SNX27_RAT
ID SNX27_RAT Reviewed; 539 AA.
AC Q8K4V4; Q8K4T6;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Sorting nexin-27;
DE AltName: Full=MAP-responsive gene protein;
DE AltName: Full=Methamphetamine-responsive transcript 1 protein;
DE AltName: Full=PDZ-protein Mrt1;
GN Name=Snx27; Synonyms=Mrt1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP INDUCTION.
RC STRAIN=Wistar; TISSUE=Brain cortex;
RX PubMed=12740601; DOI=10.1038/sj.mp.4001258;
RA Kajii Y., Muraoka S., Hiraoka S., Fujiyama K., Umino A., Nishikawa T.;
RT "A developmentally regulated and psychostimulant-inducible novel rat gene
RT mrt1 encoding PDZ-PX proteins isolated in the neocortex.";
RL Mol. Psychiatry 8:434-444(2003).
RN [2]
RP FUNCTION.
RX PubMed=18690037; DOI=10.4161/chan.5191;
RA Nassirpour R., Slesinger P.A.;
RT "Subunit-specific regulation of Kir3 channels by sorting nexin 27.";
RL Channels 1:331-333(2007).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=17351151; DOI=10.1074/mcp.m700047-mcp200;
RA Rincon E., Santos T., Avila-Flores A., Albar J.P., Lalioti V., Lei C.,
RA Hong W., Merida I.;
RT "Proteomics identification of sorting nexin 27 as a diacylglycerol kinase
RT zeta-associated protein: new diacylglycerol kinase roles in endocytic
RT recycling.";
RL Mol. Cell. Proteomics 6:1073-1087(2007).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH KCNJ6 AND KCNJ9, TISSUE
RP SPECIFICITY, PHOSPHATIDYLINOSITOL-3-PHOSPHATE-BINDING, AND MUTAGENESIS OF
RP LYS-220.
RX PubMed=17828261; DOI=10.1038/nn1953;
RA Lunn M.L., Nassirpour R., Arrabit C., Tan J., McLeod I., Arias C.M.,
RA Sawchenko P.E., Yates J.R. III, Slesinger P.A.;
RT "A unique sorting nexin regulates trafficking of potassium channels via a
RT PDZ domain interaction.";
RL Nat. Neurosci. 10:1249-1259(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) OF 36-133 IN COMPLEX WITH KCNJ9,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH KCNJ9, AND
RP MUTAGENESIS OF TYR-51.
RX PubMed=21422294; DOI=10.1073/pnas.1018645108;
RA Balana B., Maslennikov I., Kwiatkowski W., Stern K.M., Bahima L., Choe S.,
RA Slesinger P.A.;
RT "Mechanism underlying selective regulation of G protein-gated inwardly
RT rectifying potassium channels by the psychostimulant-sensitive sorting
RT nexin 27.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:5831-5836(2011).
CC -!- FUNCTION: Involved in the retrograde transport from endosome to plasma
CC membrane, a trafficking pathway that promotes the recycling of
CC internalized transmembrane proteins. Following internalization,
CC endocytosed transmembrane proteins are delivered to early endosomes and
CC recycled to the plasma membrane instead of being degraded in lysosomes.
CC SNX27 specifically binds and directs sorting of a subset of
CC transmembrane proteins containing a PDZ-binding motif at the C-
CC terminus: following interaction with target transmembrane proteins,
CC associates with the retromer complex, preventing entry into the
CC lysosomal pathway, and promotes retromer-tubule based plasma membrane
CC recycling. SNX27 also binds with the WASH complex. Interacts with
CC membranes containing phosphatidylinositol-3-phosphate (PtdIns(3P)). May
CC participate in establishment of natural killer cell polarity. Recruits
CC CYTIP to early endosomes. {ECO:0000269|PubMed:17828261,
CC ECO:0000269|PubMed:18690037}.
CC -!- SUBUNIT: Core component of the SNX27-retromer, a multiprotein complex
CC composed of SNX27, the WASH complex and the retromer complex. Interacts
CC (via PDZ domain) with a number of target transmembrane proteins (via
CC PDZ-binding motif): ABCC4, ADRB2, ARHGEF7, GRIA1, GRIA2, GRIN1, GRIN2A
CC GRIN2C, KCNJ6, KCNJ9 and SLC2A1/GLUT1. Interacts (via the FERM-like
CC regions) with the WASH complex. Interacts with SNX1. Interacts with
CC CYTIP. Interacts with DGKZ. Interacts with MCC.
CC {ECO:0000269|PubMed:17828261, ECO:0000269|PubMed:21422294}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane; Peripheral membrane
CC protein. Cytoplasm, cytosol. Note=Localizes to immunological synapse in
CC T-cells. In T-cells, recruited from the cytosol to sorting endosomes by
CC phosphoinositide-3-kinase products (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Mrt1alpha, Mrt1a, SNX27a;
CC IsoId=Q8K4V4-1; Sequence=Displayed;
CC Name=2; Synonyms=Mrt1beta, Mrt1b, SNX27b;
CC IsoId=Q8K4V4-2; Sequence=VSP_030541;
CC -!- TISSUE SPECIFICITY: Isoform 1 is predominantly expressed in the testis,
CC whereas isoform 2 is predominant in various brain regions, including,
CC neocortex, paleocortex, striatum, hippocampus, cerebellum and brain
CC stem. Expressed in cells of hematopoietic origin.
CC {ECO:0000269|PubMed:12740601, ECO:0000269|PubMed:17351151,
CC ECO:0000269|PubMed:17828261, ECO:0000269|PubMed:21422294}.
CC -!- INDUCTION: [Isoform 2]: Up-regulated by methamphetamine and cocaine in
CC the neocortex, but not by pentobarbital nor by D1 antagonist.
CC {ECO:0000269|PubMed:12740601}.
CC -!- DOMAIN: The PDZ domain mediates binding to a subset of proteins
CC containing a PDZ-binding motif at the C-terminus: the specificity for
CC PDZ-binding motif is provided by the 2 residues located upstream of the
CC canonical PDZ-binding motif (PubMed:17828261, PubMed:21422294). The PDZ
CC domain also mediates binding to the retromer complex via direct
CC interaction with VPS26 (VPS26A or VPS26B).
CC {ECO:0000269|PubMed:17828261, ECO:0000269|PubMed:21422294}.
CC -!- DOMAIN: The PX domain mediates binding to phosphatidylinositol 3-
CC phosphate (PtdIns(3P)) and localization to early endosome membranes.
CC {ECO:0000269|PubMed:17828261}.
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DR EMBL; AB010245; BAC10332.1; -; mRNA.
DR EMBL; AB051816; BAC10333.1; -; mRNA.
DR RefSeq; NP_001103621.1; NM_001110151.1.
DR RefSeq; NP_690060.2; NM_152847.2.
DR PDB; 3QDO; X-ray; 1.88 A; A=39-133.
DR PDB; 3QE1; X-ray; 1.68 A; A=39-133.
DR PDB; 3QGL; X-ray; 3.31 A; A/B/C/D/E=39-133.
DR PDB; 4P2A; X-ray; 2.70 A; B=39-133.
DR PDB; 4Z8J; X-ray; 0.95 A; A=39-133.
DR PDB; 5ELQ; X-ray; 1.10 A; A/B=39-133.
DR PDB; 5EM9; X-ray; 1.60 A; A=39-133.
DR PDB; 5EMA; X-ray; 1.32 A; A=39-133.
DR PDB; 5EMB; X-ray; 0.85 A; A=39-133.
DR PDBsum; 3QDO; -.
DR PDBsum; 3QE1; -.
DR PDBsum; 3QGL; -.
DR PDBsum; 4P2A; -.
DR PDBsum; 4Z8J; -.
DR PDBsum; 5ELQ; -.
DR PDBsum; 5EM9; -.
DR PDBsum; 5EMA; -.
DR PDBsum; 5EMB; -.
DR AlphaFoldDB; Q8K4V4; -.
DR SMR; Q8K4V4; -.
DR BioGRID; 251741; 1.
DR STRING; 10116.ENSRNOP00000067026; -.
DR iPTMnet; Q8K4V4; -.
DR PhosphoSitePlus; Q8K4V4; -.
DR jPOST; Q8K4V4; -.
DR PaxDb; Q8K4V4; -.
DR PRIDE; Q8K4V4; -.
DR GeneID; 260323; -.
DR KEGG; rno:260323; -.
DR UCSC; RGD:628705; rat. [Q8K4V4-1]
DR CTD; 81609; -.
DR RGD; 628705; Snx27.
DR eggNOG; KOG3784; Eukaryota.
DR InParanoid; Q8K4V4; -.
DR OrthoDB; 395943at2759; -.
DR PhylomeDB; Q8K4V4; -.
DR EvolutionaryTrace; Q8K4V4; -.
DR PRO; PR:Q8K4V4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0001772; C:immunological synapse; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IPI:RGD.
DR GO; GO:0035091; F:phosphatidylinositol binding; IBA:GO_Central.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEP:RGD.
DR GO; GO:0032456; P:endocytic recycling; ISS:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; IMP:UniProtKB.
DR GO; GO:0099638; P:endosome to plasma membrane protein transport; IMP:RGD.
DR GO; GO:0061951; P:establishment of protein localization to plasma membrane; IMP:RGD.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:1903609; P:negative regulation of inward rectifier potassium channel activity; IDA:RGD.
DR GO; GO:0007399; P:nervous system development; NAS:RGD.
DR GO; GO:1904719; P:positive regulation of AMPA glutamate receptor clustering; IMP:RGD.
DR GO; GO:1904313; P:response to methamphetamine hydrochloride; IEP:RGD.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR CDD; cd13338; FERM-like_C_SNX27; 1.
DR CDD; cd01777; FERM_F1_SNX27; 1.
DR CDD; cd06886; PX_SNX27; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR037831; SNX17/27/31.
DR InterPro; IPR028667; SNX27.
DR InterPro; IPR037827; SNX27_FERM-like_dom.
DR InterPro; IPR037833; SNX27_PX.
DR InterPro; IPR037835; SNX27_RA.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR12431; PTHR12431; 1.
DR PANTHER; PTHR12431:SF17; PTHR12431:SF17; 1.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF00788; RA; 1.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50195; PX; 1.
DR PROSITE; PS50200; RA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Endosome; Lipid-binding;
KW Membrane; Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..539
FT /note="Sorting nexin-27"
FT /id="PRO_0000315358"
FT DOMAIN 41..134
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 159..267
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 271..360
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..360
FT /note="FERM-like region F1"
FT /evidence="ECO:0000250"
FT REGION 371..419
FT /note="FERM-like region F2"
FT /evidence="ECO:0000250"
FT REGION 423..523
FT /note="FERM-like region F3"
FT /evidence="ECO:0000250"
FT MOD_RES 49
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96L92"
FT VAR_SEQ 525..539
FT /note="NIFQMARSQQRDVAT -> EY (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12740601"
FT /id="VSP_030541"
FT MUTAGEN 51
FT /note="Y->L: Abolishes interaction with KCNJ9."
FT /evidence="ECO:0000269|PubMed:21422294"
FT MUTAGEN 220
FT /note="K->A: Abolishes phosphatidylinositol-3-phosphate-
FT binding and impairs subcellular location."
FT /evidence="ECO:0000269|PubMed:17828261"
FT CONFLICT 236
FT /note="G -> E (in Ref. 1; BAC10332)"
FT /evidence="ECO:0000305"
FT STRAND 40..45
FT /evidence="ECO:0007829|PDB:5EMB"
FT STRAND 53..62
FT /evidence="ECO:0007829|PDB:5EMB"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:5EMB"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:5EMB"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:5EMB"
FT HELIX 87..90
FT /evidence="ECO:0007829|PDB:5EMB"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:5EMB"
FT HELIX 112..119
FT /evidence="ECO:0007829|PDB:5EMB"
FT STRAND 121..131
FT /evidence="ECO:0007829|PDB:5EMB"
SQ SEQUENCE 539 AA; 61015 MW; B5EAAD425FCD19F4 CRC64;
MADEDGEGIH PSTPHRNGGG GGGSGLHCAG NGGGGGGGPR VVRIVKSESG YGFNVRGQVS
EGGQLRSING ELYAPLQHVS AVLPGGAADR AGVRKGDRIL EVNGVNVEGA THKQVVDLIR
AGEKELILTV LSVPPHEADN LDPSDDSLGQ SFYDYTEKQA VPISVPTYKH VEQNGEKFVV
YNVYMAGRQL CSKRYREFAI LHQNLKREFA NFTFPRLPGK WPFSLSEQQL DARRRGLEEY
LEKVCSIRVI GESDIMQEFL SESDENYNGV SDVELRVALP DGATVTVRVK KNSTTDQVYQ
AIAAKVGMDS TTVNYFALFE VINHSFVRKL APNEFPHKLY VQNYTSAVPG TCLTIRKWLF
TTEEEVLLND NDLAVTYFFH QAVDDVKKGY IKAEEKSYQL QKLYEQRKMV MYLNMLRTCE
GYNEIIFPHC ACDSRRKGHV ITAISITHFK LHACTEEGQL ENQVIAFEWD EMQRWDTDEE
GMAFCFEYAR GEKKPRWVKI FTPYFNYMHE CFERVFCELK WRKENIFQMA RSQQRDVAT
