Full text data of SEC14L2
SEC14L2
(C22orf6, KIAA1186, KIAA1658)
[Confidence: low (only semi-automatic identification from reviews)]
SEC14-like protein 2 (Alpha-tocopherol-associated protein; TAP; hTAP; Squalene transfer protein; Supernatant protein factor; SPF)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
SEC14-like protein 2 (Alpha-tocopherol-associated protein; TAP; hTAP; Squalene transfer protein; Supernatant protein factor; SPF)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O76054
ID S14L2_HUMAN Reviewed; 403 AA.
AC O76054; B7Z8Q1; F5H3U4; Q53EQ2; Q6PD61; Q9ULN4;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=SEC14-like protein 2;
DE AltName: Full=Alpha-tocopherol-associated protein;
DE Short=TAP;
DE Short=hTAP;
DE AltName: Full=Squalene transfer protein;
DE AltName: Full=Supernatant protein factor;
DE Short=SPF;
GN Name=SEC14L2; Synonyms=C22orf6, KIAA1186, KIAA1658;
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP CHARACTERIZATION.
RX PubMed=10829015; DOI=10.1074/jbc.M000851200;
RA Zimmer S., Stocker A., Sarbolouki M.N., Spycher S.E., Sassoon J.,
RA Azzi A.;
RT "A novel human tocopherol-associated protein: cloning, in vitro
RT expression, and characterization.";
RL J. Biol. Chem. 275:25672-25680(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RC TISSUE=Liver;
RX PubMed=11444841; DOI=10.1006/bbrc.2001.5162;
RA Yamauchi J., Iwamoto T., Kida S., Masushige S., Yamada K., Esashi T.;
RT "Tocopherol-associated protein is a ligand-dependent transcriptional
RT activator.";
RL Biochem. Biophys. Res. Commun. 285:295-299(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RC TISSUE=Liver;
RX PubMed=11226224; DOI=10.1073/pnas.041620398;
RA Shibata N., Arita M., Misaki Y., Dohmae N., Takio K., Ono T.,
RA Inoue K., Arai H.;
RT "Supernatant protein factor, which stimulates the conversion of
RT squalene to lanosterol, is a cytosolic squalene transfer protein and
RT enhances cholesterol biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2244-2249(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis
RT from size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [5]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT
RP LYS-11.
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP LYS-11.
RC TISSUE=Kidney;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=12429094; DOI=10.1016/S0969-2126(02)00884-5;
RA Stocker A., Tomizaki T., Schulze-Briese C., Baumann U.;
RT "Crystal structure of the human supernatant protein factor.";
RL Structure 10:1533-1540(2002).
CC -!- FUNCTION: Carrier protein. Binds to some hydrophobic molecules and
CC promotes their transfer between the different cellular sites.
CC Binds with high affinity to alpha-tocopherol. Also binds with a
CC weaker affinity to other tocopherols and to tocotrienols. May have
CC a transcriptional activatory activity via its association with
CC alpha-tocopherol. Probably recognizes and binds some squalene
CC structure, suggesting that it may regulate cholesterol
CC biosynthesis by increasing the transfer of squalene to a metabolic
CC active pool in the cell.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Cytoplasmic in
CC absence of alpha-tocopherol, and nuclear in presence of alpha-
CC tocopherol.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O76054-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O76054-4; Sequence=VSP_042021;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=O76054-5; Sequence=VSP_045880;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed. Strong expression in liver,
CC brain and prostate.
CC -!- DEVELOPMENTAL STAGE: Low expression in fetal tissues.
CC -!- SIMILARITY: Contains 1 CRAL-TRIO domain.
CC -!- SIMILARITY: Contains 1 GOLD domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86500.2; Type=Erroneous initiation;
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DR EMBL; AL096881; CAB51405.1; -; mRNA.
DR EMBL; AB033012; BAA86500.2; ALT_INIT; mRNA.
DR EMBL; CR456571; CAG30457.1; -; mRNA.
DR EMBL; AK303751; BAH14037.1; -; mRNA.
DR EMBL; AK223587; BAD97307.1; -; mRNA.
DR EMBL; AC004832; AAF19256.1; -; Genomic_DNA.
DR EMBL; BC058915; AAH58915.1; -; mRNA.
DR PIR; JC7708; JC7708.
DR RefSeq; NP_001191133.1; NM_001204204.1.
DR RefSeq; NP_036561.1; NM_012429.3.
DR RefSeq; NP_203740.1; NM_033382.2.
DR UniGene; Hs.335614; -.
DR PDB; 1O6U; X-ray; 2.05 A; A/C/E=1-403.
DR PDB; 1OLM; X-ray; 1.95 A; A/C/E=1-403.
DR PDBsum; 1O6U; -.
DR PDBsum; 1OLM; -.
DR ProteinModelPortal; O76054; -.
DR SMR; O76054; 1-397.
DR IntAct; O76054; 1.
DR MINT; MINT-3002196; -.
DR STRING; 9606.ENSP00000316203; -.
DR DrugBank; DB00163; Vitamin E.
DR PhosphoSite; O76054; -.
DR PaxDb; O76054; -.
DR PeptideAtlas; O76054; -.
DR PRIDE; O76054; -.
DR DNASU; 23541; -.
DR Ensembl; ENST00000312932; ENSP00000316203; ENSG00000100003.
DR Ensembl; ENST00000402592; ENSP00000383882; ENSG00000100003.
DR Ensembl; ENST00000405717; ENSP00000385186; ENSG00000100003.
DR GeneID; 23541; -.
DR KEGG; hsa:23541; -.
DR UCSC; uc011aky.2; human.
DR CTD; 23541; -.
DR GeneCards; GC22P030792; -.
DR HGNC; HGNC:10699; SEC14L2.
DR MIM; 607558; gene.
DR neXtProt; NX_O76054; -.
DR PharmGKB; PA35622; -.
DR eggNOG; NOG309458; -.
DR HOGENOM; HOG000232201; -.
DR HOVERGEN; HBG055336; -.
DR InParanoid; O76054; -.
DR OMA; KXPKLFP; -.
DR OrthoDB; EOG7N8ZVD; -.
DR PhylomeDB; O76054; -.
DR ChiTaRS; SEC14L2; human.
DR EvolutionaryTrace; O76054; -.
DR GeneWiki; SEC14L2; -.
DR GenomeRNAi; 23541; -.
DR NextBio; 46048; -.
DR PRO; PR:O76054; -.
DR ArrayExpress; O76054; -.
DR Bgee; O76054; -.
DR CleanEx; HS_SEC14L2; -.
DR Genevestigator; O76054; -.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; NAS:UniProtKB.
DR GO; GO:0005215; F:transporter activity; IEA:InterPro.
DR GO; GO:0008431; F:vitamin E binding; NAS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; NAS:UniProtKB.
DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; NAS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 3.40.525.10; -; 1.
DR InterPro; IPR001071; CRAL-bd_toc_tran.
DR InterPro; IPR001251; CRAL-TRIO_dom.
DR InterPro; IPR011074; CRAL/TRIO_N_dom.
DR InterPro; IPR009038; GOLD.
DR Pfam; PF00650; CRAL_TRIO; 1.
DR Pfam; PF03765; CRAL_TRIO_N; 1.
DR PRINTS; PR00180; CRETINALDHBP.
DR SMART; SM01100; CRAL_TRIO_N; 1.
DR SMART; SM00516; SEC14; 1.
DR SUPFAM; SSF101576; SSF101576; 1.
DR SUPFAM; SSF46938; SSF46938; 1.
DR SUPFAM; SSF52087; SSF52087; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
DR PROSITE; PS50866; GOLD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Complete proteome;
KW Cytoplasm; Lipid-binding; Nucleus; Polymorphism; Reference proteome;
KW Transcription; Transcription regulation; Transport.
FT CHAIN 1 403 SEC14-like protein 2.
FT /FTId=PRO_0000210755.
FT DOMAIN 76 249 CRAL-TRIO.
FT DOMAIN 275 383 GOLD.
FT VAR_SEQ 58 140 Missing (in isoform 3).
FT /FTId=VSP_045880.
FT VAR_SEQ 361 403 YVLRFDNTYSFIHAKKVNFTVEVLLPDKASEEKMKQLGAGT
FT PK -> CKYLCLGNALKPHVQLSACEVPLPPWIFGSEC
FT (in isoform 2).
FT /FTId=VSP_042021.
FT VARIANT 11 11 R -> K (in dbSNP:rs757660).
FT /FTId=VAR_024626.
FT CONFLICT 36 36 Y -> H (in Ref. 2).
FT HELIX 10 23
FT HELIX 24 29
FT HELIX 35 44
FT TURN 45 47
FT HELIX 49 65
FT HELIX 68 73
FT HELIX 78 83
FT STRAND 86 91
FT STRAND 97 102
FT HELIX 108 112
FT HELIX 117 142
FT STRAND 149 154
FT HELIX 160 163
FT HELIX 165 181
FT STRAND 186 193
FT HELIX 198 205
FT HELIX 206 208
FT HELIX 211 215
FT STRAND 217 219
FT HELIX 224 228
FT TURN 229 231
FT HELIX 234 236
FT HELIX 239 241
FT STRAND 243 245
FT TURN 255 257
FT HELIX 266 268
FT STRAND 279 284
FT STRAND 289 296
FT STRAND 302 312
FT STRAND 314 320
FT STRAND 323 326
FT HELIX 330 332
FT STRAND 333 342
FT TURN 344 346
FT STRAND 349 354
FT STRAND 359 366
FT STRAND 374 384
FT HELIX 388 395
SQ SEQUENCE 403 AA; 46145 MW; D846747EC8D1513E CRC64;
MSGRVGDLSP RQKEALAKFR ENVQDVLPAL PNPDDYFLLR WLRARSFDLQ KSEAMLRKHV
EFRKQKDIDN IISWQPPEVI QQYLSGGMCG YDLDGCPVWY DIIGPLDAKG LLFSASKQDL
LRTKMRECEL LLQECAHQTT KLGRKVETIT IIYDCEGLGL KHLWKPAVEA YGEFLCMFEE
NYPETLKRLF VVKAPKLFPV AYNLIKPFLS EDTRKKIMVL GANWKEVLLK HISPDQVPVE
YGGTMTDPDG NPKCKSKINY GGDIPRKYYV RDQVKQQYEH SVQISRGSSH QVEYEILFPG
CVLRWQFMSD GADVGFGIFL KTKMGERQRA GEMTEVLPNQ RYNSHLVPED GTLTCSDPGI
YVLRFDNTYS FIHAKKVNFT VEVLLPDKAS EEKMKQLGAG TPK
//
ID S14L2_HUMAN Reviewed; 403 AA.
AC O76054; B7Z8Q1; F5H3U4; Q53EQ2; Q6PD61; Q9ULN4;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=SEC14-like protein 2;
DE AltName: Full=Alpha-tocopherol-associated protein;
DE Short=TAP;
DE Short=hTAP;
DE AltName: Full=Squalene transfer protein;
DE AltName: Full=Supernatant protein factor;
DE Short=SPF;
GN Name=SEC14L2; Synonyms=C22orf6, KIAA1186, KIAA1658;
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP CHARACTERIZATION.
RX PubMed=10829015; DOI=10.1074/jbc.M000851200;
RA Zimmer S., Stocker A., Sarbolouki M.N., Spycher S.E., Sassoon J.,
RA Azzi A.;
RT "A novel human tocopherol-associated protein: cloning, in vitro
RT expression, and characterization.";
RL J. Biol. Chem. 275:25672-25680(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RC TISSUE=Liver;
RX PubMed=11444841; DOI=10.1006/bbrc.2001.5162;
RA Yamauchi J., Iwamoto T., Kida S., Masushige S., Yamada K., Esashi T.;
RT "Tocopherol-associated protein is a ligand-dependent transcriptional
RT activator.";
RL Biochem. Biophys. Res. Commun. 285:295-299(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RC TISSUE=Liver;
RX PubMed=11226224; DOI=10.1073/pnas.041620398;
RA Shibata N., Arita M., Misaki Y., Dohmae N., Takio K., Ono T.,
RA Inoue K., Arai H.;
RT "Supernatant protein factor, which stimulates the conversion of
RT squalene to lanosterol, is a cytosolic squalene transfer protein and
RT enhances cholesterol biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2244-2249(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis
RT from size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [5]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT
RP LYS-11.
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP LYS-11.
RC TISSUE=Kidney;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=12429094; DOI=10.1016/S0969-2126(02)00884-5;
RA Stocker A., Tomizaki T., Schulze-Briese C., Baumann U.;
RT "Crystal structure of the human supernatant protein factor.";
RL Structure 10:1533-1540(2002).
CC -!- FUNCTION: Carrier protein. Binds to some hydrophobic molecules and
CC promotes their transfer between the different cellular sites.
CC Binds with high affinity to alpha-tocopherol. Also binds with a
CC weaker affinity to other tocopherols and to tocotrienols. May have
CC a transcriptional activatory activity via its association with
CC alpha-tocopherol. Probably recognizes and binds some squalene
CC structure, suggesting that it may regulate cholesterol
CC biosynthesis by increasing the transfer of squalene to a metabolic
CC active pool in the cell.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Cytoplasmic in
CC absence of alpha-tocopherol, and nuclear in presence of alpha-
CC tocopherol.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O76054-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O76054-4; Sequence=VSP_042021;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=O76054-5; Sequence=VSP_045880;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed. Strong expression in liver,
CC brain and prostate.
CC -!- DEVELOPMENTAL STAGE: Low expression in fetal tissues.
CC -!- SIMILARITY: Contains 1 CRAL-TRIO domain.
CC -!- SIMILARITY: Contains 1 GOLD domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86500.2; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
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DR EMBL; AL096881; CAB51405.1; -; mRNA.
DR EMBL; AB033012; BAA86500.2; ALT_INIT; mRNA.
DR EMBL; CR456571; CAG30457.1; -; mRNA.
DR EMBL; AK303751; BAH14037.1; -; mRNA.
DR EMBL; AK223587; BAD97307.1; -; mRNA.
DR EMBL; AC004832; AAF19256.1; -; Genomic_DNA.
DR EMBL; BC058915; AAH58915.1; -; mRNA.
DR PIR; JC7708; JC7708.
DR RefSeq; NP_001191133.1; NM_001204204.1.
DR RefSeq; NP_036561.1; NM_012429.3.
DR RefSeq; NP_203740.1; NM_033382.2.
DR UniGene; Hs.335614; -.
DR PDB; 1O6U; X-ray; 2.05 A; A/C/E=1-403.
DR PDB; 1OLM; X-ray; 1.95 A; A/C/E=1-403.
DR PDBsum; 1O6U; -.
DR PDBsum; 1OLM; -.
DR ProteinModelPortal; O76054; -.
DR SMR; O76054; 1-397.
DR IntAct; O76054; 1.
DR MINT; MINT-3002196; -.
DR STRING; 9606.ENSP00000316203; -.
DR DrugBank; DB00163; Vitamin E.
DR PhosphoSite; O76054; -.
DR PaxDb; O76054; -.
DR PeptideAtlas; O76054; -.
DR PRIDE; O76054; -.
DR DNASU; 23541; -.
DR Ensembl; ENST00000312932; ENSP00000316203; ENSG00000100003.
DR Ensembl; ENST00000402592; ENSP00000383882; ENSG00000100003.
DR Ensembl; ENST00000405717; ENSP00000385186; ENSG00000100003.
DR GeneID; 23541; -.
DR KEGG; hsa:23541; -.
DR UCSC; uc011aky.2; human.
DR CTD; 23541; -.
DR GeneCards; GC22P030792; -.
DR HGNC; HGNC:10699; SEC14L2.
DR MIM; 607558; gene.
DR neXtProt; NX_O76054; -.
DR PharmGKB; PA35622; -.
DR eggNOG; NOG309458; -.
DR HOGENOM; HOG000232201; -.
DR HOVERGEN; HBG055336; -.
DR InParanoid; O76054; -.
DR OMA; KXPKLFP; -.
DR OrthoDB; EOG7N8ZVD; -.
DR PhylomeDB; O76054; -.
DR ChiTaRS; SEC14L2; human.
DR EvolutionaryTrace; O76054; -.
DR GeneWiki; SEC14L2; -.
DR GenomeRNAi; 23541; -.
DR NextBio; 46048; -.
DR PRO; PR:O76054; -.
DR ArrayExpress; O76054; -.
DR Bgee; O76054; -.
DR CleanEx; HS_SEC14L2; -.
DR Genevestigator; O76054; -.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; NAS:UniProtKB.
DR GO; GO:0005215; F:transporter activity; IEA:InterPro.
DR GO; GO:0008431; F:vitamin E binding; NAS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; NAS:UniProtKB.
DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; NAS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 3.40.525.10; -; 1.
DR InterPro; IPR001071; CRAL-bd_toc_tran.
DR InterPro; IPR001251; CRAL-TRIO_dom.
DR InterPro; IPR011074; CRAL/TRIO_N_dom.
DR InterPro; IPR009038; GOLD.
DR Pfam; PF00650; CRAL_TRIO; 1.
DR Pfam; PF03765; CRAL_TRIO_N; 1.
DR PRINTS; PR00180; CRETINALDHBP.
DR SMART; SM01100; CRAL_TRIO_N; 1.
DR SMART; SM00516; SEC14; 1.
DR SUPFAM; SSF101576; SSF101576; 1.
DR SUPFAM; SSF46938; SSF46938; 1.
DR SUPFAM; SSF52087; SSF52087; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
DR PROSITE; PS50866; GOLD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Complete proteome;
KW Cytoplasm; Lipid-binding; Nucleus; Polymorphism; Reference proteome;
KW Transcription; Transcription regulation; Transport.
FT CHAIN 1 403 SEC14-like protein 2.
FT /FTId=PRO_0000210755.
FT DOMAIN 76 249 CRAL-TRIO.
FT DOMAIN 275 383 GOLD.
FT VAR_SEQ 58 140 Missing (in isoform 3).
FT /FTId=VSP_045880.
FT VAR_SEQ 361 403 YVLRFDNTYSFIHAKKVNFTVEVLLPDKASEEKMKQLGAGT
FT PK -> CKYLCLGNALKPHVQLSACEVPLPPWIFGSEC
FT (in isoform 2).
FT /FTId=VSP_042021.
FT VARIANT 11 11 R -> K (in dbSNP:rs757660).
FT /FTId=VAR_024626.
FT CONFLICT 36 36 Y -> H (in Ref. 2).
FT HELIX 10 23
FT HELIX 24 29
FT HELIX 35 44
FT TURN 45 47
FT HELIX 49 65
FT HELIX 68 73
FT HELIX 78 83
FT STRAND 86 91
FT STRAND 97 102
FT HELIX 108 112
FT HELIX 117 142
FT STRAND 149 154
FT HELIX 160 163
FT HELIX 165 181
FT STRAND 186 193
FT HELIX 198 205
FT HELIX 206 208
FT HELIX 211 215
FT STRAND 217 219
FT HELIX 224 228
FT TURN 229 231
FT HELIX 234 236
FT HELIX 239 241
FT STRAND 243 245
FT TURN 255 257
FT HELIX 266 268
FT STRAND 279 284
FT STRAND 289 296
FT STRAND 302 312
FT STRAND 314 320
FT STRAND 323 326
FT HELIX 330 332
FT STRAND 333 342
FT TURN 344 346
FT STRAND 349 354
FT STRAND 359 366
FT STRAND 374 384
FT HELIX 388 395
SQ SEQUENCE 403 AA; 46145 MW; D846747EC8D1513E CRC64;
MSGRVGDLSP RQKEALAKFR ENVQDVLPAL PNPDDYFLLR WLRARSFDLQ KSEAMLRKHV
EFRKQKDIDN IISWQPPEVI QQYLSGGMCG YDLDGCPVWY DIIGPLDAKG LLFSASKQDL
LRTKMRECEL LLQECAHQTT KLGRKVETIT IIYDCEGLGL KHLWKPAVEA YGEFLCMFEE
NYPETLKRLF VVKAPKLFPV AYNLIKPFLS EDTRKKIMVL GANWKEVLLK HISPDQVPVE
YGGTMTDPDG NPKCKSKINY GGDIPRKYYV RDQVKQQYEH SVQISRGSSH QVEYEILFPG
CVLRWQFMSD GADVGFGIFL KTKMGERQRA GEMTEVLPNQ RYNSHLVPED GTLTCSDPGI
YVLRFDNTYS FIHAKKVNFT VEVLLPDKAS EEKMKQLGAG TPK
//
MIM
607558
*RECORD*
*FIELD* NO
607558
*FIELD* TI
*607558 SEC14-LIKE 2; SEC14L2
;;SEC14, S. CEREVISIAE, HOMOLOG OF, 2;;
TOCOPHEROL-ASSOCIATED PROTEIN 1; TAP1;;
read moreTAP KIAA1186
*FIELD* TX
CLONING
By sequencing clones obtained from a size-fractionated human brain cDNA
library, Hirosawa et al. (1999) cloned a partial cDNA encoding SEC14L2,
which they designated KIAA1186. RT-PCR followed by ELISA detected
moderate expression in kidney, spleen, testis, ovary, and fetal liver.
Lower levels were detected in whole brain, lung, and adult liver.
Zimmer et al. (2000) sequenced peptide fragments from bovine SEC14L2,
which they called TAP, and searched a database using these sequences to
identify human TAP. Using RT-PCR they cloned full-length TAP from human
small intestine total RNA. The deduced 403-amino acid protein has a
calculated molecular mass of about 46 kD and contains a conserved
hydrophobic lipid-binding pocket called the CRAL (cis-retinal
binding)/TRIO (triple function) domain. Human and bovine TAP share about
84% amino acid identity. mRNA dot blot analysis detected broad tissue
distribution, with highest expression in liver, prostate, and brain.
Northern blot analysis detected a major transcript of 2.8 kb and 2 minor
transcripts of approximately 4.2 and 2.8 kb expressed at highest levels
in liver and brain and more weakly in kidney.
By immunocytochemical studies, Kempna et al. (2003) showed that SEC14L2
localized to intracellular membranes of the cytoplasm in HeLa cells,
including partial localization to the ER and Golgi, with more intense
staining surrounding but not within the nucleus.
GENE FUNCTION
Using a biotinylated alpha-tocopherol derivative, Zimmer et al. (2000)
demonstrated that recombinant TAP binds alpha-tocopherol at physiologic
concentrations. Binding was dose dependent and saturable.
By ligand competition analysis, Yamauchi et al. (2001) confirmed
specific interaction between recombinant TAP and alpha-tocopherol. TAP
did not significantly interact with any other tocopherols or
tocotrienols examined. Alpha-tocopherol induced the translocation of TAP
from the cytosol to the nucleus of transfected COS-7 cells. Transient
transfection experiments showed that TAP activated transcription of a
reporter gene in an alpha-tocopherol-dependent manner. Yamauchi et al.
(2001) hypothesized that alpha-tocopherol is not only an antioxidant,
but also a transcriptional regulator via its association with TAP.
Kempna et al. (2003) showed that in HeLa cells deletion of the
C-terminal Golgi dynamics (GOLD) domain reduced SEC14L2 localization in
the region surrounding the nucleus with some tubular sacs emerging. They
suggested that the SEC14L2 GOLD domain may play a role in docking to
other proteins or in intracellular transport of bound ligands. Using
several assays, Kempna et al. (2003) demonstrated that SEC14L2 bound
tocopherol, squalene, and phospholipids (phosphatidylcholine,
phosphatidylinositol, phosphatidylglycerol). Although SEC14L2 bound
phospholipids, it failed to complement an S. cerevisiae
temperature-sensitive Sec14 allele in yeast. Using immunoprecipitation
assays, Kempna et al. (2003) showed that SEC14L2 may interact with and
regulate phosphatidylinositol 3-kinase activity, and SEC14L2 displayed
low basal GTPase activity.
GENE STRUCTURE
Zimmer et al. (2000) determined that the SEC14L2 gene contains 12 exons.
MAPPING
By radiation hybrid analysis, Hirosawa et al. (1999) mapped the SEC14L2
gene to chromosome 22. By genomic sequence analysis, Zimmer et al.
(2000) mapped the SEC14L2 gene to chromosome 22q12.1-qter.
*FIELD* RF
1. Hirosawa, M.; Nagase, T.; Ishikawa, K.; Kikuno, R.; Nomura, N.;
Ohara, O.: Characterization of cDNA clones selected by the GeneMark
analysis from size-fractionated cDNA libraries from human brain. DNA
Res. 6: 329-336, 1999.
2. Kempna, P.; Zingg, J.-M.; Ricciarelli, R.; Hierl, M.; Saxena, S.;
Azzi, A.: Cloning of novel human Sec14p-like proteins: ligand binding
and functional properties. Free Radical Biol. Med. 34: 1458-1472,
2003.
3. Yamauchi, J.; Iwamoto, T.; Kida, S.; Masushige, S.; Yamada, K.;
Esashi, T.: Tocopherol-associated protein is a ligand-dependent transcriptional
activator. Biochem. Biophys. Res. Commun. 285: 295-299, 2001.
4. Zimmer, S.; Stocker, A.; Sarbolouki, M. N.; Spycher, S. E.; Sassoon,
J.; Azzi, A.: A novel human tocopherol-associated protein: cloning,
in vitro expression, and characterization. J. Biol. Chem. 275: 25672-25680,
2000.
*FIELD* CN
Dorothy S. Reilly - updated: 05/28/2009
*FIELD* CD
Patricia A. Hartz: 2/11/2003
*FIELD* ED
wwang: 05/28/2009
terry: 7/20/2004
mgross: 2/11/2003
*RECORD*
*FIELD* NO
607558
*FIELD* TI
*607558 SEC14-LIKE 2; SEC14L2
;;SEC14, S. CEREVISIAE, HOMOLOG OF, 2;;
TOCOPHEROL-ASSOCIATED PROTEIN 1; TAP1;;
read moreTAP KIAA1186
*FIELD* TX
CLONING
By sequencing clones obtained from a size-fractionated human brain cDNA
library, Hirosawa et al. (1999) cloned a partial cDNA encoding SEC14L2,
which they designated KIAA1186. RT-PCR followed by ELISA detected
moderate expression in kidney, spleen, testis, ovary, and fetal liver.
Lower levels were detected in whole brain, lung, and adult liver.
Zimmer et al. (2000) sequenced peptide fragments from bovine SEC14L2,
which they called TAP, and searched a database using these sequences to
identify human TAP. Using RT-PCR they cloned full-length TAP from human
small intestine total RNA. The deduced 403-amino acid protein has a
calculated molecular mass of about 46 kD and contains a conserved
hydrophobic lipid-binding pocket called the CRAL (cis-retinal
binding)/TRIO (triple function) domain. Human and bovine TAP share about
84% amino acid identity. mRNA dot blot analysis detected broad tissue
distribution, with highest expression in liver, prostate, and brain.
Northern blot analysis detected a major transcript of 2.8 kb and 2 minor
transcripts of approximately 4.2 and 2.8 kb expressed at highest levels
in liver and brain and more weakly in kidney.
By immunocytochemical studies, Kempna et al. (2003) showed that SEC14L2
localized to intracellular membranes of the cytoplasm in HeLa cells,
including partial localization to the ER and Golgi, with more intense
staining surrounding but not within the nucleus.
GENE FUNCTION
Using a biotinylated alpha-tocopherol derivative, Zimmer et al. (2000)
demonstrated that recombinant TAP binds alpha-tocopherol at physiologic
concentrations. Binding was dose dependent and saturable.
By ligand competition analysis, Yamauchi et al. (2001) confirmed
specific interaction between recombinant TAP and alpha-tocopherol. TAP
did not significantly interact with any other tocopherols or
tocotrienols examined. Alpha-tocopherol induced the translocation of TAP
from the cytosol to the nucleus of transfected COS-7 cells. Transient
transfection experiments showed that TAP activated transcription of a
reporter gene in an alpha-tocopherol-dependent manner. Yamauchi et al.
(2001) hypothesized that alpha-tocopherol is not only an antioxidant,
but also a transcriptional regulator via its association with TAP.
Kempna et al. (2003) showed that in HeLa cells deletion of the
C-terminal Golgi dynamics (GOLD) domain reduced SEC14L2 localization in
the region surrounding the nucleus with some tubular sacs emerging. They
suggested that the SEC14L2 GOLD domain may play a role in docking to
other proteins or in intracellular transport of bound ligands. Using
several assays, Kempna et al. (2003) demonstrated that SEC14L2 bound
tocopherol, squalene, and phospholipids (phosphatidylcholine,
phosphatidylinositol, phosphatidylglycerol). Although SEC14L2 bound
phospholipids, it failed to complement an S. cerevisiae
temperature-sensitive Sec14 allele in yeast. Using immunoprecipitation
assays, Kempna et al. (2003) showed that SEC14L2 may interact with and
regulate phosphatidylinositol 3-kinase activity, and SEC14L2 displayed
low basal GTPase activity.
GENE STRUCTURE
Zimmer et al. (2000) determined that the SEC14L2 gene contains 12 exons.
MAPPING
By radiation hybrid analysis, Hirosawa et al. (1999) mapped the SEC14L2
gene to chromosome 22. By genomic sequence analysis, Zimmer et al.
(2000) mapped the SEC14L2 gene to chromosome 22q12.1-qter.
*FIELD* RF
1. Hirosawa, M.; Nagase, T.; Ishikawa, K.; Kikuno, R.; Nomura, N.;
Ohara, O.: Characterization of cDNA clones selected by the GeneMark
analysis from size-fractionated cDNA libraries from human brain. DNA
Res. 6: 329-336, 1999.
2. Kempna, P.; Zingg, J.-M.; Ricciarelli, R.; Hierl, M.; Saxena, S.;
Azzi, A.: Cloning of novel human Sec14p-like proteins: ligand binding
and functional properties. Free Radical Biol. Med. 34: 1458-1472,
2003.
3. Yamauchi, J.; Iwamoto, T.; Kida, S.; Masushige, S.; Yamada, K.;
Esashi, T.: Tocopherol-associated protein is a ligand-dependent transcriptional
activator. Biochem. Biophys. Res. Commun. 285: 295-299, 2001.
4. Zimmer, S.; Stocker, A.; Sarbolouki, M. N.; Spycher, S. E.; Sassoon,
J.; Azzi, A.: A novel human tocopherol-associated protein: cloning,
in vitro expression, and characterization. J. Biol. Chem. 275: 25672-25680,
2000.
*FIELD* CN
Dorothy S. Reilly - updated: 05/28/2009
*FIELD* CD
Patricia A. Hartz: 2/11/2003
*FIELD* ED
wwang: 05/28/2009
terry: 7/20/2004
mgross: 2/11/2003