LOCUS       NM_004444               4353 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens EPH receptor B4 (EPHB4), mRNA.
ACCESSION   NM_004444
VERSION     NM_004444.5
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 4353)
  AUTHORS   Vanden Broek,K., Ryu,J.R., Perrier,R., Tyndall,A.V., Childs,S.J.
            and Au,P.Y.B.
  TITLE     SAM domain variants of EPHB4 associated with aberrant signaling are
            linked to lymphatic-related fetal hydrops and facial dysmorphology
  JOURNAL   Clin Genet 105 (4), 386-396 (2024)
   PUBMED   38151336
  REMARK    GeneRIF: SAM domain variants of EPHB4 associated with aberrant
            signaling are linked to lymphatic-related fetal hydrops and facial
            dysmorphology.
            Erratum:[Clin Genet. 2024 Nov;106(5):664. doi: 10.1111/cge.14597..
            PMID: 39073083]
REFERENCE   2  (bases 1 to 4353)
  AUTHORS   Ullah,A., Razzaq,A., Zhou,C., Ullah,N., Shehzadi,S., Aziz,T.,
            Alfaifi,M.Y., Elbehairi,S.E.I. and Iqbal,H.
  TITLE     Biological Significance of EphB4 Expression in Cancer
  JOURNAL   Curr Protein Pept Sci 25 (3), 244-255 (2024)
   PUBMED   37909437
  REMARK    GeneRIF: Biological Significance of EphB4 Expression in Cancer.
            Review article
REFERENCE   3  (bases 1 to 4353)
  AUTHORS   Sesen,J., Ghalali,A., Driscoll,J., Martinez,T., Lupieri,A.,
            Zurakowski,D., Alexandrescu,S., Smith,E.R. and Fehnel,K.P.
  TITLE     Discovery and Characterization of Ephrin B2 and EphB4 Dysregulation
            and Novel Mutations in Cerebral Cavernous Malformations: In Vitro
            and Patient-Derived Evidence of Ephrin-Mediated Endothelial Cell
            Pathophysiology
  JOURNAL   Cell Mol Neurobiol 44 (1), 12 (2023)
   PUBMED   38150042
  REMARK    GeneRIF: Discovery and Characterization of Ephrin B2 and EphB4
            Dysregulation and Novel Mutations in Cerebral Cavernous
            Malformations: In Vitro and Patient-Derived Evidence of
            Ephrin-Mediated Endothelial Cell Pathophysiology.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4353)
  AUTHORS   Vish,K.J., Stiegler,A.L. and Boggon,T.J.
  TITLE     Diverse p120RasGAP interactions with doubly phosphorylated partners
            EphB4, p190RhoGAP, and Dok1
  JOURNAL   J Biol Chem 299 (9), 105098 (2023)
   PUBMED   37507023
  REMARK    GeneRIF: Diverse p120RasGAP interactions with doubly phosphorylated
            partners EphB4, p190RhoGAP, and Dok1.
REFERENCE   5  (bases 1 to 4353)
  AUTHORS   Guilhem,A., Dupuis-Girod,S., Espitia,O., Riviere,S., Seguier,J.,
            Kerjouan,M., Lavigne,C., Maillard,H., Magro,P., Alric,L.,
            Lipsker,D., Parrot,A., Leguy,V., Vanlemmens,C., Guibaud,L.,
            Vikkula,M., Eyries,M., Valette,P.J. and Giraud,S.
  TITLE     Seven cases of hereditary haemorrhagic telangiectasia-like hepatic
            vascular abnormalities associated with EPHB4 pathogenic variants
  JOURNAL   J Med Genet 60 (9), 905-909 (2023)
   PUBMED   36813543
  REMARK    GeneRIF: Seven cases of hereditary haemorrhagic telangiectasia-like
            hepatic vascular abnormalities associated with EPHB4 pathogenic
            variants.
REFERENCE   6  (bases 1 to 4353)
  AUTHORS   Flanagan,J.G. and Vanderhaeghen,P.
  TITLE     The ephrins and Eph receptors in neural development
  JOURNAL   Annu Rev Neurosci 21, 309-345 (1998)
   PUBMED   9530499
  REMARK    Review article
REFERENCE   7  (bases 1 to 4353)
  AUTHORS   Berclaz,G., Andres,A.C., Albrecht,D., Dreher,E., Ziemiecki,A.,
            Gusterson,B.A. and Crompton,M.R.
  TITLE     Expression of the receptor protein tyrosine kinase myk-1/htk in
            normal and malignant mammary epithelium
  JOURNAL   Biochem Biophys Res Commun 226 (3), 869-875 (1996)
   PUBMED   8831703
REFERENCE   8  (bases 1 to 4353)
  AUTHORS   Bennett,B.D., Wang,Z., Kuang,W.J., Wang,A., Groopman,J.E.,
            Goeddel,D.V. and Scadden,D.T.
  TITLE     Cloning and characterization of HTK, a novel transmembrane tyrosine
            kinase of the EPH subfamily
  JOURNAL   J Biol Chem 269 (19), 14211-14218 (1994)
   PUBMED   8188704
REFERENCE   9  (bases 1 to 4353)
  AUTHORS   Andres,A.C., Reid,H.H., Zurcher,G., Blaschke,R.J., Albrecht,D. and
            Ziemiecki,A.
  TITLE     Expression of two novel eph-related receptor protein tyrosine
            kinases in mammary gland development and carcinogenesis
  JOURNAL   Oncogene 9 (5), 1461-1467 (1994)
   PUBMED   8152808
  REMARK    Erratum:[Oncogene 1994 Aug;9(8):2431]
REFERENCE   10 (bases 1 to 4353)
  AUTHORS   Bayrak-Toydemir,P. and Stevenson,D.A.
  TITLE     Capillary Malformation-Arteriovenous Malformation Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   21348050
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC011895.4, CB962032.1,
            BC052804.1 and AY056048.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_004444.4.
            
            Summary: Ephrin receptors and their ligands, the ephrins, mediate
            numerous developmental processes, particularly in the nervous
            system. Based on their structures and sequence relationships,
            ephrins are divided into the ephrin-A (EFNA) class, which are
            anchored to the membrane by a glycosylphosphatidylinositol linkage,
            and the ephrin-B (EFNB) class, which are transmembrane proteins.
            The Eph family of receptors are divided into 2 groups based on the
            similarity of their extracellular domain sequences and their
            affinities for binding ephrin-A and ephrin-B ligands. Ephrin
            receptors make up the largest subgroup of the receptor tyrosine
            kinase (RTK) family. The protein encoded by this gene binds to
            ephrin-B2 and plays an essential role in vascular development.
            [provided by RefSeq, Jul 2008].
            
            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 :: BC052804.1, U07695.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000358173.8/ ENSP00000350896.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2                 AC011895.4         69655-69656         c
            3-325               CB962032.1         30-352
            326-977             BC052804.1         1-652
            978-3171            AY056048.1         570-2763
            3172-4353           BC052804.1         2847-4028
FEATURES             Location/Qualifiers
     source          1..4353
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q22.1"
     gene            1..4353
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /note="EPH receptor B4"
                     /db_xref="GeneID:2050"
                     /db_xref="HGNC:HGNC:3395"
                     /db_xref="MIM:600011"
     exon            1..545
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     CDS             494..3457
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /EC_number="2.7.10.1"
                     /note="hepatoma transmembrane kinase; ephrin type-B
                     receptor 4; ephrin receptor EphB4; tyrosine-protein kinase
                     TYRO11; tyrosine-protein kinase receptor HTK"
                     /codon_start=1
                     /product="ephrin type-B receptor 4 precursor"
                     /protein_id="NP_004435.3"
                     /db_xref="CCDS:CCDS5706.1"
                     /db_xref="GeneID:2050"
                     /db_xref="HGNC:HGNC:3395"
                     /db_xref="MIM:600011"
                     /translation="MELRVLLCWASLAAALEETLLNTKLETADLKWVTFPQVDGQWEE
                     LSGLDEEQHSVRTYEVCDVQRAPGQAHWLRTGWVPRRGAVHVYATLRFTMLECLSLPR
                     AGRSCKETFTVFYYESDADTATALTPAWMENPYIKVDTVAAEHLTRKRPGAEATGKVN
                     VKTLRLGPLSKAGFYLAFQDQGACMALLSLHLFYKKCAQLTVNLTRFPETVPRELVVP
                     VAGSCVVDAVPAPGPSPSLYCREDGQWAEQPVTGCSCAPGFEAAEGNTKCRACAQGTF
                     KPLSGEGSCQPCPANSHSNTIGSAVCQCRVGYFRARTDPRGAPCTTPPSAPRSVVSRL
                     NGSSLHLEWSAPLESGGREDLTYALRCRECRPGGSCAPCGGDLTFDPGPRDLVEPWVV
                     VRGLRPDFTYTFEVTALNGVSSLATGPVPFEPVNVTTDREVPPAVSDIRVTRSSPSSL
                     SLAWAVPRAPSGAVLDYEVKYHEKGAEGPSSVRFLKTSENRAELRGLKRGASYLVQVR
                     ARSEAGYGPFGQEHHSQTQLDESEGWREQLALIAGTAVVGVVLVLVVIVVAVLCLRKQ
                     SNGREAEYSDKHGQYLIGHGTKVYIDPFTYEDPNEAVREFAKEIDVSYVKIEEVIGAG
                     EFGEVCRGRLKAPGKKESCVAIKTLKGGYTERQRREFLSEASIMGQFEHPNIIRLEGV
                     VTNSMPVMILTEFMENGALDSFLRLNDGQFTVIQLVGMLRGIASGMRYLAEMSYVHRD
                     LAARNILVNSNLVCKVSDFGLSRFLEENSSDPTYTSSLGGKIPIRWTAPEAIAFRKFT
                     SASDAWSYGIVMWEVMSFGERPYWDMSNQDVINAIEQDYRLPPPPDCPTSLHQLMLDC
                     WQKDRNARPRFPQVVSALDKMIRNPASLKIVARENGGASHPLLDQRQPHYSAFGSVGE
                     WLRAIKMGRYEESFAAAGFGSFELVSQISAEDLLRIGVTLAGHQKKILASVQHMKSQA
                     KPGTPGGTGGPAPQY"
     exon            546..616
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            617..904
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            905..1301
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            1302..1457
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            1458..1790
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            1791..1915
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            1916..2081
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            2082..2184
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            2185..2249
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            2250..2363
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            2364..2611
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            2612..2827
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            2828..2977
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            2978..3171
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            3172..3327
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     exon            3328..4353
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4317..4322
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /note="hexamer: AATAAA"
     polyA_site      4353
                     /gene="EPHB4"
                     /gene_synonym="CMAVM2; HFASD; HTK; LMPHM7; MYK1; TYRO11"
                     /note="major polyA site"
ORIGIN      
        1 agttccagcg cagctcagcc cctgcccggc ccggcccgcc cggctccgcg ccgcagtctc
       61 cctccctccc gctccgtccc cgctcgggct cccaccatcc ccgcccgcga ggagagcact
      121 cggcccggcg gcgcgagcag agccactcca gggagggggg gagaccgcga gcggccggct
      181 cagcccccgc cacccggggc gggaccccga ggccccggag ggaccccaac tccagccacg
      241 tcttgctgcg cgcccgcccg gcgcggccac tgccagcacg ctccgggccc gccgcccgcg
      301 cgcgcggcac agacgcgggg ccacacttgg cgccgccgcc cggtgccccg cacgctcgca
      361 tgggcccgcg ctgagggccc cgacgaggag tcccgcgcgg agtatcggcg tccacccgcc
      421 cagggagagt cagacctggg ggggcgaggg ccccccaaac tcagttcgga tcctacccga
      481 gtgaggcggc gccatggagc tccgggtgct gctctgctgg gcttcgttgg ccgcagcttt
      541 ggaagagacc ctgctgaaca caaaattgga aactgctgat ctgaagtggg tgacattccc
      601 tcaggtggac gggcagtggg aggaactgag cggcctggat gaggaacagc acagcgtgcg
      661 cacctacgaa gtgtgtgacg tgcagcgtgc cccgggccag gcccactggc ttcgcacagg
      721 ttgggtccca cggcggggcg ccgtccacgt gtacgccacg ctgcgcttca ccatgctcga
      781 gtgcctgtcc ctgcctcggg ctgggcgctc ctgcaaggag accttcaccg tcttctacta
      841 tgagagcgat gcggacacgg ccacggccct cacgccagcc tggatggaga acccctacat
      901 caaggtggac acggtggccg cggagcatct cacccggaag cgccctgggg ccgaggccac
      961 cgggaaggtg aatgtcaaga cgctgcgtct gggaccgctc agcaaggctg gcttctacct
     1021 ggccttccag gaccagggtg cctgcatggc cctgctatcc ctgcacctct tctacaaaaa
     1081 gtgcgcccag ctgactgtga acctgactcg attcccggag actgtgcctc gggagctggt
     1141 tgtgcccgtg gccggtagct gcgtggtgga tgccgtcccc gcccctggcc ccagccccag
     1201 cctctactgc cgtgaggatg gccagtgggc cgaacagccg gtcacgggct gcagctgtgc
     1261 tccggggttc gaggcagctg aggggaacac caagtgccga gcctgtgccc agggcacctt
     1321 caagcccctg tcaggagaag ggtcctgcca gccatgccca gccaatagcc actctaacac
     1381 cattggatca gccgtctgcc agtgccgcgt cgggtacttc cgggcacgca cagacccccg
     1441 gggtgcaccc tgcaccaccc ctccttcggc tccgcggagc gtggtttccc gcctgaacgg
     1501 ctcctccctg cacctggaat ggagtgcccc cctggagtct ggtggccgag aggacctcac
     1561 ctacgccctc cgctgccggg agtgccgacc cggaggctcc tgtgcgccct gcgggggaga
     1621 cctgactttt gaccccggcc cccgggacct ggtggagccc tgggtggtgg ttcgagggct
     1681 acgtcctgac ttcacctata cctttgaggt cactgcattg aacggggtat cctccttagc
     1741 cacggggccc gtcccatttg agcctgtcaa tgtcaccact gaccgagagg tacctcctgc
     1801 agtgtctgac atccgggtga cgcggtcctc acccagcagc ttgagcctgg cctgggctgt
     1861 tccccgggca cccagtgggg ctgtgctgga ctacgaggtc aaataccatg agaagggcgc
     1921 cgagggtccc agcagcgtgc ggttcctgaa gacgtcagaa aaccgggcag agctgcgggg
     1981 gctgaagcgg ggagccagct acctggtgca ggtacgggcg cgctctgagg ccggctacgg
     2041 gcccttcggc caggaacatc acagccagac ccaactggat gagagcgagg gctggcggga
     2101 gcagctggcc ctgattgcgg gcacggcagt cgtgggtgtg gtcctggtcc tggtggtcat
     2161 tgtggtcgca gttctctgcc tcaggaagca gagcaatggg agagaagcag aatattcgga
     2221 caaacacgga cagtatctca tcggacatgg tactaaggtc tacatcgacc ccttcactta
     2281 tgaagaccct aatgaggctg tgagggaatt tgcaaaagag atcgatgtct cctacgtcaa
     2341 gattgaagag gtgattggtg caggtgagtt tggcgaggtg tgccgggggc ggctcaaggc
     2401 cccagggaag aaggagagct gtgtggcaat caagaccctg aagggtggct acacggagcg
     2461 gcagcggcgt gagtttctga gcgaggcctc catcatgggc cagttcgagc accccaatat
     2521 catccgcctg gagggcgtgg tcaccaacag catgcccgtc atgattctca cagagttcat
     2581 ggagaacggc gccctggact ccttcctgcg gctaaacgac ggacagttca cagtcatcca
     2641 gctcgtgggc atgctgcggg gcatcgcctc gggcatgcgg taccttgccg agatgagcta
     2701 cgtccaccga gacctggctg ctcgcaacat cctagtcaac agcaacctcg tctgcaaagt
     2761 gtctgacttt ggcctttccc gattcctgga ggagaactct tccgatccca cctacacgag
     2821 ctccctggga ggaaagattc ccatccgatg gactgccccg gaggccattg ccttccggaa
     2881 gttcacttcc gccagtgatg cctggagtta cgggattgtg atgtgggagg tgatgtcatt
     2941 tggggagagg ccgtactggg acatgagcaa tcaggacgtg atcaatgcca ttgaacagga
     3001 ctaccggctg cccccgcccc cagactgtcc cacctccctc caccagctca tgctggactg
     3061 ttggcagaaa gaccggaatg cccggccccg cttcccccag gtggtcagcg ccctggacaa
     3121 gatgatccgg aaccccgcca gcctcaaaat cgtggcccgg gagaatggcg gggcctcaca
     3181 ccctctcctg gaccagcggc agcctcacta ctcagctttt ggctctgtgg gcgagtggct
     3241 tcgggccatc aaaatgggaa gatacgaaga aagtttcgca gccgctggct ttggctcctt
     3301 cgagctggtc agccagatct ctgctgagga cctgctccga atcggagtca ctctggcggg
     3361 acaccagaag aaaatcttgg ccagtgtcca gcacatgaag tcccaggcca agccgggaac
     3421 cccgggtggg acaggaggac cggccccgca gtactgacct gcaggaactc cccaccccag
     3481 ggacaccgcc tccccatttt ccggggcaga gtggggactc acagaggccc ccagccctgt
     3541 gccccgctgg attgcacttt gagcccgtgg ggtgaggagt tggcaatttg gagagacagg
     3601 atttgggggt tctgccataa taggagggga aaatcacccc ccagccacct cggggaactc
     3661 cagaccaagg gtgagggcgc ctttccctca ggactgggtg tgaccagagg aaaaggaagt
     3721 gcccaacatc tcccagcctc cccaggtgcc cccctcacct tgatgggtgc gttcccgcag
     3781 accaaagaga gtgtgactcc cttgccagct ccagagtggg ggggctgtcc cagggggcaa
     3841 gaaggggtgt cagggcccag tgacaaaatc attggggttt gtagtcccaa cttgctgctg
     3901 tcaccaccaa actcaatcat ttttttccct tgtaaatgcc cctcccccag ctgctgcctt
     3961 catattgaag gtttttgagt tttgtttttg gtcttaattt ttctccccgt tccctttttg
     4021 tttcttcgtt ttgtttttct accgtccttg tcataacttt gtgttggagg gaacctgttt
     4081 cactatggcc tcctttgccc aagttgaaac aggggcccat catcatgtct gtttccagaa
     4141 cagtgccttg gtcatcccac atccccggac cccgcctggg acccccaagc tgtgtcctat
     4201 gaaggggtgt ggggtgaggt agtgaaaagg gcggtagttg gtggtggaac ccagaaacgg
     4261 acgccggtgc ttggaggggt tcttaaatta tatttaaaaa agtaactttt tgtataaata
     4321 aaagaaaatg ggacgtgtcc cagctccagg ggt
//
