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Center for Computational Systems Medicine
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Protein Summary

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AS Summary

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Protein Functional Features

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Gene Isoform Structures and Expression Levels

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Protein Structures

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pLDDT Score Distribution

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Ramachandran Plot of Protein Structures

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Potential Active Site Information

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Protein Structure and Feature Comparision

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Protein-Protein Interaction

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Related Drugs

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Related Diseases

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Clinically Important Variants

Protein:CA4

Protein Summary

check button Gene summary
Gene name: CA4
ASpdb.0 ID: 762
Gene
Gene symbol

CA4

Gene ID

762

Gene namecarbonic anhydrase 4
SynonymsCAIV|Car4|RP17
Cytomap

17q23.1

Type of geneprotein-coding
Descriptioncarbonic anhydrase 4CA-IVcarbonate dehydratase IVcarbonic anhydrase IVcarbonic dehydratase IV
Modification date20240305
UniProtAcc

P22748


check button Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
GeneCA4

GO:0005791

rough endoplasmic reticulum

17409381

GeneCA4

GO:0005793

endoplasmic reticulum-Golgi intermediate compartment

17409381

GeneCA4

GO:0005794

Golgi apparatus

17409381

GeneCA4

GO:0005802

trans-Golgi network

17409381

GeneCA4

GO:0005886

plasma membrane

15563508

GeneCA4

GO:0009897

external side of plasma membrane

17409381

GeneCA4

GO:0009986

cell surface

15563508

GeneCA4

GO:0016323

basolateral plasma membrane

17409381

GeneCA4

GO:0016324

apical plasma membrane

17409381

GeneCA4

GO:0030658

transport vesicle membrane

17409381

GeneCA4

GO:0030667

secretory granule membrane

17409381

GeneCA4

GO:0031526

brush border membrane

17409381

GeneCA4

GO:0048471

perinuclear region of cytoplasm

17409381

GeneCA4

GO:0070062

extracellular exosome

15326289



AS Summary

check button Information of the canonical protein with experimentally identified structure from PDB (2023).
UniProt AccFile namePDB IDMethodResolutionChainStartEnd
P22748-1P22748-1_5ku6_A.pdb5KU6X-ray1.8A19284

check button ASpdb's canonical and alternatively spliced isoform information.
accession_idgene_namecanonical_idalternative_idcanonical_lengthalternative_lengthcanonical_startcanonical_endtypeoriginalSEQvariationSEQalternative_startalternative_end
P22748CA4P22748-1P22748-231210690106SubstitutionVMMLLENKASISGGGLPGWNPGERGLPATGGGTV90106
P22748CA4P22748-1P22748-2312106107312Deletionnonenone106106

check buttonMultiple sequence alignment of our canonical and alternatively spliced CA4

check button Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CA4
UniProt-idENSGENSTENSP
P22748-1ENSG00000167434.10ENST00000300900.9ENSP00000300900.3
P22748-2ENSG00000167434.10ENST00000586876.1ENSP00000467465.1

UniProt-idNM IDNP ID
P22748-1NM_000717.4NP_000708.1

check buttonAmino acid sequences of our canonical and alternatively spliced CA4
accession_idProtein sequence
P22748-1MRMLLALLALSAARPSASAESHWCYEVQAESSNYPCLVPVKWGGNCQKDRQSPINIVTTKAKVDKKLGRFFFSGYDKKQTWTVQNNGHSV
MMLLENKASISGGGLPAPYQAKQLHLHWSDLPYKGSEHSLDGEHFAMEMHIVHEKEKGTSRNVKEAQDPEDEIAVLAFLVEAGTQVNEGF
QPLVEALSNIPKPEMSTTMAESSLLDLLPKEEKLRHYFRYLGSLTTPTCDEKVVWTVFREPIQLHREQILAFSQKLYYDKEQTVSMKDNV
P22748-2MRMLLALLALSAARPSASAESHWCYEVQAESSNYPCLVPVKWGGNCQKDRQSPINIVTTKAKVDKKLGRFFFSGYDKKQTWTVQNNGHSG

Protein Functional Features

check buttonMain function of this protein. (from UniProt)
CA4 (go to UniProt):P22748

check buttonRetention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
Accession_idSubsectionStartEndFuncitonal featureSplicing information
P22748Domain21285Note=Alpha-carbonic anhydrase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01134Type=Substitution;Start=90;End=106
P22748Domain21285Note=Alpha-carbonic anhydrase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01134Type=Deletion;Start=107;End=312


Gene Isoform Structures and Expression Levels for CA4

check buttonGene structures of our canonical and alternative spliced genes of CA4
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
gene isoform structure of CA4

check button Expression levels of gene isoforms across GTEx.
gtex expression

check button Expression levels of gene isoforms across TCGA.
tcga expression


Protein Structures

check button PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
3D view using mol* of P22748-1
3D view using mol* of P22748-2


pLDDT Score Distribution

check button pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
pLDDT distribution across the protein length of P22748-1
all structure
pLDDT distribution across the protein length of P22748-2
all structure


Ramachandran Plot of Protein Structures


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.
Ramachandran plot of P22748-1
all structure
Ramachandran plot of P22748-2
all structure

Potential Active Site Information


check button The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.
UniProt-idSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
P22748-10.856700.851210.9450.6740.6490.8210.310.9950.3110.55921,22,23,24,28,31,32,33,34,35,36,87,88,193,258,259
,260,261,263,264
P22748-20.498180.47736.7010.8680.4480.5110.3140.5850.5371.18820,21,22,23,37,42,43,44

Protein Structure and Feature Comparision


check button Protein Structure Comparision Using Template Modeling Scores (TM-score).
all structure

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)
3D view using mol* of P22748-1_P22748-1_5ku6_A.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P22748-1_5ku6_A_P22748-2.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P22748-1_P22748-2.pdb

check button Protein Feature Comparison of the protein sequendary structures among the protiens.
./stats/secondary_structure/figure/P22748-1_vs_P22748-2.png
all structure<

check button Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
./stats/relative_asa/P22748-1_vs_P22748-2.png
all structure<


Protein-Protein Interaction


check button Interactors from UniProt.
Accession_idSubsectionStartEndFuncitonal featureSplicing information


check button Interactors from STRING.
Gene nameInteractors


Related Drugs to CA4


check button Drugs targeting this gene/protein.
(DrugBank)
UniProt accessionGene nameDrugBank IDDrug nameDrug groupActions
P22748CA4DB00232Methyclothiazidewithdrawninhibitor
P22748CA4DB00869Dorzolamideapprovedinhibitor
P22748CA4DB00436Bendroflumethiazideapprovedinhibitor
P22748CA4DB00273Topiramateapprovedinhibitor
P22748CA4DB08846Ellagic acidinvestigationalinhibitor
P22748CA4DB00311Ethoxzolamidewithdrawninhibitor
P22748CA4DB09460Sodium carbonateapprovedinhibitor
P22748CA4DB01144Diclofenamideapproved, investigationalinhibitor
P22748CA4DB01194Brinzolamideapprovedinhibitor
P22748CA4DB00774Hydroflumethiazideapproved, investigational, withdrawninhibitor
P22748CA4DB00819Acetazolamideapproved, vet_approvedinhibitor
P22748CA4DB00703Methazolamideapprovedinhibitor
P22748CA4DB01021Trichlormethiazideapproved, vet_approvedinhibitor
P22748CA4DB00562Benzthiazideapprovedinhibitor
P22748CA4DB00909Zonisamideapproved, investigationalinhibitor

Related Diseases to CA4


check button Previous studies relating to the alternative splicing of CA4 and disease information from the MeSH term (PubMed)
GenePMIDTitleAbstractMeSH IDMeSH term


Clinically important variants in CA4


check button (ClinVar, 04/20/2024)
accession_iduniprot_idgene_nameTypeVariantClinical_significance