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FLASH GENE
Symbol HRK contributors: mct - updated : 05-06-2013
HGNC name harakiri, BCL2 interacting protein (contains only BH3 domain)
HGNC id 5185
Location 12q24.22      Physical location : 117.299.027 - 117.319.232
Synonym name
  • BCL2-interacting protein
  • activator of apoptosis Hrk
  • harakiri, BCL2 interacting protein
  • Synonym symbol(s) DP5, HARAKIRI
    DNA
    TYPE functioning gene
    STRUCTURE 20.21 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   silencer
    text structure
  • silenced by hypermethylation of a major proximal CpG island in the HRK promoter
  • MAPPING cloned Y linked N status provisional
    Physical map
    SDS-RS1 12q24.21 serine dehydratase related sequence 1 LHX5 12q24.31-q24.32 LIM homeobox protein 5 KIAA0682 12q23.3-q24.2 LIM homeobox protein 5 TBX5 12q24.1 T-box 5 LOC387886 12 LOC387886 LOC390361 12 similar to microtubule-associated proteins 1A/1B light chain 3 LOC386654 12q24.1-q24.2 OSTF1 pseudogene TBX3 12q24.1 T-box 3 (ulnar mammary syndrome) LOC387887 12 LOC387887 KIAA1025 LOC387888 12 LOC387888 FLJ21415 12q24.22 hypothetical protein FLJ21415 FLJ14627 12q24.22-q24.23 hypothetical protein FLJ14627 HRK 12q24.23 harakiri, BCL2 interacting protein (contains only BH3 domain) FBXW8 12q24.21 F-box and WD-40 domain protein 8 TSC 12q24.23 hypothetical protein FLJ20607 FBXO21 12q24.21 F-box only protein 21 NOS1 12q24.2-q24.31 nitric oxide synthase 1 (neuronal) KSR2 12q24.23 kinase suppressor of Ras-2 RFC5 12q24.2-q24.3 replication factor C (activator 1) 5, 36.5kDa WSB2 12q24.23 WD repeat and SOCS box containing protein 2 FLJ20674 12q24.23 hypothetical protein FLJ20674 PBP 12q24.23 prostatic binding protein JIK 12q24.2 prostatic binding protein SDS3 12q24.23 likely ortholog of mouse Sds3 LOC144747 12q24.23 hypothetical protein LOC144747 H11 LOC387889 12 hypothetical gene supported by U41745; NM_014891 MGC39827 12q24.23 hypothetical protein MGC39827 LOC387890 12 similar to hypothetical protein C130069F04 PRKAB1 12q24.1-q24.3 protein kinase, AMP-activated, beta 1 non-catalytic subunit CIT 12q24.2 citron (rho-interacting, serine/threonine kinase 21) LOC92558 12q24.31 hypothetical protein LOC92558 RAB35 12q24.31 RAB35, member RAS oncogene family GCN1L1 12q24.3 GCN1 general control of amino-acid synthesis 1-like 1 (yeast) RPLP0 12q24.2 ribosomal protein, large, P0 PXN 12q24 paxillin FLJ23042 12q24.31 hypothetical protein FLJ23042 LOC283458 12q24.31 nucleoside diphosphate kinase B-like pseudogene
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 716 - 91 - -
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Nervouscentral    Homo sapiensAdult
    Nervousperipherous    Homo sapiensAdult
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • BH3 domain (BCL-2 homology domain 3)
  • transmembrane domain
  • C-terminal region adopts a predominantly alpha-helical structure whose proportion and destabilization capability varied depending on phospholipid composition
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to C.elegans F08B12.4
    homolog to rattus Bid3
    homolog to murine Hrk
    Homologene
    FAMILY
    CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    text
  • appears associated to the mitochondrial outer membrane, apparently by a putative transmembrane domain, where it exerts its function (
  • basic FUNCTION
  • activating apoptosis
  • contributes to apoptosis signalling elicited by trophic factor withdrawal in certain neuronal populations but is dispensable for apoptosis of haematopoietic cells (
  • central for beta-cell apoptosis after different stimuli, and that it can act up- and downstream of ER stress
  • may contribute to the development and progression of many human cancers
  • role of Harakiri (HRK), in disrupting the BAX-BCL2L1 interaction during nervous system development (
  • important proapoptotic mitochondrial protein of the BCL2 family
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS development , immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds to a specific region in BCL2L10
  • localizes in membranes and induces cell death by binding to prosurvival BL2L1 and BCL2
  • Harakiri (HRK), is a novel SUZ12 target gene (
  • transactivated by ATF4 in severe hypoxia through direct binding of ATF4 to the promoter region
  • synergistic effects of HRK promoter hypermethylation and loss of TFAP2A transactivation lead to HRK gene silencing and confer resistance to apoptosis and enhanced tumor growth
  • cell & other
    REGULATION
    activated by hematopoietic growth factor deprivation
    induced by ceramide induced the expression of the harikari gene(HRK) and up-regulated JNK phosphorylation
    repressed by BCL-2 BCL2L1
    DREAM (IL-3 and PI3 kinases pathways)
    Other HRK, BBC3, and PMAIP1 are transcriptionally induced in severe hypoxia and their expression is abrogated by RNA interference against ATF4
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in amyotrophic lateral sclerosis
    tumoral       loss of function
    principally by promoter hypermethylation in prostate cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS