Reviewed, UniProtKB/Swiss-Prot O54861 (SORT_RAT)

Names and origin

Protein names

Recommended name:
    Sortilin
Alternative name(s):
    Neurotensin receptor 3
      Short name=NTR3
    Glycoprotein 110
      Short name=Gp110

Gene names

Name:

Sort1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	825 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.4
Subunit structure	Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP and GM2A, LPL, PSAP and SLC2A4. Forms a complex with NGFR which binds specifically to the precursor form of NGFB (proNGFB) By similarity. Interacts with the precursor form of BDNF (proBDNF).
Subcellular location	Membrane; Single-pass type I membrane protein Potential. 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 endosomes, Golgi stack, lysosomes and nucleus. Localization to the plasma membrane in adipocytes is enhanced by insulin By similarity. Localized to the endoplasmic reticulum and the plasma membrane. Also found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes.
Tissue specificity	Highly expressed in fat, brain, and lung. Expressed in neuronal bodies and dendrites of the piriform cortex and hippocampus. Also expressed in the islands of Calleja, medial and lateral septal nuclei, amygdaloid nuclei, thalamic nuclei, the supraoptic nucleus, the substantia nigra, the Purkinje layer of the cerebellar cortex and the cranial motor nerve nuclei of the brainstem. Ref.3 Ref.5
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 By similarity. The extracellular domain may be shed following protease cleavage in some cell types By similarity.
Post-translational modification	The N-terminal propeptide is cleaved by furin and possibly other homologous proteases By similarity. Contains 8 intrachain disulfide bonds By similarity. N-glycosylated By similarity.
Sequence similarities	Contains 9 BNR repeats.

Ontologies

Keywords
Biological process	Differentiation Endocytosis Osteogenesis Transport
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Lysosome Membrane Nucleus
Domain	Repeat Signal Transmembrane
Molecular function	Developmental protein Receptor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW endocytosis Inferred from electronic annotation. Source: UniProtKB-KW intracellular protein transport Ref.2 Non-traceable author statement. Source: RGD ossification Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell soma Ref.5 Inferred from direct assay. Source: RGD dendrite Ref.5 Inferred from direct assay. Source: RGD endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Ref.5 Inferred from direct assay. Source: RGD lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Ref.2 Inferred from direct assay. Source: RGD nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Ref.2 Inferred from direct assay. Source: RGD
Molecular function	neurotensin receptor activity, G-protein coupled Ref.5 Traceable author statement. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Potential
	Propeptide	32 – 75	44	Removed in mature form By similarity		PRO_0000045157
	Chain	76 – 825	750	Sortilin		PRO_0000045158
Regions
	Topological domain	76 – 754	679	Extracellular Potential
	Transmembrane	755 – 775	21	Potential
	Topological domain	776 – 825	50	Cytoplasmic Potential
	Repeat	143 – 154	12	BNR 1
	Repeat	196 – 207	12	BNR 2
	Repeat	238 – 249	12	BNR 3
	Repeat	285 – 296	12	BNR 4
	Repeat	326 – 337	12	BNR 5
	Repeat	375 – 386	12	BNR 6
	Repeat	426 – 437	12	BNR 7
	Repeat	504 – 515	12	BNR 8
	Repeat	546 – 557	12	BNR 9
	Region	48 – 59	12	Intrachain binding of the propeptide and the extracellular domain By similarity
	Region	610 – 754	145	Interactions with LRPAP1 and NGFB By similarity
	Region	777 – 825	49	Golgi to endosome transport and interactions with GGA1 and GGA2 By similarity
	Motif	785 – 790	6	Endocytosis signal Potential
	Compositional bias	38 – 44	7	Poly-Pro
Amino acid modifications
	Modified residue	819	1	Phosphoserine By similarity
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	160	1	N-linked (GlcNAc...) Potential
	Glycosylation	272	1	N-linked (GlcNAc...) Potential
	Glycosylation	404	1	N-linked (GlcNAc...) Potential
	Glycosylation	580	1	N-linked (GlcNAc...) Potential
	Glycosylation	682	1	N-linked (GlcNAc...) Potential
	Disulfide bond	84 ↔ 554		By similarity
	Disulfide bond	255 ↔ 275		By similarity
	Disulfide bond	446 ↔ 456		By similarity
	Disulfide bond	610 ↔ 649		By similarity
	Disulfide bond	632 ↔ 664		By similarity
	Disulfide bond	666 ↔ 721		By similarity
	Disulfide bond	673 ↔ 686		By similarity
	Disulfide bond	700 ↔ 738		By similarity
Experimental info
	Sequence conflict	91	1	I → V in AAC02932. Ref.2
	Sequence conflict	276 – 277	2	KA → T in AAB81864. Ref.3
	Sequence conflict	433	1	G → R in AAB81864. Ref.3
	Sequence conflict	507	1	D → Y in AAC02932. Ref.2
	Sequence conflict	659	1	K → Q AA sequence Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O54861-1 [UniParc]. Last modified December 20, 2005. Version 3. Checksum: 060B43A54993EF06	FASTA	825	91,169
	10 20 30 40 50 60 MERPRGAADG LLRWPLGLLL LLQLLPPAAV GQDRLDAPPP PAPPLLRWAG PVGVSWGLRA 70 80 90 100 110 120 AAPGGPVPRA GRWRRGAPAE DQDCGRLPDF IAKLTNNTHQ HVFDDLSGSV SLSWVGDSTG 130 140 150 160 170 180 VILVLTTFQV PLVIVSFGQS KLYRSEDYGK NFKDITNLIN NTFIRTEFGM AIGPENSGKV 190 200 210 220 230 240 ILTAEVSGGS RGGRVFRSSD FAKNFVQTDL PFHPLTQMMY SPQNSDYLLA LSTENGLWVS 250 260 270 280 290 300 KNFGEKWEEI HKAVCLAKWG PNNIIFFTTH VNGSCKADLG ALELWRTSDL GKTFKTIGVK 310 320 330 340 350 360 IYSFGLGGRF LFASVMADKD TTRRIHVSTD QGDTWSMAQL PSVGQEQFYS ILAANDDMVF 370 380 390 400 410 420 MHVDEPGDTG FGTIFTSDDR GIVYSKSLDR HLYTTTGGET DFTNVTSLRG VYITSTLSED 430 440 450 460 470 480 NSIQSMITFD QGGRWEHLQK PENSKCDATA KNKNECSLHI HASYSISQKL NVPMAPLSEP 490 500 510 520 530 540 NAVGIVIAHG SVGDAISVMV PDVYISDDGG YSWAKMLEGP HYYTILDSGG IIVAIEHSNR 550 560 570 580 590 600 PINVIKFSTD EGQCWQSYVF SQEPVYFTGL ASEPGARSMN ISIWGFTESF LTRQWVSYTI 610 620 630 640 650 660 DFKDILERNC EENDYTTWLA HSTDPGDYKD GCILGYKEQF LRLRKSSVCQ NGRDYVVAKQ 670 680 690 700 710 720 PSICPCSLED FLCDFGYFRP ENASECVEQP ELKGHELEFC LYGKEEHLTT NGYRKIPGDR 730 740 750 760 770 780 CQGGMNPARE VKDLKKKCTS NFLNPKKQNS KSSSVPIILA IVGLMLVTVV AGVLIVKKYV 790 800 810 820 CGGRFLVHRY SVLQQHAEAD GVEALDTASH AKSGYHDDSD EDLLE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed: 15057822] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[2]	"Sortilin is the major 110-kDa protein in GLUT4 vesicles from adipocytes." Morris N.J., Ross S.A., Lane W.S., Moestrup S.K., Petersen C.M., Keller S.R., Lienhard G.E. J. Biol. Chem. 273:3582-3587(1998) [PubMed: 9452485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 89-825, PROTEIN SEQUENCE OF 78-93, PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION. Strain: Sprague-Dawley. Tissue: Adipocyte.
[3]	"Sortilin is a major protein component of Glut4-containing vesicles." Lin B.-Z., Pilch P.F., Kandror K.V. J. Biol. Chem. 272:24145-24147(1997) [PubMed: 9305862] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 121-745, PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Skeletal muscle.
[4]	"The prodomain of a secreted hydrophobic mini-protein facilitates its export from the endoplasmic reticulum by hitchhiking on sorting receptors." Conticello S.G., Kowalsman N.D., Jacobsen C., Yudkovsky G., Sato K., Elazar Z., Petersen C.M., Aronheim A., Fainzilber M. J. Biol. Chem. 278:26311-26314(2003) [PubMed: 12771154] [Abstract] Cited for: FUNCTION.
[5]	"Distribution of NTS3 receptor/sortilin mRNA and protein in the rat central nervous system." Sarret P., Krzywkowski P., Segal L., Nielsen M.S., Petersen C.M., Mazella J., Stroh T., Beaudet A. J. Comp. Neurol. 461:483-505(2003) [PubMed: 12746864] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"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: INTERACTION WITH BDNF.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AABR03012291 Genomic DNA. No translation available. AABR03012896 Genomic DNA. No translation available. AABR03017724 Genomic DNA. No translation available. AABR03019134 Genomic DNA. No translation available. AABR03020083 Genomic DNA. No translation available. AF019109 mRNA. Translation: AAC02932.1. AF023621 mRNA. Translation: AAB81864.1.
IPI	IPI00373408.
RefSeq	NP_113955.1.
UniGene	Rn.11286
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSRNOG00000031814. Rattus norvegicus. [Contig view]
GeneID	83576.
KEGG	rno:83576.
Organism-specific databases
RGD	619999. Sort1.
Phylogenomic databases
HOVERGEN	O54861.
OMA	O54861. LTQMMYS.
Gene expression databases
ArrayExpress	O54861.
GermOnline	ENSRNOG00000031814. Rattus norvegicus.
Family and domain databases
InterPro	IPR006581. VPS10. [Graphical view]
SMART	SM00602. VPS10. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	616085.

Entry information

Entry name

SORT_RAT

Accession

Primary (citable) accession number: O54861
Secondary accession number(s): O35389

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 20, 2005
Last modified:	June 16, 2009
This is version 71 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)