SORL_HUMAN » Sortilin-related receptor

SORL_HUMAN » Sortilin-related receptor
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Topology in Endosome membrane
Topologyendosome lumenal side
cytoplasmic side
SORL_HUMAN » Sortilin-related receptor » Low-density lipoprotein receptor relative with 11 ligand-binding repeats;LDLR relative with 11 ligand-binding repeats; LR11; SorLA-1;Sorting protein-related receptor containing LDLR class A repeats;SorLA;
Hydrophobic Thickness 33.2 ± 4.6 Å
Tilt Angle 35 ± 0°
ΔGtransfer -27.3 kcal/mol
ΔGfold -21.8 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 2136-2162 (2134-2165)
Pathways none
PDB 2dm4 (1651-1745), 3wsx (29-753), 3wsz (A=86-753), 3wsy (A=86-753, C=42-56), 3g2s (C/D=2202-2214), 3g2t (C/D=2202-2214)
OPM none
Complexes none
Interactions

FURIN, Complex: SORL:FURIN, PubMed

Domains

AA: 133-586, PDBID: 3WSX, Subunit A, Seq Identity:100%, Sortilin, neurotensin receptor 3,

AA: 588-752, PDBID: 3WSX, Subunit A, Seq Identity:100%, Sortilin, neurotensin receptor 3, C-terminal

AA: 844-884, PDBID: 3S2K, Subunit A, Seq Identity:47%, Low-density lipoprotein receptor repeat class B

AA: 888-929, PDBID: 3S94, Subunit B, Seq Identity:43%, Low-density lipoprotein receptor repeat class B

AA: 1076-1112, PDBID: 2M0P, Subunit A, Seq Identity:58%, Low-density lipoprotein receptor domain class A

AA: 1115-1153, PDBID: 2FYJ, Subunit A, Seq Identity:48%, Low-density lipoprotein receptor domain class A

AA: 1156-1192, PDBID: 1J8E, Subunit A, Seq Identity:60%, Low-density lipoprotein receptor domain class A

AA: 1197-1235, PDBID: 1N7D, Subunit A, Seq Identity:60%, Low-density lipoprotein receptor domain class A

AA: 1233-1271, PDBID: 2XRC, Subunit D, Seq Identity:46%, Low-density lipoprotein receptor domain class A

AA: 1323-1359, PDBID: 1J8E, Subunit A, Seq Identity:56%, Low-density lipoprotein receptor domain class A

AA: 1366-1403, PDBID: 2FYJ, Subunit A, Seq Identity:57%, Low-density lipoprotein receptor domain class A

AA: 1417-1453, PDBID: 1N7D, Subunit A, Seq Identity:50%, Low-density lipoprotein receptor domain class A

AA: 1469-1506, PDBID: 1AJJ, Subunit A, Seq Identity:50%, Low-density lipoprotein receptor domain class A

AA: 1512-1549, PDBID: 1AJJ, Subunit A, Seq Identity:55%, Low-density lipoprotein receptor domain class A

AA: 1556-1633, PDBID: 2EE3, Subunit A, Seq Identity:28%, Fibronectin type III domain

AA: 1652-1735, PDBID: 2DM4, Subunit A, Seq Identity:100%, Fibronectin type III domain

AA: 1933-2014, PDBID: 2EE3, Subunit A, Seq Identity:27%, Fibronectin type III domain

UniProt annotation for SORL_HUMAN » Sortilin-related receptor
FUNCTION: Likely to be a multifunctional endocytic receptor, that may be implicated in the uptake of lipoproteins and of proteases. Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. Binds the receptor- associated protein (RAP). Could play a role in cell-cell interaction. Involved in APP trafficking to and from the Golgi apparatus. It probably acts as a sorting receptor that protects APP from trafficking to late endosome and from processing into amyloid beta, thereby reducing the burden of amyloidogenic peptide formation. Involved in the regulation of smooth muscle cells migration, probably through PLAUR binding and decreased internalization.

SUBUNIT: Interacts with GGA1 and ROCK2. Interacts with PLAUR. Interacts with APP.

TISSUE SPECIFICITY: Expressed mainly in brain, where it is most abundant in the cerebellum, cerebral cortex and the occipital pole; low expression in the putamen and the thalamus. Expression is significantly reduced in the frontal cortex of patients suffering from Alzheimer disease. According to PubMed, found in spinal cord, testis, liver, kidney and pancreas with detectable levels in placenta, lung and heart. According to PubMed, expressed in the prostate, ovary, thyroid and spleen, but not found in kidney, liver, lung, skeletal muscle, bone marrow and adrenals.

DISEASE: Alzheimer disease (AD) OMIM: Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta- APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. Note=The gene represented in this entry is involved in disease pathogenesis.

UniProt features for SORL_HUMAN » Sortilin-related receptor
SIGNAL 1 28 Potential.
PROPEP 29 81 Removed in mature form.
CHAIN 82 2214 Sortilin-related receptor.
REPEAT 136 147 BNR 1.
REPEAT 232 243 BNR 2.
REPEAT 441 452 BNR 3.
REPEAT 521 532 BNR 4.
REPEAT 562 573 BNR 5.
REPEAT 800 843 LDL-receptor class B 1.
REPEAT 844 887 LDL-receptor class B 2.
REPEAT 888 932 LDL-receptor class B 3.
REPEAT 933 970 LDL-receptor class B 4.
REPEAT 971 1013 LDL-receptor class B 5.
DOMAIN 1026 1072 EGF-like.
DOMAIN 1076 1114 LDL-receptor class A 1.
DOMAIN 1115 1155 LDL-receptor class A 2.
DOMAIN 1156 1194 LDL-receptor class A 3.
DOMAIN 1198 1236 LDL-receptor class A 4.
DOMAIN 1238 1272 LDL-receptor class A 5.
DOMAIN 1273 1317 LDL-receptor class A 6.
DOMAIN 1323 1361 LDL-receptor class A 7.
DOMAIN 1366 1405 LDL-receptor class A 8.
DOMAIN 1417 1455 LDL-receptor class A 9.
DOMAIN 1469 1508 LDL-receptor class A 10.
DOMAIN 1512 1551 LDL-receptor class A 11.
DOMAIN 1554 1646 Fibronectin type-III 1.
DOMAIN 1651 1742 Fibronectin type-III 2.
DOMAIN 1749 1838 Fibronectin type-III 3.
DOMAIN 1843 1927 Fibronectin type-III 4.
DOMAIN 1934 2023 Fibronectin type-III 5.
DOMAIN 2024 2118 Fibronectin type-III 6.
MOTIF 63 65 Cell attachment site (Potential).
MOTIF 2172 2177 Endocytosis signal (Potential).
DISULFID 1078 1090 By similarity.
DISULFID 1085 1103 By similarity.
DISULFID 1097 1112 By similarity.
DISULFID 1117 1131 By similarity.
DISULFID 1125 1144 By similarity.
DISULFID 1138 1153 By similarity.
DISULFID 1158 1170 By similarity.
DISULFID 1165 1183 By similarity.
DISULFID 1177 1192 By similarity.
DISULFID 1199 1211 By similarity.
DISULFID 1206 1224 By similarity.
DISULFID 1218 1235 By similarity.
DISULFID 1239 1249 By similarity.
DISULFID 1244 1262 By similarity.
DISULFID 1256 1271 By similarity.
DISULFID 1275 1289 By similarity.
DISULFID 1283 1302 By similarity.
DISULFID 1296 1315 By similarity.
DISULFID 1325 1337 By similarity.
DISULFID 1332 1350 By similarity.
DISULFID 1344 1359 By similarity.
DISULFID 1368 1381 By similarity.
DISULFID 1376 1394 By similarity.
DISULFID 1388 1403 By similarity.
DISULFID 1419 1431 By similarity.
DISULFID 1426 1444 By similarity.
DISULFID 1438 1453 By similarity.
DISULFID 1471 1484 By similarity.
DISULFID 1478 1497 By similarity.
DISULFID 1491 1506 By similarity.
DISULFID 1514 1527 By similarity.
DISULFID 1521 1540 By similarity.
DISULFID 1534 1549 By similarity.
Amino Acid Sequence for SORL_HUMAN » Sortilin-related receptor
MATRSSRRES RLPFLFTLVA LLPPGALCEV WTQRLHGGSA PLPQDRGFLV VQGDPRELRL WARGDARGAS RADEKPLRRK RSAALQPEPI KVYGQVSLND SHNQMVVHWA GEKSNVIVAL ARDSLALARP KSSDVYVSYD YGKSFKKISD KLNFGLGNRS EAVIAQFYHS PADNKRYIFA DAYAQYLWIT FDFCNTLQGF SIPFRAADLL LHSKASNLLL GFDRSHPNKQ LWKSDDFGQT WIMIQEHVKS FSWGIDPYDK PNTIYIERHE PSGYSTVFRS TDFFQSRENQ EVILEEVRDF QLRDKYMFAT KVVHLLGSEQ QSSVQLWVSF GRKPMRAAQF VTRHPINEYY IADASEDQVF VCVSHSNNRT NLYISEAEGL KFSLSLENVL YYSPGGAGSD TLVRYFANEP FADFHRVEGL QGVYIATLIN GSMNEENMRS VITFDKGGTW EFLQAPAFTG YGEKINCELS QGCSLHLAQR LSQLLNLQLR RMPILSKESA PGLIIATGSV GKNLASKTNV YISSSAGARW REALPGPHYY TWGDHGGIIT AIAQGMETNE LKYSTNEGET WKTFIFSEKP VFVYGLLTEP GEKSTVFTIF GSNKENVHSW LILQVNATDA LGVPCTENDY KLWSPSDERG NECLLGHKTV FKRRTPHATC FNGEDFDRPV VVSNCSCTRE DYECDFGFKM SEDLSLEVCV PDPEFSGKSY SPPVPCPVGS TYRRTRGYRK ISGDTCSGGD VEARLEGELV PCPLAEENEF ILYAVRKSIY RYDLASGATE QLPLTGLRAA VALDFDYEHN CLYWSDLALD VIQRLCLNGS TGQEVIINSG LETVEALAFE PLSQLLYWVD AGFKKIEVAN PDGDFRLTIV NSSVLDRPRA LVLVPQEGVM FWTDWGDLKP GIYRSNMDGS AAYHLVSEDV KWPNGISVDD QWIYWTDAYL ECIERITFSG QQRSVILDNL PHPYAIAVFK NEIYWDDWSQ LSIFRASKYS GSQMEILANQ LTGLMDMKIF YKGKNTGSNA CVPRPCSLLC LPKANNSRSC RCPEDVSSSV LPSGDLMCDC PQGYQLKNNT CVKEENTCLR NQYRCSNGNC INSIWWCDFD NDCGDMSDER NCPTTICDLD TQFRCQESGT CIPLSYKCDL EDDCGDNSDE SHCEMHQCRS DEYNCSSGMC IRSSWVCDGD NDCRDWSDEA NCTAIYHTCE ASNFQCRNGH CIPQRWACDG DTDCQDGSDE DPVNCEKKCN GFRCPNGTCI PSSKHCDGLR DCSDGSDEQH CEPLCTHFMD FVCKNRQQCL FHSMVCDGII QCRDGSDEDA AFAGCSQDPE FHKVCDEFGF QCQNGVCISL IWKCDGMDDC GDYSDEANCE NPTEAPNCSR YFQFRCENGH CIPNRWKCDR ENDCGDWSDE KDCGDSHILP FSTPGPSTCL PNYYRCSSGT CVMDTWVCDG YRDCADGSDE EACPLLANVT AASTPTQLGR CDRFEFECHQ PKTCIPNWKR CDGHQDCQDG RDEANCPTHS TLTCMSREFQ CEDGEACIVL SERCDGFLDC SDESDEKACS DELTVYKVQN LQWTADFSGD VTLTWMRPKK MPSASCVYNV YYRVVGESIW KTLETHSNKT NTVLKVLKPD TTYQVKVQVQ CLSKAHNTND FVTLRTPEGL PDAPRNLQLS LPREAEGVIV GHWAPPIHTH GLIREYIVEY SRSGSKMWAS QRAASNFTEI KNLLVNTLYT VRVAAVTSRG IGNWSDSKSI TTIKGKVIPP PDIHIDSYGE NYLSFTLTME SDIKVNGYVV NLFWAFDTHK QERRTLNFRG SILSHKVGNL TAHTSYEISA WAKTDLGDSP LAFEHVMTRG VRPPAPSLKA KAINQTAVEC TWTGPRNVVY GIFYATSFLD LYRNPKSLTT SLHNKTVIVS KDEQYLFLVR VVVPYQGPSS DYVVVKMIPD SRLPPRHLHV VHTGKTSVVI KWESPYDSPD QDLLYAIAVK DLIRKTDRSY KVKSRNSTVE YTLNKLEPGG KYHIIVQLGN MSKDSSIKIT TVSLSAPDAL KIITENDHVL LFWKSLALKE KHFNESRGYE IHMFDSAMNI TAYLGNTTDN FFKISNLKMG HNYTFTVQAR CLFGNQICGE PAILLYDELG SGADASATQA ARSTDVAAVV VPILFLILLS LGVGFAILYT KHRRLQSSFT AFANSHYSSR LGSAIFSSGD DLGEDDEDAP MITGFSDDVP MVIA