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FLASH GENE
Symbol HCST contributors: mct - updated : 10-09-2011
HGNC name hematopoietic cell signal transducer
HGNC id 16977
Location 19q13.12      Physical location : 36.393.381 - 36.395.173
Synonym name
  • DNAX-activation protein 10
  • phosphoinositide-3-kinase adaptor protein
  • hematopoietic cell signal transducer, isoform 1
  • Synonym symbol(s) DAP10, DKFZP586C1522, KAP10, PIK3AP, UNQ587/PRO1157
    DNA
    TYPE functioning gene
    SPECIAL FEATURE opposite orientation, tail to tail
    text oposite orientation to the DAP12 gene, separated by ~130 bp
    STRUCTURE 1.79 kb     4 Exon(s)
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC388533 19 similar to KIPV467 ZD52F10 19q13.13 hypothetical gene ZD52F10 UNQ698 19q13.13 HLAR698 GAPDS 19q13.1 glyceraldehyde-3-phosphate dehydrogenase, testis-specific NIFIE14 19q13.1 seven transmembrane domain protein ATP4A 19q13.1 ATPase, H+/K+ exchanging, alpha polypeptide KIAA0841 19q13.13 KIAA0841 MGC10433 19q13.13 hypothetical protein MGC10433 LOC339321 19q13.13 hypothetical protein LOC339321 COX6B 19q13.1 cytochrome c oxidase subunit VIb UPK1A 19q12-q13.1 uroplakin 1A TZFP 19q13.1 uroplakin 1A MLL4 19q13.1 myeloid/lymphoid or mixed-lineage leukemia 4 FLJ22573 19q13.13 hypothetical protein FLJ22573 U2AF1L3 19q13.13 U2(RNU2) small nuclear RNA auxiliary factor 1-like 3 PEN2 19q13.13 presenilin enhancer 2 F25965 19q13.1 protein F25965 FLJ32389 19q13.13 hypothetical protein FLJ32389 LOC148137 19q13.13 hypothetical protein BC017947 SNX26 19q13.13 sorting nexin 26 PRODH2 19q13.1 proline dehydrogenase (oxidase) 2 NPHS1 19q13.1 nephrosis 1, congenital, Finnish type (nephrin) KIRREL2 19q13.13 kin of IRRE like 2 (Drosophila) APLP1 19q13.1-q13.2 amyloid beta (A4) precursor-like protein 1 TA-NFKBH 19q13.13 T-cell activation NFKB-like protein HCST 19q13.1 hematopoietic cell signal transducer TYROBP 19q13.1 TYRO protein tyrosine kinase binding protein MGC2656 FLJ36445 19q13.13 hypothetical protein FLJ36445 MGC15677 19q13.13 hypothetical protein MGC15677 CLIPR-59 19q13.13 CLIP-170-related protein THAP8 19q13.13 THAP domain containing 8 FLJ33298 19q13.13 hypothetical protein FLJ33298 DKFZP434J046 LOC390925 POLR2I 19q12 polymerase (RNA) II (DNA directed) polypeptide I, 14.5kDa CKAP1 19q13.11-q13.12 cytoskeleton-associated protein 1 CAPNS1 19q13.13 calpain, small subunit 1 COX7A1 19q13.1 cytochrome c oxidase subunit VIIa polypeptide 1 (muscle)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 524 9 93 - 2006 17100879
    4 - 521 - 92 - 2006 17100879
    uses an alternate in-frame splice site in the 3' coding region
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemuterus   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic
    Blood/Hematopoieticmonocyte
    Lymphoid/Immunenatural killer
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    SH2 domain-binding site
    conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to murine Hcst
    ortholog to rattus hcst
    Homologene
    FAMILY
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • recruiting the p85 subunit of the PI3K
  • KLRK1-HCST receptor complex may activate NK and T cell responses against MICA-bearing tumors
  • important physiological role of HCST signaling in maintaining tolerance to self, probably by controlling the development and activation threshold of autoreactive T cells
  • may be involved in innate immune surveillance
  • HCST and TYROBP, can either activate or inhibit immune responses
  • HCST trafficked to secretory lysosomes in both transfected NKL cells and in activated primary NK cells upon interaction with MICB-expressing target cells
  • signaling adaptor molecule that play a key role in the TREM2- and TYROBP-dependent recruitment of PI3K to the signaling complex
  • during Mycobacterium tuberculosis infection is required for maximal cytolytic activity of CD8 T cells
  • cancer cells themselves express KLRK1 in complex with HCST signaling adaptor
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
    a component KLRK1 in complex with the HCST signaling adaptor is expressed on most natural killer (NK) cells and CD8 T cells
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NKG2D to form an activating receptor complex for MICA
  • p85 subunit of PI3K resulting in activation of AKT
  • CLEC5A associates with both TYROBP and HCST in osteoclasts and bone marrow-derived macrophages, where HCST association depends almost entirely on TYROBP
  • HMBOX1 may act as a negative regulator of NK cell functions via suppressing the KLRK1/HCST signaling pathway
  • interacting with TGFbeta1 (TGF-BETA1 down-modulates surface KLRK1 expression by controlling the transcriptional and translational levels of HCST)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    inhibitors of HCST and TYROBP or other proteins involved in this signaling pathway will be attractive therapeutic targets for the treatment of large granular lymphocyte (LGL) leukemia
    immunologyautoimmune 
    inhibitors of HCST and TYROBP or other proteins involved in this signaling pathway will be attractive therapeutic targets for the treatment of autoimmune diseases and syndromes
    ANIMAL & CELL MODELS
    CD8+T cells from DAP-deficient mice lacked NKG2D expression and are unable to mount tumor-specific response and NK cells expressed a functional NKG2D receptor trough association with another adaptor (DAP12) to recruit protein-tyrosine-kinases