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 24-JAN-2024, entry version 179. 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. 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; 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; 91. DR IntAct; Q9UHF1; 46. DR MINT; Q9UHF1; -. DR STRING; 9606.ENSP00000360764; -. DR ChEMBL; CHEMBL3712972; -. DR GlyGen; Q9UHF1; 6 sites, 2 O-linked glycans (5 sites). 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; 9606-ENSP00000360764; -. DR PeptideAtlas; Q9UHF1; -. DR ProteomicsDB; 84339; -. DR ABCD; Q9UHF1; 1 sequenced antibody. DR Antibodypedia; 32209; 412 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 AGR; HGNC:20594; -. 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; PGWRRVH; -. DR OrthoDB; 5388104at2759; -. DR PhylomeDB; Q9UHF1; -. DR TreeFam; TF331360; -. DR PathwayCommons; Q9UHF1; -. DR SignaLink; Q9UHF1; -. DR SIGNOR; Q9UHF1; -. DR BioGRID-ORCS; 51162; 29 hits in 1158 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 175 other cell types or tissues. DR ExpressionAtlas; Q9UHF1; baseline and differential. 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: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 CDD; cd00054; EGF_CA; 1. DR Gene3D; 2.10.25.10; Laminin; 2. 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 PANTHER; PTHR14949; EGF-LIKE-DOMAIN, MULTIPLE 7, 8; 1. DR PANTHER; PTHR14949:SF21; EPIDERMAL GROWTH FACTOR-LIKE PROTEIN 7; 1. DR Pfam; PF07974; EGF_2; 1. DR Pfam; PF07546; EMI; 1. DR Pfam; PF14670; FXa_inhibition; 1. DR SMART; SM00181; EGF; 2. DR SMART; SM00179; EGF_CA; 1. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 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. DR Genevisible; Q9UHF1; HS. 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 //