SNX6_PONAB
ID SNX6_PONAB Reviewed; 406 AA.
AC Q5R613;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Sorting nexin-6;
DE Contains:
DE RecName: Full=Sorting nexin-6, N-terminally processed;
GN Name=SNX6;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Involved in several stages of intracellular trafficking.
CC Interacts with membranes phosphatidylinositol 3,4-bisphosphate and/or
CC phosphatidylinositol 4,5-bisphosphate (Probable). Acts in part as
CC component of the retromer membrane-deforming SNX-BAR subcomplex. The
CC SNX-BAR retromer mediates retrograde transport of cargo proteins from
CC endosomes to the trans-Golgi network (TGN) and is involved in endosome-
CC to-plasma membrane transport for cargo protein recycling. The SNX-BAR
CC subcomplex functions to deform the donor membrane into a tubular
CC profile called endosome-to-TGN transport carrier (ETC). Does not have
CC in vitro vesicle-to-membrane remodeling activity. Involved in
CC retrograde endosome-to-TGN transport of lysosomal enzyme receptor
CC IGF2R. May function as link between transport vesicles and dynactin.
CC Negatively regulates retrograde transport of BACE1 from the cell
CC surface to the trans-Golgi network. Involved in E-cadherin sorting and
CC degradation; inhibits PIP5K1C-mediated E-cadherin degradation. In
CC association with GIT1 involved in EGFR degradation. Promotes lysosomal
CC degradation of CDKN1B. May contribute to transcription regulation (By
CC similarity). {ECO:0000250|UniProtKB:Q6P8X1,
CC ECO:0000250|UniProtKB:Q9UNH7}.
CC -!- SUBUNIT: Forms heterodimers with BAR domain-containing sorting nexins
CC SNX1 and SNX2. The heterodimers are proposed to self-assemble into
CC helical arrays on the membrane to stabilize and expand local membrane
CC curvature underlying endosomal tubule formation. Thought to be a
CC component of the originally described retromer complex (also called
CC SNX-BAR retromer) which is a pentamer containing the heterotrimeric
CC retromer cargo-selective complex (CSC), also described as vacuolar
CC protein sorting subcomplex (VPS), and a heterodimeric membrane-
CC deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also
CC called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes
CC associate with low affinity. Interacts with SNX1, SNX2, VPS26A, VPS29,
CC VPS35, TGFB receptors, BACE1, BRMS1, PIP5K1C. Interacts with DCTN1; the
CC association with DCTN1 is involved in movement of retromer-c ontaining
CC vesicles toward the TGN. Interacts with PIM1; translocating SNX6 to the
CC nucleus. Interacts with CDKN1B and GIT1. {ECO:0000250|UniProtKB:Q6P8X1,
CC ECO:0000250|UniProtKB:Q9UNH7}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000250|UniProtKB:Q9UNH7}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9UNH7}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9UNH7}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q9UNH7}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9UNH7}. Nucleus {ECO:0000250|UniProtKB:Q9UNH7}.
CC Note=Interaction with SNX1 or SNX2 promotes location at endosome
CC membranes (By similarity). Only a minor proportion is seen in the
CC nucleus (By similarity). {ECO:0000250|UniProtKB:Q9UNH7}.
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched in
CC phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-
CC bisphosphate. {ECO:0000250|UniProtKB:B1H267}.
CC -!- PTM: In vitro phosphorylated by PIM1; not affecting PIM1-dependent
CC nuclear translocation (By similarity). {ECO:0000250|UniProtKB:Q9UNH7}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR860687; CAH92803.1; -; mRNA.
DR RefSeq; NP_001126635.1; NM_001133163.1.
DR AlphaFoldDB; Q5R613; -.
DR SMR; Q5R613; -.
DR STRING; 9601.ENSPPYP00000006518; -.
DR GeneID; 100173633; -.
DR KEGG; pon:100173633; -.
DR CTD; 58533; -.
DR eggNOG; KOG1660; Eukaryota.
DR InParanoid; Q5R613; -.
DR OrthoDB; 1009572at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0030904; C:retromer complex; ISS:UniProtKB.
DR GO; GO:0097422; C:tubular endosome; ISS:UniProtKB.
DR GO; GO:0034452; F:dynactin binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS:UniProtKB.
DR CDD; cd07292; PX_SNX6; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR042136; PX_SNX6.
DR InterPro; IPR014637; SNX5/SNX6/SNX32.
DR InterPro; IPR028657; SNX6.
DR InterPro; IPR015404; Vps5_C.
DR PANTHER; PTHR45850:SF4; PTHR45850:SF4; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF09325; Vps5; 1.
DR PIRSF; PIRSF036924; Snx5_Snx6; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Cytoplasmic vesicle; Endosome; Lipid-binding;
KW Membrane; Nucleus; Phosphoprotein; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1..406
FT /note="Sorting nexin-6"
FT /id="PRO_0000423279"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT CHAIN 2..406
FT /note="Sorting nexin-6, N-terminally processed"
FT /id="PRO_0000213847"
FT DOMAIN 26..173
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 203..406
FT /note="BAR"
FT /evidence="ECO:0000305"
FT REGION 2..179
FT /note="Interaction with PIM1"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT REGION 182..199
FT /note="Membrane-binding amphipathic helix"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT BINDING 41..47
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT BINDING 100..106
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT BINDING 114..117
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT MOD_RES 2
FT /note="N-acetylmethionine; in Sorting nexin-6, N-terminally
FT processed"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
SQ SEQUENCE 406 AA; 46621 MW; 1E659DBFAC59E1BF CRC64;
MMEGLDDGPD FLSEEDRGLK AINVDLQSDA ALQVDISDAL SERDKVKFTV HTKSSLPNFK
QNEFSVVRQH EEFIWLHDSF VENEDYAGYI IPPAPPRPDF DASREKLQKL GEGEGSMTKE
EFTKMKQELE AEYLAIFKKT VAMHEVFLCR VAAHPILRKD LNFHVFLEYN QDLSVRGKNK
KEKLEDFFKN MVKSADGVIV SGVKDVDDFF EHERTFLLEY HNRVKDASAK SDRMTRSHKS
AADDYNRIGS SLYALGTQDS TDICKFFLKV SELFDKTRKI EARVSADEDL KLSDLLKYYL
RESQAAKDLL YRRSRSLVDY ENANKALDKA RAKNKDVLQA ETSQQLCCQK FEKISESAKQ
ELIDFKTRRV AAFRKNLVEL AELELKHAKG NLQLLQNCLA VLNGDT
