Full text data of FLOT2
FLOT2
(ESA1, M17S1)
[Confidence: high (present in two of the MS resources)]
Flotillin-2 (Epidermal surface antigen; ESA; Membrane component chromosome 17 surface marker 1)
Flotillin-2 (Epidermal surface antigen; ESA; Membrane component chromosome 17 surface marker 1)
hRBCD
IPI00029625
IPI00029625 Flotillin-2 Flotillin-2 membrane 3 n/a 21 15 2 n/a 18 8 45 6 25 14 n/a 13 8 11 17 14 11 9 membrane bound n/a found at its expected molecular weight found at molecular weight
IPI00029625 Flotillin-2 Flotillin-2 membrane 3 n/a 21 15 2 n/a 18 8 45 6 25 14 n/a 13 8 11 17 14 11 9 membrane bound n/a found at its expected molecular weight found at molecular weight
UniProt
Q14254
ID FLOT2_HUMAN Reviewed; 428 AA.
AC Q14254;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 28-JUL-2009, sequence version 2.
DT 22-JAN-2014, entry version 117.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-428.
RC TISSUE=Keratinocyte;
RX PubMed=8051082;
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
RT antigen (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
RT project: 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
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ECM29.
RX PubMed=20682791; DOI=10.1074/jbc.M110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S.,
RA Hughes R.E., 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.,
RA Buerckstuemmer T., 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).
CC -!- FUNCTION: May act as a scaffolding protein within caveolar
CC membranes, functionally participating in formation of caveolae or
CC caveolae-like vesicles. May be involved in epidermal cell adhesion
CC and epidermal structure and function.
CC -!- SUBUNIT: Heterooligomeric complex of flotillin-1 and flotillin-2
CC and caveolin-1 and caveolin-2 (By similarity). Interacts with
CC ECM29.
CC -!- INTERACTION:
CC O75955:FLOT1; NbExp=2; IntAct=EBI-348613, EBI-603643;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
CC Membrane, caveola; Peripheral membrane protein. Endosome.
CC Note=Membrane-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
CC epidermis except the basal layer. In hair follicles, expressed in
CC the suprabasal layer but not the basal layer. Also expressed in
CC melanoma and carcinoma cell lines, fibroblasts and foreskin
CC melanocytes.
CC -!- PTM: ZDHHC5-catalyzed palmitoylation predominantly occurs at Cys-
CC 4. ZDHHC5-catalyzed palmitoylation may be required for the
CC formation of higher-order complexes and for neurite outgrowth in
CC cultured neural stem cells.
CC -!- SIMILARITY: Belongs to the band 7/mec-2 family. Flotillin
CC subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA65729.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; A53664; A53664.
DR RefSeq; NP_004466.2; NM_004475.2.
DR RefSeq; XP_005258009.1; XM_005257952.1.
DR UniGene; Hs.514038; -.
DR ProteinModelPortal; Q14254; -.
DR SMR; Q14254; 40-173.
DR IntAct; Q14254; 15.
DR MINT; MINT-1034434; -.
DR STRING; 9606.ENSP00000378368; -.
DR PhosphoSite; Q14254; -.
DR DMDM; 254763294; -.
DR PaxDb; Q14254; -.
DR PRIDE; Q14254; -.
DR DNASU; 2319; -.
DR Ensembl; ENST00000394908; ENSP00000378368; ENSG00000132589.
DR GeneID; 2319; -.
DR KEGG; hsa:2319; -.
DR UCSC; uc002hdc.3; human.
DR CTD; 2319; -.
DR GeneCards; GC17M027206; -.
DR H-InvDB; HIX0013665; -.
DR HGNC; HGNC:3758; FLOT2.
DR HPA; CAB004395; -.
DR HPA; HPA001396; -.
DR MIM; 131560; gene.
DR neXtProt; NX_Q14254; -.
DR PharmGKB; PA28176; -.
DR eggNOG; COG2268; -.
DR HOGENOM; HOG000240804; -.
DR HOVERGEN; HBG051628; -.
DR InParanoid; Q14254; -.
DR KO; K07192; -.
DR ChiTaRS; FLOT2; human.
DR GeneWiki; FLOT2; -.
DR GenomeRNAi; 2319; -.
DR NextBio; 9417; -.
DR PRO; PR:Q14254; -.
DR ArrayExpress; Q14254; -.
DR Bgee; Q14254; -.
DR CleanEx; HS_FLOT2; -.
DR Genevestigator; Q14254; -.
DR GO; GO:0002080; C:acrosomal membrane; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0016600; C:flotillin complex; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; NAS:ProtInc.
DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR InterPro; IPR001107; Band_7.
DR InterPro; IPR027705; Flotillin_fam.
DR PANTHER; PTHR13806; PTHR13806; 1.
DR Pfam; PF01145; Band_7; 1.
DR SMART; SM00244; PHB; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Complete proteome; Endosome;
KW Lipoprotein; Membrane; Palmitate; Polymorphism; Reference proteome.
FT CHAIN 1 428 Flotillin-2.
FT /FTId=PRO_0000094049.
FT LIPID 4 4 S-palmitoyl cysteine; by ZDHHC5.
FT LIPID 19 19 S-palmitoyl cysteine.
FT LIPID 20 20 S-palmitoyl cysteine; by ZDHHC5.
FT VARIANT 328 328 A -> T (in dbSNP:rs3736238).
FT /FTId=VAR_024375.
FT MUTAGEN 4 4 C->S: Loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-
FT 20. Partial loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-
FT 19. Complete loss of palmitoylation; when
FT associated with S-19 and S-20.
FT MUTAGEN 19 19 C->S: Partial loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-4
FT or S-20. Complete loss of palmitoylation;
FT when associated with S-4 and S-20.
FT MUTAGEN 20 20 C->S: Loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-4.
FT Partial loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-
FT 19. Complete loss of palmitoylation; when
FT associated with S-4 and S-19.
FT CONFLICT 8 8 G -> R (in Ref. 1; AC024267 and 2;
FT AAA65729).
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
//
ID FLOT2_HUMAN Reviewed; 428 AA.
AC Q14254;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 28-JUL-2009, sequence version 2.
DT 22-JAN-2014, entry version 117.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-428.
RC TISSUE=Keratinocyte;
RX PubMed=8051082;
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
RT antigen (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
RT project: 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
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ECM29.
RX PubMed=20682791; DOI=10.1074/jbc.M110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S.,
RA Hughes R.E., 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.,
RA Buerckstuemmer T., 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).
CC -!- FUNCTION: May act as a scaffolding protein within caveolar
CC membranes, functionally participating in formation of caveolae or
CC caveolae-like vesicles. May be involved in epidermal cell adhesion
CC and epidermal structure and function.
CC -!- SUBUNIT: Heterooligomeric complex of flotillin-1 and flotillin-2
CC and caveolin-1 and caveolin-2 (By similarity). Interacts with
CC ECM29.
CC -!- INTERACTION:
CC O75955:FLOT1; NbExp=2; IntAct=EBI-348613, EBI-603643;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
CC Membrane, caveola; Peripheral membrane protein. Endosome.
CC Note=Membrane-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
CC epidermis except the basal layer. In hair follicles, expressed in
CC the suprabasal layer but not the basal layer. Also expressed in
CC melanoma and carcinoma cell lines, fibroblasts and foreskin
CC melanocytes.
CC -!- PTM: ZDHHC5-catalyzed palmitoylation predominantly occurs at Cys-
CC 4. ZDHHC5-catalyzed palmitoylation may be required for the
CC formation of higher-order complexes and for neurite outgrowth in
CC cultured neural stem cells.
CC -!- SIMILARITY: Belongs to the band 7/mec-2 family. Flotillin
CC subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA65729.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; A53664; A53664.
DR RefSeq; NP_004466.2; NM_004475.2.
DR RefSeq; XP_005258009.1; XM_005257952.1.
DR UniGene; Hs.514038; -.
DR ProteinModelPortal; Q14254; -.
DR SMR; Q14254; 40-173.
DR IntAct; Q14254; 15.
DR MINT; MINT-1034434; -.
DR STRING; 9606.ENSP00000378368; -.
DR PhosphoSite; Q14254; -.
DR DMDM; 254763294; -.
DR PaxDb; Q14254; -.
DR PRIDE; Q14254; -.
DR DNASU; 2319; -.
DR Ensembl; ENST00000394908; ENSP00000378368; ENSG00000132589.
DR GeneID; 2319; -.
DR KEGG; hsa:2319; -.
DR UCSC; uc002hdc.3; human.
DR CTD; 2319; -.
DR GeneCards; GC17M027206; -.
DR H-InvDB; HIX0013665; -.
DR HGNC; HGNC:3758; FLOT2.
DR HPA; CAB004395; -.
DR HPA; HPA001396; -.
DR MIM; 131560; gene.
DR neXtProt; NX_Q14254; -.
DR PharmGKB; PA28176; -.
DR eggNOG; COG2268; -.
DR HOGENOM; HOG000240804; -.
DR HOVERGEN; HBG051628; -.
DR InParanoid; Q14254; -.
DR KO; K07192; -.
DR ChiTaRS; FLOT2; human.
DR GeneWiki; FLOT2; -.
DR GenomeRNAi; 2319; -.
DR NextBio; 9417; -.
DR PRO; PR:Q14254; -.
DR ArrayExpress; Q14254; -.
DR Bgee; Q14254; -.
DR CleanEx; HS_FLOT2; -.
DR Genevestigator; Q14254; -.
DR GO; GO:0002080; C:acrosomal membrane; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0016600; C:flotillin complex; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; NAS:ProtInc.
DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR InterPro; IPR001107; Band_7.
DR InterPro; IPR027705; Flotillin_fam.
DR PANTHER; PTHR13806; PTHR13806; 1.
DR Pfam; PF01145; Band_7; 1.
DR SMART; SM00244; PHB; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Complete proteome; Endosome;
KW Lipoprotein; Membrane; Palmitate; Polymorphism; Reference proteome.
FT CHAIN 1 428 Flotillin-2.
FT /FTId=PRO_0000094049.
FT LIPID 4 4 S-palmitoyl cysteine; by ZDHHC5.
FT LIPID 19 19 S-palmitoyl cysteine.
FT LIPID 20 20 S-palmitoyl cysteine; by ZDHHC5.
FT VARIANT 328 328 A -> T (in dbSNP:rs3736238).
FT /FTId=VAR_024375.
FT MUTAGEN 4 4 C->S: Loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-
FT 20. Partial loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-
FT 19. Complete loss of palmitoylation; when
FT associated with S-19 and S-20.
FT MUTAGEN 19 19 C->S: Partial loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-4
FT or S-20. Complete loss of palmitoylation;
FT when associated with S-4 and S-20.
FT MUTAGEN 20 20 C->S: Loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-4.
FT Partial loss of ZDHHC5-catalyzed
FT palmitoylation; when associated with S-
FT 19. Complete loss of palmitoylation; when
FT associated with S-4 and S-19.
FT CONFLICT 8 8 G -> R (in Ref. 1; AC024267 and 2;
FT AAA65729).
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
//
MIM
131560
*RECORD*
*FIELD* NO
131560
*FIELD* TI
*131560 FLOTILLIN 2; FLOT2
;;EPIDERMAL SURFACE ANTIGEN 1; ESA1;;
MEMBRANE COMPONENT, CHROMOSOME 17, SURFACE MARKER 1; M17S1
read more*FIELD* TX
CLONING
Human epidermal surface antigen-1 was identified as a 35-kD antigen by
means of a mouse monoclonal antibody raised against human keratinocytes.
The monoclonal antibody was found to cause keratinocyte dissociation in
vitro; hence, the conclusion that the native protein is involved in cell
adhesion. Cho et al. (1995) found that mouse Esa cDNA encodes a
379-amino acid protein that is 99.2% identical to the human, differing
at only 3 amino acids. Cho et al. (1995) found that both 'nude' and
control mice have a second Esa mRNA transcript that conserves amino acid
sequence and molecular mass. The mouse and human 5-prime- and 3-prime
untranslated sequences are conserved. Similar RNA folding patterns of
the 5-prime untranslated region are predicted despite a 91-bp insertion
in the mouse.
GENE FUNCTION
Bickel et al. (1997) found that mouse Flot2 consistently copurifies with
Flot1 (606998) and with caveolin-1 (601047) in the purification of
caveolin-rich membranes.
Baumann et al. (2000) screened a yeast 2-hybrid library using the
N-terminal region of CAP (605264) and identified the caveolar protein
flotillin. Flotillin forms a ternary complex with CAP and the CBL
protooncogene product (165360), directing the localization of the
CAP-CBL complex to a lipid raft subdomain of the plasma membrane.
Localization of the CBL-CAP complex to lipid rafts generates a pathway
that is crucial in the regulation of glucose uptake.
Uptake of cholesterol from intestine and liver is mediated by NPC1L1
(608010), which cycles between the plasma membrane and endocytic
recycling compartment in response to cholesterol availability. Using a
human liver cell line, rat liver cells expressing human NPC1L1, and
transgenic mice, Ge et al. (2011) found that NPC1L1 required FLOT1 and
FLOT2 for bulk endocytosis of cholesterol-enriched plasma membrane
microdomains. NPC1L1 interacted directly with FLOT1 and FLOT2, which
functioned upstream of clathrin (see 118955) in NPC1L1 cholesterol
uptake. The flotillins had no effect on recycling NPC1L1 to plasma
membranes. In addition, the hypocholesterolemic drug ezetimibe disrupted
NPC1L1-flotillin interactions, blocking formation of
cholesterol-enriched microdomains.
DHHC5 (ZDHHC5; 614586) belongs to a family of palmitoyl acyltransferases
that reversibly modify cysteine residues for the regulation of protein
trafficking, stability, and activity. Using a quantitative proteomic
analysis of cultured mouse neuronal stem cells, Li et al. (2012) found
that palmitoylation and oligomerization of flotillin-2 was abolished in
homozygous Dhhc5 mutant neuronal stem cells. The absolute amount of
flotillin-2 was not changed in Dhhc5 mutant neurons. In contrast,
overexpression of mouse Dhhc5 in COS-7 cells markedly stimulated
palmitoylation of human flotillin-2. Human flotillin-2 is myristoylated
at gly2 and palmitoylated at cys4, cys19, and cys20. Mutation analysis
of human flotillin-2 expressed in COS-7 cells revealed that coexpressed
mouse Dhhc5 and endogenous COS-7 cell enzymes palmitoylated flotillin-2
predominantly on cys4 and cys20.
MAPPING
Schroeder et al. (1991) isolated a cDNA for an epidermal surface antigen
believed to be involved in epidermal cell adhesion. By analysis of a
somatic cell hybrid panel and in situ hybridization using the ESA cDNA,
the gene was mapped to 17q11-q12 in the region containing the NF1 gene
(613113). Using a RFLP within the ESA1 gene, they showed tight linkage
of ESA1 with NF1; maximal lod = 6.92 at theta = 0.0. By studying somatic
cell hybrids carrying the 2 chromosome 17 translocations with
breakpoints within the NF1 gene, t(1;17) and t(17;22), Schroeder et al.
(1991) showed that the ESA1 gene is located centromeric to the t(1;17)
breakpoint. It remained to be determined whether this represented
another of the genes located within the NF1 gene and transcribed in the
opposite direction. Kayes et al. (1992) made that determination;
physical mapping of an M17S1 cDNA on somatic cell hybrids, yeast
artificial chromosomes, and DNA from a patient with neurofibromatosis I
(162200) with a deletion involving an entire NF1 allele showed that
M17S1 is located at least 180 kb centromeric to the NF1 gene. The
distance between the genes suggested that M17S1 is unlikely to
contribute to the NF1 phenotype.
Cho et al. (1995) mapped the mouse Esa gene to chromosome 11. Although
the mouse Esa gene and the 'nude' locus map to the same region of
chromosome 11, Cho et al. (1995) detected no abnormalities in protein,
mRNA, cDNA or genomic Esa sequences in nude mice.
*FIELD* RF
1. Baumann, C. A.; Ribon, V.; Kanzaki, M.; Thurmond, D. C.; Mora,
S.; Shigematsu, S.; Bickel, P. E.; Pessin, J. E.; Saltiel, A. R.:
CAP defines a second signalling pathway required for insulin-stimulated
glucose transport. Nature 407: 202-207, 2000.
2. Bickel, P. E.; Scherer, P. E.; Schnitzer, J. E.; Oh, P.; Lisanti,
M. P.; Lodish, H. F.: Flotillin and epidermal surface antigen define
a new family of caveolae-associated integral membrane proteins. J.
Biol. Chem. 272: 13793-13802, 1997.
3. Cho, Y.-J.; Chema, D.; Moskow, J. J.; Cho, M.; Schroeder, W. T.;
Overbeek, P.; Buchberg, A. M.; Duvic, M.: Epidermal surface antigen
(MS17S1) is highly conserved between mouse and human. Genomics 27:
251-258, 1995.
4. Ge, L.; Qi, W.; Wang, L.-J.; Miao, H.-H.; Qu, Y.-X.; Li, B.-L.;
Song, B.-L.: Flotillins play an essential role in Niemann-Pick C1-like
1-mediated cholesterol uptake. Proc. Nat. Acad. Sci. 108: 551-556,
2011.
5. Kayes, L. M.; Schroeder, W. T.; Marchuk, D. A.; Collins, F. S.;
Riccardi, V. M.; Duvic, M.; Stephens, K.: The gene for a novel epidermal
antigen maps near the neurofibromatosis 1 gene. Genomics 14: 369-376,
1992.
6. Li, Y.; Martin, B. R.; Cravatt, B. F.; Hofmann, S. L.: DHHC5 protein
palmitoylates flotillin-2 and is rapidly degraded on induction of
neuronal differentiation in cultured cells. J. Biol. Chem. 282:
523-530, 2012.
7. Schroeder, W. T.; Siciliano, M. J.; Stewart-Galetka, S. L.; Duvic,
M.: The human gene for an epidermal surface antigen (M17S1) is located
at 17q11-12. Genomics 11: 481-482, 1991.
8. Schroeder, W. T.; Stephens, K.; Stewart-Galetka, S.; Riccardi,
V.; Duvic, M.: The gene for an epidermal surface antigen is in close
proximity to the locus for von Recklinghausen neurofibromatosis. (Abstract) Clin.
Res. 39: 323A only, 1991.
*FIELD* CN
Patricia A. Hartz - updated: 2/27/2013
Patricia A. Hartz - updated: 4/19/2012
Patricia A. Hartz - updated: 5/28/2002
Ada Hamosh - updated: 9/13/2000
*FIELD* CD
Victor A. McKusick: 5/9/1991
*FIELD* ED
mgross: 03/07/2013
terry: 2/27/2013
mgross: 4/20/2012
terry: 4/19/2012
carol: 11/23/2009
carol: 5/30/2002
terry: 5/28/2002
alopez: 9/13/2000
dkim: 12/16/1998
carol: 6/16/1998
mark: 7/16/1995
carol: 10/14/1992
supermim: 3/16/1992
carol: 2/29/1992
carol: 11/6/1991
carol: 8/19/1991
*RECORD*
*FIELD* NO
131560
*FIELD* TI
*131560 FLOTILLIN 2; FLOT2
;;EPIDERMAL SURFACE ANTIGEN 1; ESA1;;
MEMBRANE COMPONENT, CHROMOSOME 17, SURFACE MARKER 1; M17S1
read more*FIELD* TX
CLONING
Human epidermal surface antigen-1 was identified as a 35-kD antigen by
means of a mouse monoclonal antibody raised against human keratinocytes.
The monoclonal antibody was found to cause keratinocyte dissociation in
vitro; hence, the conclusion that the native protein is involved in cell
adhesion. Cho et al. (1995) found that mouse Esa cDNA encodes a
379-amino acid protein that is 99.2% identical to the human, differing
at only 3 amino acids. Cho et al. (1995) found that both 'nude' and
control mice have a second Esa mRNA transcript that conserves amino acid
sequence and molecular mass. The mouse and human 5-prime- and 3-prime
untranslated sequences are conserved. Similar RNA folding patterns of
the 5-prime untranslated region are predicted despite a 91-bp insertion
in the mouse.
GENE FUNCTION
Bickel et al. (1997) found that mouse Flot2 consistently copurifies with
Flot1 (606998) and with caveolin-1 (601047) in the purification of
caveolin-rich membranes.
Baumann et al. (2000) screened a yeast 2-hybrid library using the
N-terminal region of CAP (605264) and identified the caveolar protein
flotillin. Flotillin forms a ternary complex with CAP and the CBL
protooncogene product (165360), directing the localization of the
CAP-CBL complex to a lipid raft subdomain of the plasma membrane.
Localization of the CBL-CAP complex to lipid rafts generates a pathway
that is crucial in the regulation of glucose uptake.
Uptake of cholesterol from intestine and liver is mediated by NPC1L1
(608010), which cycles between the plasma membrane and endocytic
recycling compartment in response to cholesterol availability. Using a
human liver cell line, rat liver cells expressing human NPC1L1, and
transgenic mice, Ge et al. (2011) found that NPC1L1 required FLOT1 and
FLOT2 for bulk endocytosis of cholesterol-enriched plasma membrane
microdomains. NPC1L1 interacted directly with FLOT1 and FLOT2, which
functioned upstream of clathrin (see 118955) in NPC1L1 cholesterol
uptake. The flotillins had no effect on recycling NPC1L1 to plasma
membranes. In addition, the hypocholesterolemic drug ezetimibe disrupted
NPC1L1-flotillin interactions, blocking formation of
cholesterol-enriched microdomains.
DHHC5 (ZDHHC5; 614586) belongs to a family of palmitoyl acyltransferases
that reversibly modify cysteine residues for the regulation of protein
trafficking, stability, and activity. Using a quantitative proteomic
analysis of cultured mouse neuronal stem cells, Li et al. (2012) found
that palmitoylation and oligomerization of flotillin-2 was abolished in
homozygous Dhhc5 mutant neuronal stem cells. The absolute amount of
flotillin-2 was not changed in Dhhc5 mutant neurons. In contrast,
overexpression of mouse Dhhc5 in COS-7 cells markedly stimulated
palmitoylation of human flotillin-2. Human flotillin-2 is myristoylated
at gly2 and palmitoylated at cys4, cys19, and cys20. Mutation analysis
of human flotillin-2 expressed in COS-7 cells revealed that coexpressed
mouse Dhhc5 and endogenous COS-7 cell enzymes palmitoylated flotillin-2
predominantly on cys4 and cys20.
MAPPING
Schroeder et al. (1991) isolated a cDNA for an epidermal surface antigen
believed to be involved in epidermal cell adhesion. By analysis of a
somatic cell hybrid panel and in situ hybridization using the ESA cDNA,
the gene was mapped to 17q11-q12 in the region containing the NF1 gene
(613113). Using a RFLP within the ESA1 gene, they showed tight linkage
of ESA1 with NF1; maximal lod = 6.92 at theta = 0.0. By studying somatic
cell hybrids carrying the 2 chromosome 17 translocations with
breakpoints within the NF1 gene, t(1;17) and t(17;22), Schroeder et al.
(1991) showed that the ESA1 gene is located centromeric to the t(1;17)
breakpoint. It remained to be determined whether this represented
another of the genes located within the NF1 gene and transcribed in the
opposite direction. Kayes et al. (1992) made that determination;
physical mapping of an M17S1 cDNA on somatic cell hybrids, yeast
artificial chromosomes, and DNA from a patient with neurofibromatosis I
(162200) with a deletion involving an entire NF1 allele showed that
M17S1 is located at least 180 kb centromeric to the NF1 gene. The
distance between the genes suggested that M17S1 is unlikely to
contribute to the NF1 phenotype.
Cho et al. (1995) mapped the mouse Esa gene to chromosome 11. Although
the mouse Esa gene and the 'nude' locus map to the same region of
chromosome 11, Cho et al. (1995) detected no abnormalities in protein,
mRNA, cDNA or genomic Esa sequences in nude mice.
*FIELD* RF
1. Baumann, C. A.; Ribon, V.; Kanzaki, M.; Thurmond, D. C.; Mora,
S.; Shigematsu, S.; Bickel, P. E.; Pessin, J. E.; Saltiel, A. R.:
CAP defines a second signalling pathway required for insulin-stimulated
glucose transport. Nature 407: 202-207, 2000.
2. Bickel, P. E.; Scherer, P. E.; Schnitzer, J. E.; Oh, P.; Lisanti,
M. P.; Lodish, H. F.: Flotillin and epidermal surface antigen define
a new family of caveolae-associated integral membrane proteins. J.
Biol. Chem. 272: 13793-13802, 1997.
3. Cho, Y.-J.; Chema, D.; Moskow, J. J.; Cho, M.; Schroeder, W. T.;
Overbeek, P.; Buchberg, A. M.; Duvic, M.: Epidermal surface antigen
(MS17S1) is highly conserved between mouse and human. Genomics 27:
251-258, 1995.
4. Ge, L.; Qi, W.; Wang, L.-J.; Miao, H.-H.; Qu, Y.-X.; Li, B.-L.;
Song, B.-L.: Flotillins play an essential role in Niemann-Pick C1-like
1-mediated cholesterol uptake. Proc. Nat. Acad. Sci. 108: 551-556,
2011.
5. Kayes, L. M.; Schroeder, W. T.; Marchuk, D. A.; Collins, F. S.;
Riccardi, V. M.; Duvic, M.; Stephens, K.: The gene for a novel epidermal
antigen maps near the neurofibromatosis 1 gene. Genomics 14: 369-376,
1992.
6. Li, Y.; Martin, B. R.; Cravatt, B. F.; Hofmann, S. L.: DHHC5 protein
palmitoylates flotillin-2 and is rapidly degraded on induction of
neuronal differentiation in cultured cells. J. Biol. Chem. 282:
523-530, 2012.
7. Schroeder, W. T.; Siciliano, M. J.; Stewart-Galetka, S. L.; Duvic,
M.: The human gene for an epidermal surface antigen (M17S1) is located
at 17q11-12. Genomics 11: 481-482, 1991.
8. Schroeder, W. T.; Stephens, K.; Stewart-Galetka, S.; Riccardi,
V.; Duvic, M.: The gene for an epidermal surface antigen is in close
proximity to the locus for von Recklinghausen neurofibromatosis. (Abstract) Clin.
Res. 39: 323A only, 1991.
*FIELD* CN
Patricia A. Hartz - updated: 2/27/2013
Patricia A. Hartz - updated: 4/19/2012
Patricia A. Hartz - updated: 5/28/2002
Ada Hamosh - updated: 9/13/2000
*FIELD* CD
Victor A. McKusick: 5/9/1991
*FIELD* ED
mgross: 03/07/2013
terry: 2/27/2013
mgross: 4/20/2012
terry: 4/19/2012
carol: 11/23/2009
carol: 5/30/2002
terry: 5/28/2002
alopez: 9/13/2000
dkim: 12/16/1998
carol: 6/16/1998
mark: 7/16/1995
carol: 10/14/1992
supermim: 3/16/1992
carol: 2/29/1992
carol: 11/6/1991
carol: 8/19/1991