FLOT2_HUMAN
ID FLOT2_HUMAN Reviewed; 428 AA.
AC Q14254;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Flotillin-2;
DE AltName: Full=Epidermal surface antigen;
DE Short=ESA;
DE AltName: Full=Membrane component chromosome 17 surface marker 1;
GN Name=FLOT2; Synonyms=ESA1, M17S1;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-428.
RC TISSUE=Keratinocyte;
RX PubMed=8051082; DOI=10.1016/s0021-9258(17)32117-8;
RA Schroeder W.T., Stewart-Galetka S., Mandavilli S., Parry D.A.,
RA Goldsmith L., Duvic M.;
RT "Cloning and characterization of a novel epidermal cell surface antigen
RT (ESA).";
RL J. Biol. Chem. 269:19983-19991(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-428.
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 50-428.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ECPAS.
RX PubMed=20682791; DOI=10.1074/jbc.m110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S., Hughes R.E.,
RA Rechsteiner M.;
RT "A protein interaction network for Ecm29 links the 26 S proteasome to
RT molecular motors and endosomal components.";
RL J. Biol. Chem. 285:31616-31633(2010).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP PALMITOYLATION AT CYS-4; CYS-19 AND CYS-20, AND MUTAGENESIS OF CYS-4;
RP CYS-19 AND CYS-20.
RX PubMed=22081607; DOI=10.1074/jbc.m111.306183;
RA Li Y., Martin B.R., Cravatt B.F., Hofmann S.L.;
RT "DHHC5 protein palmitoylates flotillin-2 and is rapidly degraded on
RT induction of neuronal differentiation in cultured cells.";
RL J. Biol. Chem. 287:523-530(2012).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
CC -!- FUNCTION: May act as a scaffolding protein within caveolar membranes,
CC functionally participating in formation of caveolae or caveolae-like
CC vesicles. May be involved in epidermal cell adhesion and epidermal
CC structure and function.
CC -!- SUBUNIT: Heterooligomeric complex of flotillin-1 and flotillin-2 and
CC caveolin-1 and caveolin-2 (By similarity). Interacts with ECPAS.
CC {ECO:0000250, ECO:0000269|PubMed:20682791}.
CC -!- INTERACTION:
CC Q14254; O75955: FLOT1; NbExp=6; IntAct=EBI-348613, EBI-603643;
CC Q14254; Q6FHG5: SNCG; NbExp=2; IntAct=EBI-348613, EBI-9776333;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20682791};
CC Peripheral membrane protein {ECO:0000269|PubMed:20682791}. Membrane,
CC caveola {ECO:0000269|PubMed:20682791}; Peripheral membrane protein
CC {ECO:0000269|PubMed:20682791}. Endosome {ECO:0000269|PubMed:20682791}.
CC Membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. Note=Membrane-
CC associated protein of caveolae.
CC -!- TISSUE SPECIFICITY: In skin, expressed in epidermis and epidermal
CC appendages but not in dermis. Expressed in all layers of the epidermis
CC except the basal layer. In hair follicles, expressed in the suprabasal
CC layer but not the basal layer. Also expressed in melanoma and carcinoma
CC cell lines, fibroblasts and foreskin melanocytes.
CC -!- PTM: ZDHHC5-catalyzed palmitoylation predominantly occurs at Cys-4.
CC ZDHHC5-catalyzed palmitoylation may be required for the formation of
CC higher-order complexes and for neurite outgrowth in cultured neural
CC stem cells. {ECO:0000269|PubMed:22081607}.
CC -!- SIMILARITY: Belongs to the band 7/mec-2 family. Flotillin subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA65729.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC024267; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M60922; AAA65729.1; ALT_INIT; mRNA.
DR EMBL; BC017292; AAH17292.2; -; mRNA.
DR EMBL; BT019478; AAV38285.1; -; mRNA.
DR CCDS; CCDS11245.2; -.
DR PIR; A53664; A53664.
DR RefSeq; NP_004466.2; NM_004475.2.
DR RefSeq; XP_016879883.1; XM_017024394.1.
DR RefSeq; XP_016879884.1; XM_017024395.1.
DR AlphaFoldDB; Q14254; -.
DR BMRB; Q14254; -.
DR BioGRID; 108608; 298.
DR CORUM; Q14254; -.
DR IntAct; Q14254; 117.
DR MINT; Q14254; -.
DR STRING; 9606.ENSP00000378368; -.
DR iPTMnet; Q14254; -.
DR PhosphoSitePlus; Q14254; -.
DR SwissPalm; Q14254; -.
DR BioMuta; FLOT2; -.
DR DMDM; 254763294; -.
DR EPD; Q14254; -.
DR jPOST; Q14254; -.
DR MassIVE; Q14254; -.
DR MaxQB; Q14254; -.
DR PaxDb; Q14254; -.
DR PeptideAtlas; Q14254; -.
DR PRIDE; Q14254; -.
DR ProteomicsDB; 59951; -.
DR Antibodypedia; 666; 333 antibodies from 39 providers.
DR DNASU; 2319; -.
DR Ensembl; ENST00000394908.9; ENSP00000378368.3; ENSG00000132589.16.
DR GeneID; 2319; -.
DR KEGG; hsa:2319; -.
DR MANE-Select; ENST00000394908.9; ENSP00000378368.3; NM_004475.3; NP_004466.2.
DR UCSC; uc002hdc.4; human.
DR CTD; 2319; -.
DR DisGeNET; 2319; -.
DR GeneCards; FLOT2; -.
DR HGNC; HGNC:3758; FLOT2.
DR HPA; ENSG00000132589; Low tissue specificity.
DR MIM; 131560; gene.
DR neXtProt; NX_Q14254; -.
DR OpenTargets; ENSG00000132589; -.
DR PharmGKB; PA28176; -.
DR VEuPathDB; HostDB:ENSG00000132589; -.
DR eggNOG; KOG2668; Eukaryota.
DR GeneTree; ENSGT00560000077232; -.
DR HOGENOM; CLU_038134_1_0_1; -.
DR InParanoid; Q14254; -.
DR OMA; MWRVAEP; -.
DR OrthoDB; 812555at2759; -.
DR PhylomeDB; Q14254; -.
DR TreeFam; TF324879; -.
DR PathwayCommons; Q14254; -.
DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis.
DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death.
DR Reactome; R-HSA-8849932; Synaptic adhesion-like molecules.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; Q14254; -.
DR BioGRID-ORCS; 2319; 10 hits in 1073 CRISPR screens.
DR ChiTaRS; FLOT2; human.
DR GeneWiki; FLOT2; -.
DR GenomeRNAi; 2319; -.
DR Pharos; Q14254; Tbio.
DR PRO; PR:Q14254; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q14254; protein.
DR Bgee; ENSG00000132589; Expressed in granulocyte and 194 other tissues.
DR ExpressionAtlas; Q14254; baseline and differential.
DR Genevisible; Q14254; HS.
DR GO; GO:0002080; C:acrosomal membrane; IEA:Ensembl.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005901; C:caveola; IDA:MGI.
DR GO; GO:0044291; C:cell-cell contact zone; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0032839; C:dendrite cytoplasm; IEA:GOC.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016600; C:flotillin complex; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001931; C:uropod; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0098937; P:anterograde dendritic transport; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR GO; GO:1902992; P:negative regulation of amyloid precursor protein catabolic process; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:ARUK-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0044860; P:protein localization to plasma membrane raft; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0045661; P:regulation of myoblast differentiation; IEP:UniProtKB.
DR GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; IEA:Ensembl.
DR Gene3D; 3.30.479.30; -; 1.
DR InterPro; IPR001107; Band_7.
DR InterPro; IPR036013; Band_7/SPFH_dom_sf.
DR InterPro; IPR027705; Flotillin_fam.
DR PANTHER; PTHR13806; PTHR13806; 1.
DR Pfam; PF01145; Band_7; 1.
DR SMART; SM00244; PHB; 1.
DR SUPFAM; SSF117892; SSF117892; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Endosome; Lipoprotein; Membrane; Myristate;
KW Palmitate; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..428
FT /note="Flotillin-2"
FT /id="PRO_0000094049"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:25255805"
FT LIPID 4
FT /note="S-palmitoyl cysteine; by ZDHHC5"
FT /evidence="ECO:0000269|PubMed:22081607"
FT LIPID 19
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:22081607"
FT LIPID 20
FT /note="S-palmitoyl cysteine; by ZDHHC5"
FT /evidence="ECO:0000269|PubMed:22081607"
FT VARIANT 328
FT /note="A -> T (in dbSNP:rs3736238)"
FT /id="VAR_024375"
FT MUTAGEN 4
FT /note="C->S: Loss of ZDHHC5-catalyzed palmitoylation; when
FT associated with S-20. Partial loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-19. Complete loss of
FT palmitoylation; when associated with S-19 and S-20."
FT /evidence="ECO:0000269|PubMed:22081607"
FT MUTAGEN 19
FT /note="C->S: Partial loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-4 or S-20. Complete
FT loss of palmitoylation; when associated with S-4 and S-20."
FT /evidence="ECO:0000269|PubMed:22081607"
FT MUTAGEN 20
FT /note="C->S: Loss of ZDHHC5-catalyzed palmitoylation; when
FT associated with S-4. Partial loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-19. Complete loss of
FT palmitoylation; when associated with S-4 and S-19."
FT /evidence="ECO:0000269|PubMed:22081607"
FT CONFLICT 8
FT /note="G -> R (in Ref. 1; AC024267 and 2; AAA65729)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 428 AA; 47064 MW; F690BFE0151D3BD7 CRC64;
MGNCHTVGPN EALVVSGGCC GSDYKQYVFG GWAWAWWCIS DTQRISLEIM TLQPRCEDVE
TAEGVALTVT GVAQVKIMTE KELLAVACEQ FLGKNVQDIK NVVLQTLEGH LRSILGTLTV
EQIYQDRDQF AKLVREVAAP DVGRMGIEIL SFTIKDVYDK VDYLSSLGKT QTAVVQRDAD
IGVAEAERDA GIREAECKKE MLDVKFMADT KIADSKRAFE LQKSAFSEEV NIKTAEAQLA
YELQGAREQQ KIRQEEIEIE VVQRKKQIAV EAQEILRTDK ELIATVRRPA EAEAHRIQQI
AEGEKVKQVL LAQAEAEKIR KIGEAEAAVI EAMGKAEAER MKLKAEAYQK YGDAAKMALV
LEALPQIAAK IAAPLTKVDE IVVLSGDNSK VTSEVNRLLA ELPASVHALT GVDLSKIPLI
KKATGVQV
