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Store-operated calcium entry-associated regulatory factor (SARAF) (SOCE-associated regulatory factor) (HBV X-transactivated gene 3 protein) (HBV XAg-transactivated protein 3) (Protein FOAP-7) (Transmembrane protein 66)

 SARAF_HUMAN             Reviewed;         339 AA.
Q96BY9; B3KQQ4; B7Z9J1; D3DSU7; H9MHJ8; H9MHJ9; Q53HE8; Q9UNZ3;
Q9Y683;
10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
01-DEC-2001, sequence version 1.
12-SEP-2018, entry version 120.
RecName: Full=Store-operated calcium entry-associated regulatory factor;
Short=SARAF;
Short=SOCE-associated regulatory factor;
AltName: Full=HBV X-transactivated gene 3 protein;
AltName: Full=HBV XAg-transactivated protein 3;
AltName: Full=Protein FOAP-7;
AltName: Full=Transmembrane protein 66;
Flags: Precursor;
Name=SARAF; Synonyms=TMEM66, XTP3;
ORFNames=HSPC035, NPD003, PSEC0019, UNQ1967/PRO4499;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR
LOCATION, TOPOLOGY, INTERACTION WITH STIM1, AND MUTAGENESIS OF
GLU-148.
TISSUE=Heart;
PubMed=22464749; DOI=10.1016/j.cell.2012.01.055;
Palty R., Raveh A., Kaminsky I., Meller R., Reuveny E.;
"SARAF inactivates the store operated calcium entry machinery to
prevent excess calcium refilling.";
Cell 149:425-438(2012).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
Fujii Y., Tsuritani K., Yajima Y., Amemiya T., Ukai Y., Naito K.,
Kawaguchi A., Takayama K.;
"Molecular cloning of a human novel gene, FOAP-7, which are highly
expressed in macrophages.";
Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Liu Y., Cheng J., Lu Y., Wang G., Zhang L., Chen J., Li L.;
"Cloning and identification of human gene 3 transactivated by
hepatitis B virus X antigen.";
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Umbilical cord blood;
PubMed=11042152; DOI=10.1101/gr.140200;
Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
"Cloning and functional analysis of cDNAs with open reading frames for
300 previously undefined genes expressed in CD34+ hematopoietic
stem/progenitor cells.";
Genome Res. 10:1546-1560(2000).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
PubMed=12975309; DOI=10.1101/gr.1293003;
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale
effort to identify novel human secreted and transmembrane proteins: a
bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
PubMed=16303743; DOI=10.1093/dnares/12.2.117;
Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
Isogai T.;
"Signal sequence and keyword trap in silico for selection of full-
length human cDNAs encoding secretion or membrane proteins from oligo-
capped cDNA libraries.";
DNA Res. 12:117-126(2005).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Amygdala;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Cerebellum;
Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
Tanaka A., Yokoyama S.;
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16421571; DOI=10.1038/nature04406;
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
Lander E.S.;
"DNA sequence and analysis of human chromosome 8.";
Nature 439:331-335(2006).
[10]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[11]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Uterus;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[12]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-339 (ISOFORM 1).
TISSUE=Pituitary;
Huang Q.-H., Zhou J., Song H., Peng J., Zhang Q.-H., Fu G., Dai M.,
Mao Y., Mao M., Chen Z., Chen J.;
"Human NPD003 mRNA, complete cds.";
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
[13]
PROTEIN SEQUENCE OF 31-45.
PubMed=15340161; DOI=10.1110/ps.04682504;
Zhang Z., Henzel W.J.;
"Signal peptide prediction based on analysis of experimentally
verified cleavage sites.";
Protein Sci. 13:2819-2824(2004).
-!- FUNCTION: Negative regulator of store-operated Ca(2+) entry (SOCE)
involved in protecting cells from Ca(2+) overfilling. In response
to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+)
refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)-
dependent SOCE activity: possibly act by facilitating the
deoligomerization of STIM to efficiently turn off ORAI when the
endoplasmic reticulum lumen is filled with the appropriate Ca(2+)
levels, and thus preventing the overload of the cell with
excessive Ca(2+) ions. {ECO:0000269|PubMed:22464749}.
-!- SUBUNIT: Interacts with STIM1. {ECO:0000269|PubMed:22464749}.
-!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
{ECO:0000269|PubMed:22464749}; Single-pass type I membrane protein
{ECO:0000269|PubMed:22464749}. Note=Translocates to the
endoplasmic reticulum-plasma membrane (ER-PM) region in a STIM1-
dependent manner following cytosolic Ca(2+) elevation.
-!- SUBCELLULAR LOCATION: Isoform 2: Endoplasmic reticulum membrane;
Single-pass type I membrane protein.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q96BY9-1; Sequence=Displayed;
Name=2; Synonyms=Short;
IsoId=Q96BY9-2; Sequence=VSP_043773;
-!- TISSUE SPECIFICITY: Highly expressed in macrophages.
{ECO:0000269|Ref.2}.
-!- DOMAIN: The cytoplasmic C-terminal region mediates interaction
with STIM1, while the N-terminal lumenal region mediates
regulation of SOCE activity. {ECO:0000269|PubMed:22464749}.
-!- SIMILARITY: Belongs to the SARAF family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAD44487.1; Type=Frameshift; Positions=28; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; JQ348891; AEZ06361.1; -; mRNA.
EMBL; JQ348892; AEZ06362.1; -; mRNA.
EMBL; AB028926; BAB82465.1; -; mRNA.
EMBL; AF490252; AAO85460.1; -; mRNA.
EMBL; AF100748; AAD43012.1; -; mRNA.
EMBL; AY359104; AAQ89462.1; -; mRNA.
EMBL; AK075340; BAG52116.1; -; mRNA.
EMBL; AK315956; BAH14327.1; -; mRNA.
EMBL; AK222632; BAD96352.1; -; mRNA.
EMBL; AC044849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471080; EAW63471.1; -; Genomic_DNA.
EMBL; CH471080; EAW63472.1; -; Genomic_DNA.
EMBL; CH471080; EAW63474.1; -; Genomic_DNA.
EMBL; BC015012; AAH15012.1; -; mRNA.
EMBL; AF078855; AAD44487.1; ALT_FRAME; mRNA.
CCDS; CCDS6074.1; -. [Q96BY9-1]
CCDS; CCDS64866.1; -. [Q96BY9-2]
RefSeq; NP_001271168.1; NM_001284239.1. [Q96BY9-2]
RefSeq; NP_057211.4; NM_016127.5. [Q96BY9-1]
UniGene; Hs.521487; -.
ProteinModelPortal; Q96BY9; -.
BioGrid; 119672; 35.
IntAct; Q96BY9; 23.
MINT; Q96BY9; -.
STRING; 9606.ENSP00000256255; -.
iPTMnet; Q96BY9; -.
PhosphoSitePlus; Q96BY9; -.
BioMuta; TMEM66; -.
DMDM; 74731293; -.
EPD; Q96BY9; -.
MaxQB; Q96BY9; -.
PaxDb; Q96BY9; -.
PeptideAtlas; Q96BY9; -.
PRIDE; Q96BY9; -.
ProteomicsDB; 76130; -.
ProteomicsDB; 76131; -. [Q96BY9-2]
DNASU; 51669; -.
Ensembl; ENST00000256255; ENSP00000256255; ENSG00000133872. [Q96BY9-1]
Ensembl; ENST00000545648; ENSP00000441351; ENSG00000133872. [Q96BY9-2]
GeneID; 51669; -.
KEGG; hsa:51669; -.
UCSC; uc003xhs.5; human. [Q96BY9-1]
CTD; 51669; -.
DisGeNET; 51669; -.
EuPathDB; HostDB:ENSG00000133872.13; -.
GeneCards; SARAF; -.
HGNC; HGNC:28789; SARAF.
HPA; HPA040400; -.
MIM; 614768; gene.
neXtProt; NX_Q96BY9; -.
OpenTargets; ENSG00000133872; -.
PharmGKB; PA142670779; -.
eggNOG; ENOG410IV9Z; Eukaryota.
eggNOG; ENOG4111IKY; LUCA.
GeneTree; ENSGT00390000013419; -.
HOGENOM; HOG000154648; -.
HOVERGEN; HBG059843; -.
InParanoid; Q96BY9; -.
PhylomeDB; Q96BY9; -.
TreeFam; TF314811; -.
ChiTaRS; SARAF; human.
GeneWiki; TMEM66; -.
GenomeRNAi; 51669; -.
PRO; PR:Q96BY9; -.
Proteomes; UP000005640; Chromosome 8.
Bgee; ENSG00000133872; Expressed in 239 organ(s), highest expression level in frontal cortex.
CleanEx; HS_TMEM66; -.
ExpressionAtlas; Q96BY9; baseline and differential.
Genevisible; Q96BY9; HS.
GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
GO; GO:0006816; P:calcium ion transport; IEA:UniProtKB-KW.
GO; GO:2001256; P:regulation of store-operated calcium entry; IDA:UniProtKB.
InterPro; IPR009567; SARAF.
PANTHER; PTHR15929; PTHR15929; 1.
Pfam; PF06682; SARAF; 1.
1: Evidence at protein level;
Alternative splicing; Calcium; Calcium transport; Complete proteome;
Direct protein sequencing; Endoplasmic reticulum; Ion transport;
Membrane; Polymorphism; Reference proteome; Signal; Transmembrane;
Transmembrane helix; Transport.
SIGNAL 1 30 {ECO:0000269|PubMed:15340161}.
CHAIN 31 339 Store-operated calcium entry-associated
regulatory factor.
/FTId=PRO_0000045485.
TOPO_DOM 31 173 Lumenal. {ECO:0000255}.
TRANSMEM 174 194 Helical. {ECO:0000255}.
TOPO_DOM 195 339 Cytoplasmic. {ECO:0000255}.
VAR_SEQ 1 172 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:22464749}.
/FTId=VSP_043773.
VARIANT 78 78 P -> T (in dbSNP:rs11538828).
/FTId=VAR_054042.
MUTAGEN 148 148 E->A: Dominant-negative mutant; leading
to impair inhibition of SOCE.
{ECO:0000269|PubMed:22464749}.
CONFLICT 57 58 RL -> SW (in Ref. 3; AAO85460 and 4;
AAD43012). {ECO:0000305}.
CONFLICT 57 57 R -> K (in Ref. 12; AAD44487).
{ECO:0000305}.
CONFLICT 145 145 K -> E (in Ref. 6; BAG52116).
{ECO:0000305}.
CONFLICT 231 231 E -> G (in Ref. 8; BAD96352).
{ECO:0000305}.
CONFLICT 267 267 L -> S (in Ref. 8; BAD96352).
{ECO:0000305}.
SEQUENCE 339 AA; 36975 MW; 83CC0517AB635FE9 CRC64;
MAAACGPGAA GYCLLLGLHL FLLTAGPALG WNDPDRMLLR DVKALTLHYD RYTTSRRLDP
IPQLKCVGGT AGCDSYTPKV IQCQNKGWDG YDVQWECKTD LDIAYKFGKT VVSCEGYESS
EDQYVLRGSC GLEYNLDYTE LGLQKLKESG KQHGFASFSD YYYKWSSADS CNMSGLITIV
VLLGIAFVVY KLFLSDGQYS PPPYSEYPPF SHRYQRFTNS AGPPPPGFKS EFTGPQNTGH
GATSGFGSAF TGQQGYENSG PGFWTGLGTG GILGYLFGSN RAATPFSDSW YYPSYPPSYP
GTWNRAYSPL HGGSGSYSVC SNSDTKTRTA SGYGGTRRR


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