Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTWDEIL)

DTP Name Electrogenic sodium bicarbonate cotransporter 1 (SLC4A4)
Gene Name SLC4A4
UniProt ID
Q9Y6R1 (S4A4_HUMAN)
VARIDT ID
DTD0385
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Synonyms HNBC1; KNBC; NBC1; NBCE1; NBCe1-A; Na(+)/HCO3(-) cotransporter; SLC4A4; Sodium bicarbonate cotransporter; Solute carrier family 4 member 4; hhNMC; kNBC1; pNBC
DTP Family Anion Exchanger (AE) Family ;
Tissue Specificity Isoform 1 is expressed in pancreas and to alower extent in heart, skeletal muscle, liver, parotid salivaryglands, prostate, colon, stomach, thyroid, brain and spinal chord.Corneal endothelium cells express only isoform 1 (at proteinlevel). Isoform 2 is specifically expressed in kidney at the levelof proximal tubules.
Sequence
MEDEAVLDRGASFLKHVCDEEEVEGHHTIYIGVHVPKSYRRRRRHKRKTGHKEKKEKERI
SENYSDKSDIENADESSSSILKPLISPAAERIRFILGEEDDSPAPPQLFTELDELLAVDG
QEMEWKETARWIKFEEKVEQGGERWSKPHVATLSLHSLFELRTCMEKGSIMLDREASSLP
QLVEMIVDHQIETGLLKPELKDKVTYTLLRKHRHQTKKSNLRSLADIGKTVSSASRMFTN
PDNGSPAMTHRNLTSSSLNDISDKPEKDQLKNKFMKKLPRDAEASNVLVGEVDFLDTPFI
AFVRLQQAVMLGALTEVPVPTRFLFILLGPKGKAKSYHEIGRAIATLMSDEVFHDIAYKA
KDRHDLIAGIDEFLDEVIVLPPGEWDPAIRIEPPKSLPSSDKRKNMYSGGENVQMNGDTP
HDGGHGGGGHGDCEELQRTGRFCGGLIKDIKRKAPFFASDFYDALNIQALSAILFIYLAT
VTNAITFGGLLGDATDNMQGVLESFLGTAVSGAIFCLFAGQPLTILSSTGPVLVFERLLF
NFSKDNNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEEGFSSLISFIFIYDA
FKKMIKLADYYPINSNFKVGYNTLFSCTCVPPDPANISISNDTTLAPEYLPTMSSTDMYH
NTTFDWAFLSKKECSKYGGNLVGNNCNFVPDITLMSFILFLGTYTSSMALKKFKTSPYFP
TTARKLISDFAIILSILIFCVIDALVGVDTPKLIVPSEFKPTSPNRGWFVPPFGENPWWV
CLAAAIPALLVTILIFMDQQITAVIVNRKEHKLKKGAGYHLDLFWVAILMVICSLMALPW
YVAATVISIAHIDSLKMETETSAPGEQPKFLGVREQRVTGTLVFILTGLSVFMAPILKFI
PMPVLYGVFLYMGVASLNGVQFMDRLKLLLMPLKHQPDFIYLRHVPLRRVHLFTFLQVLC
LALLWILKSTVAAIIFPVMILALVAVRKGMDYLFSQHDLSFLDDVIPEKDKKKKEDEKKK
KKKKGSLDSDNDDSDCPYSEKVPSIKIPMDIMEQQPFLSDSKPSDRERSPTFLERHTSC
Function
This transporter may regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH. Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3.
Endogenous Substrate(s) Na+
TCDB ID
2.A.31.2.12
Gene ID
8671
KEGG Pathway
Proximal tubule bicarbonate reclamation (hsa04964 )
Pancreatic secretion (hsa04972 )
Bile secretion (hsa04976 )
Reactome Pathway
Defective SLC4A4 causes renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) (R-HSA-5619054 )
Bicarbonate transporters (R-HSA-425381 )

Molecular Interaction Atlas (MIA) of This DTP

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTP
1 Approved Drug(s) Transported by This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sodium bicarbonate DMMU6BJ Metabolic acidosis 5C73 Approved [1]
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Molecular Expression Atlas (MEA) of This DTP

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTP
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 1.16E-11 -1.63E-01 -8.51E-01
Adrenocortical carcinoma 2D11.Z Kidney 9.80E-01 -1.03E-01 -6.14E-01
Alopecia ED70 Skin from scalp 2.99E-01 7.03E-02 1.87E-01
Alzheimer's disease 8A20 Entorhinal cortex 7.29E-02 4.90E-02 6.81E-02
Ankylosing spondylitis FA92.0 Pheripheral blood 2.59E-01 1.37E-01 1.01E+00
Aortic stenosis BB70 Calcified aortic valve 2.57E-01 -1.13E-01 -2.35E-01
Apnea 7A40 Hyperplastic tonsil 6.01E-01 4.20E-02 2.57E-01
Arthropathy FA00-FA5Z Peripheral blood 5.53E-02 -1.02E-01 -4.27E-01
Asthma CA23 Nasal and bronchial airway 2.46E-01 2.26E-01 2.04E-01
Atopic dermatitis EA80 Skin 5.33E-01 -4.67E-02 -6.87E-02
Autism 6A02 Whole blood 8.33E-01 -3.36E-02 -1.32E-01
Autoimmune uveitis 9A96 Peripheral monocyte 7.95E-01 1.29E-01 5.57E-01
Autosomal dominant monocytopenia 4B04 Whole blood 8.53E-01 -8.02E-02 -4.06E-01
Bacterial infection of gingival 1C1H Gingival tissue 9.82E-01 -1.11E-02 -3.91E-02
Batten disease 5C56.1 Whole blood 3.06E-01 1.60E-01 1.42E+00
Behcet's disease 4A62 Peripheral blood 6.75E-01 5.75E-02 1.92E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 7.42E-01 8.45E-03 1.88E-02
Bladder cancer 2C94 Bladder tissue 9.80E-04 -9.76E-01 -2.41E+00
Breast cancer 2C60-2C6Z Breast tissue 1.20E-50 -8.59E-01 -1.36E+00
Cardioembolic stroke 8B11.20 Whole blood 2.11E-01 1.61E-01 2.69E-01
Cervical cancer 2C77 Cervical tissue 1.50E-01 -5.96E-01 -6.44E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 7.44E-01 -2.58E-02 -1.69E-01
Chronic hepatitis C 1E51.1 Whole blood 9.93E-01 1.49E-01 2.24E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 1.25E-01 2.84E-01 4.97E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 2.95E-01 -1.34E-01 -1.87E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 5.41E-01 1.53E-01 3.31E-01
Colon cancer 2B90 Colon tissue 3.28E-118 -4.03E+00 -4.96E+00
Coronary artery disease BA80-BA8Z Peripheral blood 9.88E-01 -1.25E-01 -4.54E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 9.78E-01 8.52E-02 3.67E-01
Endometriosis GA10 Endometrium tissue 2.29E-01 2.00E-01 3.20E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 2.17E-01 -1.18E-01 -8.05E-01
Familial hypercholesterolemia 5C80.00 Whole blood 4.68E-06 -3.27E-01 -9.91E-01
Gastric cancer 2B72 Gastric tissue 2.37E-01 -4.54E-01 -1.25E+00
Glioblastopma 2A00.00 Nervous tissue 4.36E-01 6.42E-02 7.02E-02
Glioma 2A00.0Y-2A00.0Z White matter tissue 7.32E-02 5.18E-01 5.94E-01
Head and neck cancer 2D42 Head and neck tissue 1.66E-25 -1.54E+00 -1.50E+00
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 5.74E-01 -7.38E-02 -1.15E-01
Huntington's disease 8A01.10 Whole blood 5.29E-01 -5.24E-02 -5.76E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 1.14E-02 6.40E-01 1.96E+00
Immunodeficiency 4A00-4A20 Peripheral blood 6.70E-03 -1.48E-01 -1.67E+00
Influenza 1.00E+30 Whole blood 8.45E-03 4.42E-01 3.19E+00
Interstitial cystitis GC00.3 Bladder tissue 2.86E-02 -4.22E-01 -1.24E+00
Intracranial aneurysm 8B01.0 Intracranial artery 8.55E-01 7.95E-02 2.32E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 3.60E-01 -1.20E-02 -4.35E-02
Ischemic stroke 8B11 Peripheral blood 6.89E-01 9.11E-02 2.68E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 4.51E-01 -6.98E-02 -1.05E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 4.74E-01 2.63E-01 5.14E-01
Lateral sclerosis 8B60.4 Skin 6.79E-01 -6.58E-02 -2.17E-01
Liver cancer 2C12.0 Liver tissue 1.03E-08 -7.22E-01 -9.37E-01
Liver failure DB99.7-DB99.8 Liver tissue 1.85E-02 4.05E-01 1.01E+00
Lung cancer 2C25 Lung tissue 7.17E-43 -8.43E-01 -1.79E+00
Lupus erythematosus 4A40 Whole blood 4.26E-02 -1.63E-01 -3.20E-01
Major depressive disorder 6A70-6A7Z Whole blood 6.34E-01 -4.42E-02 -9.63E-02
Major depressive disorder 6A70-6A7Z Hippocampus 4.25E-02 -3.30E-01 -7.17E-01
Melanoma 2C30 Skin 4.74E-02 2.15E-01 3.07E-01
Multiple myeloma 2A83.1 Bone marrow 8.82E-01 -5.22E-02 -2.32E-01
Multiple myeloma 2A83.1 Peripheral blood 5.28E-01 1.39E-01 4.53E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 1.81E-01 -7.95E-02 -2.83E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 7.09E-01 -2.57E-03 -1.60E-02
Myelofibrosis 2A20.2 Whole blood 1.41E-01 1.80E-01 6.80E-01
Myocardial infarction BA41-BA50 Peripheral blood 3.27E-01 -1.79E-01 -2.17E-01
Myopathy 8C70.6 Muscle tissue 6.67E-01 -7.98E-03 -2.04E-02
Neonatal sepsis KA60 Whole blood 3.14E-10 -2.35E-01 -7.40E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 2.92E-11 -2.41E+00 -6.76E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 2.15E-01 1.95E-01 3.05E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 3.57E-01 6.16E-02 4.39E-01
Olive pollen allergy CA08.00 Peripheral blood 7.15E-03 3.88E-01 2.36E+00
Oral cancer 2B6E Oral tissue 2.67E-04 -3.62E-01 -8.75E-01
Osteoarthritis FA00-FA0Z Synovial tissue 4.86E-03 -5.63E-01 -1.52E+00
Osteoporosis FB83.1 Bone marrow 6.88E-01 5.94E-02 2.22E-01
Ovarian cancer 2C73 Ovarian tissue 3.17E-01 -1.76E-01 -2.01E-01
Pancreatic cancer 2C10 Pancreas 2.22E-03 -2.00E+00 -1.29E+00
Parkinson's disease 8A00.0 Substantia nigra tissue 5.40E-01 6.83E-01 9.70E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 1.10E-02 -2.50E-01 -1.85E+00
Pituitary cancer 2D12 Pituitary tissue 2.80E-06 -1.25E+00 -2.35E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 2.46E-05 -1.32E+00 -2.39E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 4.82E-01 1.10E-01 3.58E-01
Polycythemia vera 2A20.4 Whole blood 6.72E-01 2.12E-02 8.92E-02
Pompe disease 5C51.3 Biceps muscle 3.48E-01 -4.12E-01 -5.34E-01
Preterm birth KA21.4Z Myometrium 6.67E-02 1.68E-01 1.48E+00
Prostate cancer 2C82 Prostate 2.31E-02 8.27E-01 6.49E-01
Psoriasis EA90 Skin 4.60E-12 -2.72E-01 -7.79E-01
Rectal cancer 2B92 Rectal colon tissue 5.01E-07 -2.60E+00 -6.11E+00
Renal cancer 2C90-2C91 Kidney 8.30E-04 -1.22E+00 -1.30E+00
Retinoblastoma 2D02.2 Uvea 1.03E-05 -7.02E-01 -1.72E+00
Rheumatoid arthritis FA20 Synovial tissue 1.34E-03 -1.77E+00 -2.79E+00
Rhinovirus infection CA42.1 Nasal epithelium tissue 9.86E-01 -4.25E-02 -1.35E-01
Schizophrenia 6A20 Prefrontal cortex 2.72E-01 -5.00E-02 -5.72E-02
Schizophrenia 6A20 Superior temporal cortex 2.40E-01 2.74E-02 8.72E-02
Scleroderma 4A42.Z Whole blood 1.99E-05 -2.70E-01 -2.75E+00
Seizure 8A60-8A6Z Whole blood 4.82E-01 1.66E-02 9.88E-02
Sensitive skin EK0Z Skin 3.65E-01 -6.10E-02 -2.88E-01
Sepsis with septic shock 1G41 Whole blood 3.41E-27 -3.46E-01 -9.47E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 3.64E-01 3.14E-01 1.04E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 5.46E-01 -2.99E-02 -2.03E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 4.90E-02 7.95E-01 1.87E+00
Sjogren's syndrome 4A43.2 Salivary gland tissue 8.73E-01 5.03E-02 3.41E-01
Skin cancer 2C30-2C3Z Skin 7.44E-14 2.44E-01 6.29E-01
Thrombocythemia 3B63 Whole blood 7.26E-01 4.97E-02 2.28E-01
Thrombocytopenia 3B64 Whole blood 7.50E-02 -6.48E-01 -7.33E-01
Thyroid cancer 2D10 Thyroid 5.18E-44 -2.65E+00 -2.60E+00
Tibial muscular dystrophy 8C75 Muscle tissue 3.51E-01 6.95E-02 3.65E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 8.54E-01 1.92E-01 3.39E-01
Type 2 diabetes 5A11 Liver tissue 2.06E-01 -3.47E-01 -8.10E-01
Ureter cancer 2C92 Urothelium 5.53E-01 -5.05E-02 -1.62E-01
Uterine cancer 2C78 Endometrium tissue 1.57E-02 -2.55E-01 -3.87E-01
Vitiligo ED63.0 Skin 8.05E-01 -5.82E-02 -6.38E-02
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⏷ Show the Full List of Expression Under 107 Diseases

References

1 The sodium bicarbonate cotransporter (NBCe1) is essential for normal development of mouse dentition. J Biol Chem. 2010 Aug 6;285(32):24432-8.