Sortilin family proteins

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Sortilin family proteins

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 human genome has 5 genes for sortilin and sortilin-related proteins; SORT1, SOL1, and SORCS1-3. All of the proteins contain a VPS10 domain, and are involved in traffiking nascent proteins from the Golgi to other intracellular organelles (endosomes, lysosomes). SORT1 and SOL1 are of therapeutic interest as they participate in inducing neurodegenerative processes [1,3,5]. Antagonism of sortilin function provides neuroprotective effects [4,6-7].

Targets

3300

sortilin 1 Show summary »« Hide summary

Target Id

3300

Nomenclature

sortilin 1

Genes

SORT1 (Hs), Sort1 (Mm), Sort1 (Rn)

Ensembl ID

ENSG00000134243 (Hs), ENSMUSG00000068747 (Mm), ENSRNOG00000031814 (Rn)

UniProtKB AC

Q99523 (Hs), Q6PHU5 (Mm), O54861 (Rn)

Antibodies

A3-PGRNC15* (Antagonist) pK_d 9.7 [2]

latozinemab (Antagonist) [7]

nivisnebart (Antagonist)

Comment

Sortilin 1 is expressed on myeloid and neuronal cells and is localised to the Golgi and cell surface. It promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF and NGFB. It is also involved in the traffiking of progranulin (PGRN), a lysosomal chaperone, immune regulator, and neuronal survival factor. PGRN deficiency is associated with the development of neurodegenerative disorders. Blocking sortilin 1 activity has been found to increase PGRN in a preclinical model of PGRN deficiency frontotemporal dementia, and in patients with the disease [7]. Whether this increase in PGRN translates to reduced disease progression remains to be determined in clinical studies.

References

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1. Bøgh N, Sørensen CB, Alstrup AKO, Hansen ESS, Andersen OM, Laustsen C. (2024) Mice and minipigs with compromised expression of the Alzheimer's disease gene SORL1 show cerebral metabolic disturbances on hyperpolarized [1-¹³C]pyruvate and sodium MRI. Brain Commun, 6 (2): fcae114. [PMID:38650831]

2. Ek M, Nilvebrant J, Nygren PÅ, Ståhl S, Lindberg H, Löfblom J. (2024) An anti-sortilin affibody-peptide fusion inhibits sortilin-mediated progranulin degradation. Front Immunol, 15: 1437886. [PMID:39185427]

3. Grochowska MM, Carreras Mascaro A, Boumeester V, Natale D, Breedveld GJ, Geut H, van Cappellen WA, Boon AJW, Kievit AJA, Sammler E et al.. (2021) LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson's disease and dementia with Lewy bodies. Acta Neuropathol, 142 (1): 117-137. [PMID:33913039]

4. Jakobsen TS, Østergaard JA, Kjolby M, Birch EL, Bek T, Nykjaer A, Corydon TJ, Askou AL. (2023) Sortilin Inhibition Protects Neurons From Degeneration in the Diabetic Retina. Invest Ophthalmol Vis Sci, 64 (7): 8. [PMID:37272764]

5. Jiang J, Yang C, Ai JQ, Zhang QL, Cai XL, Tu T, Wan L, Wang XS, Wang H, Pan A et al.. (2022) Intraneuronal sortilin aggregation relative to granulovacuolar degeneration, tau pathogenesis and sorfra plaque formation in human hippocampal formation. Front Aging Neurosci, 14: 926904. [PMID:35978952]

6. Kashyap SN, Fox SN, Wilson KI, Murchison CF, Ambaw YA, Walther TC, Farese RV, Arrant AE, Roberson ED. (2024) Carboxy-terminal blockade of sortilin binding enhances progranulin gene therapy, a potential treatment for frontotemporal dementia. bioRxiv,. [PMID:39345608]

7. Kurnellas M, Mitra A, Schwabe T, Paul R, Arrant AE, Roberson ED, Ward M, Yeh F, Long H, Rosenthal A. (2023) Latozinemab, a novel progranulin-elevating therapy for frontotemporal dementia. J Transl Med, 21 (1): 387. [PMID:37322482]

How to cite this family page

Database page citation:

Sortilin family proteins. Accessed on 26/04/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1104.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Spedding M, Cidlowski JA, Fabbro D, Davenport AP, Striessnig J, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets. Br J Pharmacol. 180 Suppl 2:S1-22.