ID SNX33_HUMAN Reviewed; 574 AA. AC Q8WV41; B1NM17; DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 27-MAR-2024, entry version 177. DE RecName: Full=Sorting nexin-33; DE AltName: Full=SH3 and PX domain-containing protein 3; GN Name=SNX33; Synonyms=SH3PX3, SH3PXD3C, SNX30; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH ADAM15. RX PubMed=16374509; DOI=10.1038/sj.embor.7400596; RA Kaerkkaeinen S., Hiipakka M., Wang J.-H., Kleino I., Vaehae-Jaakkola M., RA Renkema G.H., Liss M., Wagner R., Saksela K.; RT "Identification of preferred protein interactions by phage-display of the RT human Src homology-3 proteome."; RL EMBO Rep. 7:186-191(2006). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH DNM1 AND DNM2, RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=18353773; DOI=10.1074/jbc.m801531200; RA Schobel S., Neumann S., Hertweck M., Dislich B., Kuhn P.H., Kremmer E., RA Seed B., Baumeister R., Haass C., Lichtenthaler S.F.; RT "A novel sorting nexin modulates endocytic trafficking and alpha-secretase RT cleavage of the amyloid precursor protein."; RL J. Biol. Chem. 283:14257-14268(2008). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Stomach; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; 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 [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [7] RP FUNCTION. RX PubMed=18419754; DOI=10.1111/j.1600-0854.2008.00750.x; RA Heiseke A., Schobel S., Lichtenthaler S.F., Vorberg I., Groschup M.H., RA Kretzschmar H., Schatzl H.M., Nunziante M.; RT "The novel sorting nexin SNX33 interferes with cellular PrP formation by RT modulation of PrP shedding."; RL Traffic 9:1116-1129(2008). RN [8] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL (CD178) by RT phage display screening."; RL BMC Immunol. 10:53-53(2009). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH WASL. RX PubMed=19487689; DOI=10.1074/jbc.m109.007278; RA Zhang J., Zhang X., Guo Y., Xu L., Pei D.; RT "Sorting nexin 33 induces mammalian cell micronucleated phenotype and actin RT polymerization by interacting with Wiskott-Aldrich syndrome protein."; RL J. Biol. Chem. 284:21659-21669(2009). RN [10] RP INTERACTION WITH ADAM15. RX PubMed=19718658; DOI=10.1002/jcb.22317; RA Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.; RT "Alternative splicing of ADAM15 regulates its interactions with cellular RT SH3 proteins."; RL J. Cell. Biochem. 108:877-885(2009). RN [11] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=21048941; DOI=10.1371/journal.pone.0013763; RA Wang J.T., Kerr M.C., Karunaratne S., Jeanes A., Yap A.S., Teasdale R.D.; RT "The SNX-PX-BAR family in macropinocytosis: the regulation of macropinosome RT formation by SNX-PX-BAR proteins."; RL PLoS ONE 5:E13763-E13763(2010). RN [12] RP FUNCTION, DOMAIN, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=20964629; DOI=10.1042/bj20100709; RA Dislich B., Than M.E., Lichtenthaler S.F.; RT "Specific amino acids in the BAR domain allow homodimerization and prevent RT heterodimerization of sorting nexin 33."; RL Biochem. J. 433:75-83(2011). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=22718350; DOI=10.1242/jcs.105981; RA Ma M.P., Chircop M.; RT "SNX9, SNX18 and SNX33 are required for progression through and completion RT of mitosis."; RL J. Cell Sci. 125:4372-4382(2012). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77 AND SER-92, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 212-574. RG Structural genomics consortium (SGC); RT "Structure of human sorting nexin 33."; RL Submitted (DEC-2012) to the PDB data bank. CC -!- FUNCTION: Plays a role in the reorganization of the cytoskeleton, CC endocytosis and cellular vesicle trafficking via its interactions with CC membranes, WASL, DNM1 and DNM2. Acts both during interphase and at the CC end of mitotic cell divisions. Required for efficient progress through CC mitosis and cytokinesis. Required for normal formation of the cleavage CC furrow at the end of mitosis. Modulates endocytosis of cell-surface CC proteins, such as APP and PRNP; this then modulates the secretion of CC APP and PRNP peptides. Promotes membrane tubulation (in vitro). May CC promote the formation of macropinosomes. {ECO:0000269|PubMed:18353773, CC ECO:0000269|PubMed:18419754, ECO:0000269|PubMed:19487689, CC ECO:0000269|PubMed:20964629, ECO:0000269|PubMed:21048941, CC ECO:0000269|PubMed:22718350}. CC -!- SUBUNIT: Homodimer (via BAR domain). Interacts with ADAM15. Interacts CC with FASLG. Interacts (via SH3 domain) with DNM1 and DNM2. Interacts CC with WASL. Interacts with FCHSD1 (via the F-BAR domain) (By CC similarity). {ECO:0000250|UniProtKB:Q4VAA7, CC ECO:0000269|PubMed:16374509, ECO:0000269|PubMed:18353773, CC ECO:0000269|PubMed:19487689, ECO:0000269|PubMed:19718658, CC ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:20964629}. CC -!- INTERACTION: CC Q8WV41; Q13444: ADAM15; NbExp=4; IntAct=EBI-2481535, EBI-77818; CC Q8WV41; Q13444-2: ADAM15; NbExp=3; IntAct=EBI-2481535, EBI-12137265; CC Q8WV41; P05067: APP; NbExp=3; IntAct=EBI-2481535, EBI-77613; CC Q8WV41; Q05193: DNM1; NbExp=2; IntAct=EBI-2481535, EBI-713135; CC Q8WV41; P50570-2: DNM2; NbExp=3; IntAct=EBI-2481535, EBI-10968534; CC Q8WV41; Q7L190: DPPA4; NbExp=5; IntAct=EBI-2481535, EBI-710457; CC Q8WV41; P48023: FASLG; NbExp=3; IntAct=EBI-2481535, EBI-495538; CC Q8WV41; P42858: HTT; NbExp=6; IntAct=EBI-2481535, EBI-466029; CC Q8WV41; Q92993: KAT5; NbExp=3; IntAct=EBI-2481535, EBI-399080; CC Q8WV41; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-2481535, EBI-11742507; CC Q8WV41; P41227: NAA10; NbExp=3; IntAct=EBI-2481535, EBI-747693; CC Q8WV41; Q96HR8: NAF1; NbExp=4; IntAct=EBI-2481535, EBI-2515597; CC Q8WV41; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-2481535, EBI-9090795; CC Q8WV41; Q8WV41: SNX33; NbExp=2; IntAct=EBI-2481535, EBI-2481535; CC Q8WV41; Q9Y5X1: SNX9; NbExp=2; IntAct=EBI-2481535, EBI-77848; CC Q8WV41; P42768: WAS; NbExp=3; IntAct=EBI-2481535, EBI-346375; CC Q8WV41; P61981: YWHAG; NbExp=3; IntAct=EBI-2481535, EBI-359832; CC Q8WV41; Q86XF7: ZNF575; NbExp=3; IntAct=EBI-2481535, EBI-14069183; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Membrane; Peripheral membrane CC protein; Cytoplasmic side. Cytoplasmic vesicle membrane; Peripheral CC membrane protein; Cytoplasmic side. Note=Primarily cytosolic, but a CC minor proportion is membrane-bound (PubMed:18353773). Not associated CC with membranes (PubMed:21048941). {ECO:0000269|PubMed:18353773, CC ECO:0000269|PubMed:21048941}. CC -!- TISSUE SPECIFICITY: Detected in heart and pancreas. CC {ECO:0000269|PubMed:18353773}. CC -!- DOMAIN: The PX and BAR domains mediate association with membranes and CC are required for membrane tubulation. {ECO:0000269|PubMed:20964629}. CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:18353773}. 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; EF219141; ABN09670.1; -; mRNA. DR EMBL; EF653821; ABV26009.1; -; mRNA. DR EMBL; AL833039; CAH56299.1; -; mRNA. DR EMBL; CH471136; EAW99243.1; -; Genomic_DNA. DR EMBL; BC018775; AAH18775.1; -; mRNA. DR CCDS; CCDS10283.1; -. DR RefSeq; NP_001305075.1; NM_001318146.1. DR RefSeq; NP_695003.1; NM_153271.1. DR PDB; 4AKV; X-ray; 2.65 A; A/B=212-574. DR PDBsum; 4AKV; -. DR AlphaFoldDB; Q8WV41; -. DR SMR; Q8WV41; -. DR BioGRID; 129214; 69. DR IntAct; Q8WV41; 46. DR MINT; Q8WV41; -. DR STRING; 9606.ENSP00000311427; -. DR TCDB; 3.A.34.1.1; the sorting nexins of the escrt complexes (sn-escrt). DR iPTMnet; Q8WV41; -. DR PhosphoSitePlus; Q8WV41; -. DR BioMuta; SNX33; -. DR DMDM; 74751538; -. DR EPD; Q8WV41; -. DR jPOST; Q8WV41; -. DR MassIVE; Q8WV41; -. DR MaxQB; Q8WV41; -. DR PaxDb; 9606-ENSP00000311427; -. DR PeptideAtlas; Q8WV41; -. DR ProteomicsDB; 74746; -. DR Pumba; Q8WV41; -. DR Antibodypedia; 27355; 146 antibodies from 24 providers. DR DNASU; 257364; -. DR Ensembl; ENST00000308527.6; ENSP00000311427.6; ENSG00000173548.9. DR GeneID; 257364; -. DR KEGG; hsa:257364; -. DR MANE-Select; ENST00000308527.6; ENSP00000311427.6; NM_153271.2; NP_695003.1. DR UCSC; uc002bau.4; human. DR AGR; HGNC:28468; -. DR CTD; 257364; -. DR GeneCards; SNX33; -. DR HGNC; HGNC:28468; SNX33. DR HPA; ENSG00000173548; Low tissue specificity. DR MIM; 619107; gene. DR neXtProt; NX_Q8WV41; -. DR OpenTargets; ENSG00000173548; -. DR PharmGKB; PA162404345; -. DR VEuPathDB; HostDB:ENSG00000173548; -. DR eggNOG; KOG2528; Eukaryota. DR GeneTree; ENSGT00940000160162; -. DR HOGENOM; CLU_021494_3_0_1; -. DR InParanoid; Q8WV41; -. DR OMA; NINSPVY; -. DR OrthoDB; 5401713at2759; -. DR PhylomeDB; Q8WV41; -. DR TreeFam; TF314082; -. DR PathwayCommons; Q8WV41; -. DR SignaLink; Q8WV41; -. DR BioGRID-ORCS; 257364; 19 hits in 1152 CRISPR screens. DR ChiTaRS; SNX33; human. DR GenomeRNAi; 257364; -. DR Pharos; Q8WV41; Tbio. DR PRO; PR:Q8WV41; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q8WV41; Protein. DR Bgee; ENSG00000173548; Expressed in pancreatic ductal cell and 176 other cell types or tissues. DR ExpressionAtlas; Q8WV41; baseline and differential. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0035091; F:phosphatidylinositol binding; IBA:GO_Central. DR GO; GO:0036089; P:cleavage furrow formation; IMP:UniProtKB. DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB. DR GO; GO:0016197; P:endosomal transport; IMP:UniProtKB. DR GO; GO:0007032; P:endosome organization; IMP:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro. DR GO; GO:0044351; P:macropinocytosis; IMP:UniProtKB. DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB. DR GO; GO:0045806; P:negative regulation of endocytosis; IDA:UniProtKB. DR GO; GO:2000009; P:negative regulation of protein localization to cell surface; IDA:UniProtKB. DR GO; GO:0097320; P:plasma membrane tubulation; IDA:UniProtKB. DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:UniProtKB. DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IDA:UniProtKB. DR GO; GO:0017038; P:protein import; IDA:UniProtKB. DR CDD; cd07669; BAR_SNX33; 1. DR CDD; cd11896; SH3_SNX33; 1. DR Gene3D; 1.20.1270.60; Arfaptin homology (AH) domain/BAR domain; 1. DR Gene3D; 3.30.1520.10; Phox-like domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR027267; AH/BAR_dom_sf. DR InterPro; IPR001683; PX_dom. DR InterPro; IPR036871; PX_dom_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR037427; SNX33_BAR. DR InterPro; IPR014536; Snx9_fam. DR InterPro; IPR019497; Sorting_nexin_WASP-bd-dom. DR PANTHER; PTHR45827; SORTING NEXIN; 1. DR PANTHER; PTHR45827:SF3; SORTING NEXIN-33; 1. DR Pfam; PF10456; BAR_3_WASP_bdg; 1. DR Pfam; PF00787; PX; 1. DR Pfam; PF14604; SH3_9; 1. DR PIRSF; PIRSF027744; Snx9; 1. DR SMART; SM00312; PX; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF64268; PX domain; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS50195; PX; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; Q8WV41; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Cell division; Cytoplasm; Cytoplasmic vesicle; KW Endocytosis; Membrane; Mitosis; Phosphoprotein; Protein transport; KW Reference proteome; SH3 domain; Transport. FT CHAIN 1..574 FT /note="Sorting nexin-33" FT /id="PRO_0000311948" FT DOMAIN 1..61 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 230..340 FT /note="PX" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147" FT DOMAIN 371..574 FT /note="BAR" FT REGION 68..119 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 68..107 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 77 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 92 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT STRAND 213..215 FT /evidence="ECO:0007829|PDB:4AKV" FT STRAND 220..223 FT /evidence="ECO:0007829|PDB:4AKV" FT STRAND 232..235 FT /evidence="ECO:0007829|PDB:4AKV" FT STRAND 252..256 FT /evidence="ECO:0007829|PDB:4AKV" FT STRAND 259..261 FT /evidence="ECO:0007829|PDB:4AKV" FT STRAND 263..265 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 267..280 FT /evidence="ECO:0007829|PDB:4AKV" FT STRAND 282..284 FT /evidence="ECO:0007829|PDB:4AKV" FT TURN 302..304 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 305..318 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 323..325 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 327..333 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 339..349 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 355..360 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 371..407 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 409..427 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 432..434 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 437..459 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 460..462 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 465..504 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 510..568 FT /evidence="ECO:0007829|PDB:4AKV" FT HELIX 569..571 FT /evidence="ECO:0007829|PDB:4AKV" SQ SEQUENCE 574 AA; 65265 MW; 7CE51C0F35DDBC3C CRC64; MALKGRALYD FHSENKEEIS IQQDEDLVIF SETSLDGWLQ GQNSRGETGL FPASYVEIVR SGISTNHADY SSSPAGSPGA QVSLYNSPSV ASPARSGGGS GFLSNQGSFE EDDDDDWDDW DDGCTVVEEP RAGGLGTNGH PPLNLSYPGA YPSQHMAFRP KPPLERQDSL ASAKRGSVVG RNLNRFSCFV RSGVEAFILG DVPMMAKIAE TYSIEMGPRG PQWKANPHPF ACSVEDPTKQ TKFKGIKSYI SYKLTPTHAA SPVYRRYKHF DWLYNRLLHK FTVISVPHLP EKQATGRFEE DFIEKRKRRL ILWMDHMTSH PVLSQYEGFQ HFLSCLDDKQ WKMGKRRAEK DEMVGASFLL TFQIPTEHQD LQDVEDRVDT FKAFSKKMDD SVLQLSTVAS ELVRKHVGGF RKEFQKLGSA FQAISHSFQM DPPFCSEALN SAISHTGRTY EAIGEMFAEQ PKNDLFQMLD TLSLYQGLLS NFPDIIHLQK GAFAKVKESQ RMSDEGRMVQ DEADGIRRRC RVVGFALQAE MNHFHQRREL DFKHMMQNYL RQQILFYQRV GQQLEKTLRM YDNL //