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FLASH GENE
Symbol UIMC1 contributors: mct/ - updated : 04-10-2017
HGNC name ubiquitin interaction motif containing 1
HGNC id 30298
Location 5q35.2      Physical location : 176.332.005 - 176.433.443
Synonym name
  • receptor associated protein 80
  • retinoid X receptor- interacting protein 110
  • nuclear zinc finger protein RAP80
  • BRCA1-A complex subunit RAP80
  • Synonym symbol(s) RAP80, RXRIP110, X2HRIP110
    DNA
    TYPE functioning gene
    STRUCTURE 117.64 kb     15 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 2825 - 719 - 2002 12080054
    15 - 2629 - 719 - 2002 12080054
    15 - 2615 - 719 - 2002 12080054
    15 - 2228 - 553 - 2002 12080054
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestivestomach   highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemuteruscervix highly
     female systemovary   
     male systemtestis  highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a bipartite nuclear localization signal at the N-terminus important in mediating nuclear transport, and two functional ubiquitin-interaction motifs (UIMs), UIM domain, which is a component of the BRCA1-A complex, interacting with Ub Lys-63 linkage conjugates and mediating the recruitment of BRCA1 to DSBs
  • a SIM domain that appears to bind specifically to SUMO2 conjugates, but not to SUMO1
  • two potential CX(2)CX(11)HX(3)C-type zinc finger motifs at its carboxyl-terminal region
  • a central region (residues 233–399), the Abraxas-Interacting Region (AIR), mediates interaction with constituents of the BRCA1–UIMC1 protein complex
  • HOMOLOGY
    Homologene
    FAMILY
  • retinoid X receptor interacting protein family
  • RAP80 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    basic FUNCTION
  • may be functioning as an active repressor of transcription
  • required for DNA damage-induced BRCA1 translocation, and functions as a partner of BRCA1-BRCTD in response to DNA damage
  • plays a critical role in the regulation of estrogen receptor alpha and DNA damage response signaling
  • ubiquitin-interaction motif (UIM) containing protein that is associated with a BRCA1/BARD1 complex through its interaction with FAM175A
  • like many ubiquitin-binding proteins, had been reported to be ubiquitinated in a manner dependent on its UIM domains
  • UIMC1/BRCA1 complex, is required for efficient BRCA1 focal recruitment, and suppress excessive DSB (DNA double-strand breaks) end processing, homologous recombination-type DSB repair, and overt chromosomal instability
  • plays a crucial role in the DNA damage response and in maintaining genomic integrity
  • play a key role in DNA damage response (DDR) signaling by facilitating the translocation of several DDR mediators, including BRCA1, to ionizing irradiation (IR)-induced foci
  • is crucial in cell cycle checkpoint activation and DNA damage repair
  • plays a central role in the damage response by targeting BRCA1/BRCA2 tumor suppressors to DNA damage foci through multivalent binding of Lys-63-linked polyubiquitin chains
  • plays a key role in the recruitment process through the binding of Lys(63)-linked poly-Ub chains by tandem Ub interacting motifs (UIM)
  • is a critical gatekeeper in impeding EMT-induced metastasis and malignant phenotypes of cancer as well as preserving DNA integrity.
  • localizes to sites of DNA insults to enhance the DNA-damage responses
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • BRCA1, FAM175A and UIMC1 form a functional complex and participate in the DNA damage response
  • with CEP57, form a complex in intact cells
  • component of UIMC1 complex, a five-member stoichiometric complex consisting of UIMC1, BRCC3, BRE, FAM175A, and MERIT40
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CCDC98 and BRCA1
  • interacts with the SUMO-conjugating enzyme UBE2I and is a novel target for sumoylation
  • interacting with MDC1 (role for the MDC1-UIMC1 interaction in focus formation by the UIMC1-BRCA1 complex
  • UIMC1 binding to both SUMO and Ub conjugates is required for proper cellular response to DNA double-strand breaks (DSBs)
  • mediates binding of the BRCA1-A complex to SUMO2 (pMID: 22689573
  • dynamic Ub and SUMO modification at DNA damage sites plays critical roles in UIMC1 and BRCA1 recruitment and efficient DNA repair
  • RNF4, a SUMO-targeted ubiquitin E3 ligase that synthesizes hybrid SUMO-ubiquitin chains, localized to DSBs and was critical for the recruitment of UIMC1 and BRCA1 to sites of DNA damage
  • CDK1 is a new UIMC1-binding protein
  • novel role for UIMC1 in preventing proteasomal degradation of BLM in unstressed cells
  • TRAIP/RNF206 is a novel UIMC1-interacting protein and TRAIP is necessary for translocation of UIMC1 to DNA lesions
  • cell & other
    REGULATION
    Phosphorylated by post-translational phosphorylation by the CDK1-CCNB1 complex is important for UIMC1 functional sensitivity to IR and G(2)/M checkpoint control
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    RAP80-deficiency promotes genomic instability and causes an increase in cancer risk consistent with the concept that UIMC1 exhibits a tumor suppressor function
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Rap80- deficient mice are prone to B-cell lymphomagenesis