Q99523 (SORT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

SORT1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	831 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.9 Ref.10 Ref.11 Ref.13 Ref.15 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22
Subunit structure	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, NTS and PSAP. 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. Ref.1 Ref.7 Ref.8 Ref.10 Ref.11 Ref.14 Ref.15 Ref.19 Ref.20 Ref.22 Ref.30 Ref.31
Subcellular location	Membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein Potential. Endosome membrane; Single-pass type I membrane protein Potential. Golgi apparatus › Golgi stack membrane; Single-pass type I membrane protein Potential. Lysosome membrane; Single-pass type I membrane protein Potential. Nucleus membrane; Single-pass type I membrane protein Potential. Cell membrane; Single-pass type I membrane protein; Extracellular side. Lysosome membrane; Single-pass type I membrane protein Potential. Note: Localized to membranes of the endoplasmic reticulum, endosomes, Golgi stack, lysosomes and nucleus. A small fraction of the protein is also localized to the plasma membrane. May also be found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes. Localization to the plasma membrane in adipocytes may be enhanced by insulin. Ref.1 Ref.15 Ref.17 Ref.18 Ref.19
Tissue specificity	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. Ref.1
Induction	During osteoblast differentiation. Ref.13
Domain	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. Ref.12 The extracellular domain may be shed following protease cleavage in some cell types. Ref.12
Post-translational modification	The N-terminal propeptide is cleaved by furin and possibly other homologous proteases. Ref.7 Ref.12
Polymorphism	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) [MIM:613589].
Involvement in disease	Note=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.
Sequence similarities	Belongs to the VPS10-related sortilin family. SORT1 subfamily. Contains 9 BNR repeats.

Ontologies

Keywords
Biological process	Differentiation Endocytosis Osteogenesis Transport
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Lysosome Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein Receptor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	Golgi to endosome transport Inferred from direct assay Ref.10. Source: BHF-UCL endocytosis Inferred from direct assay Ref.10. Source: BHF-UCL endosome to lysosome transport Inferred from direct assay Ref.10. Source: BHF-UCL endosome transport via multivesicular body sorting pathway Inferred from direct assay Ref.10. Source: BHF-UCL glucose import Inferred from mutant phenotype. Source: BHF-UCL induction of apoptosis by extracellular signals Inferred from mutant phenotype Ref.20. Source: BHF-UCL myotube differentiation Inferred from mutant phenotype. Source: BHF-UCL negative regulation of apoptotic process Inferred from direct assay Ref.20. Source: BHF-UCL negative regulation of lipoprotein lipase activity Inferred from direct assay Ref.9. Source: BHF-UCL neuropeptide signaling pathway Inferred from direct assay Ref.6. Source: BHF-UCL ossification Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane to endosome transport Inferred from direct assay Ref.10. Source: BHF-UCL regulation of gene expression Inferred from mutant phenotype. Source: BHF-UCL response to insulin stimulus Inferred from mutant phenotype. Source: BHF-UCL vesicle organization Inferred from direct assay. Source: BHF-UCL
Cellular component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell surface Inferred from direct assay Ref.9. Source: BHF-UCL coated pit Inferred from direct assay Ref.10. Source: BHF-UCL early endosome Inferred from direct assay Ref.10. Source: BHF-UCL endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from direct assay. Source: BHF-UCL lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from direct assay. Source: BHF-UCL nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from direct assay Ref.10. Source: BHF-UCL plasma membrane Inferred from direct assay Ref.10. Source: BHF-UCL
Molecular function	enzyme binding Inferred from physical interaction Ref.9. Source: BHF-UCL nerve growth factor binding Inferred from physical interaction Ref.20. Source: BHF-UCL nerve growth factor receptor activity Inferred from direct assay Ref.20. Source: BHF-UCL neurotensin receptor activity, non-G-protein coupled Inferred from direct assay Ref.6. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK2	P24941	1	EBI-1057058,EBI-375096
GGA1	Q9UJY5	1	EBI-1057058,EBI-447141

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 33

33

Potential

Propeptide

34 – 77

44

Removed in mature form

PRO_0000033162

Chain

78 – 831

754

Sortilin

PRO_0000033163

Regions

Topological domain

78 – 755

678

Extracellular Potential

Transmembrane

756 – 778

23

Helical; Potential

Topological domain

779 – 831

53

Cytoplasmic Potential

Repeat

145 – 156

12

BNR 1

Repeat

198 – 209

12

BNR 2

Repeat

240 – 251

12

BNR 3

Repeat

287 – 298

12

BNR 4

Repeat

328 – 339

12

BNR 5

Repeat

377 – 388

12

BNR 6

Repeat

428 – 439

12

BNR 7

Repeat

506 – 517

12

BNR 8

Repeat

548 – 559

12

BNR 9

Region

50 – 61

12

Intrachain binding of the propeptide and the extracellular domain

Region

612 – 756

145

Interactions with LRPAP1 and NGFB

Region

779 – 831

53

Golgi to endosome transport and interactions with GGA1 and GGA2

Motif

787 – 792

6

Endocytosis signal Probable

Amino acid modifications

Modified residue

825

1

Phosphoserine Ref.24 Ref.26

Glycosylation

98

1

N-linked (GlcNAc...) Probable

Glycosylation

162

1

N-linked (GlcNAc...) Ref.23 Ref.25

Glycosylation

163

1

N-linked (GlcNAc...) Ref.25

Glycosylation

274

1

N-linked (GlcNAc...) Potential

Glycosylation

406

1

N-linked (GlcNAc...) Ref.31

Glycosylation

582

1

N-linked (GlcNAc...) Ref.31

Glycosylation

684

1

N-linked (GlcNAc...) Potential

Disulfide bond

86 ↔ 556

Ref.19 Ref.31

Disulfide bond

257 ↔ 277

Ref.19 Ref.31

Disulfide bond

448 ↔ 458

Ref.19 Ref.31

Disulfide bond

612 ↔ 651

Ref.19 Ref.31

Disulfide bond

634 ↔ 666

Ref.19 Ref.31

Disulfide bond

668 ↔ 723

Ref.19 Ref.31

Disulfide bond

675 ↔ 688

Ref.19 Ref.31

Disulfide bond

702 ↔ 740

Ref.19 Ref.31

Natural variations

Natural variant

358

1

D → Y.
Corresponds to variant rs2228605 [ dbSNP | Ensembl ].

VAR_053681

Experimental info

Mutagenesis

74 – 77

4

RWRR → GWRA: Abrogates propeptide cleavage. Ref.7

Mutagenesis

76 – 77

2

RR → GG: Abrogates propeptide cleavage.

Mutagenesis

792

1

Y → A: Reduces endocytosis and Golgi to endosome sorting; when associated with A-795. Ref.10

Mutagenesis

795

1

L → A: Reduces endocytosis and Golgi to endosome sorting; when associated with A-792. Ref.10

Mutagenesis

823 – 824

2

DD → NN: Reduces interaction with GGA1.

Mutagenesis

825

1

S → A: Reduces interaction with GGA1. Ref.11

Mutagenesis

826 – 828

3

DED → NQN: Abrogates interaction with GGA1 and impairs localization to the Golgi. Ref.11

Mutagenesis

829 – 830

2

LL → AA: Abrogates interaction with GGA1 and impairs localization to the Golgi.

Mutagenesis

829 – 830

2

Missing: Abrogates interaction with GGA2. Reduces endocytosis and Golgi to endosome sorting; when associated with A-792 and A-795.

Sequence conflict

650

1

V → M in CAA66904. Ref.1

Secondary structure

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831

Helix Strand Turn

Details...

Helix

92 – 97

6

Beta strand

100 – 106

7

Beta strand

112 – 116

5

Beta strand

124 – 129

6

Beta strand

142 – 148

7

Helix

158 – 161

4

Beta strand

182 – 186

5

Beta strand

197 – 202

6

Beta strand

208 – 210

3

Beta strand

216 – 218

3

Beta strand

221 – 223

3

Beta strand

226 – 232

7

Beta strand

240 – 243

4

Beta strand

249 – 251

3

Beta strand

254 – 260

7

Beta strand

267 – 271

5

Turn

277 – 280

4

Beta strand

284 – 290

7

Beta strand

303 – 305

3

Beta strand

313 – 318

6

Beta strand

325 – 331

7

Beta strand

351 – 356

6

Beta strand

361 – 365

5

Beta strand

376 – 379

4

Beta strand

385 – 393

9

Beta strand

414 – 419

6

Beta strand

425 – 431

7

Beta strand

438 – 441

4

Helix

465 – 469

5

Beta strand

488 – 490

3

Beta strand

505 – 508

4

Beta strand

516 – 519

4

Beta strand

523 – 527

5

Beta strand

534 – 538

5

Beta strand

546 – 551

6

Beta strand

558 – 561

4

Beta strand

581 – 585

5

Beta strand

595 – 603

9

Helix

604 – 606

3

Helix

614 – 616

3

Beta strand

617 – 621

5

Beta strand

639 – 645

7

Beta strand

661 – 664

4

Helix

670 – 672

3

Beta strand

683 – 685

3

Helix

698 – 703

6

Helix

707 – 710

4

Beta strand

734 – 736

3

Helix

737 – 740

4

Helix

741 – 743

3

Sequences

	Sequence		Length	Mass (Da)
	Q99523 [UniParc]. Last modified December 20, 2005. Version 3. Checksum: 91F96A3035A4B43A	FASTA	831	92,068
	10 20 30 40 50 60 MERPWGAADG LSRWPHGLGL LLLLQLLPPS TLSQDRLDAP PPPAAPLPRW SGPIGVSWGL 70 80 90 100 110 120 RAAAAGGAFP RGGRWRRSAP GEDEECGRVR DFVAKLANNT HQHVFDDLRG SVSLSWVGDS 130 140 150 160 170 180 TGVILVLTTF HVPLVIMTFG QSKLYRSEDY GKNFKDITDL INNTFIRTEF GMAIGPENSG 190 200 210 220 230 240 KVVLTAEVSG GSRGGRIFRS SDFAKNFVQT DLPFHPLTQM MYSPQNSDYL LALSTENGLW 250 260 270 280 290 300 VSKNFGGKWE EIHKAVCLAK WGSDNTIFFT TYANGSCKAD LGALELWRTS DLGKSFKTIG 310 320 330 340 350 360 VKIYSFGLGG RFLFASVMAD KDTTRRIHVS TDQGDTWSMA QLPSVGQEQF YSILAANDDM 370 380 390 400 410 420 VFMHVDEPGD TGFGTIFTSD DRGIVYSKSL DRHLYTTTGG ETDFTNVTSL RGVYITSVLS 430 440 450 460 470 480 EDNSIQTMIT FDQGGRWTHL RKPENSECDA TAKNKNECSL HIHASYSISQ KLNVPMAPLS 490 500 510 520 530 540 EPNAVGIVIA HGSVGDAISV MVPDVYISDD GGYSWTKMLE GPHYYTILDS GGIIVAIEHS 550 560 570 580 590 600 SRPINVIKFS TDEGQCWQTY TFTRDPIYFT GLASEPGARS MNISIWGFTE SFLTSQWVSY 610 620 630 640 650 660 TIDFKDILER NCEEKDYTIW LAHSTDPEDY EDGCILGYKE QFLRLRKSSV CQNGRDYVVT 670 680 690 700 710 720 KQPSICLCSL EDFLCDFGYY RPENDSKCVE QPELKGHDLE FCLYGREEHL TTNGYRKIPG 730 740 750 760 770 780 DKCQGGVNPV REVKDLKKKC TSNFLSPEKQ NSKSNSVPII LAIVGLMLVT VVAGVLIVKK 790 800 810 820 830 YVCGGRFLVH RYSVLQQHAE ANGVDGVDAL DTASHTNKSG YHDDSDEDLL E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography." Petersen C.M., Nielsen M.S., Nykjaer A., Jacobsen L., Tommerup N., Rasmussen H.H., Roeigaard H., Gliemann J., Madsen P., Moestrup S.K. J. Biol. Chem. 272:3599-3605(1997) [PubMed: 9013611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, INTERACTION WITH LRPAP1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION. Tissue: T-cell.
[2]	Madsen P. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[6]	"The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor." Mazella J., Zsurger N., Navarro V., Chabry J., Kaghad M., Caput D., Ferrara P., Vita M., Gully D., Maffrand J.-P., Vincent J.-P. J. Biol. Chem. 273:26273-26276(1998) [PubMed: 9756851] [Abstract] Cited for: PROTEIN SEQUENCE OF 78-100, IDENTIFICATION AS A NEUROTENSIN RECEPTOR. Tissue: Brain.
[7]	"Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding." Petersen C.M., Nielsen M.S., Jacobsen C., Tauris J., Jacobsen L., Gliemann J., Moestrup S.K., Madsen P. EMBO J. 18:595-604(1999) [PubMed: 9927419] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, INTERACTION WITH LRPAP1, MUTAGENESIS OF 74-ARG--ARG-77 AND 76-ARG-ARG-77, CLEAVAGE BY FURIN, GLYCOSYLATION.
[8]	"The carboxy-terminal domain of the receptor-associated protein binds to the Vps10p domain of sortilin." Tauris J., Ellgaard L., Jacobsen C., Nielsen M.S., Madsen P., Thoegersen H.C., Gliemann J., Petersen C.M., Moestrup S.K. FEBS Lett. 429:27-30(1998) [PubMed: 9657377] [Abstract] Cited for: INTERACTION WITH LRPAP1.
[9]	"Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase." Nielsen M.S., Jacobsen C., Olivecrona G., Gliemann J., Petersen C.M. J. Biol. Chem. 274:8832-8836(1999) [PubMed: 10085125] [Abstract] Cited for: FUNCTION.
[10]	"The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein." Nielsen M.S., Madsen P., Christensen E.I., Nykjaer A., Gliemann J., Kasper D., Pohlmann R., Petersen C.M. EMBO J. 20:2180-2190(2001) [PubMed: 11331584] [Abstract] Cited for: FUNCTION, INTERACTION WITH GGA2, MUTAGENESIS OF TYR-792; LEU-795 AND 829-LEU-LEU-830.
[11]	"Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains." Takatsu H., Katoh Y., Shiba Y., Nakayama K. J. Biol. Chem. 276:28541-28545(2001) [PubMed: 11390366] [Abstract] Cited for: FUNCTION, INTERACTION WITH GGA1 AND GGA2, MUTAGENESIS OF 823-ASP-ASP-824; SER-825; 826-ASP--ASP-828 AND 829-LEU-LEU-830.
[12]	"Shedding of the luminal domain of the neurotensin receptor-3/sortilin in the HT29 cell line." Navarro V., Vincent J.-P., Mazella J. Biochem. Biophys. Res. Commun. 298:760-764(2002) [PubMed: 12419319] [Abstract] Cited for: CLEAVAGE OF THE EXTRACELLULAR DOMAIN.
[13]	"Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization." Maeda S., Nobukuni T., Shimo-Onoda K., Hayashi K., Yone K., Komiya S., Inoue I. J. Cell. Physiol. 193:73-79(2002) [PubMed: 12209882] [Abstract] Cited for: FUNCTION, INDUCTION.
[14]	"Structural basis for recognition of acidic-cluster dileucine sequence by GGA1." Shiba T., Takatsu H., Nogi T., Matsugaki N., Kawasaki M., Igarashi N., Suzuki M., Kato R., Earnest T., Nakayama K., Wakatsuki S. Nature 415:937-941(2002) [PubMed: 11859376] [Abstract] Cited for: INTERACTION WITH GGA1.
[15]	"The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin." Lefrancois S., Zeng J., Hassan A.J., Canuel M., Morales C.R. EMBO J. 22:6430-6437(2003) [PubMed: 14657016] [Abstract] Cited for: FUNCTION, INTERACTION WITH GM2A AND PSAP, SUBCELLULAR LOCATION.
[16]	Erratum Lefrancois S., Zeng J., Hassan A.J., Canuel M., Morales C.R. EMBO J. 23:1680-1680(2004)
[17]	"Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia." Martin S., Vincent J.-P., Mazella J. J. Neurosci. 23:1198-1205(2003) [PubMed: 12598608] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[18]	"Internalization and trafficking of neurotensin via NTS3 receptors in HT29 cells." Morinville A., Martin S., Lavallee M., Vincent J.-P., Beaudet A., Mazella J. Int. J. Biochem. Cell Biol. 36:2153-2168(2004) [PubMed: 15313463] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[19]	"Functional organization of the sortilin Vps10p domain." Westergaard U.B., Soerensen E.S., Hermey G., Nielsen M.S., Nykjaer A., Kirkegaard K., Jacobsen C., Gliemann J., Madsen P., Petersen C.M. J. Biol. Chem. 279:50221-50229(2004) [PubMed: 15364913] [Abstract] Cited for: INTERACTION WITH LRPAP1 AND NGFB, SUBCELLULAR LOCATION, MASS SPECTROMETRY, DISULFIDE BONDS.
[20]	"Sortilin is essential for proNGF-induced neuronal cell death." Nykjaer A., Lee R., Teng K.K., Jansen P., Madsen P., Nielsen M.S., Jacobsen C., Kliemannel M., Schwarz E., Willnow T.E., Hempstead B.L., Petersen C.M. Nature 427:843-848(2004) [PubMed: 14985763] [Abstract] Cited for: FUNCTION, INTERACTION WITH NGFB AND NGFR.
[21]	"ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin." Teng H.K., Teng K.K., Lee R., Wright S., Tevar S., Almeida R.D., Kermani P., Torkin R., Chen Z.-Y., Lee F.S., Kraemer R.T., Nykjaer A., Hempstead B.L. J. Neurosci. 25:5455-5463(2005) [PubMed: 15930396] [Abstract] Cited for: FUNCTION.
[22]	"Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway." Chen Z.-Y., Ieraci A., Teng H., Dall H., Meng C.-X., Herrera D.G., Nykjaer A., Hempstead B.L., Lee F.S. J. Neurosci. 25:6156-6166(2005) [PubMed: 15987945] [Abstract] Cited for: FUNCTION, INTERACTION WITH BDNF.
[23]	"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach." Lewandrowski U., Moebius J., Walter U., Sickmann A. Mol. Cell. Proteomics 5:226-233(2006) [PubMed: 16263699] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-162, MASS SPECTROMETRY. Tissue: Platelet.
[24]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-825, MASS SPECTROMETRY. Tissue: Platelet.
[25]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-162 AND ASN-163, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[26]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-825, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[27]	"Biological, clinical and population relevance of 95 loci for blood lipids." Teslovich T.M., Musunuru K., Smith A.V., Edmondson A.C., Stylianou I.M., Koseki M., Pirruccello J.P., Ripatti S., Chasman D.I., Willer C.J., Johansen C.T., Fouchier S.W., Isaacs A., Peloso G.M., Barbalic M., Ricketts S.L., Bis J.C., Aulchenko Y.S. , Thorleifsson G., Feitosa M.F., Chambers J., Orho-Melander M., Melander O., Johnson T., Li X., Guo X., Li M., Shin Cho Y., Jin Go M., Jin Kim Y., Lee J.Y., Park T., Kim K., Sim X., Twee-Hee Ong R., Croteau-Chonka D.C., Lange L.A., Smith J.D., Song K., Hua Zhao J., Yuan X., Luan J., Lamina C., Ziegler A., Zhang W., Zee R.Y., Wright A.F., Witteman J.C., Wilson J.F., Willemsen G., Wichmann H.E., Whitfield J.B., Waterworth D.M., Wareham N.J., Waeber G., Vollenweider P., Voight B.F., Vitart V., Uitterlinden A.G., Uda M., Tuomilehto J., Thompson J.R., Tanaka T., Surakka I., Stringham H.M., Spector T.D., Soranzo N., Smit J.H., Sinisalo J., Silander K., Sijbrands E.J., Scuteri A., Scott J., Schlessinger D., Sanna S., Salomaa V., Saharinen J., Sabatti C., Ruokonen A., Rudan I., Rose L.M., Roberts R., Rieder M., Psaty B.M., Pramstaller P.P., Pichler I., Perola M., Penninx B.W., Pedersen N.L., Pattaro C., Parker A.N., Pare G., Oostra B.A., O'Donnell C.J., Nieminen M.S., Nickerson D.A., Montgomery G.W., Meitinger T., McPherson R., McCarthy M.I., McArdle W., Masson D., Martin N.G., Marroni F., Mangino M., Magnusson P.K., Lucas G., Luben R., Loos R.J., Lokki M.L., Lettre G., Langenberg C., Launer L.J., Lakatta E.G., Laaksonen R., Kyvik K.O., Kronenberg F., Konig I.R., Khaw K.T., Kaprio J., Kaplan L.M., Johansson A., Jarvelin M.R., Janssens A.C., Ingelsson E., Igl W., Kees Hovingh G., Hottenga J.J., Hofman A., Hicks A.A., Hengstenberg C., Heid I.M., Hayward C., Havulinna A.S., Hastie N.D., Harris T.B., Haritunians T., Hall A.S., Gyllensten U., Guiducci C., Groop L.C., Gonzalez E., Gieger C., Freimer N.B., Ferrucci L., Erdmann J., Elliott P., Ejebe K.G., Doring A., Dominiczak A.F., Demissie S., Deloukas P., de Geus E.J., de Faire U., Crawford G., Collins F.S., Chen Y.D., Caulfield M.J., Campbell H., Burtt N.P., Bonnycastle L.L., Boomsma D.I., Boekholdt S.M., Bergman R.N., Barroso I., Bandinelli S., Ballantyne C.M., Assimes T.L., Quertermous T., Altshuler D., Seielstad M., Wong T.Y., Tai E.S., Feranil A.B., Kuzawa C.W., Adair L.S., Taylor H.A. Jr., Borecki I.B., Gabriel S.B., Wilson J.G., Holm H., Thorsteinsdottir U., Gudnason V., Krauss R.M., Mohlke K.L., Ordovas J.M., Munroe P.B., Kooner J.S., Tall A.R., Hegele R.A., Kastelein J.J., Schadt E.E., Rotter J.I., Boerwinkle E., Strachan D.P., Mooser V., Stefansson K., Reilly M.P., Samani N.J., Schunkert H., Cupples L.A., Sandhu M.S., Ridker P.M., Rader D.J., van Duijn C.M., Peltonen L., Abecasis G.R., Boehnke M., Kathiresan S. Nature 466:707-713(2010) [PubMed: 20686565] [Abstract] Cited for: INVOLVEMENT IN LDLCQ6.
[28]	"From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus." Musunuru K., Strong A., Frank-Kamenetsky M., Lee N.E., Ahfeldt T., Sachs K.V., Li X., Li H., Kuperwasser N., Ruda V.M., Pirruccello J.P., Muchmore B., Prokunina-Olsson L., Hall J.L., Schadt E.E., Morales C.R., Lund-Katz S., Phillips M.C. , Wong J., Cantley W., Racie T., Ejebe K.G., Orho-Melander M., Melander O., Koteliansky V., Fitzgerald K., Krauss R.M., Cowan C.A., Kathiresan S., Rader D.J. Nature 466:714-719(2010) [PubMed: 20686566] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO MYOCARDIAL INFARCTION.
[29]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]	"Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling." Vaegter C.B., Jansen P., Fjorback A.W., Glerup S., Skeldal S., Kjolby M., Richner M., Erdmann B., Nyengaard J.R., Tessarollo L., Lewin G.R., Willnow T.E., Chao M.V., Nykjaer A. Nat. Neurosci. 14:54-61(2011) [PubMed: 21102451] [Abstract] Cited for: INTERACTION WITH NTRK1.
[31]	"Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain." Quistgaard E.M., Madsen P., Groftehauge M.K., Nissen P., Petersen C.M., Thirup S.S. Nat. Struct. Mol. Biol. 16:96-98(2009) [PubMed: 19122660] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 78-756 IN COMPLEX WITH NTS, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-406 AND ASN-582.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X98248 mRNA. Translation: CAA66904.2.
FJ525881 Genomic DNA. Translation: ACN81319.1.
AL390252 Genomic DNA. Translation: CAI13180.1.
BC023542 mRNA. Translation: AAH23542.1.

IPI

IPI00217882.

RefSeq

NP_001192157.1. NM_001205228.1.
NP_002950.3. NM_002959.5.

UniGene

Hs.485195.
Hs.703487.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3F6K	X-ray	2.00	A	78-756	[»]
3G2U	X-ray	2.30	C/D	819-831	[»]
3G2V	X-ray	2.10	C/D	819-831	[»]

ProteinModelPortal

Q99523.

SMR

Q99523. Positions 88-749.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41798N.

IntAct

Q99523. 1 interaction.

MINT

MINT-197682.

STRING

Q99523.

PTM databases

PhosphoSite

Q99523.

Polymorphism databases

DMDM

84028263.

Proteomic databases

PRIDE

Q99523.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256637; ENSP00000256637; ENSG00000134243.

GeneID

6272.

KEGG

hsa:6272.

NMPDR

fig|9606.3.peg.1632.

UCSC

uc001dxm.1. human.

Organism-specific databases

CTD

6272.

GeneCards

GC01M109852.

H-InvDB

HIX0199828.

HGNC

HGNC:11186. SORT1.

HPA

CAB011498.
HPA006889.

MIM

602458. gene.
613589. phenotype.

neXtProt

NX_Q99523.

PharmGKB

PA36023.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12062.

GeneTree

ENSGT00510000046443.

HOGENOM

HBG443752.

HOVERGEN

HBG080235.

InParanoid

Q99523.

OMA

LTQMMYS.

OrthoDB

EOG4QVCBD.

PhylomeDB

Q99523.

Enzyme and pathway databases

Pathway_Interaction_DB

p75ntrpathway. p75(NTR)-mediated signaling.

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

Q99523.

Bgee

Q99523.

CleanEx

HS_SORT1.

Genevestigator

Q99523.

GermOnline

ENSG00000134243. Homo sapiens.

Family and domain databases

InterPro

IPR002860. BNR_rpt.
IPR006581. VPS10.
[Graphical view]

KO

K12388.

Pfam

PF02012. BNR. 4 hits.
[Graphical view]

SMART

SM00602. VPS10. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

24343.

SOURCE

Search...

Entry information

Entry name

SORT_HUMAN

Accession

Primary (citable) accession number: Q99523
Secondary accession number(s): C0JYZ0, Q8IZ49

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 20, 2005
Last modified:	January 25, 2012
This is version 114 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.