ASPH
Aspartyl/asparaginyl beta-hydroxylase
Also known as: ASPH_HUMAN, BAH, CASQ2BP1, HAAH, JCTN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q12797
- Gene
- ASPH
- Ensembl
- ENSG00000198363
- Chromosome
- 8
- Canonical length
- 758 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters
- Subcellular location
- Endoplasmic reticulum
OverviewNCBI Gene
This gene is thought to play an important role in calcium homeostasis. The gene is expressed from two promoters and undergoes extensive alternative splicing. The encoded set of proteins share varying amounts of overlap near their N-termini but have substantial variations in their C-terminal domains resulting in distinct functional properties. The longest isoforms (a and f) include a C-terminal Aspartyl/Asparaginyl beta-hydroxylase domain that hydroxylates aspartic acid or asparagine residues in the epidermal growth factor (EGF)-like domains of some proteins, including protein C, coagulation factors VII, IX, and X, and the complement factors C1R and C1S. Other isoforms differ primarily in the C-terminal sequence and lack the hydroxylase domain, and some have been localized to the endoplasmic and sarcoplasmic reticulum. Some of these isoforms are found in complexes with calsequestrin, triadin, and the ryanodine receptor, and have been shown to regulate calcium release from the sarcoplasmic reticulum. Some isoforms have been implicated in metastasis. [provided by RefSeq, Sep 2009]
Canonical amino-acid sequenceUniProt
758 residues, UniProt reviewed canonical sequence.
>Q12797|ASPH
1 MAQRKNAKSS GNSSSSGSGS GSTSAGSSSP GARRETKHGG HKNGRKGGLS GTSFFTWFMV
61 IALLGVWTSV AVVWFDLVDY EEVLGKLGIY DADGDGDFDV DDAKVLLGLK ERSTSEPAVP
121 PEEAEPHTEP EEQVPVEAEP QNIEDEAKEQ IQSLLHEMVH AEHVEGEDLQ QEDGPTGEPQ
181 QEDDEFLMAT DVDDRFETLE PEVSHEETEH SYHVEETVSQ DCNQDMEEMM SEQENPDSSE
241 PVVEDERLHH DTDDVTYQVY EEQAVYEPLE NEGIEITEVT APPEDNPVED SQVIVEEVSI
301 FPVEEQQEVP PETNRKTDDP EQKAKVKKKK PKLLNKFDKT IKAELDAAEK LRKRGKIEEA
361 VNAFKELVRK YPQSPRARYG KAQCEDDLAE KRRSNEVLRG AIETYQEVAS LPDVPADLLK
421 LSLKRRSDRQ QFLGHMRGSL LTLQRLVQLF PNDTSLKNDL GVGYLLIGDN DNAKKVYEEV
481 LSVTPNDGFA KVHYGFILKA QNKIAESIPY LKEGIESGDP GTDDGRFYFH LGDAMQRVGN
541 KEAYKWYELG HKRGHFASVW QRSLYNVNGL KAQPWWTPKE TGYTELVKSL ERNWKLIRDE
601 GLAVMDKAKG LFLPEDENLR EKGDWSQFTL WQQGRRNENA CKGAPKTCTL LEKFPETTGC
661 RRGQIKYSIM HPGTHVWPHT GPTNCRLRMH LGLVIPKEGC KIRCANETKT WEEGKVLIFD
721 DSFEHEVWQD ASSFRLIFIV DVWHPELTPQ QRRSLPAILocalizationUniProt · AlphaFold · HPA
Whether an antibody against ASPH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Other membrane
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.43
- Highest tissue expression
- 362 nTPM
Expression across tissuesHPA
Tissue
- adipose tissue: 362 nTPM
- skeletal muscle: 331 nTPM
- retina: 202 nTPM
- tongue: 155 nTPM
- adrenal gland: 151 nTPM
- urinary bladder: 104 nTPM
Single-cell type
- neutrophils: 2,306 nCPM
- adipocytes: 1,583 nCPM
- ocular epithelial cells: 1,020 nCPM
- neutrophil progenitors: 900 nCPM
- müller glia: 653 nCPM
- astrocytes: 586 nCPM
Immune cell
- plasmacytoid DC: 35 nTPM
- neutrophil: 26 nTPM
- myeloid DC: 10 nTPM
- NK-cell: 8.9 nTPM
- classical monocyte: 8.4 nTPM
- memory B-cell: 5.5 nTPM
Brain region
- cerebellum: 219 nTPM
- cerebral cortex: 192 nTPM
- choroid plexus: 187 nTPM
- thalamus: 160 nTPM
- midbrain: 155 nTPM
- basal ganglia: 153 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about ASPH.
Disease | AllUniProt
Conditions ASPH is implicated in, by any mechanism.
- Facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs (FDLAB) MIM:601552
Disease | GeneticClinVar
26 pathogenic / likely-pathogenic of 306 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome
- Thoracic aortic aneurysm or dissection
- Exercise-induced malignant hyperthermia
- Malignant hyperthermia of anesthesia
Disease | ImmuneIEDB
Conditions an epitope on ASPH was assayed in.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.82
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.21
- DepMap mean gene effect
- 0.04
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- activation of store-operated calcium channel activity
- calcium ion homeostasis
- calcium ion transmembrane transport
- cell population proliferation
- cellular response to calcium ion
- detection of calcium ion
- face morphogenesis
- limb morphogenesis
- muscle contraction
- negative regulation of cell population proliferation
- pattern specification process
- positive regulation of calcium ion transport into cytosol
- positive regulation of DNA-templated transcription
- positive regulation of intracellular protein transport
- positive regulation of proteolysis
- regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
- regulation of cell communication by electrical coupling
- regulation of cytosolic calcium ion concentration
- regulation of protein stability
- regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
- response to ATP
- roof of mouth development
- regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity
- regulation of protein depolymerization
Molecular functions
- calcium ion binding
- electron transfer activity
- peptidyl-aspartic acid 3-dioxygenase activity
- structural constituent of muscle
- structural molecule activity
- transmembrane transporter binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Aspartyl/asparaginy/proline hydroxylase
- Aspartyl beta-hydroxylase/Triadin domain
- Tetratricopeptide-like helical domain superfamily
- Tetratricopeptide repeat
- Isopenicillin N synthase-like superfamily
- Aspartyl/Asparaginyl beta-hydroxylase
- Aspartyl beta-hydroxylase N-terminal region
- Tetratricopeptide repeat
- Aspartyl/asparaginyl beta-hydroxylase family
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of ASPH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ASPH as an antibody target. Whether an autoantibody or antibody against ASPH could matter depends on whether native ASPH is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ASPH is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label ASPH as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
Loading the interactive Seroatlas protein explorer...