SORT1

Protein identityUniProt · HPA

UniProt accession

Q99523

Gene

SORT1

Ensembl

ENSG00000134243

Chromosome

1

Canonical length

831 aa

Protein class

Disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Golgi apparatus,Plasma membrane,Cytosol

OverviewNCBI Gene

This gene encodes a member of the VPS10-related sortilin family of proteins. The encoded preproprotein is proteolytically processed by furin to generate the mature receptor. This receptor plays a role in the trafficking of different proteins to either the cell surface, or subcellular compartments such as lysosomes and endosomes. Expression levels of this gene may influence the risk of myocardial infarction in human patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

Canonical amino-acid sequenceUniProt

831 residues, UniProt reviewed canonical sequence.

>Q99523|SORT1
     1  MERPWGAADG LSRWPHGLGL LLLLQLLPPS TLSQDRLDAP PPPAAPLPRW SGPIGVSWGL
    61  RAAAAGGAFP RGGRWRRSAP GEDEECGRVR DFVAKLANNT HQHVFDDLRG SVSLSWVGDS
   121  TGVILVLTTF HVPLVIMTFG QSKLYRSEDY GKNFKDITDL INNTFIRTEF GMAIGPENSG
   181  KVVLTAEVSG GSRGGRIFRS SDFAKNFVQT DLPFHPLTQM MYSPQNSDYL LALSTENGLW
   241  VSKNFGGKWE EIHKAVCLAK WGSDNTIFFT TYANGSCKAD LGALELWRTS DLGKSFKTIG
   301  VKIYSFGLGG RFLFASVMAD KDTTRRIHVS TDQGDTWSMA QLPSVGQEQF YSILAANDDM
   361  VFMHVDEPGD TGFGTIFTSD DRGIVYSKSL DRHLYTTTGG ETDFTNVTSL RGVYITSVLS
   421  EDNSIQTMIT FDQGGRWTHL RKPENSECDA TAKNKNECSL HIHASYSISQ KLNVPMAPLS
   481  EPNAVGIVIA HGSVGDAISV MVPDVYISDD GGYSWTKMLE GPHYYTILDS GGIIVAIEHS
   541  SRPINVIKFS TDEGQCWQTY TFTRDPIYFT GLASEPGARS MNISIWGFTE SFLTSQWVSY
   601  TIDFKDILER NCEEKDYTIW LAHSTDPEDY EDGCILGYKE QFLRLRKSSV CQNGRDYVVT
   661  KQPSICLCSL EDFLCDFGYY RPENDSKCVE QPELKGHDLE FCLYGREEHL TTNGYRKIPG
   721  DKCQGGVNPV REVKDLKKKC TSNFLSPEKQ NSKSNSVPII LAIVGLMLVT VVAGVLIVKK
   781  YVCGGRFLVH RYSVLQQHAE ANGVDGVDAL DTASHTNKSG YHDDSDEDLL E

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SORT1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

147 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for SORT1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.21

gnomAD pLI

1

gnomAD missense Z

2.1

DepMap mean gene effect

-0.21

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• D-glucose import
• endocytosis
• endosome to lysosome transport
• endosome transport via multivesicular body sorting pathway
• extrinsic apoptotic signaling pathway via death domain receptors
• G protein-coupled receptor signaling pathway
• Golgi to endosome transport
• Golgi to lysosome transport
• maintenance of synapse structure
• myotube differentiation
• negative regulation of fat cell differentiation
• neuropeptide signaling pathway
• neurotrophin TRK receptor signaling pathway
• ossification
• plasma membrane to endosome transport
• protein targeting to lysosome
• regulation of gene expression
• response to insulin
• vesicle organization

Molecular functions

• enzyme binding
• nerve growth factor binding
• nerve growth factor receptor activity
• retromer complex binding
• neurotensin receptor activity, non-G protein-coupled

Cellular components

• cell surface
• cerebellar climbing fiber to Purkinje cell synapse
• clathrin-coated pit
• clathrin-coated vesicle
• cytoplasmic vesicle
• cytosol
• early endosome
• endoplasmic reticulum membrane
• endosome membrane
• Golgi apparatus
• Golgi cisterna membrane
• lysosomal membrane
• lysosome
• membrane
• nuclear membrane
• perinuclear region of cytoplasm
• plasma membrane
• trans-Golgi network transport vesicle

Protein domainsUniProt · Pfam · InterPro

• VPS10
• WD40/YVTN repeat-like-containing domain superfamily
• Sortilin, C-terminal
• Sortilin, N-terminal
• VPS10-related sortilin family receptors
• Sortilin, neurotensin receptor 3, C-terminal
• Sortilin, neurotensin receptor 3,

KeywordsUniProt

• Cell membrane
• Cleavage on pair of basic residues
• Developmental protein
• Differentiation
• Disulfide bond
• Endocytosis
• Endoplasmic reticulum
• Endosome
• Glycoprotein
• Golgi apparatus
• Lipoprotein
• Lysosome
• Membrane
• Nucleus
• Osteogenesis
• Palmitate
• Phosphoprotein
• Protein transport
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of SORT1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLN5
• GGA2
• GM2A
• GRN
• LPL
• NTRK2
• NTRK3
• NTS
• PSAP
• SLC2A4
• SMPD1
• HAP1
• NTRK1
• CDK2
• GGA1
• LRPAP1
• NGF