LOCUS       NM_001270454            4487 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens WW domain containing E3 ubiquitin protein ligase 2
            (WWP2), transcript variant 5, mRNA.
ACCESSION   NM_001270454
VERSION     NM_001270454.2
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 4487)
  AUTHORS   Wang,H., Lian,X., Wang,K. and Wang,S.
  TITLE     WWP2 binds to NKRF, enhances the NF-kappaB signaling, and promotes
            malignant phenotypes of acute myeloid leukemia cells
  JOURNAL   Biochem Cell Biol 102 (1), 85-95 (2024)
   PUBMED   37921219
  REMARK    GeneRIF: WWP2 binds to NKRF, enhances the NF-kappaB signaling, and
            promotes malignant phenotypes of acute myeloid leukemia cells.
REFERENCE   2  (bases 1 to 4487)
  AUTHORS   Lee,K.T., Pranoto,I.K.A., Kim,S.Y., Choi,H.J., To,N.B., Chae,H.,
            Lee,J.Y., Kim,J.E., Kwon,Y.V. and Nam,J.W.
  TITLE     Comparative interactome analysis of alpha-arrestin families in
            human and Drosophila
  JOURNAL   Elife 12, 88328 (2024)
   PUBMED   38270169
  REMARK    Publication Status: Online-Only
REFERENCE   3  (bases 1 to 4487)
  AUTHORS   You,S., Xu,J., Yin,Z., Wu,B., Wang,P., Hao,M., Cheng,C., Liu,M.,
            Zhao,Y., Jia,P., Jiang,H., Li,D., Cao,L., Zhang,X., Zhang,Y.,
            Sun,Y. and Zhang,N.
  TITLE     Down-regulation of WWP2 aggravates Type 2 diabetes mellitus-induced
            vascular endothelial injury through modulating ubiquitination and
            degradation of DDX3X
  JOURNAL   Cardiovasc Diabetol 22 (1), 107 (2023)
   PUBMED   37149668
  REMARK    GeneRIF: Down-regulation of WWP2 aggravates Type 2 diabetes
            mellitus-induced vascular endothelial injury through modulating
            ubiquitination and degradation of DDX3X.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4487)
  AUTHORS   Chantry,A.
  TITLE     WWP2 ubiquitin ligase and its isoforms: new biological insight and
            promising disease targets
  JOURNAL   Cell Cycle 10 (15), 2437-2439 (2011)
   PUBMED   21750408
REFERENCE   5  (bases 1 to 4487)
  AUTHORS   Soond,S.M. and Chantry,A.
  TITLE     Selective targeting of activating and inhibitory Smads by distinct
            WWP2 ubiquitin ligase isoforms differentially modulates TGFbeta
            signalling and EMT
  JOURNAL   Oncogene 30 (21), 2451-2462 (2011)
   PUBMED   21258410
  REMARK    GeneRIF: Data show that the WWP2-N isoform interacts with Smad2 and
            Smad3, whereas WWP2-C interacts only with Smad7.
REFERENCE   6  (bases 1 to 4487)
  AUTHORS   McDonald,F.J., Western,A.H., McNeil,J.D., Thomas,B.C., Olson,D.R.
            and Snyder,P.M.
  TITLE     Ubiquitin-protein ligase WWP2 binds to and downregulates the
            epithelial Na(+) channel
  JOURNAL   Am J Physiol Renal Physiol 283 (3), F431-F436 (2002)
   PUBMED   12167593
  REMARK    GeneRIF: expression, binding, and functional data all suggest that
            WWP2 is a candidate to regulate ENaC-mediated Na(+) transport in
            epithelia
REFERENCE   7  (bases 1 to 4487)
  AUTHORS   Harvey,K.F., Shearwin-Whyatt,L.M., Fotia,A., Parton,R.G. and
            Kumar,S.
  TITLE     N4WBP5, a potential target for ubiquitination by the Nedd4 family
            of proteins, is a novel Golgi-associated protein
  JOURNAL   J Biol Chem 277 (11), 9307-9317 (2002)
   PUBMED   11748237
REFERENCE   8  (bases 1 to 4487)
  AUTHORS   Wood,J.D., Yuan,J., Margolis,R.L., Colomer,V., Duan,K., Kushi,J.,
            Kaminsky,Z., Kleiderlein,J.J., Sharp,A.H. and Ross,C.A.
  TITLE     Atrophin-1, the DRPLA gene product, interacts with two families of
            WW domain-containing proteins
  JOURNAL   Mol Cell Neurosci 11 (3), 149-160 (1998)
   PUBMED   9647693
REFERENCE   9  (bases 1 to 4487)
  AUTHORS   Jonsson,A.B.
  TITLE     Identification of a human cDNA clone that mediates adherence of
            pathogenic Neisseria to non-binding cells
  JOURNAL   FEMS Microbiol Lett 162 (1), 25-30 (1998)
   PUBMED   9595660
REFERENCE   10 (bases 1 to 4487)
  AUTHORS   Pirozzi,G., McConnell,S.J., Uveges,A.J., Carter,J.M., Sparks,A.B.,
            Kay,B.K. and Fowlkes,D.M.
  TITLE     Identification of novel human WW domain-containing proteins by
            cloning of ligand targets
  JOURNAL   J Biol Chem 272 (23), 14611-14616 (1997)
   PUBMED   9169421
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from JN712744.1.
            
            On Jun 2, 2019 this sequence version replaced NM_001270454.1.
            
            Summary: This gene encodes a member of the Nedd4 family of E3
            ligases, which play an important role in protein ubiquitination.
            The encoded protein contains four WW domains and may play a role in
            multiple processes including chondrogenesis and the regulation of
            oncogenic signaling pathways via interactions with Smad proteins
            and the tumor suppressor PTEN. Alternatively spliced transcript
            variants encoding multiple isoforms have been observed for this
            gene, and a pseudogene of this gene is located on the long arm of
            chromosome 10. [provided by RefSeq, Jul 2012].
            
            Transcript Variant: This variant (5) differs in the 5' UTR,
            compared to variant 1. Variants 1 and 5 encode the same isoform
            (WWP2-FL).
            
            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 :: SRR1660803.33248.1,
                                           SRR1660803.9950.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000359154.7/ ENSP00000352069.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-4487              JN712744.1         19-4505
FEATURES             Location/Qualifiers
     source          1..4487
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q22.1"
     gene            1..4487
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /note="WW domain containing E3 ubiquitin protein ligase 2"
                     /db_xref="GeneID:11060"
                     /db_xref="HGNC:HGNC:16804"
                     /db_xref="MIM:602308"
     exon            1..60
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            61..145
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     CDS             76..2688
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /EC_number="2.3.2.26"
                     /note="isoform WWP2-FL is encoded by transcript variant 5;
                     atrophin-1 interacting protein 2; NEDD4-like E3
                     ubiquitin-protein ligase WWP2; HECT-type E3 ubiquitin
                     transferase WWP2"
                     /codon_start=1
                     /product="NEDD4-like E3 ubiquitin-protein ligase WWP2
                     isoform WWP2-FL"
                     /protein_id="NP_001257383.1"
                     /db_xref="CCDS:CCDS10885.1"
                     /db_xref="GeneID:11060"
                     /db_xref="HGNC:HGNC:16804"
                     /db_xref="MIM:602308"
                     /translation="MASASSSRAGVALPFEKSQLTLKVVSAKPKVHNRQPRINSYVEV
                     AVDGLPSETKKTGKRIGSSELLWNEIIILNVTAQSHLDLKVWSCHTLRNELLGTASVN
                     LSNVLKNNGGKMENMQLTLNLQTENKGSVVSGGELTIFLDGPTVDLGNVPNGSALTDG
                     SQLPSRDSSGTAVAPENRHQPPSTNCFGGRSRTHRHSGASARTTPATGEQSPGARSRH
                     RQPVKNSGHSGLANGTVNDEPTTATDPEEPSVVGVTSPPAAPLSVTPNPNTTSLPAPA
                     TPAEGEEPSTSGTQQLPAAAQAPDALPAGWEQRELPNGRVYYVDHNTKTTTWERPLPP
                     GWEKRTDPRGRFYYVDHNTRTTTWQRPTAEYVRNYEQWQSQRNQLQGAMQHFSQRFLY
                     QSSSASTDHDPLGPLPPGWEKRQDNGRVYYVNHNTRTTQWEDPRTQGMIQEPALPPGW
                     EMKYTSEGVRYFVDHNTRTTTFKDPRPGFESGTKQGSPGAYDRSFRWKYHQFRFLCHS
                     NALPSHVKISVSRQTLFEDSFQQIMNMKPYDLRRRLYIIMRGEEGLDYGGIAREWFFL
                     LSHEVLNPMYCLFEYAGKNNYCLQINPASSINPDHLTYFRFIGRFIAMALYHGKFIDT
                     GFTLPFYKRMLNKRPTLKDLESIDPEFYNSIVWIKENNLEECGLELYFIQDMEILGKV
                     TTHELKEGGESIRVTEENKEEYIMLLTDWRFTRGVEEQTKAFLDGFNEVAPLEWLRYF
                     DEKELELMLCGMQEIDMSDWQKSTIYRHYTKNSKQIQWFWQVVKEMDNEKRIRLLQFV
                     TGTCRLPVGGFAELIGSNGPQKFCIDKVGKETWLPRSHTCFNRLDLPPYKSYEQLREK
                     LLYAIEETEGFGQE"
     exon            146..293
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            294..415
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            416..553
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            554..650
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            651..778
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            779..989
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            990..1079
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            1080..1254
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            1255..1309
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            1310..1391
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            1392..1520
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            1521..1596
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            1597..1668
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            1669..1757
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            1758..1917
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            1918..2051
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            2052..2192
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            2193..2313
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            2314..2418
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            2419..2515
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            2516..2588
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     exon            2589..4487
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4469..4474
                     /regulatory_class="polyA_signal_sequence"
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /note="hexamer: AATAAA"
     polyA_site      4487
                     /gene="WWP2"
                     /gene_synonym="AIP2; WWp2-like"
                     /note="major polyA site"
ORIGIN      
        1 gcgggcggtg gaaggcggaa gtaggagagg agttcggcgc cgcttctgtg gccacggcag
       61 cttcacggtg atgatatggc atctgccagc tctagccggg caggagtggc cctgcctttt
      121 gagaagtctc agctcacttt gaaagtggtg tccgcaaagc ccaaggtgca taatcgtcaa
      181 cctcgaatta actcctacgt ggaggtggcg gtggatggac tccccagtga gaccaagaag
      241 actgggaagc gcattgggag ctctgagctt ctctggaatg agatcatcat tttgaatgtc
      301 acggcacaga gtcatttaga tttaaaggtc tggagctgcc ataccttgag aaatgaactg
      361 ctaggcaccg catctgtcaa cctctccaac gtcttgaaga acaatggggg caaaatggag
      421 aacatgcagc tgaccctgaa cctgcagacg gagaacaaag gcagcgttgt ctcaggcgga
      481 gagctgacaa ttttcctgga cgggccaact gttgatctgg gaaatgtgcc taatggcagt
      541 gccctgacag atggatcaca gctgccttcg agagactcca gtggaacagc agtagctcca
      601 gagaaccggc accagccccc cagcacaaac tgctttggtg gaagatcccg gacgcacaga
      661 cattcgggtg cttcagccag aacaacccca gcaaccggcg agcaaagccc cggtgctcgg
      721 agccggcacc gccagcccgt caagaactca ggccacagtg gcttggccaa tggcacagtg
      781 aatgatgaac ccacaacagc cactgatccc gaagaacctt ccgttgttgg tgtgacgtcc
      841 ccacctgctg cacccttgag tgtgaccccg aatcccaaca cgacttctct ccctgcccca
      901 gccacaccgg ctgaaggaga ggaacccagc acttcgggta cacagcagct cccagcggct
      961 gcccaggccc ccgacgctct gcctgctgga tgggaacagc gagagctgcc caacggacgt
     1021 gtctattatg ttgaccacaa taccaagacc accacctggg agcggcccct tcctccaggc
     1081 tgggaaaaac gcacagatcc ccgaggcagg ttttactatg tggatcacaa tactcggacc
     1141 accacctggc agcgtccgac cgcggagtac gtgcgcaact atgagcagtg gcagtcgcag
     1201 cggaatcagc tccagggggc catgcagcac ttcagccaaa gattcctcta ccagtcttcg
     1261 agtgcttcga ctgaccatga tcccctgggc cccctccctc ctggctggga gaagagacag
     1321 gacaatggac gggtgtatta cgtgaaccat aacactcgca cgacccagtg ggaggatccc
     1381 cggacccagg ggatgatcca ggaaccagct ctgcccccag gatgggagat gaaatacacc
     1441 agcgaggggg tgcgatactt tgtggaccac aatacccgca ccaccacctt taaggatcct
     1501 cgcccggggt ttgagtcggg gacgaagcaa ggttcccctg gtgcttatga ccgcagtttt
     1561 cggtggaagt atcaccagtt ccgtttcctc tgccattcaa atgccctacc tagccacgtg
     1621 aagatcagcg tttccaggca gacgcttttc gaagattcct tccaacagat catgaacatg
     1681 aaaccctatg acctgcgccg ccggctctac atcatcatgc gtggcgagga gggcctggac
     1741 tatgggggca tcgccagaga gtggtttttc ctcctgtctc atgaggtgct caaccctatg
     1801 tattgtttat ttgaatatgc cggaaagaac aattactgcc tgcagatcaa ccccgcctcc
     1861 tccatcaacc cggaccacct cacctacttt cgctttatag gcagattcat cgccatggcg
     1921 ctgtaccatg gaaagttcat cgacacgggc ttcaccctcc ctttctacaa gcggatgctc
     1981 aataagagac caaccctgaa agacctggag tccattgacc ctgagttcta caactccatt
     2041 gtctggatca aagagaacaa cctggaagaa tgtggcctgg agctgtactt catccaggac
     2101 atggagatac tgggcaaggt gacgacccac gagctgaagg agggcggcga gagcatccgg
     2161 gtcacagagg agaacaagga agagtacatc atgctgctga ctgactggcg tttcacccga
     2221 ggcgtggaag agcagaccaa agccttcctg gatggcttca acgaggtggc cccgctggag
     2281 tggctgcgct actttgacga gaaagagctg gagctgatgc tgtgcggcat gcaggagata
     2341 gacatgagcg actggcagaa gagcaccatc taccggcact acaccaagaa cagcaagcag
     2401 atccagtggt tctggcaggt ggtgaaggag atggacaacg agaagaggat ccggctgctg
     2461 cagtttgtca ccggtacctg ccgcctgccc gtcgggggat ttgccgaact catcggtagc
     2521 aacggaccac agaagttttg cattgacaaa gttggcaagg aaacctggct gcccagaagc
     2581 cacacctgct tcaaccgtct ggatcttcca ccctacaaga gctacgaaca gctgagagag
     2641 aagctgctgt atgccattga ggagaccgag ggctttggac aggagtaacc gaggccgccc
     2701 ctcccacgcc ccccagcgca catgtagtcc tgagtcctcc ctgcctgaga ggccactggc
     2761 cccgcagccc ttgggaggcc cccgtggatg tggccctgtg tgggaccaca ctgtcatctc
     2821 gctgctggca gaaaagcctg atcccaggag gccctgcagt tcccccgacc cgcggatggc
     2881 agtctggaat aaagccccct agttgccttt ggccccacct ttgcaaagtt ccagagggct
     2941 gaccctctct gcaaaactct cccctgtcct ctagacccca ccctgggtgt atgtgagtgt
     3001 gcaagggaag gtgttgcatc cccaggggct gccgcagagg ccggagacct cctggactag
     3061 ttcggcgagg agactggcca ctgggggtgg ctgttcggga ctgagagcgc caagggtctt
     3121 tgccagcaaa ggaggttctg cctgtaattg agcctctctg atgatggaga tgaagtgaag
     3181 gtctgaggga gcgggccctg gggcgaggcc atctctgcct gcctccctag caggcgccag
     3241 cggtggaggc tgagtcgcag gacacatgcc ggccagttaa ttcattctca gccaatgaag
     3301 gtttgtctaa gctgcctggg tatccacggg acaaaaacag caaactccct cagactttgt
     3361 ccatgtataa acttgaagtg gttgtgttgt agggttgcag gttttttgtt acgctgctgt
     3421 cactttctgt ccaggagctg gcaccccagg tgttctgaga ccttgaggga cccagacctt
     3481 tgggtccaag agtttcccaa acagccacgc ctctcaggaa cccacctggc ggttccgtga
     3541 gctcaggcag gcctgacccg gcggcacagc ctggcaggga cctcgtcccc aagcctggca
     3601 gaatgagagg ggttgaggtc ccgagcgcca ctcctagcct tgccgccttc aatagagaag
     3661 aaatcccttt gctagatagg gtcccccagg cagtccccag tggcgggaca caggggtccg
     3721 gctgtggagc tcccctgcca gcccctggag ctccaggagg gcctgttggt cccctgttca
     3781 gaatggagtg cagcccgcca gcggaaagtg ttcattctgc ataggtgtga ggctttatct
     3841 gcacacagga catgaaaacc agcagaaagg ccctgagctg ctgcatagcc ccatctgatt
     3901 tctgcagttc ccgccagcct ccaacacggg gactctgccg taactggaat cttcataggt
     3961 catattgaaa tcttcaaggt gaccatgccc caccggggtg ctggggcagt agtcatggca
     4021 gactcccggc ctgggccccc aggattctag gacccccagg cagccccttg gactggtccc
     4081 gggtgccttc caagcacagt ctccatgctc ccagattctc gaccttcccc cggcccggga
     4141 ggtgcagcct gcgtctgcct ctgtcgtgtg tgctgatttg agtggcttag cttgccacag
     4201 cgcagcctct tctgtccctt tcagtcattt gctgtacttc cctgtggcac gttaccatgg
     4261 aagccgctcc agggtgggtc agggtgcaag ctgctggtga ggtttggaag catcaggctc
     4321 acgggtgttc atgtgtgttc gtgcgtgtgt gtgcgtacgt gtatataact gaagtgtctg
     4381 tacggaatgc cctttgctag ccatgggctg gtcaccagat tgttttgtaa tgcccgcccc
     4441 ttgcctcgat attgccagtt tcttgtgcaa taaacaatca gcagctg
//
