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FLASH GENE
Symbol CIT contributors: mct - updated : 13-09-2015
HGNC name citron (rho-interacting, serine/threonine kinase 21)
HGNC id 1985
Corresponding disease
MCPH17 microcephaly 17, primary
Location 12q24.23      Physical location : 120.123.597 - 120.315.092
Synonym name
  • rho-interacting, serine/threonine kinase 21
  • citron kinase
  • Synonym symbol(s) STK21, KIAA0949, CRIK, CITK
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 191.50 kb     47 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    Map cen - D12S366 - CIT - RPLP0 - NME2 - TCF1 - D12S86 - D12S349 - D12S321 - qter
    Authors GeneMap (98)
    RNA
    TRANSCRIPTS type messenger
    text at least two isoforms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    47 - 8576 240 2027 expressed by post-mitotic cells, suggesting a role for the kinase in neurogenesis 2003 12411428
  • also called long form CRIK
  • CIT-N, which is produced by alternative transcriptional initiation and lacks the kinase domain but maintains the other C-terminal domains
  • 48 - 8708 - 2069 localizes to the cleavage furrow and midbody, where it promotes cytokinesis during cell division 2003 12411428
  • also called short form CRIK-SK, or CIT-K,
  • which has N-terminal kinase, coiled-coil, zinc finger, Pleckstrin homology, and citron homology domains
  • exhibited kinase activity toward exogenous histone H1 substrate, as well as autophosphorylation activity
  • - - - 54 - - 2003 12411428
  • also called short form CRIK-SK
  • a kinase domain
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly
     nervecranial nerve  highly
    Reproductivefemale systemovary  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N-terminal kinase domain followed by the sequence of citron a Rho/Rac binding protein (CRIK short kinase, SK)
  • a coiled-coil, a leucine-rich, a zinc finger domains (its functions are mediated by its coiled-coil (CC) domain, and not by its kinase domain)
  • a pleckstrin homology domain
  • a putative SH3-binding domains
  • a number of C-terminal domains that facilitate interactions between components of the contractile ring (anillin, actin, myosin, and RhoA)
  • HOMOLOGY
    interspecies homolog to murine Cit
    homolog to C.elegans f59a6.5
    ortholog to Drosophila Sticky (Sti)
    Homologene
    FAMILY
  • myotonic dystrophy kinase family
  • protein kinase superfamily
  • AGC Ser/Thr protein kinase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    text
  • localization of KIF14 and citron kinase to the central spindle
  • CDKN1B and CIT colocalized at the contractile ring and mid-body during telophase and cytokinesis
  • co-localizes with ASPM at the midbody ring
  • localizes to the cleavage furrow and midbody of mitotic cells, where it is required for the completion of cytokinesis
  • basic FUNCTION
  • required in human cell division
  • cell cycle-dependent protein regulating the G(2)/M transition in hepatocytes
  • might function as a scaffold protein in spine organization through its ability to bind to Golgi membranes and by affecting actin remodelling
  • ASPM and CIT are expressed during neurogenesis and play important roles in neuronal progenitor cell division
  • protein essential to neurogenic cell division in the central nervous system
  • required for cytokinesis and currently considered a cytokinesis-specific effector of active RHOA
  • specifically required for abscission in mammalian cells
  • is a crucial abscission regulator that may promote midbody stability through active RHOA and ANLN
  • maintains correct RHOA localization at the cleavage site, which is necessary for proper RHOA activity and contractile ring dynamics in cytokinesis
  • is likely to act at the top of the midbody-formation hierarchy by connecting and regulating a molecular network of contractile ring components and microtubule-associated proteins
  • roles in cytokinesis, and kinase activity of CIT is required for function in controlling cytokinesis
  • CELLULAR PROCESS cell cycle, division
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    TTC3-RhoA-CIT-K pathway that could be a crucial determinant of neuronal development, whose hyperactivity may result in detrimental effects on the normal differentiation program (Berto 2007)
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • rho-binding
  • rac-binding and rac (GTP bound form)
  • DLG5, a member of the MAGUK family, is an interactor of CIT required for CIT polarization
  • is capable of physically and functionally interacting with the actin-binding protein ANLN
  • by binding to CIT, CDKN1B prevented the interaction of CIT with its activator RHOA
  • SRCIN1 regulates memory and synaptic plasticity through SRC-mediated and CIT-N-mediated actin reorganization
  • expression of relatively low levels of TUBB3 in mitotic cells can be detrimental for their cytokinesis and underscore the importance of CIT in counteracting this event
  • interacting of KIF14 with CIT
  • KIF14 is a mitotic motor protein that is required for spindle localization of the mitotic citron rho-interacting kinase, CIT, also mutated in microcephaly
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MCPH17
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    malformation syndromes of central nervous system
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    citron-K-/- mice