Molecule Information

General Information of the Molecule (ID: Mol04161)

• Name: Solute carrier family 4 member 4 (SLC4A4) ,Homo sapiens
• Synonyms: Na(+)/HCO3(-) cotransporter; Solute carrier family 4 member 4; kNBC1
• Molecule Type: Protein
• Gene Name: SLC4A4
• Gene ID: 8671
• Location: chr4:71062667-71572087[+]
• Sequence:
  MEDEAVLDRGASFLKHVCDEEEVEGHHTIYIGVHVPKSYRRRRRHKRKTGHKEKKEKERI
  SENYSDKSDIENADESSSSILKPLISPAAERIRFILGEEDDSPAPPQLFTELDELLAVDG
  QEMEWKETARWIKFEEKVEQGGERWSKPHVATLSLHSLFELRTCMEKGSIMLDREASSLP
  QLVEMIVDHQIETGLLKPELKDKVTYTLLRKHRHQTKKSNLRSLADIGKTVSSASRMFTN
  PDNGSPAMTHRNLTSSSLNDISDKPEKDQLKNKFMKKLPRDAEASNVLVGEVDFLDTPFI
  AFVRLQQAVMLGALTEVPVPTRFLFILLGPKGKAKSYHEIGRAIATLMSDEVFHDIAYKA
  KDRHDLIAGIDEFLDEVIVLPPGEWDPAIRIEPPKSLPSSDKRKNMYSGGENVQMNGDTP
  HDGGHGGGGHGDCEELQRTGRFCGGLIKDIKRKAPFFASDFYDALNIQALSAILFIYLAT
  VTNAITFGGLLGDATDNMQGVLESFLGTAVSGAIFCLFAGQPLTILSSTGPVLVFERLLF
  NFSKDNNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEEGFSSLISFIFIYDA
  FKKMIKLADYYPINSNFKVGYNTLFSCTCVPPDPANISISNDTTLAPEYLPTMSSTDMYH
  NTTFDWAFLSKKECSKYGGNLVGNNCNFVPDITLMSFILFLGTYTSSMALKKFKTSPYFP
  TTARKLISDFAIILSILIFCVIDALVGVDTPKLIVPSEFKPTSPNRGWFVPPFGENPWWV
  CLAAAIPALLVTILIFMDQQITAVIVNRKEHKLKKGAGYHLDLFWVAILMVICSLMALPW
  YVAATVISIAHIDSLKMETETSAPGEQPKFLGVREQRVTGTLVFILTGLSVFMAPILKFI
  PMPVLYGVFLYMGVASLNGVQFMDRLKLLLMPLKHQPDFIYLRHVPLRRVHLFTFLQVLC
  LALLWILKSTVAAIIFPVMILALVAVRKGMDYLFSQHDLSFLDDVIPEKDKKKKEDEKKK
  KKKKGSLDSDNDDSDCPYSEKVPSIKIPMDIMEQQPFLSDSKPSDRERSPTFLERHTSC
• 3D-structure: PDB ID: 6CAA; Classification: Transport protein; Method: Electron microscopy; Resolution: 3.90 Å
• Function: Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH. .
• Uniprot ID: S4A4_HUMAN
• Ensembl ID: ENSG00000080493
• HGNC ID: HGNC:11030

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Enzalutamide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Enzalutamide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• Experiment for Molecule Alteration: Transcriptome datasets
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-kappaB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo.

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Enzalutamide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PCa cells; Prostate; Homo sapiens (Human); CVCL_VF94
• Experiment for Molecule Alteration: Transcriptome datasets
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-kappaB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo.

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Enzalutamide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Male BALB/c nude mice, overexpression of SLC4A4 in LNCaP cells; Mice
• Experiment for Molecule Alteration: Transcriptome datasets
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-kappaB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Sensitive Drug: Enzalutamide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: SLC4A4 knockdown male BALB/c nude mice; STAT3 knockdown male BALB/c nude mice; Mice
• Experiment for Molecule Alteration: Transcriptome datasets
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-kappaB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo.

References

• Ref 1: SLC4A4 is a novel driver of enzalutamide resistance in prostate cancer. Cancer Lett. 2024 Aug 10;597:217070.