Protein detail

S4A4

Electrogenic sodium bicarbonate cotransporter 1 (Sodium bicarbonate cotransporter) (Na(+)/HCO3(-) cotransporter) (Solute carrier family 4 member 4) (kNBC1)

Entry name S4A4	UniProt ID Q9Y6R1	EVMP confidence score 0.50
Supporting publications (n) 1	Transmembrane count 12	Protein classification Disease related genesHuman disease related genesMetabolic proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

Electrogenic sodium bicarbonate cotransporter 1 (Sodium bicarbonate cotransporter) (Na(+)/HCO3(-) cotransporter) (Solute carrier family 4 member 4) (kNBC1)

Protein Class (7)

Disease related genesHuman disease related genesMetabolic proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters

Protein Function (5)

Human disease related genes:Urinary system diseases:Kidney diseases
Predicted intracellular proteins
Potential drug targets
Transporters:Electrochemical Potential-driven transporters
Disease related genes

Transmembrane

467..491; Helical; Name=1; 502..520; Helical; Name=2; 522..542; Discontinuously helical; Name=3; 551..571; Helical; Name=4; 586..609; Helical; Name=5; 693..710; Helical; Name=6; 726..745; Helical; Name=7; 780..807; Helical; Name=8; 820..836; Helical; Name=9; 838..855; Discontinuously helical; Name=10; 878..894; Helical; Name=11; 902..918; Helical; Name=12

Transmembrane Count

Ensembl

ENSG00000080493

Entrez Gene Symbol

SLC4A4

Gene Synonym (6)

hhNMCHNBC1NBC1NBC2pNBCSLC4A5

Gene Description

Solute carrier family 4 member 4

Chromosome

Position

71062667-71572087

Supporting publications (n)

EVMP confidence score

0.50

Function & Pathway8

Protein Function (5)

Human disease related genes:Urinary system diseases:Kidney diseases
Predicted intracellular proteins
Potential drug targets
Transporters:Electrochemical Potential-driven transporters
Disease related genes

Cellular Component (5)

Molecular Function (6)

Biological Process (3)

KEGG (3)

Reactome (9)

Canonical Pathways (3)

M3008 Naba ecm glycoproteins
M5884 Naba core matrisome
M5889 Naba matrisome

Mediation Categories (2)

Clinical-translation mediationFusion and delivery mediation

Relations & Evidence44

Enzyme-Mediated Modification (7)

7 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
SLC4A4	STK39	Q9UEW8	S	65	phosphorylation	PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper
SLC4A4	PRKACA	P17612	S	1,026	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPProtMapperPhosphoSitePhosphoSite_ProtMapper
SLC4A4	PRKACA	P17612	S	982	phosphorylation	KEA	KEA:11744745
SLC4A4	TTK	P33981	S	12	phosphorylation	PhosphoSite
SLC4A4	PRKX	P51817	S	1,026	phosphorylation	MIMPHPRD_MIMPphosphoELM_MIMPPhosphoSite_MIMP
SLC4A4	PRKY	O43930	S	1,026	phosphorylation	MIMPHPRD_MIMPphosphoELM_MIMPPhosphoSite_MIMP
SLC4A4	PRKCA	P17252	S	1,026	phosphorylation	KEA	KEA:17570479

Ligand-Receptor Signaling (32)

32 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
receptor	receptor	scConnect	No	Yes	No	No	No
transmembrane	transmembrane_predicted	Phobius	No	No	No	No	No

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Regulatory Interaction Network (3)

3 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
STK39	Q9UEW8	S4A4	Q9Y6R1	Yes	No	Yes	PhosphoSite_MIMPMIMPiPTMnetSIGNORProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:30377224 SIGNOR:21317537 PhosphoSite:23431199
SAHH2	O43865	S4A4	Q9Y6R1	Yes	Yes	No	SIGNOR	SIGNOR:21317537
KAPCA	P17612	S4A4	Q9Y6R1	Yes	No	No	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEAPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:12730338 HPRD:11744745 PhosphoSite:12411514 KEA:11744745

Protein Complex Composition (1)

1 record.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	SLC4A4	Q9Y6R1	2	PDB	PDB:6caa

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion ChromatographyImmunoaffinity Capture	Mass spectrometry	1	36114323

Sequence, Structure & Domains10

Sequences

Length

1,079

Mass

121,461

Sequence

MEDEAVLDRGASFLKHVCDEEEVEGHHTIYIGVHVPKSYRRRRRHKRKTGHKEKKEKERISENYSDKSDIENADESSSSILKPLISPAAERIRFILGEEDDSPAPPQLFTELDELLAVDGQEMEWKETARWIKFEEKVEQGGERWSKPHVATLSLHSLFELRTCMEKGSIMLDREASSLPQLVEMIVDHQIETGLLKPELKDKVTYTLLRKHRHQTKKSNLRSLADIGKTVSSASRMFTNPDNGSPAMTHRNLTSSSLNDISDKPEKDQLKNKFMKKLPRDAEASNVLVGEVDFLDTPFIAFVRLQQAVMLGALTEVPVPTRFLFILLGPKGKAKSYHEIGRAIATLMSDEVFHDIAYKAKDRHDLIAGIDEFLDEVIVLPPGEWDPAIRIEPPKSLPSSDKRKNMYSGGENVQMNGDTPHDGGHGGGGHGDCEELQRTGRFCGGLIKDIKRKAPFFASDFYDALNIQALSAILFIYLATVTNAITFGGLLGDATDNMQGVLESFLGTAVSGAIFCLFAGQPLTILSSTGPVLVFERLLFNFSKDNNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEEGFSSLISFIFIYDAFKKMIKLADYYPINSNFKVGYNTLFSCTCVPPDPANISISNDTTLAPEYLPTMSSTDMYHNTTFDWAFLSKKECSKYGGNLVGNNCNFVPDITLMSFILFLGTYTSSMALKKFKTSPYFPTTARKLISDFAIILSILIFCVIDALVGVDTPKLIVPSEFKPTSPNRGWFVPPFGENPWWVCLAAAIPALLVTILIFMDQQITAVIVNRKEHKLKKGAGYHLDLFWVAILMVICSLMALPWYVAATVISIAHIDSLKMETETSAPGEQPKFLGVREQRVTGTLVFILTGLSVFMAPILKFIPMPVLYGVFLYMGVASLNGVQFMDRLKLLLMPLKHQPDFIYLRHVPLRRVHLFTFLQVLCLALLWILKSTVAAIIFPVMILALVAVRKGMDYLFSQHDLSFLDDVIPEKDKKKKEDEKKKKKKKGSLDSDNDDSDCPYSEKVPSIKIPMDIMEQQPFLSDSKPSDRERSPTFLERHTSC

Alternative Products

Event=Alternative splicing; Named isoforms=5; Name=1; Synonyms=hcNBC, hhNBC, hNBC1, pNBC, pNCB1, pNBC-1, NBC1b; IsoId=Q9Y6R1-1; Sequence=Displayed; Name=2; Synonyms=hkNBC, hkNBCe1, kNBC, kNBC1, kNBC-1, NBC1a; IsoId=Q9Y6R1-2; Sequence=VSP_016704, VSP_016705; Name=3; IsoId=Q9Y6R1-3; Sequence=VSP_016704, VSP_016705, VSP_016706, VSP_016707; Name=4; IsoId=Q9Y6R1-4; Sequence=VSP_016708; Name=5; IsoId=Q9Y6R1-5; Sequence=VSP_041003

Alternative Sequence

1..44; Missing (in isoform 2 and isoform 3); 45..85; HKRKTGHKEKKEKERISENYSDKSDIENADESSSSILKPLI -> MSTENVEGKPSNLGERGRARSSTFLRVVQPMFNHSIFTSAV (in isoform 2 and isoform 3); 635..690; ANISISNDTTLAPEYLPTMSSTDMYHNTTFDWAFLSKKECSKYGGNLVGNNCNFVP -> GEGITLCVYARFVFGGRCRLHACKFSTCCHGPQELVLFFSLKNSATEFDVSLPEVF (in isoform 3); 691..1079; Missing (in isoform 3); 813..896; Missing (in isoform 4); 1034..1079; SDCPYSEKVPSIKIPMDIMEQQPFLSDSKPSDRERSPTFLERHTSC -> EKDHQHSLNATHHADKIPFLQSLGMPSPPRTPVKVVPQIRIELEPEDNDYFWRSKGTETTL (in isoform 5)

3D Structural Models

3D Structure

Electron microscopy (1)

Domain & Motif Annotations

Compositional Bias

39..52; Basic residues; 53..70; Basic and acidic residues; 251..260; Polar residues; 1062..1079; Basic and acidic residues

Region

1..62; Required for interaction with AHCYL1; 39..78; Disordered; 238..265; Disordered; 748..779; Interaction with CA4; 1002..1004; CA2-binding; 1012..1079; Disordered; 1030..1033; CA2-binding; 1057..1059; Required for basolateral targeting

Protein Families

Anion exchanger (TC 2.A.31) family

Sequence Similarities

Belongs to the anion exchanger (TC 2.A.31) family.

Clinical Relevance2

Disease Involvement (2)

Disease variantRetinitis pigmentosa

Antibody (4)

CAB022493 HPA035628 HPA035629 HPA079220

Supporting Publications1

PMID	Title	Abstract
32384937	Alzheimer's disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles.	No abstract available