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FLASH GENE
Symbol ASPH contributors: mct/npt/pgu - updated : 09-05-2016
HGNC name aspartate beta-hydroxylase
HGNC id 757
Corresponding disease
FDLAB facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs
Location 8q12.3      Physical location : 62.413.115 - 62.627.199
Synonym name
  • junctin, calsequestrin binding protein
  • peptide-aspartate beta-dioxygenase
  • humbug
  • junctate
  • A beta H-J-J
  • cardiac junctin
  • Synonym symbol(s) HAAH, BAH, JCTN, CASQ2BP1, JCN, AAH, FDLAB, junctin, JCT
    EC.number 1.14.11.16
    DNA
    TYPE functioning gene
    STRUCTURE 214.08 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D8S507 - RAB2 - D8S260 - D8S510 - qter
    Authors GeneMap (98)
    Physical map
    RDH-E2 8q12.1 retinal short chain dehydrogenase reductase PENK 8q11.23-q12 proenkephalin LOC389662 8 similar to septin 10 isoform 1 LOC346950 8q11.23 similar to ribosomal protein L37 FLJ20421 8q11.23 hypothetical protein FLJ20421 DKFZP434F122 8q12.1 DKFZP434F122 protein LOC389663 8 similar to hypothetical protein MGC39325 8q12.1 hypothetical protein MGC39325 LOC137886 8q12.1 hypothetical protein LOC137886 CYP7A1 8q11-q12 cytochrome P450, family 7, subfamily A, polypeptide 1 LOC137885 8q12.1 similar to peptidylprolyl isomerase A SDCBP 8q12 syndecan binding protein (syntenin) NSMAF 8q12-q13 neutral sphingomyelinase (N-SMase) activation associated factor TOX 8q11.23 neutral sphingomyelinase (N-SMase) activation associated factor CA8 8q11-q12 carbonic anhydrase VIII LOC392225 8 similar to IAP-associated factor VIAF1; phosducin-like 2 RAB2 8q12.1 RAB2, member RAS oncogene family KIAA1416 8q12.1 KIAA1416 protein LOC282694 LOC157813 8q12.2 hypothetical LOC157813 NPM1P6 8q12.2 nucleophosmin 1 (nucleolar phosphoprotein B23, numatrin) pseudogene 6 MGC34646 8q12.2 hypothetical protein MGC34646 ASPH 8q12.1 aspartate beta-hydroxylase LOC392226 8 similar to Serine/threonine-protein kinase PLK (PLK-1) (Serine-threonine protein kinase 13) (STPK13) FLJ39630 8q12.2 hypothetical protein FLJ39630 GGH 8q12-q13 gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase) TTPA 8q13 tocopherol (alpha) transfer protein (ataxia (Friedreich-like) with vitamin E deficiency) FLJ31657 8q12.2 hypothetical protein FLJ31657 LOC346974 8q12.3 similar to Interferon-induced transmembrane protein 3 (Interferon-inducible protein 1-8U) BHLHB5 8q13 basic helix-loop-helix domain containing, class B, 5 CYP7B1 8q21.3 cytochrome P450, family 7, subfamily B, polypeptide 1 LOC389665 8 LOC389665 LOC392227 8 similar to peptidylprolyl isomerase A FLJ10511 8q12.3 armadillo repeat containing protein CHPPR 8q12.3 likely ortholog of chicken chondrocyte protein with a poly-proline region PDE7A 8q13 phosphodiesterase 7A MGC26226 8q12.3 beta cysteine string protein RNF29 8q12.3 ring finger protein 29 CRH 8q13 corticotropin releasing hormone RRS1 8q12.3 RRS1 ribosome biogenesis regulator homolog (S. cerevisiae) ADHFE1 8q12.3 alcohol dehydrogenase, iron containing, 1 MGC33510 8q12.3 hypothetical protein MGC33510 MYBL1 8q22 v-myb myeloblastosis viral oncogene homolog (avian)-like 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 5349 - 758 widely expressed among heart, placenta, skeletal muscle, kidney, and lung tissues 2015 26446257
    also called ASPH-FL
    6 splicing 3287 26 225 only in cardiac and skeletal muscle 2015 26446257
    also called ASPHIe, junctin isoform 1
    14 splicing 3792 33 313 placenta, brain, heart, lung, kidney, skeletal muscle 2015 26446257
    also called ASPHIc
    5 splicing 3242 - 210 cardiac and skeletal muscle 2015 26446257
    also called ASPHId, variant 4, junctin
    15 - 3642 - 299 heart, brain, pancreas, placenta, lung, liver, kidney, skeletal muscle 2015 26446257
    also called ASPHIb, Variant 2,junctate
    - - 5203 - 729 - 2015 26446257
    - - 3639 - 298 - 2015 26446257
    - - 3582 - 279 - 2015 26446257
  • isoform 8
  • targeting STIM1 to ER-plasma-membrane contacts upon Ca(2+)-store depletion
  • - - 3735 - 294 - 2015 26446257
    - - 1712 - 203 - 2015 26446257
    - - 3513 - 256 - 2015 26446257
    - - 3663 - 270 - 2015 26446257
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Nervousbrain    
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • extended N-terminus with potential transmembrane (TM ) type II signal anchor domain directing the catalytic domain into the endoplasmic reticulum, N terminus comprising &
  • 8764;26 amino acids (a truncation of these AAs prevents junctional accumulation of ASPH)
  • a Ca(2+)-binding EF-hand motif
  • a compact C terminus catalytic domain, and Ca2+-sensing role of junctate was demonstrated after uncovering an EF-hand domain in the ER-luminal region, in its C terminus
  • mono polymer monomer
    HOMOLOGY
    interspecies homolog to murine Asph
    intraspecies homolog to TRDN
    Homologene
    FAMILY
  • aspartyl/asparaginyl beta-hydroxylase family
  • CATEGORY enzyme , structural protein , transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • potentially cleaved into a 56kDa protein in the lumen of ER
  • with SERCA2 co-localized in the sarcoplasmic reticulum of cardiomyocytes
  • intra-sarcoplasmic reticulum (SR) protein
  • inserted into the membrane of the sarcoplasmic reticulum (SR) Ca(2+) store where it modifies Ca(2+) signalling in the heart and skeletal muscle
  • basic FUNCTION
  • potentially involved in divalent cation binding and protein-protein interaction for a number of vitamin K dependent proteins, like proC, F7, F9, F10, complement factors C1R, C1S
  • may play an important role in the regulation of SR Ca(2+) cycling through the interaction with ATP2A2 in the murine heart
  • SR membrane protein, which is part of the SR Ca(2+) release quaternary structure that also includes the ryanodine receptor, triadin and calsequestrin
  • serves as a bridge between calsequestrin and the Ca(2+) release channel, ryanodine receptor
  • involved in calcium homeostasis with calsquestrin, triadin, ryanodine receptor
  • involved in calcium homeostasis in eukaryotic cells
  • essential factor in maintaining normal cardiac Ca handling and cardiac function
  • triadin and junctin are integral sarcoplasmic reticulum membrane proteins that form a macromolecular complex with the skeletal muscle ryanodine receptor (RYR1)
  • has a role in maintaining sarcoplasmic reticulum Ca2+ store size in myotubes
  • ASPH and TRDN each activate skeletal ryanodine receptors but ASPH alone mediates functional interactions with CASQ1
  • normally acts as an activator of RYR channels at low luminal [Ca(2+)], and as an inhibitor at high luminal [Ca(2+)]
  • Ca2+-sensing ER protein, and structural component of the ER-PM junctions where ORAI1 and STIM1 cluster and interact in T cells
  • cell surface protein that catalyzes the hydroxylation of epidermal growth factor (EGF)-like repeats in Notch receptors and ligands
  • mediates an alternative mechanism for generating localized Ca(2+) elevations within cells, promoting Ca(2+) release from internal stores recruited to phagosomes, thereby boosting phagocytosis
  • CELLULAR PROCESS protein, post translation
    PHYSIOLOGICAL PROCESS
    text hydroxylation of ASP or ASN in EGF-like domains of several proteins
    PATHWAY
    metabolism aminoacid
    signaling
    a component
  • CASQ2, TRDN and ASPH form a protein complex that is associated with cardiac ryanodine receptor 2 (RYR2) SR Ca(2+) release channels
  • forms a quaternary protein complex with the ryanodine receptor, calsequestrin, and triadin in the SR lumen of cardiac muscle
  • indirect role for triadin in regulating myoplasmic Ca(2+) homeostasis and organizing the molecular complex of the triad but not in regulating skeletal-type excitation-contraction coupling
  • Ca(2+)-sensing ER protein, and is a structural component of the ER-plasma membrane junctions where ORAI1 and STIM1 cluster and interact in T cells
  • plays an additional role in STIM1 recruitment by defining the ER-PM junctions for clustering of ORAI1 and STIM1 in a Ca2+-dependent manner
  • mediates an alternative mechanism for generating localized Ca(2+) elevations within cells, promoting Ca(2+) release from internal stores recruited to phagosomes, thereby boosting phagocytosis
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • iron Fe2+
  • protein
  • interacting with ATP2A2 (binding of the C-terminal region of junctate (AAs 79-270) and luminal domain of ATP2A2 (AAs 70-89)
  • constant interactions between CASQ2 and ASPH, regardless of the SR Ca(2+) concentration, implying that ASPH is an essential component of the CASQ2 scaffold
  • ASPH is an interacting partner of ORAI1-STIM1 complex
  • TRDN and ASPH are structurally related transmembrane proteins thought to be key mediators of structural and functional interactions between calsequestrin (CASQ1) and ryanodine receptor (RyRs) at the junctional sarcoplasmic reticulum
  • C-terminal domain of ASPH binds to residues including the S1-S2 linker of RYR1 and N-terminal domain of ASPH binds between RYR1 residues 1078 and 2156
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) FDLAB
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in hepatocellular carcinoma
    constitutional     --low  
    may contribute to Ca(2+) cycling perturbations manifest in the failing heart
    constitutional     --over  
    leads to a severe cardiac remodeling and arrhythmias
    tumoral     --over  
    highly overexpressed in pancreatic cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS