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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:SLC4A4

Protein Summary

check button Gene summary
Gene name: SLC4A4
ASpdb.0 ID: 8671
Gene
Gene symbol

SLC4A4

Gene ID

8671

Gene namesolute carrier family 4 member 4
SynonymsHNBC1|KNBC|NBC1|NBC2|NBCe1|NBCe1-A|SLC4A5|hhNMC|kNBC1|pNBC
Cytomap

4q13.3

Type of geneprotein-coding
Descriptionelectrogenic sodium bicarbonate cotransporter 1Na(+)/HCO3(-) cotransporterkidney type Na+/HCO3- cotransporterpancreatic sodium bicarbonate cotransportersodium bicarbonate cotransporter 1 (sodium bicarbonate cotransporter, kidney; sodium bicarbonate co
Modification date20240403
UniProtAcc

Q9Y6R1


check button Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
GeneSLC4A4

GO:0005886

plasma membrane

16636648

GeneSLC4A4

GO:0005886

plasma membrane

10069984|16636648|23324180|29500354

GeneSLC4A4

GO:0006814

sodium ion transport

16769890

GeneSLC4A4

GO:0008510

sodium:bicarbonate symporter activity

9235899|9651366|10069984|11744745|12411514|12730338|12907161|23324180

GeneSLC4A4

GO:0009986

cell surface

29500354

GeneSLC4A4

GO:0015701

bicarbonate transport

10069984

GeneSLC4A4

GO:0016020

membrane

10069984

GeneSLC4A4

GO:0016020

membrane

27717805

GeneSLC4A4

GO:0016323

basolateral plasma membrane

12907161|15273250|17182531|17661077

GeneSLC4A4

GO:0035725

sodium ion transmembrane transport

10069984

GeneSLC4A4

GO:0042391

regulation of membrane potential

10069984|15273250

GeneSLC4A4

GO:0051453

regulation of intracellular pH

10069984



AS Summary

check button Information of the canonical protein with experimentally identified structure from PDB (2023).
UniProt AccFile namePDB IDMethodResolutionChainStartEnd
Q9Y6R1-1Q9Y6R1-1_6caa_A.pdb6CAAEM3.9A4451009

check button ASpdb's canonical and alternatively spliced isoform information.
accession_idgene_namecanonical_idalternative_idcanonical_lengthalternative_lengthcanonical_startcanonical_endtypeoriginalSEQvariationSEQalternative_startalternative_end
Q9Y6R1SLC4A4Q9Y6R1-1Q9Y6R1-31079646144Deletionnonenone00
Q9Y6R1SLC4A4Q9Y6R1-1Q9Y6R1-310796464585SubstitutionHKRKTGHKEKKEKERISENYSDKSDIENADESSSSILKPLIMSTENVEGKPSNLGERGRARSSTFLRVVQPMFNHSIFTSAV141
Q9Y6R1SLC4A4Q9Y6R1-1Q9Y6R1-31079646635690SubstitutionANISISNDTTLAPEYLPTMSSTDMYHNTTFDWAFLSKKECSKYGGNLVGNNCNFVPGEGITLCVYARFVFGGRCRLHACKFSTCCHGPQELVLFFSLKNSATEFDVSLPEVF591646
Q9Y6R1SLC4A4Q9Y6R1-1Q9Y6R1-310796466911079Deletionnonenone646646
Q9Y6R1SLC4A4Q9Y6R1-1Q9Y6R1-41079995813896Deletionnonenone812812

check buttonMultiple sequence alignment of our canonical and alternatively spliced SLC4A4

check button Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of SLC4A4
UniProt-idENSGENSTENSP
Q9Y6R1-1ENSG00000080493.19ENST00000264485.11ENSP00000264485.5
Q9Y6R1-1ENSG00000080493.19ENST00000649996.1ENSP00000497468.1
Q9Y6R1-3ENSG00000080493.19ENST00000512686.5ENSP00000422400.1
Q9Y6R1-4ENSG00000080493.19ENST00000351898.10ENSP00000307349.7

UniProt-idNM IDNP ID
Q9Y6R1-1NM_001098484.2NP_001091954.1

check buttonAmino acid sequences of our canonical and alternatively spliced SLC4A4
accession_idProtein sequence
Q9Y6R1-1MEDEAVLDRGASFLKHVCDEEEVEGHHTIYIGVHVPKSYRRRRRHKRKTGHKEKKEKERISENYSDKSDIENADESSSSILKPLISPAAE
RIRFILGEEDDSPAPPQLFTELDELLAVDGQEMEWKETARWIKFEEKVEQGGERWSKPHVATLSLHSLFELRTCMEKGSIMLDREASSLP
QLVEMIVDHQIETGLLKPELKDKVTYTLLRKHRHQTKKSNLRSLADIGKTVSSASRMFTNPDNGSPAMTHRNLTSSSLNDISDKPEKDQL
KNKFMKKLPRDAEASNVLVGEVDFLDTPFIAFVRLQQAVMLGALTEVPVPTRFLFILLGPKGKAKSYHEIGRAIATLMSDEVFHDIAYKA
KDRHDLIAGIDEFLDEVIVLPPGEWDPAIRIEPPKSLPSSDKRKNMYSGGENVQMNGDTPHDGGHGGGGHGDCEELQRTGRFCGGLIKDI
KRKAPFFASDFYDALNIQALSAILFIYLATVTNAITFGGLLGDATDNMQGVLESFLGTAVSGAIFCLFAGQPLTILSSTGPVLVFERLLF
NFSKDNNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEEGFSSLISFIFIYDAFKKMIKLADYYPINSNFKVGYNTLFSCTCV
PPDPANISISNDTTLAPEYLPTMSSTDMYHNTTFDWAFLSKKECSKYGGNLVGNNCNFVPDITLMSFILFLGTYTSSMALKKFKTSPYFP
TTARKLISDFAIILSILIFCVIDALVGVDTPKLIVPSEFKPTSPNRGWFVPPFGENPWWVCLAAAIPALLVTILIFMDQQITAVIVNRKE
HKLKKGAGYHLDLFWVAILMVICSLMALPWYVAATVISIAHIDSLKMETETSAPGEQPKFLGVREQRVTGTLVFILTGLSVFMAPILKFI
PMPVLYGVFLYMGVASLNGVQFMDRLKLLLMPLKHQPDFIYLRHVPLRRVHLFTFLQVLCLALLWILKSTVAAIIFPVMILALVAVRKGM
Q9Y6R1-3MSTENVEGKPSNLGERGRARSSTFLRVVQPMFNHSIFTSAVSPAAERIRFILGEEDDSPAPPQLFTELDELLAVDGQEMEWKETARWIKF
EEKVEQGGERWSKPHVATLSLHSLFELRTCMEKGSIMLDREASSLPQLVEMIVDHQIETGLLKPELKDKVTYTLLRKHRHQTKKSNLRSL
ADIGKTVSSASRMFTNPDNGSPAMTHRNLTSSSLNDISDKPEKDQLKNKFMKKLPRDAEASNVLVGEVDFLDTPFIAFVRLQQAVMLGAL
TEVPVPTRFLFILLGPKGKAKSYHEIGRAIATLMSDEVFHDIAYKAKDRHDLIAGIDEFLDEVIVLPPGEWDPAIRIEPPKSLPSSDKRK
NMYSGGENVQMNGDTPHDGGHGGGGHGDCEELQRTGRFCGGLIKDIKRKAPFFASDFYDALNIQALSAILFIYLATVTNAITFGGLLGDA
TDNMQGVLESFLGTAVSGAIFCLFAGQPLTILSSTGPVLVFERLLFNFSKDNNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFT
EEGFSSLISFIFIYDAFKKMIKLADYYPINSNFKVGYNTLFSCTCVPPDPGEGITLCVYARFVFGGRCRLHACKFSTCCHGPQELVLFFS
Q9Y6R1-4MEDEAVLDRGASFLKHVCDEEEVEGHHTIYIGVHVPKSYRRRRRHKRKTGHKEKKEKERISENYSDKSDIENADESSSSILKPLISPAAE
RIRFILGEEDDSPAPPQLFTELDELLAVDGQEMEWKETARWIKFEEKVEQGGERWSKPHVATLSLHSLFELRTCMEKGSIMLDREASSLP
QLVEMIVDHQIETGLLKPELKDKVTYTLLRKHRHQTKKSNLRSLADIGKTVSSASRMFTNPDNGSPAMTHRNLTSSSLNDISDKPEKDQL
KNKFMKKLPRDAEASNVLVGEVDFLDTPFIAFVRLQQAVMLGALTEVPVPTRFLFILLGPKGKAKSYHEIGRAIATLMSDEVFHDIAYKA
KDRHDLIAGIDEFLDEVIVLPPGEWDPAIRIEPPKSLPSSDKRKNMYSGGENVQMNGDTPHDGGHGGGGHGDCEELQRTGRFCGGLIKDI
KRKAPFFASDFYDALNIQALSAILFIYLATVTNAITFGGLLGDATDNMQGVLESFLGTAVSGAIFCLFAGQPLTILSSTGPVLVFERLLF
NFSKDNNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEEGFSSLISFIFIYDAFKKMIKLADYYPINSNFKVGYNTLFSCTCV
PPDPANISISNDTTLAPEYLPTMSSTDMYHNTTFDWAFLSKKECSKYGGNLVGNNCNFVPDITLMSFILFLGTYTSSMALKKFKTSPYFP
TTARKLISDFAIILSILIFCVIDALVGVDTPKLIVPSEFKPTSPNRGWFVPPFGENPWWVCLAAAIPALLVTILIFMDQQITAVIVNRKE
HKLKFIPMPVLYGVFLYMGVASLNGVQFMDRLKLLLMPLKHQPDFIYLRHVPLRRVHLFTFLQVLCLALLWILKSTVAAIIFPVMILALV
AVRKGMDYLFSQHDLSFLDDVIPEKDKKKKEDEKKKKKKKGSLDSDNDDSDCPYSEKVPSIKIPMDIMEQQPFLSDSKPSDRERSPTFLE

Protein Functional Features

check buttonMain function of this protein. (from UniProt)
SLC4A4 (go to UniProt):Q9Y6R1

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
Q9Y6R1Topological domain1466"Note=Cytoplasmic;Ontology_term=ECO:0000269ECO:0000305;evidence=ECO:0000269|PubMed:12534288
Q9Y6R1Topological domain1466"Note=Cytoplasmic;Ontology_term=ECO:0000269ECO:0000305;evidence=ECO:0000269|PubMed:12534288
Q9Y6R1Topological domain610692"Note=Extracellular;Ontology_term=ECO:0000269ECO:0000305;evidence=ECO:0000269|PubMed:12534288
Q9Y6R1Topological domain610692"Note=Extracellular;Ontology_term=ECO:0000269ECO:0000305;evidence=ECO:0000269|PubMed:12534288
Q9Y6R1Transmembrane693710"Note=Helical%3B Name%3D6;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Topological domain711725"Note=Cytoplasmic;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Transmembrane726745"Note=Helical%3B Name%3D7;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Topological domain746779"Note=Extracellular;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Transmembrane780807"Note=Helical%3B Name%3D8;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Topological domain808819"Note=Cytoplasmic;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Topological domain808819"Note=Cytoplasmic;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Transmembrane820836"Note=Helical%3B Name%3D9;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Transmembrane820836"Note=Helical%3B Name%3D9;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Topological domain837837"Note=Extracellular;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Topological domain837837"Note=Extracellular;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Transmembrane838855Note=Discontinuously helical%3B Name%3D10;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:29500354;Dbxref=PMID:29500354Type=Deletion;Start=691;End=1079
Q9Y6R1Transmembrane838855Note=Discontinuously helical%3B Name%3D10;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:29500354;Dbxref=PMID:29500354Type=Deletion;Start=813;End=896
Q9Y6R1Topological domain856877"Note=Cytoplasmic;Ontology_term=ECO:0000269ECO:0000305;evidence=ECO:0000269|PubMed:12534288
Q9Y6R1Topological domain856877"Note=Cytoplasmic;Ontology_term=ECO:0000269ECO:0000305;evidence=ECO:0000269|PubMed:12534288
Q9Y6R1Transmembrane878894"Note=Helical%3B Name%3D11;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Transmembrane878894"Note=Helical%3B Name%3D11;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Topological domain895901"Note=Extracellular;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Topological domain895901"Note=Extracellular;Ontology_term=ECO:0000305ECO:0000305;evidence=ECO:0000305|PubMed:12534288
Q9Y6R1Transmembrane902918Note=Helical%3B Name%3D12;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:29500354;Dbxref=PMID:29500354Type=Deletion;Start=691;End=1079
Q9Y6R1Topological domain919960"Note=Cytoplasmic;Ontology_term=ECO:0000269ECO:0000305;evidence=ECO:0000269|PubMed:12534288
Q9Y6R1Intramembrane961986Note=Discontinuously helical;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:29500354;Dbxref=PMID:29500354Type=Deletion;Start=691;End=1079
Q9Y6R1Topological domain9871079"Note=Cytoplasmic;Ontology_term=ECO:0000269ECO:0000305;evidence=ECO:0000269|PubMed:12534288
Q9Y6R1Region162Note=Required for interaction with AHCYL1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16769890;Dbxref=PMID:16769890Type=Deletion;Start=1;End=44
Q9Y6R1Region162Note=Required for interaction with AHCYL1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16769890;Dbxref=PMID:16769890Type=Substitution;Start=45;End=85
Q9Y6R1Region3978Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=1;End=44
Q9Y6R1Region3978Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Substitution;Start=45;End=85
Q9Y6R1Region748779Note=Interaction with CA4Type=Deletion;Start=691;End=1079
Q9Y6R1Region10021004Note=CA2-bindingType=Deletion;Start=691;End=1079
Q9Y6R1Region10121079Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=691;End=1079
Q9Y6R1Region10301033Note=CA2-bindingType=Deletion;Start=691;End=1079
Q9Y6R1Region10571059Note=Required for basolateral targetingType=Deletion;Start=691;End=1079
Q9Y6R1Compositional bias3953Note=Basic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=1;End=44
Q9Y6R1Compositional bias3953Note=Basic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Substitution;Start=45;End=85
Q9Y6R1Compositional bias5473Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Substitution;Start=45;End=85
Q9Y6R1Compositional bias10121039Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=691;End=1079
Q9Y6R1Compositional bias10601079Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=691;End=1079


Gene Isoform Structures and Expression Levels for SLC4A4

check buttonGene structures of our canonical and alternative spliced genes of SLC4A4
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
gene isoform structure of SLC4A4

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 Q9Y6R1-1
3D view using mol* of Q9Y6R1-3
3D view using mol* of Q9Y6R1-4


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 Q9Y6R1-1
all structure
pLDDT distribution across the protein length of Q9Y6R1-3
all structure
pLDDT distribution across the protein length of Q9Y6R1-4
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 Q9Y6R1-1
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
Q9Y6R1-11.061801.02509.0120.4710.7881.0070.6911.2040.5730.943468,475,585,586,589,708,711,712,714,725,728,729,73
2,805,808,810,811,845,846,849,850,852,853,854,856,
858,870,911,912,914,915,916,918,919,920,927
Q9Y6R1-30.9993331.0291074.9620.6130.6770.8420.430.9740.4421.16754,55,56,57,58,59,60,61,62,63,64,82,83,84,87,88,89
,90,91,93,94,95,96,97,98,105,106,107,108,109,110,1
11,112,114,171,260,278,294,295,298,302,305,306,307
,310,311,314,315,329,332,333,334,335,336,338,341,3
43,344,345,346,347,353,354,355,356,357,359,360
Q9Y6R1-41.1471881.233597.5060.5350.7650.8941.6790.5083.3031.352482,485,486,489,490,599,602,603,604,606,607,610,69
6,699,700,703,736,739,740,743,750,751,752,753,754,
820,821,822,823

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 Q9Y6R1-1_Q9Y6R1-1_6caa_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 Q9Y6R1-1_6caa_A_Q9Y6R1-3.pdb
3D view using mol* of Q9Y6R1-1_6caa_A_Q9Y6R1-4.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 Q9Y6R1-1_Q9Y6R1-3.pdb
3D view using mol* of Q9Y6R1-1_Q9Y6R1-4.pdb

check button Protein Feature Comparison of the protein sequendary structures among the protiens.
./stats/secondary_structure/figure/Q9Y6R1-1_vs_Q9Y6R1-3.png
all structure<
./stats/secondary_structure/figure/Q9Y6R1-1_vs_Q9Y6R1-4.png
all structure<

check button Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
./stats/relative_asa/Q9Y6R1-1_vs_Q9Y6R1-3.png
all structure<
./stats/relative_asa/Q9Y6R1-1_vs_Q9Y6R1-4.png
all structure<


Protein-Protein Interaction


check button Interactors from UniProt.
Accession_idSubsectionStartEndFuncitonal featureSplicing information
Q9Y6R1Region162Note=Required for interaction with AHCYL1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16769890;Dbxref=PMID:16769890Type=Deletion;Start=1;End=44
Q9Y6R1Region162Note=Required for interaction with AHCYL1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16769890;Dbxref=PMID:16769890Type=Substitution;Start=45;End=85
Q9Y6R1Region748779Note=Interaction with CA4Type=Deletion;Start=691;End=1079


check button Interactors from STRING.
Gene nameInteractors


Related Drugs to SLC4A4


check button Drugs targeting this gene/protein.
(DrugBank)
UniProt accessionGene nameDrugBank IDDrug nameDrug groupActions

Related Diseases to SLC4A4


check button Previous studies relating to the alternative splicing of SLC4A4 and disease information from the MeSH term (PubMed)
GenePMIDTitleAbstractMeSH IDMeSH term


Clinically important variants in SLC4A4


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