structurei

Interacts with TECPR1, ATG16L1 and ATG5.2 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi117550, 31 interactors
IntActiQ9Y4P8, 35 interactors
STRINGi9606.ENSP00000288828

Structurei

3D structure databases

ProteinModelPortaliQ9Y4P8
SMRiQ9Y4P8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati15 – 60WD 1Sequence analysisAdd BLAST46
Repeati67 – 104WD 2Sequence analysisAdd BLAST38
Repeati110 – 142WD 3Sequence analysisAdd BLAST33
Repeati149 – 189WD 4Sequence analysisAdd BLAST41
Repeati193 – 232WD 5Sequence analysisAdd BLAST40
Repeati238 – 277WD 6Sequence analysisAdd BLAST40
Repeati320 – 359WD 7Sequence analysisAdd BLAST40

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi241 – 244FRRG motif1 Publication4

Domaini

The FRRG motif is required for recruitment to PtdIns3P.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
InParanoidiQ9Y4P8
KOiK17908
OMAiRRMCAIT
OrthoDBiEOG091G08ZS
PhylomeDBiQ9Y4P8
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
IPR032911 WIPI2
PANTHERiPTHR11227:SF27 PTHR11227:SF27, 1 hit
SMARTiView protein in SMART
SM00320 WD40, 3 hits
SUPFAMiSSF50978 SSF50978, 1 hit

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9Y4P8-1) [UniParc]FASTAAdd to basket
Also known as: WIPI-2 alpha, WIPI2a

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
MNLASQSGEA GAGQLLFANF NQDNTEVKGA SRAAGLGRRA VVWSLAVGSK
60 70 80 90 100
SGYKFFSLSS VDKLEQIYEC TDTEDVCIVE RLFSSSLVAI VSLKAPRKLK
110 120 130 140 150
VCHFKKGTEI CNYSYSNTIL AVKLNRQRLI VCLEESLYIH NIRDMKVLHT
160 170 180 190 200
IRETPPNPAG LCALSINNDN CYLAYPGSAT IGEVQVFDTI NLRAANMIPA
210 220 230 240 250
HDSPLAALAF DASGTKLATA SEKGTVIRVF SIPEGQKLFE FRRGVKRCVS
260 270 280 290 300
ICSLAFSMDG MFLSASSNTE TVHIFKLETV KEKPPEEPTT WTGYFGKVLM
310 320 330 340 350
ASTSYLPSQV TEMFNQGRAF ATVRLPFCGH KNICSLATIQ KIPRLLVGAA
360 370 380 390 400
DGYLYMYNLD PQEGGECALM KQHRLDGSLE TTNEILDSAS HDCPLVTQTY
410 420 430 440 450
GAAAGKGTYV PSSPTRLAYT DDLGAVGGAC LEDEASALRL DEDSEHPPMI

LRTD
Length:454
Mass (Da):49,408
Last modified:November 1, 1999 - v1
Checksum:iB69CEC399B56F35C
GO
Isoform 2 (identifier: Q9Y4P8-2) [UniParc]FASTAAdd to basket
Also known as: WIPI-2 beta, WIPI2d

The sequence of this isoform differs from the canonical sequence as follows:
     26-43: Missing.
     407-417: Missing.

Show »
Length:425
Mass (Da):46,384
Checksum:i5FD85B554CA97F41
GO
Isoform 3 (identifier: Q9Y4P8-3) [UniParc]FASTAAdd to basket
Also known as: WIPI2e

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.
     60-71: SVDKLEQIYECT → MFTHVLPFVISA
     407-417: Missing.

Note: No experimental confirmation available.
Show »
Length:384
Mass (Da):42,077
Checksum:iE4C83CA999C10460
GO
Isoform 4 (identifier: Q9Y4P8-4) [UniParc]FASTAAdd to basket
Also known as: WIPI2b

The sequence of this isoform differs from the canonical sequence as follows:
     26-43: Missing.

Show »
Length:436
Mass (Da):47,543
Checksum:i0266FEC9E5338877
GO
Isoform 5 (identifier: Q9Y4P8-5) [UniParc]FASTAAdd to basket
Also known as: WIPI-2 delta

The sequence of this isoform differs from the canonical sequence as follows:
     1-71: MNLASQSGEA...DKLEQIYECT → MLLRLQRIKT...THVLPFVISA
     407-417: Missing.

Show »
Length:438
Mass (Da):48,251
Checksum:iD9F056ACE602F833
GO
Isoform 6 (identifier: Q9Y4P8-6) [UniParc]FASTAAdd to basket
Also known as: WIPI2c

The sequence of this isoform differs from the canonical sequence as follows:
     407-417: Missing.

Note: No experimental confirmation available.
Show »
Length:443
Mass (Da):48,249
Checksum:iA07814F3A3C402A1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti139I → T in CAG38561 (PubMed:15602573).Curated1
Sequence conflicti165S → P in AAV80761 (PubMed:15602573).Curated1
Sequence conflicti380E → K in AAD34045 (PubMed:10810093).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0169711 – 71MNLAS…IYECT → MLLRLQRIKTLRPPGCPHPM TTCSAGTLSAVPCVSPRQVF VFERRFCLWHSHVEMFTHVL PFVISA in isoform 5. 2 PublicationsAdd BLAST71
Alternative sequenceiVSP_0169701 – 59Missing in isoform 3. CuratedAdd BLAST59
Alternative sequenceiVSP_01697226 – 43Missing in isoform 2 and isoform 4. 3 PublicationsAdd BLAST18
Alternative sequenceiVSP_01697360 – 71SVDKL…IYECT → MFTHVLPFVISA in isoform 3. CuratedAdd BLAST12
Alternative sequenceiVSP_016974407 – 417Missing in isoform 2, isoform 3, isoform 5 and isoform 6. 3 PublicationsAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY691425 mRNA Translation: AAV80761.1
AY691426 mRNA Translation: AAV80762.1
AF151808 mRNA Translation: AAD34045.1
AL080155 mRNA Translation: CAB45746.1
CR533530 mRNA Translation: CAG38561.1
AK024279 mRNA Translation: BAG51284.1
AC093376 Genomic DNA Translation: AAQ96865.1
AC093376 Genomic DNA Translation: AAQ96866.1
AC093376 Genomic DNA Translation: AAQ96867.1
CH471144 Genomic DNA Translation: EAW87328.1
BC004116 mRNA Translation: AAH04116.1
BC007596 mRNA Translation: AAH07596.1
BC021068 mRNA No translation available.
BC021200 mRNA Translation: AAH21200.1
CCDSiCCDS34593.1 [Q9Y4P8-4]
CCDS47531.1 [Q9Y4P8-6]
CCDS47532.1 [Q9Y4P8-2]
CCDS47533.1 [Q9Y4P8-3]
CCDS5339.1 [Q9Y4P8-1]
PIRiT12539
RefSeqiNP_001028690.1, NM_001033518.1 [Q9Y4P8-6]
NP_001028691.1, NM_001033519.1 [Q9Y4P8-2]
NP_001028692.1, NM_001033520.1 [Q9Y4P8-3]
NP_001265228.1, NM_001278299.1
NP_056425.1, NM_015610.3 [Q9Y4P8-1]
NP_057087.2, NM_016003.3 [Q9Y4P8-4]
UniGeneiHs.122363

Genome annotation databases

EnsembliENST00000288828; ENSP00000288828; ENSG00000157954 [Q9Y4P8-1]
ENST00000382384; ENSP00000371821; ENSG00000157954 [Q9Y4P8-2]
ENST00000401525; ENSP00000384945; ENSG00000157954 [Q9Y4P8-4]
ENST00000404704; ENSP00000385297; ENSG00000157954 [Q9Y4P8-6]
ENST00000484262; ENSP00000429654; ENSG00000157954 [Q9Y4P8-3]
GeneIDi26100
KEGGihsa:26100
UCSCiuc003snv.4 human [Q9Y4P8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY691425 mRNA Translation: AAV80761.1
AY691426 mRNA Translation: AAV80762.1
AF151808 mRNA Translation: AAD34045.1
AL080155 mRNA Translation: CAB45746.1
CR533530 mRNA Translation: CAG38561.1
AK024279 mRNA Translation: BAG51284.1
AC093376 Genomic DNA Translation: AAQ96865.1
AC093376 Genomic DNA Translation: AAQ96866.1
AC093376 Genomic DNA Translation: AAQ96867.1
CH471144 Genomic DNA Translation: EAW87328.1
BC004116 mRNA Translation: AAH04116.1
BC007596 mRNA Translation: AAH07596.1
BC021068 mRNA No translation available.
BC021200 mRNA Translation: AAH21200.1
CCDSiCCDS34593.1 [Q9Y4P8-4]
CCDS47531.1 [Q9Y4P8-6]
CCDS47532.1 [Q9Y4P8-2]
CCDS47533.1 [Q9Y4P8-3]
CCDS5339.1 [Q9Y4P8-1]
PIRiT12539
RefSeqiNP_001028690.1, NM_001033518.1 [Q9Y4P8-6]
NP_001028691.1, NM_001033519.1 [Q9Y4P8-2]
NP_001028692.1, NM_001033520.1 [Q9Y4P8-3]
NP_001265228.1, NM_001278299.1
NP_056425.1, NM_015610.3 [Q9Y4P8-1]
NP_057087.2, NM_016003.3 [Q9Y4P8-4]
UniGeneiHs.122363

3D structure databases

ProteinModelPortaliQ9Y4P8
SMRiQ9Y4P8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117550, 31 interactors
IntActiQ9Y4P8, 35 interactors
STRINGi9606.ENSP00000288828

PTM databases

iPTMnetiQ9Y4P8
PhosphoSitePlusiQ9Y4P8

Polymorphism and mutation databases

BioMutaiWIPI2
DMDMi74762063

Proteomic databases

EPDiQ9Y4P8
PaxDbiQ9Y4P8
PeptideAtlasiQ9Y4P8
PRIDEiQ9Y4P8
ProteomicsDBi86236
86237 [Q9Y4P8-2]
86238 [Q9Y4P8-3]
86239 [Q9Y4P8-4]
86240 [Q9Y4P8-5]
86241 [Q9Y4P8-6]

Protocols and materials databases

DNASUi26100
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000288828; ENSP00000288828; ENSG00000157954 [Q9Y4P8-1]
ENST00000382384; ENSP00000371821; ENSG00000157954 [Q9Y4P8-2]
ENST00000401525; ENSP00000384945; ENSG00000157954 [Q9Y4P8-4]
ENST00000404704; ENSP00000385297; ENSG00000157954 [Q9Y4P8-6]
ENST00000484262; ENSP00000429654; ENSG00000157954 [Q9Y4P8-3]
GeneIDi26100
KEGGihsa:26100
UCSCiuc003snv.4 human [Q9Y4P8-1]

Organism-specific databases

CTDi26100
DisGeNETi26100
EuPathDBiHostDB:ENSG00000157954.14
GeneCardsiWIPI2
HGNCiHGNC:32225 WIPI2
HPAiHPA019852
HPA021488
MIMi609225 gene
neXtProtiNX_Q9Y4P8
OpenTargetsiENSG00000157954
PharmGKBiPA142670576
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2110 Eukaryota
ENOG410XP6Y LUCA
GeneTreeiENSGT00730000110845
HOGENOMiHOG000217544
HOVERGENiHBG056639
InParanoidiQ9Y4P8
KOiK17908
OMAiRRMCAIT
OrthoDBiEOG091G08ZS
PhylomeDBiQ9Y4P8
TreeFamiTF314879

Enzyme and pathway databases

ReactomeiR-HSA-1632852 Macroautophagy
SignaLinkiQ9Y4P8
SIGNORiQ9Y4P8

Miscellaneous databases

ChiTaRSiWIPI2 human
GeneWikiiWIPI2
GenomeRNAii26100
PROiPR:Q9Y4P8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157954 Expressed in 243 organ(s), highest expression level in middle temporal gyrus
CleanExiHS_WIPI2
ExpressionAtlasiQ9Y4P8 baseline and differential
GenevisibleiQ9Y4P8 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
IPR032911 WIPI2
PANTHERiPTHR11227:SF27 PTHR11227:SF27, 1 hit
SMARTiView protein in SMART
SM00320 WD40, 3 hits
SUPFAMiSSF50978 SSF50978, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiWIPI2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y4P8
Secondary accession number(s): B3KNC2
, Q5MNZ8, Q6FI96, Q75L50, Q96IE4, Q9Y364
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: November 1, 1999
Last modified: November 7, 2018
This is version 159 of the entry and version 1 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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