DP13B_HUMAN
ID DP13B_HUMAN Reviewed; 664 AA.
AC Q8NEU8; B7Z411; B7Z4B0; F5GZG0; F8W1P5; Q8N4R7; Q9NVL2;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 3.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=DCC-interacting protein 13-beta {ECO:0000305};
DE Short=Dip13-beta {ECO:0000303|Ref.1};
DE AltName: Full=Adapter protein containing PH domain, PTB domain and leucine zipper motif 2 {ECO:0000305};
GN Name=APPL2 {ECO:0000312|HGNC:HGNC:18242}; Synonyms=DIP13B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000312|EMBL:AAM55530.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Chen Y.Q.;
RT "Identification of DIP13 beta, a novel protein related to the DCC-
RT interacting protein 13 alpha (DIP13alpha).";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP VAL-433.
RC TISSUE=Colon, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4] {ECO:0000312|EMBL:AAH33731.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-433.
RC TISSUE=Brain {ECO:0000312|EMBL:AAH33731.1};
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 [5] {ECO:0000305}
RP CHROMOSOMAL TRANSLOCATION WITH SHANK3, AND TISSUE SPECIFICITY.
RX PubMed=11431708; DOI=10.1086/321293;
RA Bonaglia M.C., Giorda R., Borgatti R., Felisari G., Gagliardi C.,
RA Selicorni A., Zuffardi O.;
RT "Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated
RT with the 22q13.3 deletion syndrome.";
RL Am. J. Hum. Genet. 69:261-268(2001).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB5A AND NURD/MECP1
RP COMPLEX, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15016378; DOI=10.1016/s0092-8674(04)00117-5;
RA Miaczynska M., Christoforidis S., Giner A., Shevchenko A.,
RA Uttenweiler-Joseph S., Habermann B., Wilm M., Parton R.G., Zerial M.;
RT "APPL proteins link Rab5 to nuclear signal transduction via an endosomal
RT compartment.";
RL Cell 116:445-456(2004).
RN [7]
RP INTERACTION WITH FSHR AND APPL1.
RX PubMed=17030088; DOI=10.1016/j.mce.2006.08.014;
RA Nechamen C.A., Thomas R.M., Dias J.A.;
RT "APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling
RT complex.";
RL Mol. Cell. Endocrinol. 260:93-99(2007).
RN [8]
RP SUBUNIT, INTERACTION WITH APPL1, DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=18034774; DOI=10.1111/j.1600-0854.2007.00680.x;
RA Chial H.J., Wu R., Ustach C.V., McPhail L.C., Mobley W.C., Chen Y.Q.;
RT "Membrane targeting by APPL1 and APPL2: dynamic scaffolds that oligomerize
RT and bind phosphoinositides.";
RL Traffic 9:215-229(2008).
RN [9]
RP INTERACTION WITH RUVBL2; CTNNB1; APPL1; HDAC1 AND HDAC2, FUNCTION, AND
RP DOMAIN.
RX PubMed=19433865; DOI=10.1074/jbc.m109.007237;
RA Rashid S., Pilecka I., Torun A., Olchowik M., Bielinska B., Miaczynska M.;
RT "Endosomal adaptor proteins APPL1 and APPL2 are novel activators of beta-
RT catenin/TCF-mediated transcription.";
RL J. Biol. Chem. 284:18115-18128(2009).
RN [10]
RP INTERACTION WITH ANXA2, AND SUBCELLULAR LOCATION.
RX PubMed=21645192; DOI=10.1111/j.1600-0854.2011.01226.x;
RA Urbanska A., Sadowski L., Kalaidzidis Y., Miaczynska M.;
RT "Biochemical characterization of APPL endosomes: the role of annexin A2 in
RT APPL membrane recruitment.";
RL Traffic 12:1227-1241(2011).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP FUNCTION, AND INTERACTION WITH TBC1D1.
RX PubMed=24879834; DOI=10.2337/db14-0337;
RA Cheng K.K., Zhu W., Chen B., Wang Y., Wu D., Sweeney G., Wang B., Lam K.S.,
RA Xu A.;
RT "The adaptor protein APPL2 inhibits insulin-stimulated glucose uptake by
RT interacting with TBC1D1 in skeletal muscle.";
RL Diabetes 63:3748-3758(2014).
RN [13]
RP FUNCTION.
RX PubMed=26583432; DOI=10.18632/oncotarget.6346;
RA Song J., Mu Y., Li C., Bergh A., Miaczynska M., Heldin C.H., Landstroem M.;
RT "APPL proteins promote TGFbeta-induced nuclear transport of the TGFbeta
RT type I receptor intracellular domain.";
RL Oncotarget 7:279-292(2016).
RN [14] {ECO:0007744|PDB:4H8S}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 2-384 IN COMPLEX WITH RAB31, AND
RP SUBUNIT.
RX PubMed=23055524; DOI=10.1074/jbc.m112.349803;
RA King G.J., Stockli J., Hu S.H., Winnen B., Duprez W.G., Meoli C.C.,
RA Junutula J.R., Jarrott R.J., James D.E., Whitten A.E., Martin J.L.;
RT "Membrane curvature protein exhibits interdomain flexibility and binds a
RT small GTPase.";
RL J. Biol. Chem. 287:40996-41006(2012).
RN [15] {ECO:0007744|PDB:5C5B}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 1-375.
RA Chen Y.J., Chen B.;
RT "Crystal Structure of Human APPL BAR-PH Heterodimer.";
RL Submitted (JUN-2015) to the PDB data bank.
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 (PubMed:26583432, PubMed:15016378,
CC PubMed:24879834). Regulates signaling pathway leading to cell
CC proliferation through interaction with RAB5A and subunits of the
CC NuRD/MeCP1 complex (PubMed:15016378). Plays a role in immune response
CC by modulating phagocytosis, inflammatory and innate immune responses.
CC In macrophages, enhances Fc-gamma receptor-mediated phagocytosis
CC through interaction with RAB31 leading to activation of PI3K/Akt
CC signaling. In response to LPS, modulates inflammatory responses by
CC playing a key role on the regulation of TLR4 signaling and in the
CC nuclear translocation of RELA/NF-kappa-B p65 and the secretion of
CC pro- and anti-inflammatory cytokines. Also functions as a negative
CC regulator of innate immune response via inhibition of AKT1 signaling
CC pathway by forming a complex with APPL1 and PIK3R1 (By similarity).
CC Plays a role in endosomal trafficking of TGFBR1 from the endosomes to
CC the nucleus (PubMed:26583432). Plays a role in cell metabolism by
CC regulating adiponecting ans insulin signaling pathways and adaptative
CC thermogenesis (PubMed:24879834) (By similarity). In muscle, negatively
CC regulates adiponectin-simulated glucose uptake and fatty acid oxidation
CC by inhibiting adiponectin signaling pathway through APPL1 sequestration
CC thereby antagonizing APPL1 action (By similarity). In muscles,
CC negativeliy regulates insulin-induced plasma membrane recruitment of
CC GLUT4 and glucose uptake through interaction with TBC1D1
CC (PubMed:24879834). Plays a role in cold and diet-induced adaptive
CC thermogenesis by activating ventromedial hypothalamus (VMH) neurons
CC throught AMPK inhibition which enhances sympathetic outflow to
CC subcutaneous white adipose tissue (sWAT), sWAT beiging and cold
CC tolerance (By similarity). Also plays a role in other signaling
CC pathways namely Wnt/beta-catenin, HGF and glucocorticoid receptor
CC signaling (PubMed:19433865) (By similarity). Positive regulator of
CC beta-catenin/TCF-dependent transcription through direct interaction
CC with RUVBL2/reptin resulting in the relief of RUVBL2-mediated
CC repression of beta-catenin/TCF target genes by modulating the
CC interactions within the beta-catenin-reptin-HDAC complex
CC (PubMed:19433865). May affect adult neurogenesis in hippocampus and
CC olfactory system via regulating the sensitivity of glucocorticoid
CC receptor. Required for fibroblast migration through HGF cell signaling
CC (By similarity). {ECO:0000250|UniProtKB:Q8K3G9,
CC ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:19433865,
CC ECO:0000269|PubMed:24879834, ECO:0000269|PubMed:26583432}.
CC -!- SUBUNIT: Homodimer (PubMed:18034774, PubMed:23055524). Homotetramer
CC (PubMed:23055524). Binds RAB5A/Rab5 through an N-terminal domain. This
CC interaction is essential for its recruitment to endosomal membranes as
CC well as its role in cell proliferation (PubMed:15016378). Binds
CC subunits of the NuRD/MeCP1 complex (PubMed:15016378). Interacts with
CC FSHR; interaction is independent of follicle stimulating hormone
CC stimulation (PubMed:17030088). Interacts with APPL1; the interaction is
CC decreased by adiponectin in a time-dependent manner (PubMed:17030088,
CC PubMed:18034774). Forms a complex comprising APPL1, RUVBL2, CTNNB1,
CC HDAC1 and HDAC2; interaction reduces interaction between CTNNB1, HDAC1,
CC HDAC2 and RUVBL2 leading to the decrease of deacetylase activity of
CC this complex; affects the recruitment of repressive complexes to the
CC Wnt target genes (PubMed:19433865). Interacts (via BAR domain) with
CC TBC1D1; interaction is dependent of TBC1D1 phosphorylation at 'Ser-
CC 235'; interaction diminishes the phosphorylation of TBC1D1 at 'Thr-
CC 596', resulting in inhibition of SLC2A4 translocation and glucose
CC uptake (PubMed:24879834). Interacts with ANXA2; targets APPL2 to
CC endosomes and acting in parallel to RAB5A (PubMed:21645192). Interacts
CC with 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 (PubMed:23055524). Interacts with PIK3R1; forms a complex
CC with PIK3R1 and APPL1 (By similarity). Interacts (via BAR domain) with
CC ADIPOR1; hinders the accessibility of APPL1 to ADIPOR1; negatively
CC regulates adiponectin signaling; ADIPOQ dissociates this interaction
CC and facilitates the recruitment of APPL1 to ADIPOR1 (By similarity).
CC Interacts (via BAR domain) with ADIPOR2; ADIPOQ dissociates this
CC interaction (By similarity). {ECO:0000250|UniProtKB:Q8K3G9,
CC ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:17030088,
CC ECO:0000269|PubMed:18034774, ECO:0000269|PubMed:19433865,
CC ECO:0000269|PubMed:21645192, ECO:0000269|PubMed:23055524,
CC ECO:0000269|PubMed:24879834}.
CC -!- INTERACTION:
CC Q8NEU8; Q9UKG1: APPL1; NbExp=19; IntAct=EBI-741261, EBI-741243;
CC Q8NEU8; Q8NEU8: APPL2; NbExp=4; IntAct=EBI-741261, EBI-741261;
CC Q8NEU8; P78560: CRADD; NbExp=4; IntAct=EBI-741261, EBI-520375;
CC Q8NEU8; Q7L775: EPM2AIP1; NbExp=3; IntAct=EBI-741261, EBI-6255981;
CC Q8NEU8; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-741261, EBI-14069005;
CC Q8NEU8; Q9UPY8: MAPRE3; NbExp=3; IntAct=EBI-741261, EBI-726739;
CC Q8NEU8; P0CG20: PRR35; NbExp=3; IntAct=EBI-741261, EBI-11986293;
CC Q8NEU8; Q9UL26: RAB22A; NbExp=8; IntAct=EBI-741261, EBI-399456;
CC Q8NEU8; P51148: RAB5C; NbExp=8; IntAct=EBI-741261, EBI-1054923;
CC Q8NEU8; Q9H5I1: SUV39H2; NbExp=6; IntAct=EBI-741261, EBI-723127;
CC Q8NEU8; Q9H5I1-2: SUV39H2; NbExp=3; IntAct=EBI-741261, EBI-11977575;
CC Q8NEU8; Q86TI0: TBC1D1; NbExp=4; IntAct=EBI-741261, EBI-1644036;
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000269|PubMed:15016378}; Peripheral membrane protein
CC {ECO:0000269|PubMed:15016378}. Nucleus {ECO:0000269|PubMed:15016378,
CC ECO:0000269|PubMed:18034774}. Cell membrane
CC {ECO:0000269|PubMed:18034774}. Endosome membrane
CC {ECO:0000269|PubMed:21645192}. 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 (PubMed:15016378). Translocated into the nucleus upon release
CC from endosomal membranes following internalization of EGF
CC (PubMed:15016378). Associates dynamically with cytoplasmic membrane
CC structures that undergo changes in shape, movement, fusion and fission
CC events (PubMed:18034774). PI(4,5)P2 levels are important for membrane
CC association of APPL2 (PubMed:18034774). Absent of endosome in
CC macrophage. Colocalized with RAB31 at early-stage phagosome (By
CC similarity). Localized on macropinosomes in LPS-activated macrophages.
CC Associated with membrane domains in contact with pathogens and
CC pathogen-derived ligands like LPS. First recruited to the ruffles, and
CC accumulates on macropinosomes (By similarity).
CC {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000269|PubMed:15016378,
CC ECO:0000269|PubMed:18034774}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NEU8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NEU8-2; Sequence=VSP_044771;
CC Name=3;
CC IsoId=Q8NEU8-3; Sequence=VSP_044772;
CC -!- TISSUE SPECIFICITY: High levels in brain, heart, kidney and skeletal
CC muscle. {ECO:0000269|PubMed:11431708}.
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
CC (PubMed:18034774) (By similarity). The PH and PID domains mediate
CC phosphoinositide binding (PubMed:18034774). The PID domain mediates
CC phosphatidylserine binding and allows localization to cytosolic
CC membrane structures and nucleus (PubMed:18034774). The PH domain allows
CC localization to the plasma membrane, cytosolic vesicles and distinct
CC nuclear and perinuclear structures and is sufficient for RUVBL2
CC interaction (PubMed:18034774, PubMed:19433865).
CC {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000269|PubMed:18034774,
CC ECO:0000269|PubMed:19433865}.
CC -!- DISEASE: Note=A chromosomal aberration involving APPL2/DIP13B is found
CC in patients with chromosome 22q13.3 deletion syndrome. Translocation
CC t(12;22)(q24.1;q13.3) with SHANK3/PSAP2. {ECO:0000269|PubMed:11431708}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY113704; AAM55530.1; -; mRNA.
DR EMBL; AK001521; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK296610; BAH12397.1; -; mRNA.
DR EMBL; AK297100; BAH12496.1; -; mRNA.
DR EMBL; AC016257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC078874; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033731; AAH33731.1; -; mRNA.
DR CCDS; CCDS58275.1; -. [Q8NEU8-2]
DR CCDS; CCDS58276.1; -. [Q8NEU8-3]
DR CCDS; CCDS9101.1; -. [Q8NEU8-1]
DR RefSeq; NP_001238833.1; NM_001251904.1. [Q8NEU8-3]
DR RefSeq; NP_001238834.1; NM_001251905.1. [Q8NEU8-2]
DR RefSeq; NP_060641.2; NM_018171.3. [Q8NEU8-1]
DR RefSeq; XP_016875041.1; XM_017019552.1. [Q8NEU8-2]
DR RefSeq; XP_016875042.1; XM_017019553.1. [Q8NEU8-2]
DR PDB; 4H8S; X-ray; 3.50 A; A/B/C/D=2-384.
DR PDB; 5C5B; X-ray; 2.90 A; B/D=1-375.
DR PDBsum; 4H8S; -.
DR PDBsum; 5C5B; -.
DR AlphaFoldDB; Q8NEU8; -.
DR SASBDB; Q8NEU8; -.
DR SMR; Q8NEU8; -.
DR BioGRID; 120495; 63.
DR IntAct; Q8NEU8; 41.
DR MINT; Q8NEU8; -.
DR STRING; 9606.ENSP00000446917; -.
DR MoonDB; Q8NEU8; Curated.
DR iPTMnet; Q8NEU8; -.
DR MetOSite; Q8NEU8; -.
DR PhosphoSitePlus; Q8NEU8; -.
DR BioMuta; APPL2; -.
DR DMDM; 160419148; -.
DR EPD; Q8NEU8; -.
DR jPOST; Q8NEU8; -.
DR MassIVE; Q8NEU8; -.
DR MaxQB; Q8NEU8; -.
DR PaxDb; Q8NEU8; -.
DR PeptideAtlas; Q8NEU8; -.
DR PRIDE; Q8NEU8; -.
DR ProteomicsDB; 25020; -.
DR ProteomicsDB; 29665; -.
DR ProteomicsDB; 73219; -. [Q8NEU8-1]
DR Antibodypedia; 30637; 158 antibodies from 22 providers.
DR DNASU; 55198; -.
DR Ensembl; ENST00000258530.8; ENSP00000258530.3; ENSG00000136044.12. [Q8NEU8-1]
DR Ensembl; ENST00000539978.6; ENSP00000444472.2; ENSG00000136044.12. [Q8NEU8-2]
DR Ensembl; ENST00000551662.5; ENSP00000446917.1; ENSG00000136044.12. [Q8NEU8-3]
DR GeneID; 55198; -.
DR KEGG; hsa:55198; -.
DR MANE-Select; ENST00000258530.8; ENSP00000258530.3; NM_018171.5; NP_060641.2.
DR UCSC; uc001tlf.2; human. [Q8NEU8-1]
DR CTD; 55198; -.
DR DisGeNET; 55198; -.
DR GeneCards; APPL2; -.
DR HGNC; HGNC:18242; APPL2.
DR HPA; ENSG00000136044; Low tissue specificity.
DR MIM; 606231; gene.
DR neXtProt; NX_Q8NEU8; -.
DR OpenTargets; ENSG00000136044; -.
DR VEuPathDB; HostDB:ENSG00000136044; -.
DR eggNOG; KOG0521; Eukaryota.
DR eggNOG; KOG3536; Eukaryota.
DR GeneTree; ENSGT00940000158319; -.
DR HOGENOM; CLU_025935_0_0_1; -.
DR InParanoid; Q8NEU8; -.
DR OMA; ENDEWIC; -.
DR OrthoDB; 253010at2759; -.
DR PhylomeDB; Q8NEU8; -.
DR TreeFam; TF328669; -.
DR PathwayCommons; Q8NEU8; -.
DR SignaLink; Q8NEU8; -.
DR BioGRID-ORCS; 55198; 16 hits in 1082 CRISPR screens.
DR ChiTaRS; APPL2; human.
DR GeneWiki; APPL2; -.
DR GenomeRNAi; 55198; -.
DR Pharos; Q8NEU8; Tbio.
DR PRO; PR:Q8NEU8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8NEU8; protein.
DR Bgee; ENSG00000136044; Expressed in skin of leg and 180 other tissues.
DR ExpressionAtlas; Q8NEU8; baseline and differential.
DR Genevisible; Q8NEU8; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0036186; C:early phagosome membrane; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0044354; C:macropinosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR GO; GO:0033211; P:adiponectin-activated signaling pathway; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0009631; P:cold acclimation; ISS:UniProtKB.
DR GO; GO:0002024; P:diet induced thermogenesis; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:1900077; P:negative regulation of cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; ISS:UniProtKB.
DR GO; GO:0046325; P:negative regulation of glucose import; IMP:UniProtKB.
DR GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; ISS:UniProtKB.
DR GO; GO:0050768; P:negative regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:UniProtKB.
DR GO; GO:1905451; P:positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis; ISS:UniProtKB.
DR GO; GO:1905303; P:positive regulation of macropinocytosis; ISS:UniProtKB.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0010762; P:regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0034143; P:regulation of toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:UniProtKB.
DR GO; GO:0023052; P:signaling; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Cell membrane;
KW Cell projection; Chromosomal rearrangement; Cytoplasm; Cytoplasmic vesicle;
KW Endosome; Membrane; Nucleus; Reference proteome.
FT CHAIN 1..664
FT /note="DCC-interacting protein 13-beta"
FT /id="PRO_0000079987"
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 488..637
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 1..428
FT /note="Required for RAB5A binding"
FT /evidence="ECO:0000250"
FT REGION 643..664
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 234..235
FT /note="Breakpoint for chromosomal translocation"
FT /evidence="ECO:0000269|PubMed:11431708"
FT VAR_SEQ 1..43
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044771"
FT VAR_SEQ 138
FT /note="N -> NDVCLFL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044772"
FT VARIANT 433
FT /note="A -> V (in dbSNP:rs2272495)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_021505"
FT CONFLICT 295
FT /note="T -> A (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 448
FT /note="T -> A (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="N -> S (in Ref. 2; BAH12496)"
FT /evidence="ECO:0000305"
FT CONFLICT 575
FT /note="L -> P (in Ref. 2; BAH12397)"
FT /evidence="ECO:0000305"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:5C5B"
FT TURN 12..14
FT /evidence="ECO:0007829|PDB:5C5B"
FT HELIX 17..70
FT /evidence="ECO:0007829|PDB:5C5B"
FT HELIX 80..110
FT /evidence="ECO:0007829|PDB:5C5B"
FT HELIX 112..148
FT /evidence="ECO:0007829|PDB:5C5B"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:5C5B"
FT HELIX 157..217
FT /evidence="ECO:0007829|PDB:5C5B"
FT HELIX 220..254
FT /evidence="ECO:0007829|PDB:5C5B"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:5C5B"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:5C5B"
FT STRAND 281..288
FT /evidence="ECO:0007829|PDB:5C5B"
FT STRAND 291..293
FT /evidence="ECO:0007829|PDB:5C5B"
FT STRAND 296..305
FT /evidence="ECO:0007829|PDB:5C5B"
FT STRAND 308..312
FT /evidence="ECO:0007829|PDB:5C5B"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:5C5B"
FT STRAND 329..333
FT /evidence="ECO:0007829|PDB:5C5B"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:5C5B"
FT STRAND 351..356
FT /evidence="ECO:0007829|PDB:5C5B"
FT HELIX 360..373
FT /evidence="ECO:0007829|PDB:5C5B"
SQ SEQUENCE 664 AA; 74493 MW; 359404B1CBA813DB CRC64;
MPAVDKLLLE EALQDSPQTR SLLSVFEEDA GTLTDYTNQL LQAMQRVYGA QNEMCLATQQ
LSKQLLAYEK QNFALGKGDE EVISTLHYFS KVVDELNLLH TELAKQLADT MVLPIIQFRE
KDLTEVSTLK DLFGLASNEH DLSMAKYSRL PKKKENEKVK TEVGKEVAAA RRKQHLSSLQ
YYCALNALQY RKQMAMMEPM IGFAHGQINF FKKGAEMFSK RMDSFLSSVA DMVQSIQVEL
EAEAEKMRVS QQELLSVDES VYTPDSDVAA PQINRNLIQK AGYLNLRNKT GLVTTTWERL
YFFTQGGNLM CQPRGAVAGG LIQDLDNCSV MAVDCEDRRY CFQITTPNGK SGIILQAESR
KENEEWICAI NNISRQIYLT DNPEAVAIKL NQTALQAVTP ITSFGKKQES SCPSQNLKNS
EMENENDKIV PKATASLPEA EELIAPGTPI QFDIVLPATE FLDQNRGSRR TNPFGETEDE
SFPEAEDSLL QQMFIVRFLG SMAVKTDSTT EVIYEAMRQV LAARAIHNIF RMTESHLMVT
SQSLRLIDPQ TQVSRANFEL TSVTQFAAHQ ENKRLVGFVI RVPESTGEES LSTYIFESNS
EGEKICYAIN LGKEIIEVQK DPEALAQLML SIPLTNDGKY VLLNDQPDDD DGNPNEHRGA
ESEA
