SNX27_MOUSE
ID SNX27_MOUSE Reviewed; 539 AA.
AC Q3UHD6; Q7TQL6; Q80TZ1; Q9CYB5;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Sorting nexin-27;
GN Name=Snx27; Synonyms=Kiaa0488;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-526 (ISOFORM 2).
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-526 (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
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 [5]
RP INTERACTION WITH HT4R.
RX PubMed=15466885; DOI=10.1242/jcs.01379;
RA Joubert L., Hanson B., Barthet G., Sebben M., Claeysen S., Hong W.,
RA Marin P., Dumuis A., Bockaert J.;
RT "New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a
RT receptor splice variant: roles in receptor targeting.";
RL J. Cell Sci. 117:5367-5379(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=21300787; DOI=10.1128/mcb.01044-10;
RA Cai L., Loo L.S., Atlashkin V., Hanson B.J., Hong W.;
RT "Deficiency of sorting nexin 27 (SNX27) leads to growth retardation and
RT elevated levels of N-methyl-D-aspartate receptor 2C (NR2C).";
RL Mol. Cell. Biol. 31:1734-1747(2011).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH GRIA1; GRIA2; GRIN1
RP AND GRIN2A.
RX PubMed=23524343; DOI=10.1038/nm.3117;
RA Wang X., Zhao Y., Zhang X., Badie H., Zhou Y., Mu Y., Loo L.S., Cai L.,
RA Thompson R.C., Yang B., Chen Y., Johnson P.F., Wu C., Bu G., Mobley W.C.,
RA Zhang D., Gage F.H., Ranscht B., Zhang Y.W., Lipton S.A., Hong W., Xu H.;
RT "Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by
RT modulating glutamate receptor recycling in Down's syndrome.";
RL Nat. Med. 19:473-480(2013).
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:23524343}.
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 the FERM-like regions) with the WASH complex. Interacts with SNX1.
CC Interacts with CYTIP. Interacts with DGKZ. Interacts with MCC (By
CC similarity). Interacts (via PDZ domain) with a number of target
CC transmembrane proteins (via PDZ-binding motif): ABCC4, ADRB2, ARHGEF7,
CC GRIA1, GRIA2, GRIN1, GRIN2A GRIN2C, KCNJ6, KCNJ9 and SLC2A1/GLUT1.
CC {ECO:0000250, ECO:0000269|PubMed:15466885,
CC ECO:0000269|PubMed:23524343}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}.
CC Note=Localizes to immunological synapse in T-cells. In T-cells,
CC recruited from the cytosol to sorting endosomes by phosphoinositide-3-
CC kinase products (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=SNX27a;
CC IsoId=Q3UHD6-1; Sequence=Displayed;
CC Name=2; Synonyms=SNX27b;
CC IsoId=Q3UHD6-2; Sequence=VSP_030540;
CC -!- TISSUE SPECIFICITY: Expressed in cells of hematopoietic origin.
CC {ECO:0000269|PubMed:17351151}.
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. The PDZ domain also mediates binding to
CC the retromer complex via direct interaction with VPS26 (VPS26A or
CC VPS26B). {ECO:0000250}.
CC -!- DOMAIN: The PX domain mediates binding to phosphatidylinositol 3-
CC phosphate (PtdIns(3P)) and localization to early endosome membranes.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Growth retardation followed by lethality. Some
CC mice die in the uterus during embryonic development. Newborn mice that
CC survive fail to thrive and all die at different times within the first
CC 3 weeks. The body weight of newborn is lower than wild-type mice, and
CC the postnatal growth is severely retarded, with a clear retardation of
CC body weight gain. The growth retardation is not only reflected in the
CC body weight, but also in multiple organs, such as the spleen, kidney,
CC liver, heart and intestine. Mice also show neuronal deficits in the
CC hippocampus and cortex: despite a normal neuroanatomy, defects in
CC synaptic function, learning and memory and a reduction in the amounts
CC of ionotropic glutamate receptors (NMDA and AMPA receptors) are
CC observed. {ECO:0000269|PubMed:21300787, ECO:0000269|PubMed:23524343}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB30966.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB30966.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={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; AK017836; BAB30966.1; ALT_SEQ; mRNA.
DR EMBL; AK147452; BAE27921.1; -; mRNA.
DR EMBL; AK122296; BAC65578.1; -; mRNA.
DR EMBL; BC053495; AAH53495.1; -; mRNA.
DR CCDS; CCDS38537.1; -. [Q3UHD6-1]
DR CCDS; CCDS38538.1; -. [Q3UHD6-2]
DR RefSeq; NP_001075953.1; NM_001082484.2. [Q3UHD6-1]
DR RefSeq; NP_083997.1; NM_029721.2. [Q3UHD6-2]
DR AlphaFoldDB; Q3UHD6; -.
DR SMR; Q3UHD6; -.
DR BioGRID; 218291; 24.
DR DIP; DIP-60337N; -.
DR ELM; Q3UHD6; -.
DR IntAct; Q3UHD6; 7.
DR MINT; Q3UHD6; -.
DR STRING; 10090.ENSMUSP00000102904; -.
DR iPTMnet; Q3UHD6; -.
DR PhosphoSitePlus; Q3UHD6; -.
DR SwissPalm; Q3UHD6; -.
DR EPD; Q3UHD6; -.
DR MaxQB; Q3UHD6; -.
DR PaxDb; Q3UHD6; -.
DR PeptideAtlas; Q3UHD6; -.
DR PRIDE; Q3UHD6; -.
DR ProteomicsDB; 261470; -. [Q3UHD6-1]
DR ProteomicsDB; 261471; -. [Q3UHD6-2]
DR Antibodypedia; 46991; 290 antibodies from 25 providers.
DR Ensembl; ENSMUST00000029783; ENSMUSP00000029783; ENSMUSG00000028136. [Q3UHD6-2]
DR Ensembl; ENSMUST00000107283; ENSMUSP00000102904; ENSMUSG00000028136. [Q3UHD6-1]
DR GeneID; 76742; -.
DR KEGG; mmu:76742; -.
DR UCSC; uc008qgr.2; mouse. [Q3UHD6-2]
DR UCSC; uc008qgs.2; mouse. [Q3UHD6-1]
DR CTD; 81609; -.
DR MGI; MGI:1923992; Snx27.
DR VEuPathDB; HostDB:ENSMUSG00000028136; -.
DR eggNOG; KOG3784; Eukaryota.
DR GeneTree; ENSGT00950000183212; -.
DR HOGENOM; CLU_028138_0_0_1; -.
DR InParanoid; Q3UHD6; -.
DR OMA; NCSKDNM; -.
DR OrthoDB; 395943at2759; -.
DR PhylomeDB; Q3UHD6; -.
DR TreeFam; TF318398; -.
DR BioGRID-ORCS; 76742; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Snx27; mouse.
DR PRO; PR:Q3UHD6; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q3UHD6; protein.
DR Bgee; ENSMUSG00000028136; Expressed in ear vesicle and 225 other tissues.
DR ExpressionAtlas; Q3UHD6; baseline and differential.
DR Genevisible; Q3UHD6; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0001772; C:immunological synapse; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0030904; C:retromer complex; ISO:MGI.
DR GO; GO:0071203; C:WASH complex; ISO:MGI.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISO:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; IBA:GO_Central.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; ISS:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; ISS:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; IMP:MGI.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:MGI.
DR GO; GO:0099638; P:endosome to plasma membrane protein transport; ISO:MGI.
DR GO; GO:0061951; P:establishment of protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR GO; GO:1903609; P:negative regulation of inward rectifier potassium channel activity; ISO:MGI.
DR GO; GO:1904719; P:positive regulation of AMPA glutamate receptor clustering; ISO:MGI.
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 Alternative splicing; Cytoplasm; Endosome; Lipid-binding; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..539
FT /note="Sorting nexin-27"
FT /id="PRO_0000315357"
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:21183079"
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:14621295,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_030540"
SQ SEQUENCE 539 AA; 60989 MW; 0EF5B84253A90B4D CRC64;
MADEDGEGIH PSAPHRNGGG 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 DGTTVTVRVK KNSTTDQVYQ
AIAAKVGMDS TTVNYFALFE VINHSFVRKL APNEFPHKLY VQNYTSAVPG TCLTIRKWLF
TTEEEVLLND NDLAVTYFFH QAVDDVKKGY IKAEEKSYQL QKLHEQRKMV MYLNMLRTCE
GYNEIIFPHC ACDSRRKGHV ITAISITHFK LHACTEEGQL ENQVIAFEWD EMQRWDTDEE
GMAFCFEYAR GEKKPRWVKI FTPYFNYMHE CFERVFCELK WRKENIFQMA RSQQRDVAT
