ID   RUBIC_HUMAN             Reviewed;         972 AA.
AC   Q92622; Q96CK5;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 4.
DT   28-JAN-2026, entry version 173.
DE   RecName: Full=Run domain Beclin-1-interacting and cysteine-rich domain-containing protein {ECO:0000312|HGNC:HGNC:28991};
DE            Short=Rubicon;
DE   AltName: Full=Beclin-1 associated RUN domain containing protein;
DE            Short=Baron;
GN   Name=RUBCN {ECO:0000312|HGNC:HGNC:28991}; Synonyms=KIAA0226;
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]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Bone marrow;
RX   PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA   Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA   Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT   "Prediction of the coding sequences of unidentified human genes. VI. The
RT   coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT   cDNA clones from cell line KG-1 and brain.";
RL   DNA Res. 3:321-329(1996).
RN   [2]
RP   SEQUENCE REVISION.
RA   Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA   Tanaka A., Kotani H., Miyajima N., Nomura N.;
RL   Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA   Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-228 (ISOFORM 1).
RC   TISSUE=Thymus;
RA   Li W.B., Gruber C., Jessee J., Polayes D.;
RT   "Full-length cDNA libraries and normalization.";
RL   Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 239-972.
RC   TISSUE=Kidney;
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   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197 AND SER-671, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT   kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197; SER-266 AND SER-528, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [8]
RP   FUNCTION, INTERACTION WITH BECN1; PIK3C3; PIK3R4 AND UVRAG, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=19270696; DOI=10.1038/ncb1846;
RA   Matsunaga K., Saitoh T., Tabata K., Omori H., Satoh T., Kurotori N.,
RA   Maejima I., Shirahama-Noda K., Ichimura T., Isobe T., Akira S., Noda T.,
RA   Yoshimori T.;
RT   "Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate
RT   autophagy at different stages.";
RL   Nat. Cell Biol. 11:385-396(2009).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-671, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [10]
RP   INVOLVEMENT IN SCAR15.
RX   PubMed=20826435; DOI=10.1093/brain/awq181;
RA   Assoum M., Salih M.A., Drouot N., H'Mida-Ben Brahim D., Lagier-Tourenne C.,
RA   AlDrees A., Elmalik S.A., Ahmed T.S., Seidahmed M.Z., Kabiraj M.M.,
RA   Koenig M.;
RT   "Rundataxin, a novel protein with RUN and diacylglycerol binding domains,
RT   is mutant in a new recessive ataxia.";
RL   Brain 133:2439-2447(2010).
RN   [11]
RP   INTERACTION WITH RAB7 AND PI3K COMPLEX, AND MUTAGENESIS OF CYS-912;
RP   CYS-915; HIS-920 AND CYS-923.
RX   PubMed=20943950; DOI=10.1091/mbc.e10-06-0495;
RA   Tabata K., Matsunaga K., Sakane A., Sasaki T., Noda T., Yoshimori T.;
RT   "Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway
RT   via a novel Rab7-binding domain.";
RL   Mol. Biol. Cell 21:4162-4172(2010).
RN   [12]
RP   FUNCTION, INTERACTION WITH UVRAG AND RAB7A, AND SUBCELLULAR LOCATION.
RX   PubMed=20974968; DOI=10.1073/pnas.1010554107;
RA   Sun Q., Westphal W., Wong K.N., Tan I., Zhong Q.;
RT   "Rubicon controls endosome maturation as a Rab7 effector.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:19338-19343(2010).
RN   [13]
RP   SUBUNIT, AND FUNCTION.
RX   PubMed=21062745; DOI=10.1074/jbc.m110.126425;
RA   Sun Q., Zhang J., Fan W., Wong K.N., Ding X., Chen S., Zhong Q.;
RT   "The RUN domain of rubicon is important for hVps34 binding, lipid kinase
RT   inhibition, and autophagy suppression.";
RL   J. Biol. Chem. 286:185-191(2011).
RN   [14]
RP   FUNCTION, AND INTERACTION WITH BECN1; CYBA; CYBB AND NOX4.
RX   PubMed=22423966; DOI=10.1016/j.chom.2012.01.018;
RA   Yang C.S., Lee J.S., Rodgers M., Min C.K., Lee J.Y., Kim H.J., Lee K.H.,
RA   Kim C.J., Oh B., Zandi E., Yue Z., Kramnik I., Liang C., Jung J.U.;
RT   "Autophagy protein Rubicon mediates phagocytic NADPH oxidase activation in
RT   response to microbial infection or TLR stimulation.";
RL   Cell Host Microbe 11:264-276(2012).
RN   [15]
RP   FUNCTION, INTERACTION WITH CARD9 AND YWHAB, AND MUTAGENESIS OF SER-248.
RX   PubMed=22423967; DOI=10.1016/j.chom.2012.01.019;
RA   Yang C.S., Rodgers M., Min C.K., Lee J.S., Kingeter L., Lee J.Y., Jong A.,
RA   Kramnik I., Lin X., Jung J.U.;
RT   "The autophagy regulator Rubicon is a feedback inhibitor of CARD9-mediated
RT   host innate immunity.";
RL   Cell Host Microbe 11:277-289(2012).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197; SER-248; SER-266;
RP   SER-388 AND SER-562, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
CC   -!- FUNCTION: Inhibits PIK3C3 activity; under basal conditions negatively
CC       regulates PI3K complex II (PI3KC3-C2) function in autophagy. Negatively
CC       regulates endosome maturation and degradative endocytic trafficking and
CC       impairs autophagosome maturation process. Can sequester UVRAG from
CC       association with a class C Vps complex (possibly the HOPS complex) and
CC       negatively regulates Rab7 activation (PubMed:20974968,
CC       PubMed:21062745). {ECO:0000269|PubMed:20974968,
CC       ECO:0000269|PubMed:21062745}.
CC   -!- FUNCTION: Involved in regulation of pathogen-specific host defense of
CC       activated macrophages. Following bacterial infection promotes NADH
CC       oxidase activity by association with CYBA thereby affecting TLR2
CC       signaling and probably other TLR-NOX pathways. Stabilizes the CYBA:CYBB
CC       NADPH oxidase heterodimer, increases its association with TLR2 and its
CC       phagosome trafficking to induce antimicrobial burst of ROS and
CC       production of inflammatory cytokines (PubMed:22423966). Following
CC       fungal or viral infection (implicating CLEC7A (dectin-1)-mediated
CC       myeloid cell activation or RIGI-dependent sensing of RNA viruses)
CC       negatively regulates pro-inflammatory cytokine production by
CC       association with CARD9 and sequestering it from signaling complexes
CC       (PubMed:22423967). {ECO:0000269|PubMed:22423966,
CC       ECO:0000269|PubMed:22423967}.
CC   -!- SUBUNIT: Associates with PI3K (PI3KC3/PI3K-III/class III
CC       phosphatidylinositol 3-kinase) complex II (PI3KC3-C2) in which the core
CC       composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4
CC       and BECN1 is associated with UVRAG; in the complex interacts directly
CC       with PI3KC3 and UVRAG (PubMed:19270696, PubMed:21062745). Interacts
CC       with Rab7 (RAB7A or RAB7B) (GTP-bound form); Rab7 and UVRAG compete for
CC       RUBCN binding; can interact simultaneously with Rab7 and the PI3K
CC       complex (PubMed:20943950, PubMed:20974968, PubMed:21062745). Interacts
CC       with CYBA and CYBB; indicative for the association with the CYBA:CYBB
CC       NADPH oxidase heterodimer. Interacts with NOX4 and probably associates
CC       with the CYBA:NOX4 complex (PubMed:22423966). Interacts with YWHAB and
CC       CARD9 in a competitive and stimulation-dependent manner; RUBCN
CC       exchanges interaction from YWHAB to CARD9 upon stimulation with
CC       beta-1,3-glucan (PubMed:22423967). {ECO:0000269|PubMed:19270696,
CC       ECO:0000269|PubMed:20943950, ECO:0000269|PubMed:20974968,
CC       ECO:0000269|PubMed:21062745, ECO:0000269|PubMed:22423966,
CC       ECO:0000269|PubMed:22423967}.
CC   -!- INTERACTION:
CC       Q92622; X5D778: ANKRD11; NbExp=3; IntAct=EBI-2952709, EBI-17183751;
CC       Q92622; Q14457: BECN1; NbExp=16; IntAct=EBI-2952709, EBI-949378;
CC       Q92622; O95696: BRD1; NbExp=3; IntAct=EBI-2952709, EBI-714754;
CC       Q92622; Q13895: BYSL; NbExp=3; IntAct=EBI-2952709, EBI-358049;
CC       Q92622; Q92785: DPF2; NbExp=3; IntAct=EBI-2952709, EBI-359932;
CC       Q92622; P00533: EGFR; NbExp=4; IntAct=EBI-2952709, EBI-297353;
CC       Q92622; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-2952709, EBI-744099;
CC       Q92622; Q3B820: FAM161A; NbExp=3; IntAct=EBI-2952709, EBI-719941;
CC       Q92622; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-2952709, EBI-10175124;
CC       Q92622; O95995: GAS8; NbExp=3; IntAct=EBI-2952709, EBI-1052570;
CC       Q92622; Q9Y5B8: NME7; NbExp=3; IntAct=EBI-2952709, EBI-744782;
CC       Q92622; Q8NEB9: PIK3C3; NbExp=9; IntAct=EBI-2952709, EBI-1056470;
CC       Q92622; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-2952709, EBI-11955057;
CC       Q92622; Q9P2Y5: UVRAG; NbExp=11; IntAct=EBI-2952709, EBI-2952704;
CC       Q92622; Q14119: VEZF1; NbExp=3; IntAct=EBI-2952709, EBI-11980193;
CC       Q92622; P15622-3: ZNF250; NbExp=3; IntAct=EBI-2952709, EBI-10177272;
CC       Q92622; Q5T619: ZNF648; NbExp=3; IntAct=EBI-2952709, EBI-11985915;
CC   -!- SUBCELLULAR LOCATION: Late endosome {ECO:0000269|PubMed:19270696}.
CC       Lysosome {ECO:0000269|PubMed:19270696}. Early endosome
CC       {ECO:0000269|PubMed:19270696, ECO:0000269|PubMed:20974968}.
CC       Note=Predominantly located in late endosomes/lysosomes, only partially
CC       detected in early endosome and not at all in the Golgi apparatus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q92622-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q92622-2; Sequence=VSP_039160, VSP_039161;
CC       Name=3;
CC         IsoId=Q92622-3; Sequence=VSP_039471, VSP_039472, VSP_039473;
CC   -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 15 (SCAR15)
CC       [MIM:615705]: A form of spinocerebellar ataxia, a clinically and
CC       genetically heterogeneous group of cerebellar disorders. Patients show
CC       progressive incoordination of gait and often poor coordination of
CC       hands, speech and eye movements, due to degeneration of the cerebellum
CC       with variable involvement of the brainstem and spinal cord. SCAR15
CC       patients manifest cerebellar ataxia in early childhood and delayed
CC       motor development with delayed walking. Additional features include
CC       dysarthria, upper limb involvement, abnormal eye movements, and
CC       hyporeflexia. {ECO:0000269|PubMed:20826435}. Note=The disease is caused
CC       by variants affecting the gene represented in this entry.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA13215.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; D86979; BAA13215.3; ALT_INIT; mRNA.
DR   EMBL; AC024560; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BX437131; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; BC014173; AAH14173.2; -; mRNA.
DR   CCDS; CCDS43195.1; -. [Q92622-1]
DR   CCDS; CCDS46987.1; -. [Q92622-2]
DR   RefSeq; NP_001139114.1; NM_001145642.5. [Q92622-2]
DR   RefSeq; NP_055502.1; NM_014687.4. [Q92622-1]
DR   PDB; 6WCW; X-ray; 2.80 A; A=699-949.
DR   PDBsum; 6WCW; -.
DR   AlphaFoldDB; Q92622; -.
DR   SMR; Q92622; -.
DR   BioGRID; 115062; 69.
DR   FunCoup; Q92622; 3781.
DR   IntAct; Q92622; 37.
DR   STRING; 9606.ENSP00000296343; -.
DR   iPTMnet; Q92622; -.
DR   PhosphoSitePlus; Q92622; -.
DR   BioMuta; RUBCN; -.
DR   DMDM; 296439479; -.
DR   jPOST; Q92622; -.
DR   MassIVE; Q92622; -.
DR   PaxDb; 9606-ENSP00000296343; -.
DR   PeptideAtlas; Q92622; -.
DR   ProteomicsDB; 75375; -. [Q92622-1]
DR   ProteomicsDB; 75376; -. [Q92622-2]
DR   ProteomicsDB; 75377; -. [Q92622-3]
DR   Pumba; Q92622; -.
DR   Antibodypedia; 54002; 196 antibodies from 27 providers.
DR   DNASU; 9711; -.
DR   Ensembl; ENST00000273582.9; ENSP00000273582.5; ENSG00000145016.18. [Q92622-2]
DR   Ensembl; ENST00000296343.10; ENSP00000296343.5; ENSG00000145016.18. [Q92622-1]
DR   GeneID; 9711; -.
DR   KEGG; hsa:9711; -.
DR   MANE-Select; ENST00000296343.10; ENSP00000296343.5; NM_014687.4; NP_055502.1.
DR   UCSC; uc003fyc.3; human. [Q92622-1]
DR   AGR; HGNC:28991; -.
DR   ClinPGx; PA134887849; -.
DR   CTD; 9711; -.
DR   DisGeNET; 9711; -.
DR   GeneCards; RUBCN; -.
DR   HGNC; HGNC:28991; RUBCN.
DR   HPA; ENSG00000145016; Low tissue specificity.
DR   MalaCards; RUBCN; -.
DR   MIM; 613516; gene.
DR   MIM; 615705; phenotype.
DR   OpenTargets; ENSG00000145016; -.
DR   Orphanet; 404499; Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to RUBCN deficiency.
DR   VEuPathDB; HostDB:ENSG00000145016; -.
DR   eggNOG; KOG1829; Eukaryota.
DR   eggNOG; KOG4381; Eukaryota.
DR   GeneTree; ENSGT00940000160658; -.
DR   InParanoid; Q92622; -.
DR   OMA; CADLEKX; -.
DR   OrthoDB; 10067503at2759; -.
DR   PAN-GO; Q92622; 6 GO annotations based on evolutionary models.
DR   PhylomeDB; Q92622; -.
DR   PathwayCommons; Q92622; -.
DR   SignaLink; Q92622; -.
DR   SIGNOR; Q92622; -.
DR   Agora; ENSG00000145016; -.
DR   BioGRID-ORCS; 9711; 23 hits in 1140 CRISPR screens.
DR   ChiTaRS; RUBCN; human.
DR   GenomeRNAi; 9711; -.
DR   Pharos; Q92622; Tbio.
DR   PRO; PR:Q92622; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q92622; protein.
DR   Bgee; ENSG00000145016; Expressed in sural nerve and 197 other cell types or tissues.
DR   ExpressionAtlas; Q92622; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR   GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0141039; F:phosphatidylinositol 3-kinase inhibitor activity; IDA:GO_Central.
DR   GO; GO:1901981; F:phosphatidylinositol phosphate binding; IBA:GO_Central.
DR   GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR   GO; GO:0071985; P:multivesicular body sorting pathway; TAS:ParkinsonsUK-UCL.
DR   GO; GO:1901097; P:negative regulation of autophagosome maturation; IMP:UniProtKB.
DR   GO; GO:0010507; P:negative regulation of autophagy; IMP:UniProtKB.
DR   GO; GO:0045806; P:negative regulation of endocytosis; IMP:UniProtKB.
DR   GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB.
DR   GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR   CDD; cd17686; RUN_RUBCN; 1.
DR   FunFam; 1.20.58.900:FF:000014; Run domain Beclin-1-interacting and cysteine-rich domain-containing protein; 1.
DR   Gene3D; 1.20.58.900; -; 1.
DR   InterPro; IPR052428; Autophagy_HostDef_Reg.
DR   InterPro; IPR025258; RH_dom.
DR   InterPro; IPR048569; RUBC_PIKBD.
DR   InterPro; IPR004012; Run_dom.
DR   InterPro; IPR037213; Run_dom_sf.
DR   PANTHER; PTHR45971; PHOX (PX) DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR45971:SF3; RUN DOMAIN BECLIN-1-INTERACTING AND CYSTEINE-RICH DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF13901; RH_dom; 1.
DR   Pfam; PF21054; RUBC_PIKBD; 1.
DR   Pfam; PF02759; RUN; 1.
DR   SMART; SM01175; DUF4206; 1.
DR   SMART; SM00593; RUN; 1.
DR   SUPFAM; SSF140741; RUN domain-like; 1.
DR   PROSITE; PS50826; RUN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Autophagy; Endocytosis; Endosome;
KW   Immunity; Lysosome; Neurodegeneration; Phagocytosis; Phosphoprotein;
KW   Proteomics identification; Reference proteome.
FT   CHAIN           1..972
FT                   /note="Run domain Beclin-1-interacting and cysteine-rich
FT                   domain-containing protein"
FT                   /id="PRO_0000050736"
FT   DOMAIN          48..189
FT                   /note="RUN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00178"
FT   REGION          1..22
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          49..180
FT                   /note="Interaction with PIK3C3"
FT                   /evidence="ECO:0000269|PubMed:19270696,
FT                   ECO:0000269|PubMed:21062745"
FT   REGION          204..447
FT                   /note="Interaction with YWHAB"
FT                   /evidence="ECO:0000269|PubMed:22423967"
FT   REGION          233..279
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          300..600
FT                   /note="Interaction with UVRAG"
FT                   /evidence="ECO:0000269|PubMed:21062745"
FT   REGION          307..446
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          505..557
FT                   /note="Interaction with BECN1"
FT                   /evidence="ECO:0000269|PubMed:22423966"
FT   REGION          562..589
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          567..625
FT                   /note="Interaction with CYBA"
FT                   /evidence="ECO:0000269|PubMed:22423966"
FT   REGION          672..760
FT                   /note="Interaction with CARD9"
FT                   /evidence="ECO:0000269|PubMed:22423967"
FT   REGION          721..972
FT                   /note="Interaction with Rab7"
FT                   /evidence="ECO:0000269|PubMed:20943950"
FT   COMPBIAS        13..22
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        338..368
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        378..401
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        436..446
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        563..581
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         197
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976,
FT                   ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT   MOD_RES         248
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         266
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19369195,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         388
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         410
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q80U62"
FT   MOD_RES         528
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19369195"
FT   MOD_RES         562
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         671
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976,
FT                   ECO:0007744|PubMed:19690332"
FT   VAR_SEQ         1..60
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:9039502"
FT                   /id="VSP_039160"
FT   VAR_SEQ         420
FT                   /note="P -> PGGPRNITIIVEDPIA (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:9039502"
FT                   /id="VSP_039161"
FT   VAR_SEQ         596
FT                   /note="D -> DGSEGSNLTHISKNGLSVSLASMFSD (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_039471"
FT   VAR_SEQ         883..896
FT                   /note="LCQAKGFICEFCQN -> VRKSHCSMQLSPCF (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_039472"
FT   VAR_SEQ         897..972
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_039473"
FT   MUTAGEN         248
FT                   /note="S->A: Disrupts interaction with YWHAB."
FT                   /evidence="ECO:0000269|PubMed:22423967"
FT   MUTAGEN         912
FT                   /note="C->G: Disrupts interaction with Rab7, translocation
FT                   to cytoplasm; when associated with G-915, L-920 and G-923."
FT                   /evidence="ECO:0000269|PubMed:20943950"
FT   MUTAGEN         915
FT                   /note="C->G: Disrupts interaction with Rab7, translocation
FT                   to cytoplasm; when associated with G-912, L-920 and G-923."
FT                   /evidence="ECO:0000269|PubMed:20943950"
FT   MUTAGEN         920
FT                   /note="H->L: Disrupts interaction with Rab7, translocation
FT                   to cytoplasm; when associated with G-912,G-915 and G-923."
FT                   /evidence="ECO:0000269|PubMed:20943950"
FT   MUTAGEN         923
FT                   /note="C->G: Disrupts interaction with Rab7, translocation
FT                   to cytoplasm; when associated with G-912, G-915 and L-920."
FT                   /evidence="ECO:0000269|PubMed:20943950"
FT   HELIX           708..716
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   TURN            717..719
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   TURN            722..724
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           730..735
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   TURN            740..742
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   STRAND          744..746
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   TURN            748..750
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   STRAND          754..756
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           759..763
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   STRAND          771..773
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           775..783
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   TURN            784..786
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           792..795
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           799..802
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           804..823
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           830..835
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           841..845
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   STRAND          847..850
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           852..859
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           863..880
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   TURN            882..884
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           885..887
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   TURN            892..894
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   TURN            906..908
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   STRAND          909..911
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   STRAND          913..915
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   STRAND          918..920
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   TURN            921..923
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   STRAND          924..927
FT                   /evidence="ECO:0007829|PDB:6WCW"
FT   HELIX           930..942
FT                   /evidence="ECO:0007829|PDB:6WCW"
SQ   SEQUENCE   972 AA;  108622 MW;  4B76166F29F5AF97 CRC64;
     MRPEGAGMEL GGGEERLPEE SRREHWQLLG NLKTTVEGLV STNSPNVWSK YGGLERLCRD
     MQSILYHGLI RDQACRRQTD YWQFVKDIRW LSPHSALHVE KFISVHENDQ SSADGASERA
     VAELWLQHSL QYHCLSAQLR PLLGDRQYIR KFYTDAAFLL SDAHVTAMLQ CLEAVEQNNP
     RLLAQIDASM FARKHESPLL VTKSQSLTAL PSSTYTPPNS YAQHSYFGSF SSLHQSVPNN
     GSERRSTSFP LSGPPRKPQE SRGHVSPAED QTIQAPPVSV SALARDSPLT PNEMSSSTLT
     SPIEASWVSS QNDSPGDASE GPEYLAIGNL DPRGRTASCQ SHSSNAESSS SNLFSSSSSQ
     KPDSAASSLG DQEGGGESQL SSVLRRSSFS EGQTLTVTSG AKKSHIRSHS DTSIASRGAP
     ESCNDKAKLR GPLPYSGQSS EVSTPSSLYM EYEGGRYLCS GEGMFRRPSE GQSLISYLSE
     QDFGSCADLE KENAHFSISE SLIAAIELMK CNMMSQCLEE EEVEEEDSDR EIQELKQKIR
     LRRQQIRTKN LLPMYQEAEH GSFRVTSSSS QFSSRDSAQL SDSGSADEVD EFEIQDADIR
     RNTASSSKSF VSSQSFSHCF LHSTSAEAVA MGLLKQFEGM QLPAASELEW LVPEHDAPQK
     LLPIPDSLPI SPDDGQHADI YKLRIRVRGN LEWAPPRPQI IFNVHPAPTR KIAVAKQNYR
     CAGCGIRTDP DYIKRLRYCE YLGKYFCQCC HENAQMAIPS RVLRKWDFSK YYVSNFSKDL
     LIKIWNDPLF NVQDINSALY RKVKLLNQVR LLRVQLCHMK NMFKTCRLAK ELLDSFDTVP
     GHLTEDLHLY SLNDLTATRK GELGPRLAEL TRAGATHVER CMLCQAKGFI CEFCQNEDDI
     IFPFELHKCR TCEECKACYH KACFKSGSCP RCERLQARRE ALARQSLESY LSDYEEEPAE
     ALALEAAVLE AT
//