Q5MNZ9 (WIPI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	WIPI1
Synonyms:	WIPI49

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	446 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in autophagy. May regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway. Ref.1 Ref.5
Subunit structure	Probably interacts with androgen (AR) and the estrogen receptor (ER). Binds PtdIns3P and to a lesser extent, PtdIns3,5P2 and PtdIns5P in vitro. Interaction with PtdIns3P is required for recruitment to membranes.
Subcellular location	Golgi apparatus › trans-Golgi network. Endosome. Cytoplasmic vesicle › clathrin-coated vesicle. Note: Trans elements of the Golgi and peripheral endosomes. Dynamically cycles through these compartments and is susceptible to conditions that modulate membrane flux. Enriched in clathrin-coated vesicles. Ref.5
Tissue specificity	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. Ref.1
Sequence similarities	Belongs to the WD repeat SVP1 family. Contains 3 WD repeats.

Ontologies

Keywords
Biological process	Autophagy
Cellular component	Cytoplasmic vesicle Endosome Golgi apparatus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat WD repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome autophagic vacuole assembly Inferred from Biological aspect of Ancestor. Source: RefGenome vesicle targeting, trans-Golgi to endosome Inferred from direct assay Ref.5. Source: UniProtKB
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome autophagic vacuole membrane Inferred from direct assay PubMed 17618624. Source: UniProtKB clathrin-coated vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome endosome membrane Inferred from direct assay Ref.5. Source: UniProtKB pre-autophagosomal structure membrane Inferred from direct assay PubMed 17618624. Source: UniProtKB trans-Golgi network Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	androgen receptor binding Inferred from direct assay Ref.1. Source: UniProtKB estrogen receptor binding Inferred from direct assay Ref.1. Source: UniProtKB phosphatidylinositol-3,5-bisphosphate binding Inferred from direct assay PubMed 20505359. Source: UniProtKB phosphatidylinositol-3-phosphate binding Inferred from direct assay Ref.5PubMed 20505359. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5MNZ9-1)

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.

Isoform 2 (identifier: Q5MNZ9-2)

Also known as: WIPI-1 beta;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 446	446	WD repeat domain phosphoinositide-interacting protein 1		PRO_0000051437
Regions
	Repeat	184 – 224	41	WD 1
	Repeat	230 – 269	40	WD 2
	Repeat	312 – 351	40	WD 3
	Motif	131 – 136	6	Nuclear receptor interaction
Natural variations
	Alternative sequence	1 – 6	6	MEAEAA → M in isoform 2.		VSP_016966
	Natural variant	31	1	T → I. Ref.1 Ref.4 Corresponds to variant rs883541 [ dbSNP | Ensembl ].		VAR_024848
	Natural variant	308	1	R → H. Corresponds to variant rs36084378 [ dbSNP | Ensembl ].		VAR_053439
Experimental info
	Mutagenesis	226 – 227	2	RR → AA: Loss of binding to phosphoinositides, does not disrupt the MPR pathway. Ref.5
	Sequence conflict	63	1	V → A in AAV80760. Ref.1
	Sequence conflict	249	1	A → AA Ref.1
	Sequence conflict	358	1	S → R in BAA91423. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (WIPI-1 alpha) [UniParc]. Last modified May 1, 2007. Version 3. Checksum: 35B5650990B62E31	FASTA	446	48,673
	10 20 30 40 50 60 MEAEAADAPP GGVESALSCF SFNQDCTSLA TGTKAGYKLF SLSSVEQLDQ VHGSNEIPDV 70 80 90 100 110 120 YIVERLFSSS LVVVVSHTKP RQMNVYHFKK GTEICNYSYS SNILSIRLNR QRLLVCLEES 130 140 150 160 170 180 IYIHNIKDMK LLKTLLDIPA NPTGLCALSI NHSNSYLAYP GSLTSGEIVL YDGNSLKTVC 190 200 210 220 230 240 TIAAHEGTLA AITFNASGSK LASASEKGTV IRVFSVPDGQ KLYEFRRGMK RYVTISSLVF 250 260 270 280 290 300 SMDSQFLCAS SNTETVHIFK LEQVTNSRPE EPSTWSGYMG KMFMAATNYL PTQVSDMMHQ 310 320 330 340 350 360 DRAFATARLN FSGQRNICTL STIQKLPRLL VASSSGHLYM YNLDPQDGGE CVLIKTHSLL 370 380 390 400 410 420 GSGTTEENKE NDLRPSLPQS YAATVARPSA SSASTVPGYS EDGGALRGEV IPEHEFATGP 430 440 VCLDDENEFP PIILCRGNQK GKTKQS
	Isoform 2 (WIPI-1 beta) [UniParc]. Checksum: 969C220C162DC7F6	FASTA	441	48,202
	10 20 30 40 50 60 MDAPPGGVES ALSCFSFNQD CTSLATGTKA GYKLFSLSSV EQLDQVHGSN EIPDVYIVER 70 80 90 100 110 120 LFSSSLVVVV SHTKPRQMNV YHFKKGTEIC NYSYSSNILS IRLNRQRLLV CLEESIYIHN 130 140 150 160 170 180 IKDMKLLKTL LDIPANPTGL CALSINHSNS YLAYPGSLTS GEIVLYDGNS LKTVCTIAAH 190 200 210 220 230 240 EGTLAAITFN ASGSKLASAS EKGTVIRVFS VPDGQKLYEF RRGMKRYVTI SSLVFSMDSQ 250 260 270 280 290 300 FLCASSNTET VHIFKLEQVT NSRPEEPSTW SGYMGKMFMA ATNYLPTQVS DMMHQDRAFA 310 320 330 340 350 360 TARLNFSGQR NICTLSTIQK LPRLLVASSS GHLYMYNLDP QDGGECVLIK THSLLGSGTT 370 380 390 400 410 420 EENKENDLRP SLPQSYAATV ARPSASSAST VPGYSEDGGA LRGEVIPEHE FATGPVCLDD 430 440 ENEFPPIILC RGNQKGKTKQ S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy." Proikas-Cezanne T., Waddell S., Gaugel A., Frickey T., Lupas A., Nordheim A. Oncogene 23:9314-9325(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, VARIANT ILE-31. Tissue: Testis.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Embryo.
[3]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ILE-31. Tissue: Skin.
[5]	"PtdIns-specific MPR pathway association of a novel WD40 repeat protein, WIPI49." Jeffries T.R., Dove S.K., Michell R.H., Parker P.J. Mol. Biol. Cell 15:2652-2663(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, FUNCTION, SUBCELLULAR LOCATION, BINDING TO PHOSPHOINOSITIDES, MUTAGENESIS OF 226-ARG-ARG-227.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY691424 mRNA. Translation: AAV80760.1. AK000917 mRNA. Translation: BAA91423.1. AC007780 Genomic DNA. No translation available. BC039867 mRNA. Translation: AAH39867.1.
IPI	IPI00217556. IPI00658123.
RefSeq	NP_060453.3. NM_017983.5.
UniGene	Hs.463964.
3D structure databases
ProteinModelPortal	Q5MNZ9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q5MNZ9. 6 interactions.
MINT	MINT-1392030.
STRING	9606.ENSP00000262139.
PTM databases
PhosphoSite	Q5MNZ9.
Polymorphism databases
DMDM	146291100.
Proteomic databases
PaxDb	Q5MNZ9.
PRIDE	Q5MNZ9.
Protocols and materials databases
DNASU	55062.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262139; ENSP00000262139; ENSG00000070540.
GeneID	55062.
KEGG	hsa:55062.
UCSC	uc010dey.3. human.
Organism-specific databases
CTD	55062.
GeneCards	GC17M066417.
H-InvDB	HIX0014115.
HGNC	HGNC:25471. WIPI1.
HPA	HPA007493.
MIM	609224. gene.
neXtProt	NX_Q5MNZ9.
PharmGKB	PA142670575.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG317564.
HOGENOM	HOG000217544.
HOVERGEN	HBG056639.
InParanoid	Q5MNZ9.
OMA	TNSRPEE.
OrthoDB	EOG4Z36DZ.
PhylomeDB	Q5MNZ9.
Enzyme and pathway databases
Reactome	REACT_116125. Disease.
Gene expression databases
ArrayExpress	Q5MNZ9.
Bgee	Q5MNZ9.
CleanEx	HS_WIPI1.
Genevestigator	Q5MNZ9.
GermOnline	ENSG00000070540. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 1 hit.
InterPro	IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF00400. WD40. 1 hit. [Graphical view]
SMART	SM00320. WD40. 2 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS00678. WD_REPEATS_1. False negative. PS50082. WD_REPEATS_2. False negative. PS50294. WD_REPEATS_REGION. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	WIPI1. human.
GenomeRNAi	55062.
NextBio	58557.
SOURCE	Search...

Entry information

Entry name

WIPI1_HUMAN

Accession

Primary (citable) accession number: Q5MNZ9
Secondary accession number(s): Q8IXM5, Q9NWF8

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2006
Last sequence update:	May 1, 2007
Last modified:	May 1, 2013
This is version 87 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.