SLC34 family of sodium phosphate co-transporters | Transporters

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SLC34 family of sodium phosphate co-transporters

SLC34 family of sodium phosphate co-transporters C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The SLC34 family are sometimes referred to as Type II sodium-phosphate co-transporters, alongside Type I (SLC17 family) and Type III (SLC20 family) transporters. Topological modelling suggests eight TM domains with C- and N- termini in the cytoplasm, and a re-entrant loop at TM7/8. SLC34 family members are expressed on the apical surfaces of epithelia in the intestine and kidneys to regulate body phosphate levels, principally NaPi-IIa and NaPi-IIb, respectively. NaPi-IIa and NaPi-IIb are electrogenic, while NaPiIIc is electroneutral [1].

Transporters

1137

NaPi-IIa (Sodium phosphate 1 / SLC34A1) C Show summary »« Hide summary

Target Id	1135
Nomenclature	Sodium phosphate 1
Systematic nomenclature	SLC34A1
Common abbreviation	NaPi-IIa
Previous and unofficial names	NPT2 \| NPTIIa \| SLC11 \| NAPI-3 \| SLC17A2 \| Na+-phosphate cotransporter type II \| solute carrier family 17 (sodium phosphate), member 2 \| Na(+)-dependent phosphate cotransporter 2A \| NAPI2A \| sodium/phosphate cotransporter 2A \| sodium-dependent phosphate transport protein 2A \| sodium-phosphate transport protein 2A \| solute carrier family 17 (sodium/hydrogen exchanger) member 2 \| solute carrier family 34 (sodium phosphate) member 1 \| Na/Pi cotransporter \| renal Na+/Pi transporter \| solute carrier family 34 (type II sodium/phosphate contransporter), member 1 \| solute carrier family 34 (type II sodium/phosphate cotransporter), member 1 \| solute carrier family 34 (sodium phosphate)
Genes	SLC34A1 (Hs), Slc34a1 (Mm), Slc34a1 (Rn)
Ensembl ID	ENSG00000131183 (Hs), ENSMUSG00000021490 (Mm), ENSRNOG00000015262 (Rn)
UniProtKB AC	Q06495 (Hs), Q60825 (Mm), Q06496 (Rn)
Bioparadigms SLC Tables	SLC34A1 (Hs)
RESOLUTE	SLC34A1 (Hs)
Stoichiometry	3 Na⁺ : 1 HPO₄^2- (in) [4]

NaPi-IIb (Sodium phosphate 2 / SLC34A2) C Show summary »« Hide summary

Target Id

1136

Nomenclature

Sodium phosphate 2

Systematic nomenclature

SLC34A2

Common abbreviation

NaPi-IIb

Previous and unofficial names

Genes

SLC34A2 (Hs), Slc34a2 (Mm), Slc34a2 (Rn)

Ensembl ID

ENSG00000157765 (Hs), ENSMUSG00000029188 (Mm), ENSRNOG00000004626 (Rn)

UniProtKB AC

O95436 (Hs), Q9DBP0 (Mm), Q9JJ09 (Rn)

Bioparadigms SLC Tables

SLC34A2 (Hs)

RESOLUTE

SLC34A2 (Hs)

Inhibitors

compound 15 [PMID: 35034442] pIC₅₀ 7.2 [5]

Antibodies

lifastuzumab vedotin (Binding) [3]

Stoichiometry

3 Na⁺ : 1 HPO₄^2-(in) [1]

Comment

NaPi2b is highly expressed by ovarian and non-small cell lung cancer (NSCLC) carcinomas, and is being actively pursued as a drug target for these tumours. XMT-1536 (Mersana Therapeutics) has entered Phase 1 proof-of-concept trial NCT03319628. Lifastuzumab vedotin (Genentech) reached Phase 2 evaluation, but trial NCT01991210 was terminated as the test agent failed to increase progression-free survival compared to standard-of-care pegylated liposomal doxorubicin, in ovarian cancer patients [2]. XMT-1536 and lifastuzumab vedotin are NaPi2b-directed monoclonal antibody-drug conjugates (ADCs).

NaPi-IIc (Sodium phosphate 3 / SLC34A3) C Show summary »« Hide summary

Target Id	1137
Nomenclature	Sodium phosphate 3
Systematic nomenclature	SLC34A3
Common abbreviation	NaPi-IIc
Previous and unofficial names	Na(+)/Pi cotransporter 2C \| Na(+)-dependent phosphate cotransporter 2C \| Na+/Pi-cotransporter type IIc \| naPi-2c \| sodium/phosphate cotransporter 2C \| sodium-dependent phosphate transport protein 2C \| sodium-phosphate transport protein 2C \| solute carrier family 34 (sodium phosphate), member 3 \| solute carrier family 34 (type II sodium/phosphate contransporter), member 3 \| solute carrier family 34 (type II sodium/phosphate cotransporter), member 3 \| solute carrier family 34 (sodium phosphate)
Genes	SLC34A3 (Hs), Slc34a3 (Mm), Slc34a3 (Rn)
Ensembl ID	ENSG00000198569 (Hs), ENSMUSG00000006469 (Mm), ENSRNOG00000010451 (Rn)
UniProtKB AC	Q8N130 (Hs), Q80SU6 (Mm), Q8K4R8 (Rn)
Bioparadigms SLC Tables	SLC34A3 (Hs)
RESOLUTE	SLC34A3 (Hs)
Stoichiometry	2 Na⁺ : 1 HPO₄^2- (in) [1]

Comments

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References

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1. Andrini O, Ghezzi C, Murer H, Forster IC. (2008) The leak mode of type II Na(+)-P(i) cotransporters. Channels (Austin), 2 (5): 346-57. [PMID:18989094]

2. Banerjee S, Oza AM, Birrer MJ, Hamilton EP, Hasan J, Leary A, Moore KN, Mackowiak-Matejczyk B, Pikiel J, Ray-Coquard I et al.. (2018) Anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study. Ann Oncol, 29 (4): 917-923. [PMID:29401246]

3. Dennis M, Rubinfeld B, Polakis P. (2013) Compositions and methods for the diagnosis and treatment of tumor. Patent number: US8535675 B2. Assignee: Genentech, Inc.. Priority date: 30/11/2009. Publication date: 17/09/2013.

4. Forster IC, Loo DD, Eskandari S. (1999) Stoichiometry and Na+ binding cooperativity of rat and flounder renal type II Na+-Pi cotransporters. Am J Physiol, 276 (4 Pt 2): F644-9. [PMID:10198426]

5. Maemoto M, Hirata Y, Hosoe S, Ouchi J, Narushima K, Akizawa E, Tsuji Y, Takada H, Yanagisawa A, Shuto S. (2022) Discovery of Gut-Restricted Small-Molecule Inhibitors of Intestinal Sodium-Dependent Phosphate Transport Protein 2b (NaPi2b) for the Treatment of Hyperphosphatemia. J Med Chem, 65 (3): 1946-1960. [PMID:35034442]

How to cite this family page

Database page citation:

SLC34 family of sodium phosphate co-transporters. Accessed on 26/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=221.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Transporters. Br J Pharmacol. 180 Suppl 2:S374-469.

SLC34 family of sodium phosphate co-transporters C

Overview

Transporters

Comments

Further reading

References

How to cite this family page