LOCUS       NM_001025366            3660 bp    mRNA    linear   PRI 22-MAR-2025
DEFINITION  Homo sapiens vascular endothelial growth factor A (VEGFA),
            transcript variant 1, mRNA.
ACCESSION   NM_001025366
VERSION     NM_001025366.3
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3660)
  AUTHORS   Liu,C.I., Liu,C.C., Huang,S.P., Geng,J.H. and Lee,Y.C.
  TITLE     Association of the VEGF 2578C>A Polymorphism With Metabolic
            Syndrome and Erectile Dysfunction
  JOURNAL   Am J Mens Health 18 (5), 15579883241282385 (2024)
   PUBMED   39397482
  REMARK    GeneRIF: Association of the VEGF 2578C>A Polymorphism With
            Metabolic Syndrome and Erectile Dysfunction.
REFERENCE   2  (bases 1 to 3660)
  AUTHORS   Eswarappa,S.M., Potdar,A.A., Koch,W.J., Fan,Y., Vasu,K.,
            Lindner,D., Willard,B., Graham,L.M., DiCorleto,P.E. and Fox,P.L.
  TITLE     Programmed translational readthrough generates antiangiogenic
            VEGF-Ax
  JOURNAL   Cell 157 (7), 1605-1618 (2014)
   PUBMED   24949972
  REMARK    GeneRIF: Study shows that VEGFA mRNA in mammalian endothelial cells
            undergoes programmed translational readthrough (PTR) generating
            VEGF-Ax, an isoform containing a unique 22-amino-acid C terminus
            extension. VEGF-Ax was detected in tissue slices from human brain,
            colon, small intestine, spleen, and pancreas and from serum from
            healthy human subjects.
REFERENCE   3  (bases 1 to 3660)
  AUTHORS   Bastide,A., Karaa,Z., Bornes,S., Hieblot,C., Lacazette,E., Prats,H.
            and Touriol,C.
  TITLE     An upstream open reading frame within an IRES controls expression
            of a specific VEGF-A isoform
  JOURNAL   Nucleic Acids Res 36 (7), 2434-2445 (2008)
   PUBMED   18304943
REFERENCE   4  (bases 1 to 3660)
  AUTHORS   Bates,D.O., Cui,T.G., Doughty,J.M., Winkler,M., Sugiono,M.,
            Shields,J.D., Peat,D., Gillatt,D. and Harper,S.J.
  TITLE     VEGF165b, an inhibitory splice variant of vascular endothelial
            growth factor, is down-regulated in renal cell carcinoma
  JOURNAL   Cancer Res 62 (14), 4123-4131 (2002)
   PUBMED   12124351
REFERENCE   5  (bases 1 to 3660)
  AUTHORS   Huez,I., Bornes,S., Bresson,D., Creancier,L. and Prats,H.
  TITLE     New vascular endothelial growth factor isoform generated by
            internal ribosome entry site-driven CUG translation initiation
  JOURNAL   Mol Endocrinol 15 (12), 2197-2210 (2001)
   PUBMED   11731620
  REMARK    GeneRIF: Includes data regarding non-AUG translation initiation
            (CUG) of VEGF
REFERENCE   6  (bases 1 to 3660)
  AUTHORS   Tee,M.K. and Jaffe,R.B.
  TITLE     A precursor form of vascular endothelial growth factor arises by
            initiation from an upstream in-frame CUG codon
  JOURNAL   Biochem J 359 (Pt 1), 219-226 (2001)
   PUBMED   11563986
  REMARK    GeneRIF: Includes data regarding non-AUG translation initiation
            (CUG) of VEGF
REFERENCE   7  (bases 1 to 3660)
  AUTHORS   Meiron,M., Anunu,R., Scheinman,E.J., Hashmueli,S. and Levi,B.Z.
  TITLE     New isoforms of VEGF are translated from alternative initiation CUG
            codons located in its 5'UTR
  JOURNAL   Biochem Biophys Res Commun 282 (4), 1053-1060 (2001)
   PUBMED   11352659
  REMARK    GeneRIF: Includes data regarding non-AUG translation initiation
            (CUG) of VEGF
REFERENCE   8  (bases 1 to 3660)
  AUTHORS   Akiri,G., Nahari,D., Finkelstein,Y., Le,S.Y., Elroy-Stein,O. and
            Levi,B.Z.
  TITLE     Regulation of vascular endothelial growth factor (VEGF) expression
            is mediated by internal initiation of translation and alternative
            initiation of transcription
  JOURNAL   Oncogene 17 (2), 227-236 (1998)
   PUBMED   9674707
REFERENCE   9  (bases 1 to 3660)
  AUTHORS   de Vries,C., Escobedo,J.A., Ueno,H., Houck,K., Ferrara,N. and
            Williams,L.T.
  TITLE     The fms-like tyrosine kinase, a receptor for vascular endothelial
            growth factor
  JOURNAL   Science 255 (5047), 989-991 (1992)
   PUBMED   1312256
REFERENCE   10 (bases 1 to 3660)
  AUTHORS   Tischer,E., Mitchell,R., Hartman,T., Silva,M., Gospodarowicz,D.,
            Fiddes,J.C. and Abraham,J.A.
  TITLE     The human gene for vascular endothelial growth factor. Multiple
            protein forms are encoded through alternative exon splicing
  JOURNAL   J Biol Chem 266 (18), 11947-11954 (1991)
   PUBMED   1711045
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA237741.1, CN256173.1,
            BU153227.1, S85192.1, AF024710.1, BF700556.1 and BM661679.1.
            
            On Jun 2, 2019 this sequence version replaced NM_001025366.2.
            
            Summary: This gene is a member of the PDGF/VEGF growth factor
            family. It encodes a heparin-binding protein, which exists as a
            disulfide-linked homodimer. This growth factor induces
            proliferation and migration of vascular endothelial cells, and is
            essential for both physiological and pathological angiogenesis.
            Disruption of this gene in mice resulted in abnormal embryonic
            blood vessel formation. This gene is upregulated in many known
            tumors and its expression is correlated with tumor stage and
            progression. Elevated levels of this protein are found in patients
            with POEMS syndrome, also known as Crow-Fukase syndrome. Allelic
            variants of this gene have been associated with microvascular
            complications of diabetes 1 (MVCD1) and atherosclerosis.
            Alternatively spliced transcript variants encoding different
            isoforms have been described. There is also evidence for
            alternative translation initiation from upstream non-AUG (CUG)
            codons resulting in additional isoforms. A recent study showed that
            a C-terminally extended isoform is produced by use of an
            alternative in-frame translation termination codon via a stop codon
            readthrough mechanism, and that this isoform is antiangiogenic.
            Expression of some isoforms derived from the AUG start codon is
            regulated by a small upstream open reading frame, which is located
            within an internal ribosome entry site. The levels of VEGF are
            increased during infection with severe acute respiratory syndrome
            coronavirus 2 (SARS-CoV-2), thus promoting inflammation by
            facilitating recruitment of inflammatory cells, and by increasing
            the level of angiopoietin II (Ang II), one of two products of the
            SARS-CoV-2 binding target, angiotensin-converting enzyme 2 (ACE2).
            In turn, Ang II facilitates the elevation of VEGF, thus forming a
            vicious cycle in the release of inflammatory cytokines. [provided
            by RefSeq, Jun 2020].
            
            CCDS Note: This CCDS representation starts at an upstream non-AUG
            (CUG) translation start codon that is supported by conservation
            data and experimental evidence, including that in PMIDs:11352659,
            11563986 and 11731620. Most of the publicly available long mRNAs at
            this locus do not extend far enough 5' to include the CUG start
            codon, including S85192.1 which supports this variant. However,
            BC058855.1, several unspliced partial transcripts and the
            aforementioned publications all support transcription initiation
            further upstream. Hence, this CCDS representation includes the
            extended 5' CDS. Alternative translation initiation from a
            downstream AUG codon (Met-181), which results in a shorter isoform
            with a predicted signal peptide, has also been shown for this gene.
            The shorter isoform encoded by this variant is represented by CCDS
            55010.1.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: S85192.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA2145240
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            coronavirus related      :: involved in cytokine storm inflammatory
                                        response
            non-AUG initiation codon :: PMID: 11352659, 11563986, 11731620
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-189               DA237741.1         29-217
            190-636             CN256173.1         166-612
            637-1072            BU153227.1         76-511
            1073-1742           S85192.1           105-774
            1743-2647           AF024710.1         8-912
            2648-2654           BF700556.1         171-177
            2655-3624           AF024710.1         920-1889
            3625-3660           BM661679.1         16-51               c
FEATURES             Location/Qualifiers
     source          1..3660
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p21.1"
     gene            1..3660
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /note="vascular endothelial growth factor A"
                     /db_xref="GeneID:7422"
                     /db_xref="HGNC:HGNC:12680"
                     /db_xref="MIM:192240"
     exon            1..1102
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /inference="alignment:Splign:2.1.0"
     CDS             497..1735
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /note="isoform a is encoded by transcript variant 1;
                     non-AUG (CUG) translation initiation codon; vascular
                     endothelial growth factor A165; vascular permeability
                     factor; vascular endothelial growth factor A121; vascular
                     endothelial growth factor A, long form"
                     /codon_start=1
                     /product="vascular endothelial growth factor A, long form
                     isoform a"
                     /protein_id="NP_001020537.2"
                     /db_xref="CCDS:CCDS34457.1"
                     /db_xref="GeneID:7422"
                     /db_xref="HGNC:HGNC:12680"
                     /db_xref="MIM:192240"
                     /translation="MTDRQTDTAPSPSYHLLPGRRRTVDAAASRGQGPEPAPGGGVEG
                     VGARGVALKLFVQLLGCSRFGGAVVRAGEAEPSGAARSASSGREEPQPEEGEEEEEKE
                     EERGPQWRLGARKPGSWTGEAAVCADSAPAARAPQALARASGRGGRVARRGAEESGPP
                     HSPSRRGSASRAGPGRASETMNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHH
                     EVVKFMDVYQRSYCHPIETLVDIFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVP
                     TEESNITMQIMRIKPHQGQHIGEMSFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRK
                     RKKSRYKSWSVYVGARCCLMPWSLPGPHPCGPCSERRKHLFVQDPQTCKCSCKNTDSR
                     CKARQLELNERTCRCDKPRR"
     exon            1103..1154
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /inference="alignment:Splign:2.1.0"
     exon            1155..1351
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /inference="alignment:Splign:2.1.0"
     exon            1352..1428
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /inference="alignment:Splign:2.1.0"
     exon            1429..1458
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /inference="alignment:Splign:2.1.0"
     exon            1459..1581
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /inference="alignment:Splign:2.1.0"
     exon            1582..1713
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /inference="alignment:Splign:2.1.0"
     exon            1714..3660
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3410..3415
                     /regulatory_class="polyA_signal_sequence"
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /note="hexamer: AATAGA"
     polyA_site      3432
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
     regulatory      3634..3639
                     /regulatory_class="polyA_signal_sequence"
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /note="hexamer: ATTAAA"
     polyA_site      3660
                     /gene="VEGFA"
                     /gene_synonym="L-VEGF; MVCD1; VEGF; VPF"
                     /note="major polyA site"
ORIGIN      
        1 gcggaggctt ggggcagccg ggtagctcgg aggtcgtggc gctgggggct agcaccagcg
       61 ctctgtcggg aggcgcagcg gttaggtgga ccggtcagcg gactcaccgg ccagggcgct
      121 cggtgctgga atttgatatt cattgatccg ggttttatcc ctcttctttt ttcttaaaca
      181 ttttttttta aaactgtatt gtttctcgtt ttaatttatt tttgcttgcc attccccact
      241 tgaatcgggc cgacggcttg gggagattgc tctacttccc caaatcactg tggattttgg
      301 aaaccagcag aaagaggaaa gaggtagcaa gagctccaga gagaagtcga ggaagagaga
      361 gacggggtca gagagagcgc gcgggcgtgc gagcagcgaa agcgacaggg gcaaagtgag
      421 tgacctgctt ttgggggtga ccgccggagc gcggcgtgag ccctccccct tgggatcccg
      481 cagctgacca gtcgcgctga cggacagaca gacagacacc gcccccagcc ccagctacca
      541 cctcctcccc ggccggcggc ggacagtgga cgcggcggcg agccgcgggc aggggccgga
      601 gcccgcgccc ggaggcgggg tggagggggt cggggctcgc ggcgtcgcac tgaaactttt
      661 cgtccaactt ctgggctgtt ctcgcttcgg aggagccgtg gtccgcgcgg gggaagccga
      721 gccgagcgga gccgcgagaa gtgctagctc gggccgggag gagccgcagc cggaggaggg
      781 ggaggaggaa gaagagaagg aagaggagag ggggccgcag tggcgactcg gcgctcggaa
      841 gccgggctca tggacgggtg aggcggcggt gtgcgcagac agtgctccag ccgcgcgcgc
      901 tccccaggcc ctggcccggg cctcgggccg gggaggaaga gtagctcgcc gaggcgccga
      961 ggagagcggg ccgccccaca gcccgagccg gagagggagc gcgagccgcg ccggccccgg
     1021 tcgggcctcc gaaaccatga actttctgct gtcttgggtg cattggagcc ttgccttgct
     1081 gctctacctc caccatgcca agtggtccca ggctgcaccc atggcagaag gaggagggca
     1141 gaatcatcac gaagtggtga agttcatgga tgtctatcag cgcagctact gccatccaat
     1201 cgagaccctg gtggacatct tccaggagta ccctgatgag atcgagtaca tcttcaagcc
     1261 atcctgtgtg cccctgatgc gatgcggggg ctgctgcaat gacgagggcc tggagtgtgt
     1321 gcccactgag gagtccaaca tcaccatgca gattatgcgg atcaaacctc accaaggcca
     1381 gcacatagga gagatgagct tcctacagca caacaaatgt gaatgcagac caaagaaaga
     1441 tagagcaaga caagaaaaaa aatcagttcg aggaaaggga aaggggcaaa aacgaaagcg
     1501 caagaaatcc cggtataagt cctggagcgt gtacgttggt gcccgctgct gtctaatgcc
     1561 ctggagcctc cctggccccc atccctgtgg gccttgctca gagcggagaa agcatttgtt
     1621 tgtacaagat ccgcagacgt gtaaatgttc ctgcaaaaac acagactcgc gttgcaaggc
     1681 gaggcagctt gagttaaacg aacgtacttg cagatgtgac aagccgaggc ggtgagccgg
     1741 gcaggaggaa ggagcctccc tcagggtttc gggaaccaga tctctcacca ggaaagactg
     1801 atacagaacg atcgatacag aaaccacgct gccgccacca caccatcacc atcgacagaa
     1861 cagtccttaa tccagaaacc tgaaatgaag gaagaggaga ctctgcgcag agcactttgg
     1921 gtccggaggg cgagactccg gcggaagcat tcccgggcgg gtgacccagc acggtccctc
     1981 ttggaattgg attcgccatt ttatttttct tgctgctaaa tcaccgagcc cggaagatta
     2041 gagagtttta tttctgggat tcctgtagac acacccaccc acatacatac atttatatat
     2101 atatatatta tatatatata aaaataaata tctctatttt atatatataa aatatatata
     2161 ttcttttttt aaattaacag tgctaatgtt attggtgtct tcactggatg tatttgactg
     2221 ctgtggactt gagttgggag gggaatgttc ccactcagat cctgacaggg aagaggagga
     2281 gatgagagac tctggcatga tctttttttt gtcccacttg gtggggccag ggtcctctcc
     2341 cctgcccagg aatgtgcaag gccagggcat gggggcaaat atgacccagt tttgggaaca
     2401 ccgacaaacc cagccctggc gctgagcctc tctaccccag gtcagacgga cagaaagaca
     2461 gatcacaggt acagggatga ggacaccggc tctgaccagg agtttgggga gcttcaggac
     2521 attgctgtgc tttggggatt ccctccacat gctgcacgcg catctcgccc ccaggggcac
     2581 tgcctggaag attcaggagc ctgggcggcc ttcgcttact ctcacctgct tctgagttgc
     2641 ccaggagacc actggcagat gtcccggcga agagaagaga cacattgttg gaagaagcag
     2701 cccatgacag ctccccttcc tgggactcgc cctcatcctc ttcctgctcc ccttcctggg
     2761 gtgcagccta aaaggaccta tgtcctcaca ccattgaaac cactagttct gtccccccag
     2821 gagacctggt tgtgtgtgtg tgagtggttg accttcctcc atcccctggt ccttcccttc
     2881 ccttcccgag gcacagagag acagggcagg atccacgtgc ccattgtgga ggcagagaaa
     2941 agagaaagtg ttttatatac ggtacttatt taatatccct ttttaattag aaattaaaac
     3001 agttaattta attaaagagt agggtttttt ttcagtattc ttggttaata tttaatttca
     3061 actatttatg agatgtatct tttgctctct cttgctctct tatttgtacc ggtttttgta
     3121 tataaaattc atgtttccaa tctctctctc cctgatcggt gacagtcact agcttatctt
     3181 gaacagatat ttaattttgc taacactcag ctctgccctc cccgatcccc tggctcccca
     3241 gcacacattc ctttgaaata aggtttcaat atacatctac atactatata tatatttggc
     3301 aacttgtatt tgtgtgtata tatatatata tatgtttatg tatatatgtg attctgataa
     3361 aatagacatt gctattctgt tttttatatg taaaaacaaa acaagaaaaa atagagaatt
     3421 ctacatacta aatctctctc cttttttaat tttaatattt gttatcattt atttattggt
     3481 gctactgttt atccgtaata attgtgggga aaagatatta acatcacgtc tttgtctcta
     3541 gtgcagtttt tcgagatatt ccgtagtaca tatttatttt taaacaacga caaagaaata
     3601 cagatatatc ttaaaaaaaa aaaagcattt tgtattaaag aatttaattc tgatctcaaa
//
