EGFL7_HUMAN
ID EGFL7_HUMAN Reviewed; 273 AA.
AC Q9UHF1; B3KRP0; M9VTX9; Q5M7Y5; Q5VUD5; Q96EG0;
DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Epidermal growth factor-like protein 7;
DE Short=EGF-like protein 7;
DE AltName: Full=Multiple epidermal growth factor-like domains protein 7;
DE Short=Multiple EGF-like domains protein 7;
DE AltName: Full=NOTCH4-like protein;
DE AltName: Full=Vascular endothelial statin;
DE Short=VE-statin;
DE AltName: Full=Zneu1;
DE Flags: Precursor;
GN Name=EGFL7; Synonyms=MEGF7; ORFNames=UNQ187/PRO1449;
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].
RA Sheppard P., Jelinek L., Whitmore T., Blumberg H., Lehner J., O'Hara P.;
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-153.
RA Tanaka S., Maehara M.;
RT "A novel gene regulating tumor angiogenesis.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-114.
RA Hong S.M., Sung H.S.;
RT "Characterization of recombinant human epidermal growth factor like-7
RT (rhEGFL7) produced by Bombyx mori.";
RL Submitted (DEC-2012) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-153.
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-153.
RC TISSUE=Brain, and Ovary;
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 [9]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, CELL ATTACHMENT MOTIF, AND
RP MUTAGENESIS OF GLY-131.
RX PubMed=23386126; DOI=10.1182/blood-2011-11-394882;
RA Nikolic I., Stankovic N.D., Bicker F., Meister J., Braun H., Awwad K.,
RA Baumgart J., Simon K., Thal S.C., Patra C., Harter P.N., Plate K.H.,
RA Engel F.B., Dimmeler S., Eble J.A., Mittelbronn M., Schafer M.K.,
RA Jungblut B., Chavakis E., Fleming I., Schmidt M.H.;
RT "EGFL7 ligates alphavbeta3 integrin to enhance vessel formation.";
RL Blood 121:3041-3050(2013).
RN [10]
RP FUNCTION, AND MISCELLANEOUS.
RX PubMed=23639441; DOI=10.1016/j.devcel.2013.03.003;
RA Charpentier M.S., Christine K.S., Amin N.M., Dorr K.M., Kushner E.J.,
RA Bautch V.L., Taylor J.M., Conlon F.L.;
RT "CASZ1 promotes vascular assembly and morphogenesis through the direct
RT regulation of an EGFL7/RhoA-mediated pathway.";
RL Dev. Cell 25:132-143(2013).
CC -!- FUNCTION: Regulates vascular tubulogenesis in vivo. Inhibits platelet-
CC derived growth factor (PDGF)-BB-induced smooth muscle cell migration
CC and promotes endothelial cell adhesion to the extracellular matrix and
CC angiogenesis. {ECO:0000269|PubMed:23386126,
CC ECO:0000269|PubMed:23639441}.
CC -!- SUBUNIT: Interacts with ITGAV/ITGB3 in an RGD-dependent manner,
CC increasing endothelial cell's motility. {ECO:0000269|PubMed:23386126}.
CC -!- INTERACTION:
CC Q9UHF1; Q9Y223-2: GNE; NbExp=3; IntAct=EBI-949532, EBI-11975289;
CC Q9UHF1; Q96MH2: HEXIM2; NbExp=3; IntAct=EBI-949532, EBI-5460660;
CC Q9UHF1; O14964: HGS; NbExp=3; IntAct=EBI-949532, EBI-740220;
CC Q9UHF1; P49639: HOXA1; NbExp=4; IntAct=EBI-949532, EBI-740785;
CC Q9UHF1; Q9H2F3: HSD3B7; NbExp=3; IntAct=EBI-949532, EBI-3918847;
CC Q9UHF1; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-949532, EBI-10172526;
CC Q9UHF1; A6NK89: RASSF10; NbExp=3; IntAct=EBI-949532, EBI-6912267;
CC Q9UHF1; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-949532, EBI-11959123;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC {ECO:0000269|PubMed:23386126}.
CC -!- MISCELLANEOUS: Endothelial cells depleted in EGFL7 by siRNAs display
CC dramatic alterations in adhesion, morphology, and sprouting. The
CC defects are in part due to diminished RhoA expression and impaired
CC focal adhesion localization.
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DR EMBL; AF186111; AAF01429.1; -; mRNA.
DR EMBL; AB125649; BAD01469.1; -; mRNA.
DR EMBL; KC485578; AGJ83826.1; -; mRNA.
DR EMBL; AL512735; CAC21666.1; -; mRNA.
DR EMBL; AY358901; AAQ89260.1; -; mRNA.
DR EMBL; AY358902; AAQ89261.1; -; mRNA.
DR EMBL; AY358903; AAQ89262.1; -; mRNA.
DR EMBL; AK091964; BAG52452.1; -; mRNA.
DR EMBL; AL590226; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012377; AAH12377.1; -; mRNA.
DR EMBL; BC088371; AAH88371.1; -; mRNA.
DR CCDS; CCDS7002.1; -.
DR RefSeq; NP_057299.1; NM_016215.4.
DR RefSeq; NP_958854.1; NM_201446.2.
DR RefSeq; XP_011517066.1; XM_011518764.1.
DR RefSeq; XP_011517067.1; XM_011518765.1.
DR RefSeq; XP_011517068.1; XM_011518766.1.
DR AlphaFoldDB; Q9UHF1; -.
DR BioGRID; 119343; 87.
DR IntAct; Q9UHF1; 45.
DR MINT; Q9UHF1; -.
DR STRING; 9606.ENSP00000360764; -.
DR ChEMBL; CHEMBL3712972; -.
DR GlyGen; Q9UHF1; 1 site.
DR iPTMnet; Q9UHF1; -.
DR PhosphoSitePlus; Q9UHF1; -.
DR BioMuta; EGFL7; -.
DR DMDM; 92090985; -.
DR EPD; Q9UHF1; -.
DR jPOST; Q9UHF1; -.
DR MassIVE; Q9UHF1; -.
DR MaxQB; Q9UHF1; -.
DR PaxDb; Q9UHF1; -.
DR PeptideAtlas; Q9UHF1; -.
DR PRIDE; Q9UHF1; -.
DR ProteomicsDB; 84339; -.
DR ABCD; Q9UHF1; 1 sequenced antibody.
DR Antibodypedia; 32209; 353 antibodies from 37 providers.
DR DNASU; 51162; -.
DR Ensembl; ENST00000308874.12; ENSP00000307843.7; ENSG00000172889.16.
DR Ensembl; ENST00000371698.3; ENSP00000360763.3; ENSG00000172889.16.
DR Ensembl; ENST00000371699.5; ENSP00000360764.1; ENSG00000172889.16.
DR Ensembl; ENST00000406555.7; ENSP00000385639.3; ENSG00000172889.16.
DR GeneID; 51162; -.
DR KEGG; hsa:51162; -.
DR MANE-Select; ENST00000308874.12; ENSP00000307843.7; NM_016215.5; NP_057299.1.
DR UCSC; uc004cid.3; human.
DR CTD; 51162; -.
DR DisGeNET; 51162; -.
DR GeneCards; EGFL7; -.
DR HGNC; HGNC:20594; EGFL7.
DR HPA; ENSG00000172889; Low tissue specificity.
DR MIM; 608582; gene.
DR neXtProt; NX_Q9UHF1; -.
DR OpenTargets; ENSG00000172889; -.
DR PharmGKB; PA134928613; -.
DR VEuPathDB; HostDB:ENSG00000172889; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000160015; -.
DR HOGENOM; CLU_083642_0_0_1; -.
DR InParanoid; Q9UHF1; -.
DR OMA; CPGWRRV; -.
DR OrthoDB; 749722at2759; -.
DR PhylomeDB; Q9UHF1; -.
DR TreeFam; TF331360; -.
DR PathwayCommons; Q9UHF1; -.
DR SignaLink; Q9UHF1; -.
DR SIGNOR; Q9UHF1; -.
DR BioGRID-ORCS; 51162; 14 hits in 1074 CRISPR screens.
DR ChiTaRS; EGFL7; human.
DR GeneWiki; EGFL7; -.
DR GenomeRNAi; 51162; -.
DR Pharos; Q9UHF1; Tbio.
DR PRO; PR:Q9UHF1; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9UHF1; protein.
DR Bgee; ENSG00000172889; Expressed in right lung and 173 other tissues.
DR ExpressionAtlas; Q9UHF1; baseline and differential.
DR Genevisible; Q9UHF1; HS.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0001568; P:blood vessel development; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IMP:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:MGI.
DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR013111; EGF_extracell.
DR InterPro; IPR011489; EMI_domain.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR Pfam; PF07974; EGF_2; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF07546; EMI; 1.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS51041; EMI; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Calcium; Cell adhesion; Coiled coil; Developmental protein;
KW Differentiation; Disulfide bond; EGF-like domain; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..273
FT /note="Epidermal growth factor-like protein 7"
FT /id="PRO_0000007528"
FT DOMAIN 27..104
FT /note="EMI"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00384"
FT DOMAIN 103..135
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 137..177
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT COILED 192..219
FT /evidence="ECO:0000255"
FT MOTIF 130..132
FT /note="Cell attachment site"
FT DISULFID 31..89
FT /evidence="ECO:0000250"
FT DISULFID 56..62
FT /evidence="ECO:0000250"
FT DISULFID 88..102
FT /evidence="ECO:0000250"
FT DISULFID 107..117
FT /evidence="ECO:0000250"
FT DISULFID 111..123
FT /evidence="ECO:0000250"
FT DISULFID 125..134
FT /evidence="ECO:0000250"
FT DISULFID 141..152
FT /evidence="ECO:0000250"
FT DISULFID 148..161
FT /evidence="ECO:0000250"
FT DISULFID 163..176
FT /evidence="ECO:0000250"
FT VARIANT 114
FT /note="G -> R (in dbSNP:rs61736886)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_070951"
FT VARIANT 153
FT /note="V -> I (in dbSNP:rs2297538)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_019791"
FT VARIANT 183
FT /note="P -> S (in dbSNP:rs35863900)"
FT /id="VAR_048981"
FT VARIANT 186
FT /note="A -> G (in dbSNP:rs34142075)"
FT /id="VAR_048982"
FT MUTAGEN 131
FT /note="G->A: Disrupts RGD motif and results in a 79% loss
FT of cell adhesion."
FT /evidence="ECO:0000269|PubMed:23386126"
SQ SEQUENCE 273 AA; 29618 MW; 5740BB845ED5A988 CRC64;
MRGSQEVLLM WLLVLAVGGT EHAYRPGRRV CAVRAHGDPV SESFVQRVYQ PFLTTCDGHR
ACSTYRTIYR TAYRRSPGLA PARPRYACCP GWKRTSGLPG ACGAAICQPP CRNGGSCVQP
GRCRCPAGWR GDTCQSDVDE CSARRGGCPQ RCVNTAGSYW CQCWEGHSLS ADGTLCVPKG
GPPRVAPNPT GVDSAMKEEV QRLQSRVDLL EEKLQLVLAP LHSLASQALE HGLPDPGSLL
VHSFQQLGRI DSLSEQISFL EEQLGSCSCK KDS
