ID WIF1_HUMAN Reviewed; 379 AA.
AC Q9Y5W5; Q6UXI1; Q8WVG4;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 3.
DT 27-MAR-2024, entry version 196.
DE RecName: Full=Wnt inhibitory factor 1;
DE Short=WIF-1;
DE Flags: Precursor;
GN Name=WIF1; ORFNames=UNQ191/PRO217;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10201374; DOI=10.1038/18899;
RA Hsieh J.-C., Kodjabachian L., Rebbert M.L., Rattner A., Smallwood P.M.,
RA Samos C.H., Nusse R., Dawid I.B., Nathans J.;
RT "A new secreted protein that binds to Wnt proteins and inhibits their
RT activities.";
RL Nature 398:431-436(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH MYOC.
RX PubMed=19188438; DOI=10.1128/mcb.01274-08;
RA Kwon H.S., Lee H.S., Ji Y., Rubin J.S., Tomarev S.I.;
RT "Myocilin is a modulator of Wnt signaling.";
RL Mol. Cell. Biol. 29:2139-2154(2009).
RN [5]
RP STRUCTURE BY NMR OF 32-181, AND DISULFIDE BOND.
RX PubMed=16476441; DOI=10.1016/j.jmb.2006.01.047;
RA Liepinsh E., Banyai L., Patthy L., Otting G.;
RT "NMR structure of the WIF domain of the human Wnt-inhibitory factor-1.";
RL J. Mol. Biol. 357:942-950(2006).
CC -!- FUNCTION: Binds to WNT proteins and inhibits their activities. May be
CC involved in mesoderm segmentation.
CC -!- SUBUNIT: Interacts with MYOC. {ECO:0000269|PubMed:19188438}.
CC -!- INTERACTION:
CC Q9Y5W5; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-3922719, EBI-3867333;
CC Q9Y5W5; P60410: KRTAP10-8; NbExp=6; IntAct=EBI-3922719, EBI-10171774;
CC Q9Y5W5; P41221: WNT5A; NbExp=2; IntAct=EBI-3922719, EBI-6594545;
CC Q9Y5W5; O00755: WNT7A; NbExp=3; IntAct=EBI-3922719, EBI-727198;
CC Q9Y5W5; P27467: Wnt3a; Xeno; NbExp=8; IntAct=EBI-3922719, EBI-2899665;
CC Q9Y5W5; P22725: Wnt5a; Xeno; NbExp=7; IntAct=EBI-3922719, EBI-1570983;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/44085/WIF1";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF122922; AAD25402.1; -; mRNA.
DR EMBL; AY358344; AAQ88710.1; -; mRNA.
DR EMBL; BC018037; AAH18037.1; -; mRNA.
DR CCDS; CCDS8971.1; -.
DR PIR; A59180; A59180.
DR RefSeq; NP_009122.2; NM_007191.4.
DR PDB; 2D3J; NMR; -; A=32-181.
DR PDB; 2YGN; X-ray; 1.85 A; A=35-178.
DR PDB; 2YGO; X-ray; 1.85 A; A=35-210.
DR PDB; 2YGP; X-ray; 2.22 A; A=35-210.
DR PDB; 2YGQ; X-ray; 3.95 A; A=35-346.
DR PDBsum; 2D3J; -.
DR PDBsum; 2YGN; -.
DR PDBsum; 2YGO; -.
DR PDBsum; 2YGP; -.
DR PDBsum; 2YGQ; -.
DR AlphaFoldDB; Q9Y5W5; -.
DR BMRB; Q9Y5W5; -.
DR SMR; Q9Y5W5; -.
DR BioGRID; 116366; 172.
DR DIP; DIP-59097N; -.
DR IntAct; Q9Y5W5; 16.
DR MINT; Q9Y5W5; -.
DR STRING; 9606.ENSP00000286574; -.
DR GlyCosmos; Q9Y5W5; 2 sites, No reported glycans.
DR GlyGen; Q9Y5W5; 2 sites.
DR iPTMnet; Q9Y5W5; -.
DR PhosphoSitePlus; Q9Y5W5; -.
DR BioMuta; WIF1; -.
DR DMDM; 61252765; -.
DR MassIVE; Q9Y5W5; -.
DR PaxDb; 9606-ENSP00000286574; -.
DR PeptideAtlas; Q9Y5W5; -.
DR ProteomicsDB; 86517; -.
DR Antibodypedia; 29209; 532 antibodies from 33 providers.
DR DNASU; 11197; -.
DR Ensembl; ENST00000286574.9; ENSP00000286574.4; ENSG00000156076.10.
DR GeneID; 11197; -.
DR KEGG; hsa:11197; -.
DR MANE-Select; ENST00000286574.9; ENSP00000286574.4; NM_007191.5; NP_009122.2.
DR UCSC; uc001ssk.4; human.
DR AGR; HGNC:18081; -.
DR CTD; 11197; -.
DR DisGeNET; 11197; -.
DR GeneCards; WIF1; -.
DR HGNC; HGNC:18081; WIF1.
DR HPA; ENSG00000156076; Tissue enriched (retina).
DR MIM; 605186; gene.
DR neXtProt; NX_Q9Y5W5; -.
DR OpenTargets; ENSG00000156076; -.
DR PharmGKB; PA38291; -.
DR VEuPathDB; HostDB:ENSG00000156076; -.
DR eggNOG; KOG1225; Eukaryota.
DR GeneTree; ENSGT00940000160401; -.
DR HOGENOM; CLU_041961_0_0_1; -.
DR InParanoid; Q9Y5W5; -.
DR OMA; YPNCMNG; -.
DR OrthoDB; 5475408at2759; -.
DR PhylomeDB; Q9Y5W5; -.
DR PathwayCommons; Q9Y5W5; -.
DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-HSA-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR SignaLink; Q9Y5W5; -.
DR SIGNOR; Q9Y5W5; -.
DR BioGRID-ORCS; 11197; 8 hits in 1143 CRISPR screens.
DR ChiTaRS; WIF1; human.
DR EvolutionaryTrace; Q9Y5W5; -.
DR GeneWiki; WIF1; -.
DR GenomeRNAi; 11197; -.
DR Pharos; Q9Y5W5; Tbio.
DR PRO; PR:Q9Y5W5; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9Y5W5; Protein.
DR Bgee; ENSG00000156076; Expressed in lower lobe of lung and 175 other cell types or tissues.
DR ExpressionAtlas; Q9Y5W5; baseline and differential.
DR Genevisible; Q9Y5W5; HS.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0070697; F:activin receptor binding; IBA:GO_Central.
DR GO; GO:0038100; F:nodal binding; IBA:GO_Central.
DR GO; GO:0017147; F:Wnt-protein binding; NAS:ParkinsonsUK-UCL.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0001568; P:blood vessel development; IBA:GO_Central.
DR GO; GO:0007368; P:determination of left/right symmetry; IBA:GO_Central.
DR GO; GO:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; NAS:ParkinsonsUK-UCL.
DR GO; GO:0038092; P:nodal signaling pathway; IBA:GO_Central.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd00054; EGF_CA; 2.
DR Gene3D; 2.10.25.10; Laminin; 2.
DR Gene3D; 2.60.40.2170; Wnt, WIF domain; 1.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR003306; WIF.
DR InterPro; IPR038677; WIF_sf.
DR InterPro; IPR013309; Wnt-inh.
DR PANTHER; PTHR14949; EGF-LIKE-DOMAIN, MULTIPLE 7, 8; 1.
DR PANTHER; PTHR14949:SF32; WNT INHIBITORY FACTOR 1; 1.
DR Pfam; PF21700; DL-JAG_EGF-like; 1.
DR Pfam; PF12661; hEGF; 4.
DR Pfam; PF02019; WIF; 1.
DR PRINTS; PR01901; WIFPROTEIN.
DR SMART; SM00181; EGF; 5.
DR SMART; SM00469; WIF; 1.
DR PROSITE; PS00022; EGF_1; 5.
DR PROSITE; PS01186; EGF_2; 4.
DR PROSITE; PS50026; EGF_3; 5.
DR PROSITE; PS50814; WIF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Developmental protein; Disulfide bond; EGF-like domain;
KW Glycoprotein; Reference proteome; Repeat; Secreted; Signal;
KW Wnt signaling pathway.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..379
FT /note="Wnt inhibitory factor 1"
FT /id="PRO_0000007775"
FT DOMAIN 38..177
FT /note="WIF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00222"
FT DOMAIN 178..210
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 211..242
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 243..271
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 274..306
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 307..338
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 354..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 361..379
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 140..177
FT /evidence="ECO:0000269|PubMed:16476441"
FT DISULFID 182..192
FT /evidence="ECO:0000250"
FT DISULFID 186..198
FT /evidence="ECO:0000250"
FT DISULFID 200..209
FT /evidence="ECO:0000250"
FT DISULFID 214..224
FT /evidence="ECO:0000250"
FT DISULFID 218..230
FT /evidence="ECO:0000250"
FT DISULFID 232..241
FT /evidence="ECO:0000250"
FT DISULFID 246..256
FT /evidence="ECO:0000250"
FT DISULFID 250..262
FT /evidence="ECO:0000250"
FT DISULFID 278..288
FT /evidence="ECO:0000250"
FT DISULFID 282..294
FT /evidence="ECO:0000250"
FT DISULFID 296..305
FT /evidence="ECO:0000250"
FT DISULFID 310..320
FT /evidence="ECO:0000250"
FT DISULFID 314..326
FT /evidence="ECO:0000250"
FT DISULFID 328..337
FT /evidence="ECO:0000250"
FT CONFLICT 166
FT /note="Q -> K (in Ref. 3; AAH18037)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="Q -> L (in Ref. 1; AAD25402)"
FT /evidence="ECO:0000305"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:2YGN"
FT HELIX 42..49
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:2YGN"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:2YGO"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 85..93
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 99..109
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:2D3J"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 131..137
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 146..158
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:2YGN"
FT STRAND 173..177
FT /evidence="ECO:0007829|PDB:2YGN"
FT TURN 206..209
FT /evidence="ECO:0007829|PDB:2YGO"
SQ SEQUENCE 379 AA; 41528 MW; 32ADFA6644833E9D CRC64;
MARRSAFPAA ALWLWSILLC LLALRAEAGP PQEESLYLWI DAHQARVLIG FEEDILIVSE
GKMAPFTHDF RKAQQRMPAI PVNIHSMNFT WQAAGQAEYF YEFLSLRSLD KGIMADPTVN
VPLLGTVPHK ASVVQVGFPC LGKQDGVAAF EVDVIVMNSE GNTILQTPQN AIFFKTCQQA
ECPGGCRNGG FCNERRICEC PDGFHGPHCE KALCTPRCMN GGLCVTPGFC ICPPGFYGVN
CDKANCSTTC FNGGTCFYPG KCICPPGLEG EQCEISKCPQ PCRNGGKCIG KSKCKCSKGY
QGDLCSKPVC EPGCGAHGTC HEPNKCQCQE GWHGRHCNKR YEASLIHALR PAGAQLRQHT
PSLKKAEERR DPPESNYIW
//
