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Protein

Run domain Beclin-1-interacting and cysteine-rich domain-containing protein

Gene

RUBCN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Inhibits PIK3C3 activity; under basal conditions negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy. Negatively regulates endosome maturation and degradative endocytic trafficking and impairs autophagosome maturation process. Can sequester UVRAG from association with a class C Vps complex (possibly the HOPS complex) and negatively regulates Rab7 activation (PubMed:20974968, PubMed:21062745).2 Publications
Involved in regulation of pathogen-specific host defense of activated macrophages. Following bacterial infection promotes NADH oxidase activity by association with CYBA thereby affecting TLR2 signaling and probably other TLR-NOX pathways. Stabilizes the CYBA:CYBB NADPH oxidase heterodimer, increases its association with TLR2 and its phagosome trafficking to induce antimicrobial burst of ROS and production of inflammatory cytokines (PubMed:22423966). Following fungal or viral infection (implicating CLEC7A (dectin-1)-mediated myeloid cell activation or DDX58/RIG-I-dependent sensing of RNA viruses) negatively regulates pro-inflammatory cytokine production by association with CARD9 and sequestering it from signaling complexes (PubMed:22423967).2 Publications

GO - Biological processi

  • autophagosome maturation Source: ParkinsonsUK-UCL
  • immune system process Source: UniProtKB-KW
  • multivesicular body sorting pathway Source: ParkinsonsUK-UCL
  • negative regulation of autophagosome maturation Source: UniProtKB
  • negative regulation of autophagy Source: UniProtKB
  • negative regulation of endocytosis Source: UniProtKB
  • negative regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
  • phagocytosis Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Autophagy, Endocytosis, Immunity, Phagocytosis

Enzyme and pathway databases

SIGNORiQ92622.

Names & Taxonomyi

Protein namesi
Recommended name:
Run domain Beclin-1-interacting and cysteine-rich domain-containing proteinImported
Short name:
Rubicon
Alternative name(s):
Beclin-1 associated RUN domain containing protein
Short name:
Baron
Gene namesi
Name:RUBCNImported
Synonyms:KIAA0226
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:28991. RUBCN.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • early endosome Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • late endosome Source: UniProtKB
  • lysosome Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Lysosome

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia, autosomal recessive, 15 (SCAR15)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSpinocerebellar ataxia defines a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR15 patients manifest cerebellar ataxia in early childhood and delayed motor development with delayed walking. Additional features include dysarthria, upper limb involvement, abnormal eye movements, and hyporeflexia.
See also OMIM:615705

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi248 – 2481S → A: Disrupts interaction with YWHAB. 1 Publication
Mutagenesisi912 – 9121C → G: Disrupts interaction with Rab7, translocation to cytoplasm; when associated with G-915, L-920 and G-923. 1 Publication
Mutagenesisi915 – 9151C → G: Disrupts interaction with Rab7, translocation to cytoplasm; when associated with G-912, L-920 and G-923. 1 Publication
Mutagenesisi920 – 9201H → L: Disrupts interaction with Rab7, translocation to cytoplasm; when associated with G-912,G-915 and G-923. 1 Publication
Mutagenesisi923 – 9231C → G: Disrupts interaction with Rab7, translocation to cytoplasm; when associated with G-912, G-915 and L-920. 1 Publication

Keywords - Diseasei

Neurodegeneration

Organism-specific databases

MalaCardsiKIAA0226.
MIMi615705. phenotype.
Orphaneti404499. Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to KIAA0226 deficiency.
PharmGKBiPA134887849.

Polymorphism and mutation databases

BioMutaiKIAA0226.
DMDMi296439479.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 972972Run domain Beclin-1-interacting and cysteine-rich domain-containing proteinPRO_0000050736Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei197 – 1971PhosphoserineCombined sources
Modified residuei248 – 2481PhosphoserineCombined sources
Modified residuei266 – 2661PhosphoserineCombined sources
Modified residuei388 – 3881PhosphoserineCombined sources
Modified residuei410 – 4101PhosphoserineBy similarity
Modified residuei528 – 5281PhosphoserineCombined sources
Modified residuei562 – 5621PhosphoserineCombined sources
Modified residuei671 – 6711PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ92622.
MaxQBiQ92622.
PaxDbiQ92622.
PeptideAtlasiQ92622.
PRIDEiQ92622.

PTM databases

iPTMnetiQ92622.
PhosphoSiteiQ92622.

Expressioni

Gene expression databases

BgeeiENSG00000145016.
CleanExiHS_KIAA0226.
ExpressionAtlasiQ92622. baseline and differential.
GenevisibleiQ92622. HS.

Organism-specific databases

HPAiHPA050908.
HPA054497.

Interactioni

Subunit structurei

Associates with PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex II (PI3KC3-C2) in which the core composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 is associated with UVRAG; in the complex interacts directly with PI3KC3 and UVRAG (PubMed:19270696, PubMed:21062745). Interacts with Rab7 (RAB7A or RAB7B) (GTP-bound form); Rab7 and UVRAG compete for RUBCN binding; can interact simultaneously with Rab7 and the PI3K complex (PubMed:20943950, PubMed:20974968, PubMed:21062745). Interacts with CYBA and CYBB; indicative for the association with the CYBA:CYBB NADPH oxidase heterodimer. Interacts with NOX4 and probably associates with the CYBA:NOX4 complex (PubMed:22423966). Interacts with YWHAB and CARD9 in a competetive and stimulation-dependent manner; RUBCN exchanges interaction from YWHAB to CARD9 upon stimulation with beta-1,3-glucan (PubMed:22423967).6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BECN1Q1445715EBI-2952709,EBI-949378
EGFRP005333EBI-2952709,EBI-297353
PIK3C3Q8NEB97EBI-2952709,EBI-1056470
UVRAGQ9P2Y57EBI-2952709,EBI-2952704

Protein-protein interaction databases

BioGridi115062. 8 interactions.
IntActiQ92622. 5 interactions.
STRINGi9606.ENSP00000296343.

Structurei

3D structure databases

ProteinModelPortaliQ92622.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini48 – 189142RUNPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni49 – 180132Interaction with PIK3C31 PublicationAdd
BLAST
Regioni204 – 447244Interaction with YWHAB1 PublicationAdd
BLAST
Regioni300 – 600301Interaction with UVRAG1 PublicationAdd
BLAST
Regioni505 – 55753Interaction with BECN11 PublicationAdd
BLAST
Regioni567 – 62559Interaction with CYBA1 PublicationAdd
BLAST
Regioni672 – 76089Interaction with CARD91 PublicationAdd
BLAST
Regioni721 – 972252Interaction with Rab71 PublicationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi204 – 447244Ser-richAdd
BLAST
Compositional biasi567 – 62559Ser-richAdd
BLAST
Compositional biasi881 – 93252Cys-richAdd
BLAST

Sequence similaritiesi

Contains 1 RUN domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1829. Eukaryota.
KOG4381. Eukaryota.
ENOG410XQ7T. LUCA.
GeneTreeiENSGT00550000074570.
HOGENOMiHOG000113142.
HOVERGENiHBG062207.
InParanoidiQ92622.
KOiK19330.
OMAiLYHGLIH.
OrthoDBiEOG091G05ZY.
PhylomeDBiQ92622.
TreeFamiTF317067.

Family and domain databases

InterProiIPR004012. Run_dom.
IPR025258. Zf-RING_9.
[Graphical view]
PfamiPF02759. RUN. 1 hit.
PF13901. zf-RING_9. 1 hit.
[Graphical view]
SMARTiSM01175. DUF4206. 1 hit.
SM00593. RUN. 1 hit.
[Graphical view]
PROSITEiPS50826. RUN. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92622-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRPEGAGMEL GGGEERLPEE SRREHWQLLG NLKTTVEGLV STNSPNVWSK
60 70 80 90 100
YGGLERLCRD MQSILYHGLI RDQACRRQTD YWQFVKDIRW LSPHSALHVE
110 120 130 140 150
KFISVHENDQ SSADGASERA VAELWLQHSL QYHCLSAQLR PLLGDRQYIR
160 170 180 190 200
KFYTDAAFLL SDAHVTAMLQ CLEAVEQNNP RLLAQIDASM FARKHESPLL
210 220 230 240 250
VTKSQSLTAL PSSTYTPPNS YAQHSYFGSF SSLHQSVPNN GSERRSTSFP
260 270 280 290 300
LSGPPRKPQE SRGHVSPAED QTIQAPPVSV SALARDSPLT PNEMSSSTLT
310 320 330 340 350
SPIEASWVSS QNDSPGDASE GPEYLAIGNL DPRGRTASCQ SHSSNAESSS
360 370 380 390 400
SNLFSSSSSQ KPDSAASSLG DQEGGGESQL SSVLRRSSFS EGQTLTVTSG
410 420 430 440 450
AKKSHIRSHS DTSIASRGAP ESCNDKAKLR GPLPYSGQSS EVSTPSSLYM
460 470 480 490 500
EYEGGRYLCS GEGMFRRPSE GQSLISYLSE QDFGSCADLE KENAHFSISE
510 520 530 540 550
SLIAAIELMK CNMMSQCLEE EEVEEEDSDR EIQELKQKIR LRRQQIRTKN
560 570 580 590 600
LLPMYQEAEH GSFRVTSSSS QFSSRDSAQL SDSGSADEVD EFEIQDADIR
610 620 630 640 650
RNTASSSKSF VSSQSFSHCF LHSTSAEAVA MGLLKQFEGM QLPAASELEW
660 670 680 690 700
LVPEHDAPQK LLPIPDSLPI SPDDGQHADI YKLRIRVRGN LEWAPPRPQI
710 720 730 740 750
IFNVHPAPTR KIAVAKQNYR CAGCGIRTDP DYIKRLRYCE YLGKYFCQCC
760 770 780 790 800
HENAQMAIPS RVLRKWDFSK YYVSNFSKDL LIKIWNDPLF NVQDINSALY
810 820 830 840 850
RKVKLLNQVR LLRVQLCHMK NMFKTCRLAK ELLDSFDTVP GHLTEDLHLY
860 870 880 890 900
SLNDLTATRK GELGPRLAEL TRAGATHVER CMLCQAKGFI CEFCQNEDDI
910 920 930 940 950
IFPFELHKCR TCEECKACYH KACFKSGSCP RCERLQARRE ALARQSLESY
960 970
LSDYEEEPAE ALALEAAVLE AT
Length:972
Mass (Da):108,622
Last modified:May 18, 2010 - v4
Checksum:i4B76166F29F5AF97
GO
Isoform 2 (identifier: Q92622-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: Missing.
     420-420: P → PGGPRNITIIVEDPIA

Show »
Length:927
Mass (Da):103,459
Checksum:iA5C4783CEEC0988A
GO
Isoform 3 (identifier: Q92622-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     596-596: D → DGSEGSNLTHISKNGLSVSLASMFSD
     883-896: LCQAKGFICEFCQN → VRKSHCSMQLSPCF
     897-972: Missing.

Note: No experimental confirmation available.
Show »
Length:921
Mass (Da):102,506
Checksum:iEC978A4C7F1948A9
GO

Sequence cautioni

The sequence BAA13215 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6060Missing in isoform 2. 1 PublicationVSP_039160Add
BLAST
Alternative sequencei420 – 4201P → PGGPRNITIIVEDPIA in isoform 2. 1 PublicationVSP_039161
Alternative sequencei596 – 5961D → DGSEGSNLTHISKNGLSVSL ASMFSD in isoform 3. CuratedVSP_039471
Alternative sequencei883 – 89614LCQAK…EFCQN → VRKSHCSMQLSPCF in isoform 3. CuratedVSP_039472Add
BLAST
Alternative sequencei897 – 97276Missing in isoform 3. CuratedVSP_039473Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86979 mRNA. Translation: BAA13215.3. Different initiation.
AC024560 Genomic DNA. No translation available.
BX437131 mRNA. No translation available.
BC014173 mRNA. Translation: AAH14173.2.
CCDSiCCDS43195.1. [Q92622-1]
CCDS46987.1. [Q92622-2]
RefSeqiNP_001139114.1. NM_001145642.3. [Q92622-2]
NP_055502.1. NM_014687.2. [Q92622-1]
UniGeneiHs.478868.

Genome annotation databases

EnsembliENST00000273582; ENSP00000273582; ENSG00000145016. [Q92622-2]
ENST00000296343; ENSP00000296343; ENSG00000145016. [Q92622-1]
GeneIDi9711.
KEGGihsa:9711.
UCSCiuc003fyc.3. human. [Q92622-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86979 mRNA. Translation: BAA13215.3. Different initiation.
AC024560 Genomic DNA. No translation available.
BX437131 mRNA. No translation available.
BC014173 mRNA. Translation: AAH14173.2.
CCDSiCCDS43195.1. [Q92622-1]
CCDS46987.1. [Q92622-2]
RefSeqiNP_001139114.1. NM_001145642.3. [Q92622-2]
NP_055502.1. NM_014687.2. [Q92622-1]
UniGeneiHs.478868.

3D structure databases

ProteinModelPortaliQ92622.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115062. 8 interactions.
IntActiQ92622. 5 interactions.
STRINGi9606.ENSP00000296343.

PTM databases

iPTMnetiQ92622.
PhosphoSiteiQ92622.

Polymorphism and mutation databases

BioMutaiKIAA0226.
DMDMi296439479.

Proteomic databases

EPDiQ92622.
MaxQBiQ92622.
PaxDbiQ92622.
PeptideAtlasiQ92622.
PRIDEiQ92622.

Protocols and materials databases

DNASUi9711.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273582; ENSP00000273582; ENSG00000145016. [Q92622-2]
ENST00000296343; ENSP00000296343; ENSG00000145016. [Q92622-1]
GeneIDi9711.
KEGGihsa:9711.
UCSCiuc003fyc.3. human. [Q92622-1]

Organism-specific databases

CTDi9711.
GeneCardsiKIAA0226.
HGNCiHGNC:28991. RUBCN.
HPAiHPA050908.
HPA054497.
MalaCardsiKIAA0226.
MIMi613516. gene.
615705. phenotype.
neXtProtiNX_Q92622.
Orphaneti404499. Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to KIAA0226 deficiency.
PharmGKBiPA134887849.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1829. Eukaryota.
KOG4381. Eukaryota.
ENOG410XQ7T. LUCA.
GeneTreeiENSGT00550000074570.
HOGENOMiHOG000113142.
HOVERGENiHBG062207.
InParanoidiQ92622.
KOiK19330.
OMAiLYHGLIH.
OrthoDBiEOG091G05ZY.
PhylomeDBiQ92622.
TreeFamiTF317067.

Enzyme and pathway databases

SIGNORiQ92622.

Miscellaneous databases

ChiTaRSiKIAA0226. human.
GenomeRNAii9711.
PROiQ92622.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145016.
CleanExiHS_KIAA0226.
ExpressionAtlasiQ92622. baseline and differential.
GenevisibleiQ92622. HS.

Family and domain databases

InterProiIPR004012. Run_dom.
IPR025258. Zf-RING_9.
[Graphical view]
PfamiPF02759. RUN. 1 hit.
PF13901. zf-RING_9. 1 hit.
[Graphical view]
SMARTiSM01175. DUF4206. 1 hit.
SM00593. RUN. 1 hit.
[Graphical view]
PROSITEiPS50826. RUN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRUBIC_HUMAN
AccessioniPrimary (citable) accession number: Q92622
Secondary accession number(s): Q96CK5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 18, 2010
Last modified: September 7, 2016
This is version 122 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.