SORT_HUMAN » Sortilin

SORT_HUMAN » Sortilin
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Topology in Golgi apparatus membrane
TopologyGolgi lumenal side
cytoplasmic side
SORT_HUMAN » Sortilin » 100 kDa NT receptor;Glycoprotein 95;Gp95; Neurotensin receptor 3;NT3; NTR3;
Hydrophobic Thickness 34.4 ± 3.8 Å
Tilt Angle 22 ± 4°
ΔGtransfer -27.2 kcal/mol
ΔGfold -18.8 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome, HMDB
Topology Out
TM Segments 756-781 (756-781)
Pathways

Lysosome (KEGG)

Membrane Trafficking (Reactome)

Neurotrophin signaling pathway (KEGG)

PDB 4msl (78-756), 4n7e (78-756), 3f6k (A=78-756), 4po7 (A=78-756), 3g2u (C/D=819-831), 3g2v (C/D=819-831)
OPM none
Complexes none
Interactions

NTRK1, Complex: NTRK1:SORT, PubMed

NTRK2, Complex: NTRK2:SORT, PubMed

NTRK3, Complex: NTRK3:SORT, PubMed

SORC1, Complex: SORT:SORC1, PubMed

TNR16, Complex: SORT:TNR16, PubMed

Domains

AA: 142-572, PDBID: 3F6K, Subunit A, Seq Identity:100%, Sortilin, neurotensin receptor 3,

AA: 574-740, PDBID: 3F6K, Subunit A, Seq Identity:100%, Sortilin, neurotensin receptor 3, C-terminal

UniProt annotation for SORT_HUMAN » Sortilin
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.

SUBUNIT: 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.

TISSUE SPECIFICITY: 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.

INDUCTION: During osteoblast differentiation.

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.

DOMAIN: The extracellular domain may be shed following protease cleavage in some cell types.

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.

UniProt features for SORT_HUMAN » Sortilin
SIGNAL 1 33 Potential.
PROPEP 34 77 Removed in mature form.
CHAIN 78 831 Sortilin.
REPEAT 145 156 BNR 1.
REPEAT 198 209 BNR 2.
REPEAT 240 251 BNR 3.
REPEAT 287 298 BNR 4.
REPEAT 328 339 BNR 5.
REPEAT 377 388 BNR 6.
REPEAT 428 439 BNR 7.
REPEAT 506 517 BNR 8.
REPEAT 548 559 BNR 9.
REGION 50 61 Intrachain binding of the propeptide and the extracellular domain.
REGION 612 756 Interactions with LRPAP1 and NGFB.
REGION 779 831 Golgi to endosome transport and interactions with GGA1 and GGA2.
MOTIF 787 792 Endocytosis signal (Probable).
DISULFID 86 556
DISULFID 257 277
DISULFID 448 458
DISULFID 612 651
DISULFID 634 666
DISULFID 668 723
DISULFID 675 688
DISULFID 702 740
Amino Acid Sequence for SORT_HUMAN » Sortilin
MERPWGAADG LSRWPHGLGL LLLLQLLPPS TLSQDRLDAP PPPAAPLPRW SGPIGVSWGL RAAAAGGAFP RGGRWRRSAP GEDEECGRVR DFVAKLANNT HQHVFDDLRG SVSLSWVGDS TGVILVLTTF HVPLVIMTFG QSKLYRSEDY GKNFKDITDL INNTFIRTEF GMAIGPENSG KVVLTAEVSG GSRGGRIFRS SDFAKNFVQT DLPFHPLTQM MYSPQNSDYL LALSTENGLW VSKNFGGKWE EIHKAVCLAK WGSDNTIFFT TYANGSCKAD LGALELWRTS DLGKSFKTIG VKIYSFGLGG RFLFASVMAD KDTTRRIHVS TDQGDTWSMA QLPSVGQEQF YSILAANDDM VFMHVDEPGD TGFGTIFTSD DRGIVYSKSL DRHLYTTTGG ETDFTNVTSL RGVYITSVLS EDNSIQTMIT FDQGGRWTHL RKPENSECDA TAKNKNECSL HIHASYSISQ KLNVPMAPLS EPNAVGIVIA HGSVGDAISV MVPDVYISDD GGYSWTKMLE GPHYYTILDS GGIIVAIEHS SRPINVIKFS TDEGQCWQTY TFTRDPIYFT GLASEPGARS MNISIWGFTE SFLTSQWVSY TIDFKDILER NCEEKDYTIW LAHSTDPEDY EDGCILGYKE QFLRLRKSSV CQNGRDYVVT KQPSICLCSL EDFLCDFGYY RPENDSKCVE QPELKGHDLE FCLYGREEHL TTNGYRKIPG DKCQGGVNPV REVKDLKKKC TSNFLSPEKQ NSKSNSVPII LAIVGLMLVT VVAGVLIVKK YVCGGRFLVH RYSVLQQHAE ANGVDGVDAL DTASHTNKSG YHDDSDEDLL E