LOCUS       NM_018171               3171 bp    mRNA    linear   PRI 21-SEP-2024
DEFINITION  Homo sapiens adaptor protein, phosphotyrosine interacting with PH
            domain and leucine zipper 2 (APPL2), transcript variant 1, mRNA.
ACCESSION   NM_018171
VERSION     NM_018171.5
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 3171)
  AUTHORS   Cho,N.H., Cheveralls,K.C., Brunner,A.D., Kim,K., Michaelis,A.C.,
            Raghavan,P., Kobayashi,H., Savy,L., Li,J.Y., Canaj,H., Kim,J.Y.S.,
            Stewart,E.M., Gnann,C., McCarthy,F., Cabrera,J.P., Brunetti,R.M.,
            Chhun,B.B., Dingle,G., Hein,M.Y., Huang,B., Mehta,S.B.,
            Weissman,J.S., Gomez-Sjoberg,R., Itzhak,D.N., Royer,L.A., Mann,M.
            and Leonetti,M.D.
  TITLE     OpenCell: Endogenous tagging for the cartography of human cellular
            organization
  JOURNAL   Science 375 (6585), eabi6983 (2022)
   PUBMED   35271311
REFERENCE   2  (bases 1 to 3171)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   3  (bases 1 to 3171)
  AUTHORS   Wang,B., Lin,H., Li,X., Lu,W., Kim,J.B., Xu,A. and Cheng,K.K.Y.
  TITLE     The adaptor protein APPL2 controls glucose-stimulated insulin
            secretion via F-actin remodeling in pancreatic beta-cells
  JOURNAL   Proc Natl Acad Sci U S A 117 (45), 28307-28315 (2020)
   PUBMED   33122440
  REMARK    GeneRIF: The adaptor protein APPL2 controls glucose-stimulated
            insulin secretion via F-actin remodeling in pancreatic beta-cells.
REFERENCE   4  (bases 1 to 3171)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   5  (bases 1 to 3171)
  AUTHORS   Fragoza,R., Das,J., Wierbowski,S.D., Liang,J., Tran,T.N., Liang,S.,
            Beltran,J.F., Rivera-Erick,C.A., Ye,K., Wang,T.Y., Yao,L., Mort,M.,
            Stenson,P.D., Cooper,D.N., Wei,X., Keinan,A., Schimenti,J.C.,
            Clark,A.G. and Yu,H.
  TITLE     Extensive disruption of protein interactions by genetic variants
            across the allele frequency spectrum in human populations
  JOURNAL   Nat Commun 10 (1), 4141 (2019)
   PUBMED   31515488
  REMARK    Publication Status: Online-Only
REFERENCE   6  (bases 1 to 3171)
  AUTHORS   Chial,H.J., Wu,R., Ustach,C.V., McPhail,L.C., Mobley,W.C. and
            Chen,Y.Q.
  TITLE     Membrane targeting by APPL1 and APPL2: dynamic scaffolds that
            oligomerize and bind phosphoinositides
  JOURNAL   Traffic 9 (2), 215-229 (2008)
   PUBMED   18034774
  REMARK    GeneRIF: The findings suggest a role for APPL1 and APPL2 protein as
            dynamic scaffolds that modulate RAB5-associated signaling endosomal
            membranes by their ability to undergo domain-mediated
            oligomerization, membrane targeting and phosphoinositide binding.
            Erratum:[Traffic. 2008 Apr;9(4):623-4]
REFERENCE   7  (bases 1 to 3171)
  AUTHORS   Nechamen,C.A., Thomas,R.M. and Dias,J.A.
  TITLE     APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential
            signaling complex
  JOURNAL   Mol Cell Endocrinol 260-262, 93-99 (2007)
   PUBMED   17030088
REFERENCE   8  (bases 1 to 3171)
  AUTHORS   Mao,X., Kikani,C.K., Riojas,R.A., Langlais,P., Wang,L., Ramos,F.J.,
            Fang,Q., Christ-Roberts,C.Y., Hong,J.Y., Kim,R.Y., Liu,F. and
            Dong,L.Q.
  TITLE     APPL1 binds to adiponectin receptors and mediates adiponectin
            signalling and function
  JOURNAL   Nat Cell Biol 8 (5), 516-523 (2006)
   PUBMED   16622416
  REMARK    Erratum:[Nat Cell Biol. 2006 Jun;8(6):642]
REFERENCE   9  (bases 1 to 3171)
  AUTHORS   Miaczynska,M., Christoforidis,S., Giner,A., Shevchenko,A.,
            Uttenweiler-Joseph,S., Habermann,B., Wilm,M., Parton,R.G. and
            Zerial,M.
  TITLE     APPL proteins link Rab5 to nuclear signal transduction via an
            endosomal compartment
  JOURNAL   Cell 116 (3), 445-456 (2004)
   PUBMED   15016378
  REMARK    GeneRIF: identification of a pathway directly linking the small
            GTPase Rab5, a key regulator of endocytosis, to signal transduction
            and mitogenesis via APPL1 and APPL2, two Rab5 effectors
REFERENCE   10 (bases 1 to 3171)
  AUTHORS   Bonaglia,M.C., Giorda,R., Borgatti,R., Felisari,G., Gagliardi,C.,
            Selicorni,A. and Zuffardi,O.
  TITLE     Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is
            associated with the 22q13.3 deletion syndrome
  JOURNAL   Am J Hum Genet 69 (2), 261-268 (2001)
   PUBMED   11431708
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC078874.13 and AC016257.22.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 31, 2019 this sequence version replaced NM_018171.4.
            
            Summary: The protein encoded by this gene is one of two effectors
            of the small GTPase RAB5A/Rab5, which are involved in a signal
            transduction pathway. Both effectors contain an N-terminal
            Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology
            (PH) domain, and a C-terminal phosphotyrosine binding (PTB) domain,
            and they bind the Rab5 through the BAR domain. They are associated
            with endosomal membranes and can be translocated to the nucleus in
            response to the EGF stimulus. They interact with the NuRD/MeCP1
            complex (nucleosome remodeling and deacetylase /methyl-CpG-binding
            protein 1 complex) and are required for efficient cell
            proliferation. A chromosomal aberration t(12;22)(q24.1;q13.3)
            involving this gene and the PSAP2 gene results in 22q13.3 deletion
            syndrome, also known as Phelan-McDermid syndrome. [provided by
            RefSeq, Oct 2011].
            
            Transcript Variant: This variant (1) encodes the predominant
            isoform (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 :: BC033731.1, AY113704.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000258530.8/ ENSP00000258530.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-216               AC078874.13        19770-19985
            217-315             AC078874.13        26721-26819
            316-375             AC016257.22        10869-10928
            376-447             AC016257.22        11454-11525
            448-535             AC016257.22        17277-17364
            536-577             AC016257.22        20395-20436
            578-636             AC016257.22        20565-20623
            637-783             AC016257.22        21387-21533
            784-866             AC016257.22        24809-24891
            867-1025            AC016257.22        29063-29221
            1026-1214           AC016257.22        30641-30829
            1215-1257           AC016257.22        32967-33009
            1258-1314           AC016257.22        33093-33149
            1315-1403           AC016257.22        33245-33333
            1404-1568           AC016257.22        38439-38603
            1569-1621           AC016257.22        38770-38822
            1622-1796           AC016257.22        40147-40321
            1797-1833           AC016257.22        51332-51368
            1834-1974           AC016257.22        51578-51718
            1975-2022           AC016257.22        52512-52559
            2023-3171           AC016257.22        54146-55294
FEATURES             Location/Qualifiers
     source          1..3171
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q23.3"
     gene            1..3171
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /note="adaptor protein, phosphotyrosine interacting with
                     PH domain and leucine zipper 2"
                     /db_xref="GeneID:55198"
                     /db_xref="HGNC:HGNC:18242"
                     /db_xref="MIM:606231"
     exon            1..216
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     CDS             163..2157
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /note="isoform 1 is encoded by transcript variant 1;
                     DCC-interacting protein 13-beta; DIP13 beta; adapter
                     protein containing PH domain, PTB domain and leucine
                     zipper motif 2; adaptor protein, phosphotyrosine
                     interaction, PH domain and leucine zipper containing 2"
                     /codon_start=1
                     /product="DCC-interacting protein 13-beta isoform 1"
                     /protein_id="NP_060641.2"
                     /db_xref="CCDS:CCDS9101.1"
                     /db_xref="GeneID:55198"
                     /db_xref="HGNC:HGNC:18242"
                     /db_xref="MIM:606231"
                     /translation="MPAVDKLLLEEALQDSPQTRSLLSVFEEDAGTLTDYTNQLLQAM
                     QRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTE
                     LAKQLADTMVLPIIQFREKDLTEVSTLKDLFGLASNEHDLSMAKYSRLPKKKENEKVK
                     TEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKGAEMF
                     SKRMDSFLSSVADMVQSIQVELEAEAEKMRVSQQELLSVDESVYTPDSDVAAPQINRN
                     LIQKAGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVMAVD
                     CEDRRYCFQITTPNGKSGIILQAESRKENEEWICAINNISRQIYLTDNPEAVAIKLNQ
                     TALQAVTPITSFGKKQESSCPSQNLKNSEMENENDKIVPKATASLPEAEELIAPGTPI
                     QFDIVLPATEFLDQNRGSRRTNPFGETEDESFPEAEDSLLQQMFIVRFLGSMAVKTDS
                     TTEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQSLRLIDPQTQVSRANFELTSVTQF
                     AAHQENKRLVGFVIRVPESTGEESLSTYIFESNSEGEKICYAINLGKEIIEVQKDPEA
                     LAQLMLSIPLTNDGKYVLLNDQPDDDDGNPNEHRGAESEA"
     exon            217..315
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            316..375
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            376..447
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            448..535
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            536..577
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            578..636
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            637..783
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            784..866
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            867..1025
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1026..1214
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1215..1257
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1258..1314
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1315..1403
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1404..1568
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1569..1621
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1622..1796
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1797..1833
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1834..1974
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            1975..2022
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     exon            2023..3171
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3152..3157
                     /regulatory_class="polyA_signal_sequence"
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /note="hexamer: AATAAA"
     polyA_site      3171
                     /gene="APPL2"
                     /gene_synonym="DIP13B"
                     /note="major polyA site"
ORIGIN      
        1 aggcggcggc ggccactggc caggcgtgga cgcgcgcggg gccgccgcgg gcacggagtg
       61 gccgccgcgt cgcctgagcc cagagccggg gagtgctctc ggccgccgcg tctcctgccc
      121 tctgtccttc caacccagcc ctcggctgag ccgcgccgca ccatgcccgc cgtggacaag
      181 ctcctgctag aggaggcgtt gcaggacagc ccccagactc gctctttact gagcgtgttt
      241 gaagaagatg ctggcaccct cacagactat accaaccagc tgctccaggc aatgcagcgc
      301 gtctatggag cccagaatga gatgtgcctg gccacacaac agctttctaa gcaactgctg
      361 gcatatgaaa aacagaactt tgctcttggc aaaggtgatg aagaagtaat ttcaacactc
      421 cactattttt ccaaagtggt ggatgagctt aatcttctcc atacagagct ggctaaacag
      481 ttggcagaca caatggttct acctatcata caattccgag aaaaggatct cacagaagta
      541 agcactttaa aggatctatt tggactcgct agcaatgagc atgacctctc aatggcaaaa
      601 tacagcaggc tgcctaagaa aaaggagaat gagaaggtga agaccgaagt cggaaaagag
      661 gtggccgcgg cccggcggaa gcagcacctc tcctcccttc agtactactg tgccctcaac
      721 gcgctgcagt acagaaagca aatggccatg atggagccca tgataggctt tgcccatgga
      781 cagattaact tttttaagaa gggagcagag atgttttcca aacgtatgga cagcttttta
      841 tcctccgttg cagacatggt tcaaagcatt caggtagaac tggaagccga ggcggaaaag
      901 atgcgggtgt cccagcaaga attactttct gttgatgaat ctgtttacac tccagactct
      961 gatgtggccg caccacagat caacaggaac ctcatccaga aggctggtta ccttaatctt
     1021 agaaacaaaa cagggctggt caccaccacc tgggagaggc tttatttctt cacccaaggc
     1081 gggaatctca tgtgtcagcc caggggagcc gtggctggag gtttgatcca ggacctggac
     1141 aactgctcag tgatggccgt ggattgcgaa gaccggcgct actgcttcca gatcaccacg
     1201 cccaatggaa aatcgggaat aatcctccag gctgagagca gaaaggaaaa tgaagagtgg
     1261 atatgtgcaa taaacaacat ctccagacag atctacctga ccgacaaccc tgaggcagtc
     1321 gcgatcaagt tgaatcagac cgctctgcaa gcagtgactc ccattacaag ttttggaaaa
     1381 aaacaagaaa gctcatgccc cagccagaac ctgaaaaatt cagagatgga aaatgaaaat
     1441 gacaagattg ttcccaaagc aacagccagt ctacctgaag cagaggagct gatcgcgcct
     1501 ggaacgccga ttcaattcga tattgtgctt cctgctacag aattccttga tcagaacaga
     1561 gggagcaggc gtaccaaccc ttttggtgaa actgaggatg aatcatttcc agaagcagaa
     1621 gattctcttt tgcagcagat gtttatagtt cggtttttgg gatcaatggc agttaaaaca
     1681 gacagcacta ctgaagtgat ttatgaagcg atgagacaag tattggctgc tcgggctatt
     1741 cataacatct tccgcatgac agaatcccat ctgatggtca ccagtcaatc tttgaggttg
     1801 atagatccac agactcaagt atcaagggcc aattttgaac ttaccagtgt cacacaattt
     1861 gctgctcatc aagaaaacaa gagactggtt ggttttgtca tccgtgttcc tgaatccact
     1921 ggagaagaat ctctgagtac atacattttt gaaagcaact cagaaggcga aaagatatgt
     1981 tatgctatta atttgggaaa agaaattatt gaggttcaga aggatccaga agcactggct
     2041 caattaatgc tgtccatacc actaaccaat gacggaaaat atgtactgtt aaacgatcaa
     2101 ccagatgacg atgatggaaa tccaaacgaa catagaggcg cagaatccga agcataactc
     2161 acttgcgcct gtgggggaag agcaaacagg aaggagagct acctcctaag ggttttaacg
     2221 tctctgacat acaggcacac tgacctgatt tccgaaggct gacaatcgtt tgtggaatgt
     2281 aatcttgatg ccttgatact gagacttggg agggaaacta agaaatggtt gacagcgttc
     2341 ccacccatct acaatgttat tttaggtgct ttgtggtaag tcttttttct tagattgcgc
     2401 taaaatttct tagattgttc agcgctcaga acaaaagttt gaaaaatgca ttgttcatat
     2461 gaatgtcatc tcttttcagt ttccagtatc ctttttaaaa aatggcaaaa gcctagattt
     2521 acaatttgat gaacactaaa tatttcttat taatataatc tatttttgta ttttacttaa
     2581 tgagctttaa gtgcctgtcg ttctgaaaat tgtgtattta taattcagct tatctcataa
     2641 ttggacctaa tagcatttct ttgtgcagtt aggtgatgag cactgctttg aggcccaagc
     2701 actagtagag atgcgcgata caggtctagt ttcggtaact gttccagaca tcaagcaata
     2761 aaaaaatgaa taccacaaaa gatgtttgat tttacagtgg agccttactg aaccagcatt
     2821 cagaagttta aggtcctcct aggtatgagt atttttagta gtggatcact gtggacaggg
     2881 tgcagctcta ccagttcctg tttcttctga gccagaccct cttcagggaa gggaccaatt
     2941 aattttaaaa ctcacttgaa gcacagctgg tcatggggct tggtataaag ttcctatttc
     3001 caccctgata cttccaattc ctggaacccc agcccactcc cccatccctc ctccctatca
     3061 aactagtata atgattttga atcggtacag tgtgtttaac tgtaactaag ttcaacagac
     3121 tattattatc tttgtaataa attaacctag caataaaaaa tattctgttt c
//
