LOCUS       NM_001127496            4904 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens sprouty RTK signaling antagonist 4 (SPRY4), transcript
            variant 2, mRNA.
ACCESSION   NM_001127496
VERSION     NM_001127496.3
KEYWORDS    RefSeq; MANE Select.
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 4904)
  AUTHORS   Stuckel,A.J., Zeng,S., Lyu,Z., Zhang,W., Zhang,X., Dougherty,U.,
            Mustafi,R., Khare,T., Zhang,Q., Joshi,T., Bissonnette,M. and
            Khare,S.
  TITLE     Sprouty4 is epigenetically upregulated in human colorectal cancer
  JOURNAL   Epigenetics 18 (1), 2145068 (2023)
   PUBMED   36384366
  REMARK    GeneRIF: Sprouty4 is epigenetically upregulated in human colorectal
            cancer.
REFERENCE   2  (bases 1 to 4904)
  AUTHORS   Zhang,Y., Chen,H., Yuan,R., Wang,Y., Zhang,D., Zeng,Q., Jiang,W.,
            Zhang,R., Chen,T., Chai,C. and Guo,B.
  TITLE     PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer progression
            via activating NF-kappaB signaling pathway
  JOURNAL   Mol Carcinog 62 (7), 1009-1024 (2023)
   PUBMED   37042573
  REMARK    GeneRIF: PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer
            progression via activating NF-kappaB signaling pathway.
REFERENCE   3  (bases 1 to 4904)
  AUTHORS   Li,N., Chen,Y., Wang,H., Li,J. and Zhao,R.C.
  TITLE     SPRY4 promotes adipogenic differentiation of human mesenchymal stem
            cells through the MEK-ERK1/2 signaling pathway
  JOURNAL   Adipocyte 11 (1), 588-600 (2022)
   PUBMED   36082406
  REMARK    GeneRIF: SPRY4 promotes adipogenic differentiation of human
            mesenchymal stem cells through the MEK-ERK1/2 signaling pathway.
REFERENCE   4  (bases 1 to 4904)
  AUTHORS   Ma,Q., Xu,Q., Zhao,J., Zhang,W., Wang,Q., Fang,J., Lu,Z., Liu,J.
            and Ma,L.
  TITLE     Coupling HDAC4 with transcriptional factor MEF2D abrogates
            SPRY4-mediated suppression of ERK activation and elicits
            hepatocellular carcinoma drug resistance
  JOURNAL   Cancer Lett 520, 243-254 (2021)
   PUBMED   34339801
  REMARK    GeneRIF: Coupling HDAC4 with transcriptional factor MEF2D abrogates
            SPRY4-mediated suppression of ERK activation and elicits
            hepatocellular carcinoma drug resistance.
REFERENCE   5  (bases 1 to 4904)
  AUTHORS   Tsumura,Y., Toshima,J., Leeksma,O.C., Ohashi,K. and Mizuno,K.
  TITLE     Sprouty-4 negatively regulates cell spreading by inhibiting the
            kinase activity of testicular protein kinase
  JOURNAL   Biochem J 387 (Pt 3), 627-637 (2005)
   PUBMED   15584898
REFERENCE   6  (bases 1 to 4904)
  AUTHORS   Ding,W., Bellusci,S., Shi,W. and Warburton,D.
  TITLE     Genomic structure and promoter characterization of the human
            Sprouty4 gene, a novel regulator of lung morphogenesis
  JOURNAL   Am J Physiol Lung Cell Mol Physiol 287 (1), L52-L59 (2004)
   PUBMED   14977631
  REMARK    GeneRIF: Core promoter activity is located within proximal 0.4-kb
            region. Minimal ERK-inducible promoter activity is between -69 and
            -31. Core promoter region of hSpry4 gene exhibits significant
            homology to 5'-flanking region of mouse gene.
REFERENCE   7  (bases 1 to 4904)
  AUTHORS   Sasaki,A., Taketomi,T., Kato,R., Saeki,K., Nonami,A., Sasaki,M.,
            Kuriyama,M., Saito,N., Shibuya,M. and Yoshimura,A.
  TITLE     Mammalian Sprouty4 suppresses Ras-independent ERK activation by
            binding to Raf1
  JOURNAL   Nat Cell Biol 5 (5), 427-432 (2003)
   PUBMED   12717443
  REMARK    GeneRIF: Sprouty4 suppresses vascular epithelial growth factor
            (VEGF)-induced, Ras-independent activation of Raf1 but does not
            affect epidermal growth factor (EGF)-induced, Ras-dependent
            activation of Raf1.
REFERENCE   8  (bases 1 to 4904)
  AUTHORS   Leeksma,O.C., Van Achterberg,T.A., Tsumura,Y., Toshima,J.,
            Eldering,E., Kroes,W.G., Mellink,C., Spaargaren,M., Mizuno,K.,
            Pannekoek,H. and de Vries,C.J.
  TITLE     Human sprouty 4, a new ras antagonist on 5q31, interacts with the
            dual specificity kinase TESK1
  JOURNAL   Eur J Biochem 269 (10), 2546-2556 (2002)
   PUBMED   12027893
  REMARK    GeneRIF: interacts with the dual specificity kinase TESK1; maps to
            5q31.3
REFERENCE   9  (bases 1 to 4904)
  AUTHORS   Sasaki,A., Taketomi,T., Wakioka,T., Kato,R. and Yoshimura,A.
  TITLE     Identification of a dominant negative mutant of Sprouty that
            potentiates fibroblast growth factor- but not epidermal growth
            factor-induced ERK activation
  JOURNAL   J Biol Chem 276 (39), 36804-36808 (2001)
   PUBMED   11495895
REFERENCE   10 (bases 1 to 4904)
  AUTHORS   Balasubramanian,R. and Crowley,W.F. Jr.
  TITLE     Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301509
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK096464.1, AK226147.1,
            BP387943.1, T32786.1 and AC091825.4.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Feb 27, 2020 this sequence version replaced NM_001127496.2.
            
            Summary: This gene encodes a member of a family of cysteine- and
            proline-rich proteins. The encoded protein is an inhibitor of the
            receptor-transduced mitogen-activated protein kinase (MAPK)
            signaling pathway. Activity of this protein impairs the formation
            of active GTP-RAS. Nucleotide variation in this gene has been
            associated with hypogonadotropic hypogonadism 17 with or without
            anosmia. Alternative splicing results in a multiple transcript
            variants. [provided by RefSeq, Jun 2014].
            
            Transcript Variant: This variant (2) differs in the 5' UTR, lacks a
            portion of the 5' coding region, and initiates translation at a
            downstream in-frame start codon, compared to variant 1. The encoded
            isoform (2) has a shorter N-terminus than isoform 1. Variants 2, 3,
            and 4 encode the same isoform (2).
            
            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 :: SRR14372080.630492.1,
                                           SRR11853566.23064.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1966682, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000434127.3/ ENSP00000399468.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1305              AK096464.1         20-1324
            1306-4480           AK226147.1         1763-4937
            4481-4897           BP387943.1         82-498
            4898-4899           T32786.1           9-10                c
            4900-4904           AC091825.4         50974-50978
FEATURES             Location/Qualifiers
     source          1..4904
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q31.3"
     gene            1..4904
                     /gene="SPRY4"
                     /gene_synonym="HH17"
                     /note="sprouty RTK signaling antagonist 4"
                     /db_xref="GeneID:81848"
                     /db_xref="HGNC:HGNC:15533"
                     /db_xref="MIM:607984"
     exon            1..178
                     /gene="SPRY4"
                     /gene_synonym="HH17"
                     /inference="alignment:Splign:2.1.0"
     exon            179..4904
                     /gene="SPRY4"
                     /gene_synonym="HH17"
                     /inference="alignment:Splign:2.1.0"
     CDS             226..1125
                     /gene="SPRY4"
                     /gene_synonym="HH17"
                     /note="isoform 2 is encoded by transcript variant 2;
                     protein sprouty homolog 4"
                     /codon_start=1
                     /product="protein sprouty homolog 4 isoform 2"
                     /protein_id="NP_001120968.1"
                     /db_xref="CCDS:CCDS47296.1"
                     /db_xref="GeneID:81848"
                     /db_xref="HGNC:HGNC:15533"
                     /db_xref="MIM:607984"
                     /translation="MEPPIPQSAPLTPNSVMVQPLLDSRMSHSRLQHPLTILPIDQVK
                     TSHVENDYIDNPSLALTTGPKRTRGGAPELAPTPARCDQDVTHHWISFSGRPSSVSSS
                     SSTSSDQRLLDHMAPPPVADQASPRAVRIQPKVVHCQPLDLKGPAVPPELDKHFLLCE
                     ACGKCKCKECASPRTLPSCWVCNQECLCSAQTLVNYGTCMCLVQGIFYHCTNEDDEGS
                     CADHPCSCSRSNCCARWSFMGALSVVLPCLLCYLPATGCVKLAQRGYDRLRRPGCRCK
                     HTNSVICKAASGDAKTSRPDKPF"
     regulatory      4873..4878
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SPRY4"
                     /gene_synonym="HH17"
                     /note="hexamer: AATATA"
     regulatory      4887..4892
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SPRY4"
                     /gene_synonym="HH17"
                     /note="hexamer: AATATA"
     polyA_site      4899
                     /gene="SPRY4"
                     /gene_synonym="HH17"
                     /note="major polyA site"
     polyA_site      4904
                     /gene="SPRY4"
                     /gene_synonym="HH17"
                     /note="major polyA site"
ORIGIN      
        1 gcaacatcgc cgcggaggta gcgagctgag ctgacagcgc ggagctggcg ctgtggagcg
       61 cagggagcct tgccggttcc tccgaccggc gtctgcgagt acagcggcgg ctaacctgcc
      121 ccggcttcag gatttacaca gacgtggggc gatgcttgtg accctgcagc tcctcaaagg
      181 cccctagaag cctgtttctc cgtacagtcc aggacctcca gccccatgga gcccccgatc
      241 ccacagagcg cccccttgac tcccaactca gtcatggtcc agccccttct tgacagccgg
      301 atgtcccaca gccggctcca gcacccactc accatcctac ccattgacca ggtgaagacc
      361 agccatgtgg agaatgacta catagacaac cctagcctgg ccctgaccac cggcccaaag
      421 cggacccggg gcggggcccc agagctggcc ccgacgcccg cccgctgtga ccaggatgtc
      481 acccaccatt ggatctcctt cagcgggcgc cccagctctg tgagcagcag cagcagcaca
      541 tcctctgacc aacggctctt agaccacatg gcaccaccac ccgtggctga ccaggcctca
      601 ccaagggctg tgcgcatcca gcccaaggtg gtccactgcc agccgctgga cctcaagggc
      661 ccggcggtcc cacccgagct ggacaagcac ttcttgctgt gcgaggcctg tgggaagtgt
      721 aaatgcaagg agtgtgcatc cccccggacg ttgccttcct gctgggtctg caaccaggag
      781 tgcctgtgct cagcccagac tctggtcaac tatggcacgt gcatgtgttt ggtgcagggc
      841 atcttctacc actgcacgaa tgaggacgat gagggctcct gcgctgacca cccctgctcc
      901 tgctcccgct ccaactgctg cgcccgctgg tccttcatgg gtgctctctc cgtggtgctg
      961 ccctgcctgc tctgctacct gcctgccacc ggctgcgtga agctggccca gcgtggctac
     1021 gaccgtctgc gccgccctgg ttgccgctgc aagcacacga acagcgtcat ctgcaaagca
     1081 gccagcgggg atgccaagac cagcaggccc gacaagcctt tctgacagtt tgtgtcgaag
     1141 ccccagtgct ctgcctggaa acctggttct cttctgacat ctaagaagac tgcagcaagg
     1201 tcagaggttt tagcctcctg aggctgacct tgctagtctg cccactccct acccccagct
     1261 tcggaaaata cagagaccac caccacgtac cctgtattcc ccaaggtgat gaagaagcac
     1321 tttggggctt tttttcaggg tcctgaaact ttgtgtcaaa cagacaatgc aggggcaggg
     1381 tgtggtttgg ggggaaattt ttctttttca gaagacagaa cacagatgtg gacacatatc
     1441 cggaaactgc agctgcttga atgccttccc agcccctcct tctccctccc tccctccgcc
     1501 ccccccccct tcctcttttc cattgtcttt ggctctcaca ggagctagct gcctgggagg
     1561 aattgttaac tgagtaccag ggtaccttta aagaagaccc ttggagtctt ctataccttc
     1621 ttctccttcc ccatctcact ccaccccact ttgtccctga tgtcttgggg aaggtgtaga
     1681 acaccctagc agttcctatt gtatatactt gggagccact gagaacagag gacggccagt
     1741 gagtccaagc ctcgttcctc cttctgcctc cccggagcca caggatggat ttaggagcca
     1801 ctgctcagtg cacttctccc ttccaactgc atcaactaac tctcgggggt gttctgctca
     1861 ccacaccgtc cttcggttct tactgagtca cagactcgcc tgcccactac gtgtcctggg
     1921 ttctctctac tcagatccct tccagaaact ttatatgggt agaggaagcc agggcggcaa
     1981 atgcgagacc aaatatcatt ttgccaatga gtctgaggct gtggtctctg gatccagtca
     2041 ttatgttttt atagaataat taaaccggat gctaacggtg ttttaaaaaa taataataaa
     2101 acaacttgtt tccttttggc cacccccagg aagggctgat ttcaaaatct gggggcgagc
     2161 aacctcaagg aacacaattt ccctccctat caacaagagg attttaacag caaagaagag
     2221 aggcagcacc tcccattggc agaatgaccg ctgagccagg ctgggtttgg gtttcttctc
     2281 ttctgattct gctgctcact gtcatagcct tttgtgtata gtgatgtgtc tgtatcttta
     2341 atgtaaatag agagatgatg aaaaaagagt ctattttagt gttaggaagc cccagcaggg
     2401 gagtcggaag agcttggaag agctggggag agggtagggg aaaggttttt ccaggggcca
     2461 ctgggtttga gccctgcttc tgtgcacagc cacaccaccc tctcccgaca gccctcaaag
     2521 acgtagcaac tctttctctc aaggtgctaa aggactcaga aggtgcagca cgtccagtgg
     2581 gtaggtactt gttgcatgca aaagctgtag tgtatctggt ccttcctccc cagcttttgt
     2641 gtggggttct tgctttgtgt ggtattttgt tttcccctct aatgagaggg catggcctga
     2701 gtcagaagag ctaccccagg tgaaactgga agtgcatgag gcagagcgtc cgtagcattt
     2761 ccagtttgtt ctgtatagga acagaggtgc ctccgggaag gaggcagcga ggtaggtagc
     2821 tatgataggc acctaatgct tctcaaggac ttattttttc cttcttgaag actagtagta
     2881 acatcttatg atttagagta agttgattgt aaccataggt atttattgat tggaggaagg
     2941 gagggtcata ttattttcgg ctttatttat gtaacatttg ctagcttgta aaaggcgaat
     3001 gtgaaatatt gcatctgcat tttccaaggc tgattcgtgt agctaccctt gccacagttg
     3061 tgacggatgt atggatgttc ttgaacattt cagaaggagt ggtagaaaaa aacacacatt
     3121 cagccaacca cttatatgaa ttgaatgtat cagaagtgta ctgaagggac tggagatggt
     3181 tttcctcaga tgagggggcc ccaaaattga tagtgcacat ctgcacgctt tctgcgaggc
     3241 ctcagaactt cccagggccc ctccctcaaa ttgtctccat gggaaacttg acccagtggc
     3301 aagttgcact ttggtgatct tggtggtcta cacacccgtt ctgtggagag tcgatttaca
     3361 taagctgtgt atacacacac acacacacac acacacaccc ctaccccaca ctgactgtct
     3421 accgacaaag accctatttc ctggcaaacg gcctcctgaa ccctgacttt ttgtgtacat
     3481 acttgtaaac acggattttt ctgggttttg gtttgctttt tccttttttc cccctgcccc
     3541 tgttctagct tgttcttctt ggtttgcttt caacctgctt gatggatgtc tgcagagtgc
     3601 tctctaagag tccacctcag tgcctcgtgt gctcagtggt catgggaaag gagcgaagga
     3661 accatccttg gttctcccag cttggttgtg tagcaatccc tcagcattgt ttttctcagc
     3721 ttcttggcaa aaattaaaac aacaacaaca acaacaacaa caacaacaaa cagaaggata
     3781 aactggcttg cctgtggacc ctccccggct ctggggccag tcgagagcca ctgagggacc
     3841 cagcactcag agacacaaca cacatgtgta gctgcttctg gctgagtgtg tttcctgtca
     3901 ccaatggcct gtttggctgg acgatgcctc ggcttgacct tttttgaaaa gtgctggtta
     3961 gttcccgccc ctggtaaacc tggggtaggt gggggttctg tcttaactcg aggggcacct
     4021 gggatccagg acgcttctag ggggctctgg ctgcccgtgt taatgaagga cagcgcttcc
     4081 gcgagcaccc tgggaactgg gtcttgggta gcaaagccct cccagagaaa agattgggca
     4141 caactaaggc tttcctgagc aggaaggggg tgaagaccaa tcccttcctt tggtcctttg
     4201 gtacgcaccc cctcagagct gagatggaag acatggctag ttcttttcag ccttgtggag
     4261 cctgtcagtc gccatcatac ctcgagtgag gcccagctag ataatgactt gtccaagatg
     4321 gcacacgtgg aaagttgatc tgcaccagaa cccggatgac tgtcaccttg aagcatcctg
     4381 ttctccttct gtgctgtccc aggaagtgtc tggcgggcgt gggcagcaca gctctacact
     4441 gtacgattca ctagggcatc ctgcgagcct cactagcctt ctggttcatg cctttgacaa
     4501 gcatttttgt gccccctctg cttactgtga cagtcgatga tgaatcttgc gttgccattt
     4561 tctgctgtgg gtaactgcgt gcagtgtctt gccttgcttt ctcttcttac tgtcccacag
     4621 cttggtttca tgttacaaac agaaaagctc gaggctccca ccccgccaca tcccaacttc
     4681 atttccccct cactgtagcc catttccacc ccaccacaaa gttgccacag gttttctttg
     4741 tatagaatat ttattttgaa gctctatttt aatagtattt attttagaaa gtctactatt
     4801 gtaagagttc ttctgtttgt gaagaaaaaa acaagttaaa aactgaatgt actgatttag
     4861 aaaatatata taaatatata ttgttaaata tacacgggac tgcc
//
