DP13B_RAT
ID DP13B_RAT Reviewed; 662 AA.
AC B4F779;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=DCC-interacting protein 13-beta {ECO:0000250|UniProtKB:Q8NEU8};
DE AltName: Full=Adapter protein containing PH domain, PTB domain and leucine zipper motif 2 {ECO:0000250|UniProtKB:Q8NEU8};
GN Name=Appl2 {ECO:0000312|RGD:1563028};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INDUCTION.
RX PubMed=30189216; DOI=10.1016/j.lfs.2018.09.006;
RA Canciglieri P.H., Kuga G.K., Munoz V.R., Gaspar R.C., da Rocha A.L.,
RA Breda L., Anaruma C.P., Minuzzi L.G., da Silva A.S.R., Cintra D.E.,
RA de Moura L.P., Ropelle E.R., Pauli J.R.;
RT "The reversal effect of physical exercise on aging-related increases in
RT APPL2 content in skeletal muscle.";
RL Life Sci. 210:209-213(2018).
CC -!- FUNCTION: Multifunctional adapter protein that binds to various
CC membrane receptors, nuclear factors and signaling proteins to regulate
CC many processes, such as cell proliferation, immune response, endosomal
CC trafficking and cell metabolism. Regulates signaling pathway leading to
CC cell proliferation through interaction with RAB5A and subunits of the
CC NuRD/MeCP1 complex (By similarity). Plays a role in immune response by
CC modulating phagocytosis, inflammatory and innate immune responses. In
CC macrophages, enhances Fc-gamma receptor-mediated phagocytosis through
CC interaction with RAB31 leading to activation of PI3K/Akt signaling. In
CC response to LPS, modulates inflammatory responses by playing a key role
CC on the regulation of TLR4 signaling and in the nuclear translocation of
CC RELA/NF-kappa-B p65 and the secretion of pro- and anti-inflammatory
CC cytokines. Also functions as a negative regulator of innate immune
CC response via inhibition of AKT1 signaling pathway by forming a complex
CC with APPL1 and PIK3R1 (By similarity). Plays a role in endosomal
CC trafficking of TGFBR1 from the endosomes to the nucleus (By
CC similarity). Plays a role in cell metabolism by regulating adiponecting
CC ans insulin signaling pathways and adaptative thermogenesis (By
CC similarity). In muscle, negatively regulates adiponectin-simulated
CC glucose uptake and fatty acid oyidation by inhibiting adiponectin
CC signaling pathway through APPL1 sequestration thereby antagonizing
CC APPL1 action (By similarity). In muscles, negativeliy regulates
CC insulin-induced plasma membrane recruitment of GLUT4 and glucose uptake
CC through interaction with TBC1D1 (By similarity). Plays a role in cold
CC and diet-induced adaptive thermogenesis by activating ventromedial
CC hypothalamus (VMH) neurons throught AMPK inhibition which enhances
CC sympathetic outflow to subcutaneous white adipose tissue (sWAT), sWAT
CC beiging and cold tolerance (By similarity). Also plays a role in other
CC signaling pathways namely Wnt/beta-catenin, HGF and glucocorticoid
CC receptor signaling (By similarity). Positive regulator of beta-
CC catenin/TCF-dependent transcription through direct interaction with
CC RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of
CC beta-catenin/TCF target genes by modulating the interactions within the
CC beta-catenin-reptin-HDAC complex (By similarity). May affect adult
CC neurogenesis in hippocampus and olfactory system via regulating the
CC sensitivity of glucocorticoid receptor. Required for fibroblast
CC migration through HGF cell signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000250|UniProtKB:Q8NEU8}.
CC -!- SUBUNIT: Homodimer. Homotetramer. Binds RAB5A/Rab5 through an N-
CC terminal domain. This interaction is essential for its recruitment to
CC endosomal membranes as well as its role in cell proliferation. Binds
CC subunits of the NuRD/MeCP1 complex. Interacts with FSHR; interaction is
CC independent of follicle stimulating hormone stimulation. Interacts with
CC APPL1; the interaction is decreased by adiponectin in a time-dependent
CC manner. Forms a complex comprising APPL1, RUVBL2, CTNNB1, HDAC1 and
CC HDAC2; interaction reduces interaction between CTNNB1, HDAC1, HDAC2 and
CC RUVBL2 leading to the decrease of deacetylase activity of this complex;
CC affects the recruitment of repressive complexes to the Wnt target
CC genes. Interacts (via BAR domain) with TBC1D1; interaction is dependent
CC of TBC1D1 phosphorylation at 'Ser-235'; interaction diminishes the
CC phosphorylation of TBC1D1 at 'Thr-596', resulting in inhibition of
CC SLC2A4 translocation and glucose uptake. Interacts with ANXA2; targets
CC APPL2 to endosomes and acting in parallel to RAB5A. Interacts with
CC RAB31 (in GTP-bound form); interaction contributes to or enhances
CC recruitment of APPL2 to the phagosomes; interaction enhances Fc-gamma
CC receptor-mediated phagocytosis through PI3K/Akt signaling in
CC macrophages (By similarity). Interacts with PIK3R1; forms a complex
CC with PIK3R1 and APPL1. Interacts (via BAR domain) with ADIPOR1; hinders
CC the accessibility of APPL1 to ADIPOR1; negatively regulates adiponectin
CC signaling; ADIPOQ dissociates this interaction and facilitates the
CC recruitment of APPL1 to ADIPOR1. Interacts (via BAR domain) with
CC ADIPOR2; ADIPOQ dissociates this interaction (By similarity).
CC {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000250|UniProtKB:Q8NEU8}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000250|UniProtKB:Q8NEU8}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8NEU8}. Nucleus {ECO:0000250|UniProtKB:Q8NEU8}.
CC Cell membrane {ECO:0000250|UniProtKB:Q8NEU8}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q8NEU8}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8K3G9}. Cytoplasmic vesicle, phagosome
CC {ECO:0000250|UniProtKB:Q8K3G9}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:Q8K3G9}. Cell projection, ruffle membrane
CC {ECO:0000250|UniProtKB:Q8K3G9}. Cell membrane
CC {ECO:0000250|UniProtKB:Q8K3G9}. Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000250|UniProtKB:Q8K3G9}. Note=Early endosomal membrane-bound and
CC nuclear. Translocated into the nucleus upon release from endosomal
CC membranes following internalization of EGF. Associates dynamically with
CC cytoplasmic membrane structures that undergo changes in shape,
CC movement, fusion and fission events. PI(4,5)P2 levels are important for
CC membrane association of APPL2 (By similarity). Absent of endosome in
CC macrophage. Colocalized with RAB31 at early-stage phagosome. Localized
CC on macropinosomes in LPS-activated macrophages. Associated with
CC membrane domains in contact with pathogens and pathogen-derived ligands
CC like LPS. First recruited to the ruffles, and accumulates on
CC macropinosomes (By similarity). {ECO:0000250|UniProtKB:Q8K3G9,
CC ECO:0000250|UniProtKB:Q8NEU8}.
CC -!- INDUCTION: Increases with aging and decreases by short-term exercise
CC training in aging skeletal muscle. {ECO:0000269|PubMed:30189216}.
CC -!- DOMAIN: The BAR domain is necessary and sufficient for mediating
CC homotypic and heterotypic interactions; associates with cytoplasmic
CC membrane structures; mediates interaction with TBC1D1 and ADIPOR1 (By
CC similarity). The PH and PID domains mediate phosphoinositide binding.
CC The PID domain mediates phosphatidylserine binding and allows
CC localization to cytosolic membrane structures and nucleus. The PH
CC domain allows localization to the plasma membrane, cytosolic vesicles
CC and distinct nuclear and perinuclear structures and is sufficient for
CC RUVBL2 interaction (By similarity). {ECO:0000250|UniProtKB:Q8K3G9,
CC ECO:0000250|UniProtKB:Q8NEU8}.
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DR EMBL; AABR07056466; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473960; EDM17085.1; -; Genomic_DNA.
DR EMBL; BC168167; AAI68167.1; -; mRNA.
DR RefSeq; NP_001102211.1; NM_001108741.1.
DR AlphaFoldDB; B4F779; -.
DR SMR; B4F779; -.
DR IntAct; B4F779; 6.
DR STRING; 10116.ENSRNOP00000010986; -.
DR iPTMnet; B4F779; -.
DR PhosphoSitePlus; B4F779; -.
DR PaxDb; B4F779; -.
DR PeptideAtlas; B4F779; -.
DR PRIDE; B4F779; -.
DR Ensembl; ENSRNOT00000010986; ENSRNOP00000010986; ENSRNOG00000008174.
DR GeneID; 362860; -.
DR KEGG; rno:362860; -.
DR UCSC; RGD:1563028; rat.
DR CTD; 55198; -.
DR RGD; 1563028; Appl2.
DR eggNOG; KOG0521; Eukaryota.
DR eggNOG; KOG3536; Eukaryota.
DR GeneTree; ENSGT00940000158319; -.
DR HOGENOM; CLU_025935_0_0_1; -.
DR InParanoid; B4F779; -.
DR OMA; ENDEWIC; -.
DR OrthoDB; 253010at2759; -.
DR PhylomeDB; B4F779; -.
DR TreeFam; TF328669; -.
DR PRO; PR:B4F779; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Proteomes; UP000234681; Chromosome 7.
DR Bgee; ENSRNOG00000008174; Expressed in cerebellum and 20 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032009; C:early phagosome; ISO:RGD.
DR GO; GO:0036186; C:early phagosome membrane; ISO:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; ISO:RGD.
DR GO; GO:0044354; C:macropinosome; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0001726; C:ruffle; ISO:RGD.
DR GO; GO:0032587; C:ruffle membrane; ISO:RGD.
DR GO; GO:0031982; C:vesicle; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISO:RGD.
DR GO; GO:0001786; F:phosphatidylserine binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0033211; P:adiponectin-activated signaling pathway; ISO:RGD.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; ISO:RGD.
DR GO; GO:0009631; P:cold acclimation; ISO:RGD.
DR GO; GO:0002024; P:diet induced thermogenesis; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:1900077; P:negative regulation of cellular response to insulin stimulus; ISO:RGD.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISO:RGD.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; ISO:RGD.
DR GO; GO:0046325; P:negative regulation of glucose import; ISS:UniProtKB.
DR GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; ISO:RGD.
DR GO; GO:0050768; P:negative regulation of neurogenesis; ISO:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISO:RGD.
DR GO; GO:1905451; P:positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis; ISO:RGD.
DR GO; GO:1905303; P:positive regulation of macropinocytosis; ISO:RGD.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; ISO:RGD.
DR GO; GO:0051289; P:protein homotetramerization; ISO:RGD.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:0010762; P:regulation of fibroblast migration; ISO:RGD.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0045088; P:regulation of innate immune response; ISO:RGD.
DR GO; GO:0034143; P:regulation of toll-like receptor 4 signaling pathway; ISO:RGD.
DR GO; GO:0023052; P:signaling; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR006020; PTB/PI_dom.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00640; PID; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00462; PTB; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS01179; PID; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cell membrane; Cell projection; Cytoplasm; Cytoplasmic vesicle;
KW Endosome; Membrane; Nucleus; Reference proteome.
FT CHAIN 1..662
FT /note="DCC-interacting protein 13-beta"
FT /id="PRO_0000446255"
FT DOMAIN 3..268
FT /note="BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00361"
FT DOMAIN 277..375
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 486..635
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 643..662
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 662 AA; 74117 MW; 998A98E521F5BCDB CRC64;
MPAVDKLLLE EALQDSPQTR SLLSVFEEDA GTLTDYTNQL LQAMQRVYGA QNEMCLATQQ
LSRQLLAYEK QNFALGKGDE EVISTLHYFS KVMDELNGLH SELAKQLADT MVLPVIQFRE
KDLTEVSTLK DLFGLASNEH DLSMAKYSRL PKRKENERVK TDVAKEVAAA RRKQHLSSLQ
YYCALNALQY RKRAAMMEPL IGFAHGQINF FKKGAEMFSK SMDGFLSSVT DMVQSIQVEL
EAEADKMRVS QQELLSVSES VYTPDIDVAT PQINRNLIQK TGYLNLRNKT GLVTTTWERL
YFFTQGGNLM CQPRGAVAGG LIQDLDNCSV MAVDCEDRRY CFQISTPSGK PGIILQAESR
KEYEEWICAI NNISRQIYLT DNPEAVAIKL NQTALQAVTP ITSFGKKQES FYFSQNIKNS
DTGYVKIVPK AAASIPETEE LIAPGTPIQF DIVLPATEFL DQNRGSRRIN PFGETEDDSF
PDAEDSLLQQ MFIVRFLGSM AVKTDSTTEV IYEAMRQVLA ARAIHNIFRT TESHLMVTSQ
TLRLIDPQTQ VSRACFELTS VTQFAAHQEN KRLVGFVIRV PESTGEESLS TYIFESNSEG
EKICYAINLG KEIIEVQKDP EALARLMLSV PLTNDGKYVL LNDQADDTGG SPSDHRGAES
EA
