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UniProtKB - Q99523 (SORT_HUMAN)

Protein

Sortilin

Gene

SORT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.10 Publications

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • nerve growth factor binding Source: BHF-UCL
  • nerve growth factor receptor activity Source: BHF-UCL
  • neurotensin receptor activity, non-G protein-coupled Source: BHF-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processDifferentiation, Endocytosis, Osteogenesis, Transport

Enzyme and pathway databases

ReactomeiR-HSA-432722 Golgi Associated Vesicle Biogenesis

Protein family/group databases

TCDBi9.A.63.1.3 the retromer-dependent vacuolar protein sorting (r-vps) family

Names & Taxonomyi

Protein namesi
Recommended name:
Sortilin
Alternative name(s):
100 kDa NT receptor
Glycoprotein 95
Short name:
Gp95
Neurotensin receptor 3
Short name:
NT3
Short name:
NTR3
Gene namesi
Name:SORT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000134243.11
HGNCiHGNC:11186 SORT1
MIMi602458 gene
neXtProtiNX_Q99523

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini78 – 755ExtracellularSequence analysisAdd BLAST678
Transmembranei756 – 778HelicalSequence analysisAdd BLAST23
Topological domaini779 – 831CytoplasmicSequence analysisAdd BLAST53

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi74 – 77RWRR → GWRA: Abrogates propeptide cleavage. 1 Publication4
Mutagenesisi76 – 77RR → GG: Abrogates propeptide cleavage. 1 Publication2
Mutagenesisi792Y → A: Reduces endocytosis and Golgi to endosome sorting; when associated with A-795. 1 Publication1
Mutagenesisi795L → A: Reduces endocytosis and Golgi to endosome sorting; when associated with A-792. 1 Publication1
Mutagenesisi823 – 824DD → NN: Reduces interaction with GGA1. 1 Publication2
Mutagenesisi825S → A: Reduces interaction with GGA1. 1 Publication1
Mutagenesisi826 – 828DED → NQN: Abrogates interaction with GGA1 and impairs localization to the Golgi. 1 Publication3
Mutagenesisi829 – 830LL → AA: Abrogates interaction with GGA1 and impairs localization to the Golgi. 2 Publications2
Mutagenesisi829 – 830Missing : Abrogates interaction with GGA2. Reduces endocytosis and Golgi to endosome sorting; when associated with A-792 and A-795. 2 Publications2

Organism-specific databases

DisGeNETi6272
MalaCardsiSORT1
MIMi613589 phenotype
OpenTargetsiENSG00000134243
PharmGKBiPA36023

Chemistry databases

ChEMBLiCHEMBL3091

Polymorphism and mutation databases

BioMutaiSORT1
DMDMi84028263

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33By similarityAdd BLAST33
PropeptideiPRO_000003316234 – 77Removed in mature form1 PublicationAdd BLAST44
ChainiPRO_000003316378 – 831SortilinAdd BLAST754

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi86 ↔ 556
Glycosylationi98N-linked (GlcNAc...) asparagineCurated1
Glycosylationi162N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi257 ↔ 277
Glycosylationi274N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi406N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi448 ↔ 458
Glycosylationi582N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi612 ↔ 651
Disulfide bondi634 ↔ 666
Disulfide bondi668 ↔ 723
Disulfide bondi675 ↔ 688
Glycosylationi684N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi702 ↔ 740
Modified residuei814PhosphoserineCombined sources1
Modified residuei819PhosphoserineCombined sources1
Modified residuei825PhosphoserineCombined sources1

Post-translational modificationi

The N-terminal propeptide is cleaved by furin and possibly other homologous proteases.2 Publications

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ99523
MaxQBiQ99523
PaxDbiQ99523
PeptideAtlasiQ99523
PRIDEiQ99523
ProteomicsDBi78309

PTM databases

GlyConnecti1765
iPTMnetiQ99523
PhosphoSitePlusiQ99523
SwissPalmiQ99523

Expressioni

Tissue specificityi

Expressed in brain and prostate (at protein level). Expressed at high levels in brain, spinal cord, heart, skeletal muscle, thyroid, placenta and testis. Expressed at lower levels in lymphoid organs, kidney, colon and liver.2 Publications

Inductioni

During osteoblast differentiation.1 Publication

Gene expression databases

BgeeiENSG00000134243 Expressed in 229 organ(s), highest expression level in globus pallidus
CleanExiHS_SORT1
ExpressionAtlasiQ99523 baseline and differential
GenevisibleiQ99523 HS

Organism-specific databases

HPAiCAB011498
HPA006889

Interactioni

Subunit structurei

Interacts with LPL and SLC2A4 (By similarity). Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP, GM2A and NTS. Forms a complex with NGFR which binds specifically to the precursor forms of NGFB (proNGFB) and BDNF (proBDNF). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; may regulate their anterograde axonal transport and signaling. Interacts with CLN5 (PubMed:22431521). Interacts with PSAP (PubMed:22431521, PubMed:14657016).By similarity13 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112180, 130 interactors
CORUMiQ99523
DIPiDIP-41798N
ELMiQ99523
IntActiQ99523, 142 interactors
MINTiQ99523
STRINGi9606.ENSP00000256637

Chemistry databases

BindingDBiQ99523

Structurei

Secondary structure

1831
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ99523
SMRiQ99523
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99523

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati145 – 156BNR 1Add BLAST12
Repeati198 – 209BNR 2Add BLAST12
Repeati240 – 251BNR 3Add BLAST12
Repeati287 – 298BNR 4Add BLAST12
Repeati328 – 339BNR 5Add BLAST12
Repeati377 – 388BNR 6Add BLAST12
Repeati428 – 439BNR 7Add BLAST12
Repeati506 – 517BNR 8Add BLAST12
Repeati548 – 559BNR 9Add BLAST12

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni50 – 61Intrachain binding of the propeptide and the extracellular domainAdd BLAST12
Regioni612 – 756Interactions with LRPAP1 and NGFBAdd BLAST145
Regioni779 – 831Golgi to endosome transport and interactions with GGA1 and GGA2Add BLAST53

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi787 – 792Endocytosis signalCurated6

Domaini

The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding.
The extracellular domain may be shed following protease cleavage in some cell types.

Sequence similaritiesi

Belongs to the VPS10-related sortilin family. SORT1 subfamily.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ISX8 Eukaryota
ENOG410ZJ6Q LUCA
GeneTreeiENSGT00510000046443
HOGENOMiHOG000231347
HOVERGENiHBG080235
InParanoidiQ99523
KOiK12388
OMAiWTKMLEG
OrthoDBiEOG091G0ETU
PhylomeDBiQ99523
TreeFamiTF324918

Family and domain databases

Gene3Di2.130.10.10, 2 hits
InterProiView protein in InterPro
IPR031777 Sortilin_C
IPR031778 Sortilin_N
IPR006581 VPS10
IPR015943 WD40/YVTN_repeat-like_dom_sf
PfamiView protein in Pfam
PF15902 Sortilin-Vps10, 1 hit
PF15901 Sortilin_C, 1 hit
SMARTiView protein in SMART
SM00602 VPS10, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q99523-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MERPWGAADG LSRWPHGLGL LLLLQLLPPS TLSQDRLDAP PPPAAPLPRW 
        60         70         80         90        100
SGPIGVSWGL RAAAAGGAFP RGGRWRRSAP GEDEECGRVR DFVAKLANNT 
       110        120        130        140        150
HQHVFDDLRG SVSLSWVGDS TGVILVLTTF HVPLVIMTFG QSKLYRSEDY 
       160        170        180        190        200
GKNFKDITDL INNTFIRTEF GMAIGPENSG KVVLTAEVSG GSRGGRIFRS 
       210        220        230        240        250
SDFAKNFVQT DLPFHPLTQM MYSPQNSDYL LALSTENGLW VSKNFGGKWE 
       260        270        280        290        300
EIHKAVCLAK WGSDNTIFFT TYANGSCKAD LGALELWRTS DLGKSFKTIG 
       310        320        330        340        350
VKIYSFGLGG RFLFASVMAD KDTTRRIHVS TDQGDTWSMA QLPSVGQEQF 
       360        370        380        390        400
YSILAANDDM VFMHVDEPGD TGFGTIFTSD DRGIVYSKSL DRHLYTTTGG 
       410        420        430        440        450
ETDFTNVTSL RGVYITSVLS EDNSIQTMIT FDQGGRWTHL RKPENSECDA 
       460        470        480        490        500
TAKNKNECSL HIHASYSISQ KLNVPMAPLS EPNAVGIVIA HGSVGDAISV 
       510        520        530        540        550
MVPDVYISDD GGYSWTKMLE GPHYYTILDS GGIIVAIEHS SRPINVIKFS 
       560        570        580        590        600
TDEGQCWQTY TFTRDPIYFT GLASEPGARS MNISIWGFTE SFLTSQWVSY 
       610        620        630        640        650
TIDFKDILER NCEEKDYTIW LAHSTDPEDY EDGCILGYKE QFLRLRKSSV 
       660        670        680        690        700
CQNGRDYVVT KQPSICLCSL EDFLCDFGYY RPENDSKCVE QPELKGHDLE 
       710        720        730        740        750
FCLYGREEHL TTNGYRKIPG DKCQGGVNPV REVKDLKKKC TSNFLSPEKQ 
       760        770        780        790        800
NSKSNSVPII LAIVGLMLVT VVAGVLIVKK YVCGGRFLVH RYSVLQQHAE 
       810        820        830 
ANGVDGVDAL DTASHTNKSG YHDDSDEDLL E
Length:831
Mass (Da):92,068
Last modified:December 20, 2005 - v3
Checksum:i91F96A3035A4B43A
GO
Isoform 2 (identifier: Q99523-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-136: Missing.
     278-279: KA → T

Note: No experimental confirmation available.
Show »
Length:694
Mass (Da):77,375
Checksum:i4F80EC724C360750
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0J9YVU2A0A0J9YVU2_HUMAN
Sortilin
SORT1
104Annotation score:
A0A0J9YVX1A0A0J9YVX1_HUMAN
Sortilin
SORT1
60Annotation score:
A0A0J9YX61A0A0J9YX61_HUMAN
Sortilin
SORT1
118Annotation score:
A0A0J9YY30A0A0J9YY30_HUMAN
Sortilin
SORT1
20Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti650V → M in CAA66904 (PubMed:9013611).Curated1

Polymorphismi

Genetic variations in SORT1 influence low density lipoprotein cholesterol (LDL-C) variability and contribute to the low density lipoprotein cholesterol level quantitative trait locus 6 (LDLCQ6) [MIMi:613589].

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053681358D → Y. Corresponds to variant dbSNP:rs2228605Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0462391 – 136Missing in isoform 2. 1 PublicationAdd BLAST136
Alternative sequenceiVSP_046240278 – 279KA → T in isoform 2. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98248 mRNA Translation: CAA66904.2
FJ525881 Genomic DNA Translation: ACN81319.1
AK301548 mRNA Translation: BAG63045.1
AL390252 Genomic DNA No translation available.
BC023542 mRNA Translation: AAH23542.1
CCDSiCCDS55618.1 [Q99523-2]
CCDS798.1 [Q99523-1]
RefSeqiNP_001192157.1, NM_001205228.1 [Q99523-2]
NP_002950.3, NM_002959.6 [Q99523-1]
UniGeneiHs.485195
Hs.703487

Genome annotation databases

EnsembliENST00000256637; ENSP00000256637; ENSG00000134243 [Q99523-1]
ENST00000538502; ENSP00000438597; ENSG00000134243 [Q99523-2]
GeneIDi6272
KEGGihsa:6272
UCSCiuc001dxm.3 human [Q99523-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98248 mRNA Translation: CAA66904.2
FJ525881 Genomic DNA Translation: ACN81319.1
AK301548 mRNA Translation: BAG63045.1
AL390252 Genomic DNA No translation available.
BC023542 mRNA Translation: AAH23542.1
CCDSiCCDS55618.1 [Q99523-2]
CCDS798.1 [Q99523-1]
RefSeqiNP_001192157.1, NM_001205228.1 [Q99523-2]
NP_002950.3, NM_002959.6 [Q99523-1]
UniGeneiHs.485195
Hs.703487

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3F6KX-ray2.00A78-756[»]
3G2UX-ray2.30C/D819-831[»]
3G2VX-ray2.10C/D819-831[»]
4MSLX-ray2.70A78-756[»]
4N7EX-ray2.70A78-756[»]
4PO7X-ray2.66A78-756[»]
5MRHX-ray2.50A78-756[»]
5MRIX-ray2.00A78-756[»]
6EHOX-ray3.50A34-756[»]
ProteinModelPortaliQ99523
SMRiQ99523
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112180, 130 interactors
CORUMiQ99523
DIPiDIP-41798N
ELMiQ99523
IntActiQ99523, 142 interactors
MINTiQ99523
STRINGi9606.ENSP00000256637

Chemistry databases

BindingDBiQ99523
ChEMBLiCHEMBL3091

Protein family/group databases

TCDBi9.A.63.1.3 the retromer-dependent vacuolar protein sorting (r-vps) family

PTM databases

GlyConnecti1765
iPTMnetiQ99523
PhosphoSitePlusiQ99523
SwissPalmiQ99523

Polymorphism and mutation databases

BioMutaiSORT1
DMDMi84028263

Proteomic databases

EPDiQ99523
MaxQBiQ99523
PaxDbiQ99523
PeptideAtlasiQ99523
PRIDEiQ99523
ProteomicsDBi78309

Protocols and materials databases

DNASUi6272
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256637; ENSP00000256637; ENSG00000134243 [Q99523-1]
ENST00000538502; ENSP00000438597; ENSG00000134243 [Q99523-2]
GeneIDi6272
KEGGihsa:6272
UCSCiuc001dxm.3 human [Q99523-1]

Organism-specific databases

CTDi6272
DisGeNETi6272
EuPathDBiHostDB:ENSG00000134243.11
GeneCardsiSORT1
HGNCiHGNC:11186 SORT1
HPAiCAB011498
HPA006889
MalaCardsiSORT1
MIMi602458 gene
613589 phenotype
neXtProtiNX_Q99523
OpenTargetsiENSG00000134243
PharmGKBiPA36023
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ISX8 Eukaryota
ENOG410ZJ6Q LUCA
GeneTreeiENSGT00510000046443
HOGENOMiHOG000231347
HOVERGENiHBG080235
InParanoidiQ99523
KOiK12388
OMAiWTKMLEG
OrthoDBiEOG091G0ETU
PhylomeDBiQ99523
TreeFamiTF324918

Enzyme and pathway databases

ReactomeiR-HSA-432722 Golgi Associated Vesicle Biogenesis

Miscellaneous databases

ChiTaRSiSORT1 human
EvolutionaryTraceiQ99523
GeneWikiiSortilin_1
GenomeRNAii6272
PROiPR:Q99523
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134243 Expressed in 229 organ(s), highest expression level in globus pallidus
CleanExiHS_SORT1
ExpressionAtlasiQ99523 baseline and differential
GenevisibleiQ99523 HS

Family and domain databases

Gene3Di2.130.10.10, 2 hits
InterProiView protein in InterPro
IPR031777 Sortilin_C
IPR031778 Sortilin_N
IPR006581 VPS10
IPR015943 WD40/YVTN_repeat-like_dom_sf
PfamiView protein in Pfam
PF15902 Sortilin-Vps10, 1 hit
PF15901 Sortilin_C, 1 hit
SMARTiView protein in SMART
SM00602 VPS10, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSORT_HUMAN
AccessioniPrimary (citable) accession number: Q99523
Secondary accession number(s): B4DWI3, C0JYZ0, Q8IZ49
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 20, 2005
Last modified: November 7, 2018
This is version 184 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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