Q96BY9 (SARAF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Store-operated calcium entry-associated regulatory factor
Short name=SARAF
Short name=SOCE-associated regulatory factor

Alternative name(s):
HBV X-transactivated gene 3 protein
HBV XAg-transactivated protein 3
Protein FOAP-7
Transmembrane protein 66

Gene names

Name:	TMEM66
Synonyms:	SARAF, XTP3
ORF Names:	HSPC035, NPD003, PSEC0019, UNQ1967/PRO4499

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	339 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Negative regulator of store-operated Ca2+ entry (SOCE) involved in protecting cells from Ca2+ overfilling. In response to cytosolic Ca2+ elevation after endoplasmic reticulum Ca2+ 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 Ca2+ levels, and thus preventing the overload of the cell with excessive Ca2+ ions. Ref.1
Subunit structure	Interacts with STIM1. Ref.1
Subcellular location	Endoplasmic reticulum membrane; Single-pass type I membrane protein Ref.1. Note: Translocates to the endoplasmic reticulum-plasma membrane (ER-PM) region in a STIM1-dependent manner following cytosolic Ca2+ elevation. Ref.1 Isoform 2: Endoplasmic reticulum membrane; Single-pass type I membrane protein Ref.1.
Tissue specificity	Highly expressed in macrophages. Ref.2
Domain	The cytoplasmic C-terminal region mediates interaction with STIM1, while the N-terminal lumenal region mediates regulation of SOCE activity (Ref.1).
Sequence similarities	Belongs to the SARAF family.
Sequence caution	The sequence AAD44487.1 differs from that shown. Reason: Frameshift at position 28.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	Calcium
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	regulation of store-operated calcium entry Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	integral to endoplasmic reticulum membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	store-operated calcium channel activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96BY9-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96BY9-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30	Ref.13
	Chain	31 – 339	309	Store-operated calcium entry-associated regulatory factor		PRO_0000045485
Regions
	Topological domain	31 – 173	143	Lumenal Potential
	Transmembrane	174 – 194	21	Helical; Potential
	Topological domain	195 – 339	145	Cytoplasmic Potential
Natural variations
	Alternative sequence	1 – 172	172	Missing in isoform 2.		VSP_043773
	Natural variant	78	1	P → T. Corresponds to variant rs11538828 [ dbSNP | Ensembl ].		VAR_054042
Experimental info
	Mutagenesis	148	1	E → A: Dominant-negative mutant; leading to impair inhibition of SOCE. Ref.1
	Sequence conflict	57 – 58	2	RL → SW in AAO85460. Ref.3
	Sequence conflict	57 – 58	2	RL → SW in AAD43012. Ref.4
	Sequence conflict	57	1	R → K in AAD44487. Ref.12
	Sequence conflict	145	1	K → E in BAG52116. Ref.6
	Sequence conflict	231	1	E → G in BAD96352. Ref.8
	Sequence conflict	267	1	L → S in BAD96352. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 83CC0517AB635FE9	FASTA	339	36,975
	10 20 30 40 50 60 MAAACGPGAA GYCLLLGLHL FLLTAGPALG WNDPDRMLLR DVKALTLHYD RYTTSRRLDP 70 80 90 100 110 120 IPQLKCVGGT AGCDSYTPKV IQCQNKGWDG YDVQWECKTD LDIAYKFGKT VVSCEGYESS 130 140 150 160 170 180 EDQYVLRGSC GLEYNLDYTE LGLQKLKESG KQHGFASFSD YYYKWSSADS CNMSGLITIV 190 200 210 220 230 240 VLLGIAFVVY KLFLSDGQYS PPPYSEYPPF SHRYQRFTNS AGPPPPGFKS EFTGPQNTGH 250 260 270 280 290 300 GATSGFGSAF TGQQGYENSG PGFWTGLGTG GILGYLFGSN RAATPFSDSW YYPSYPPSYP 310 320 330 GTWNRAYSPL HGGSGSYSVC SNSDTKTRTA SGYGGTRRR
	Isoform 2 (Short) [UniParc]. Checksum: 19AD430329A55D3E	FASTA	167	17,876
	10 20 30 40 50 60 MSGLITIVVL LGIAFVVYKL FLSDGQYSPP PYSEYPPFSH RYQRFTNSAG PPPPGFKSEF 70 80 90 100 110 120 TGPQNTGHGA TSGFGSAFTG QQGYENSGPG FWTGLGTGGI LGYLFGSNRA ATPFSDSWYY 130 140 150 160 PSYPPSYPGT WNRAYSPLHG GSGSYSVCSN SDTKTRTASG YGGTRRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"SARAF inactivates the store operated calcium entry machinery to prevent excess calcium refilling." Palty R., Raveh A., Kaminsky I., Meller R., Reuveny E. Cell 149:425-438(2012) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, INTERACTION WITH STIM1, MUTAGENESIS OF GLU-148. Tissue: Heart.
[2]	"Molecular cloning of a human novel gene, FOAP-7, which are highly expressed in macrophages." Fujii Y., Tsuritani K., Yajima Y., Amemiya T., Ukai Y., Naito K., Kawaguchi A., Takayama K. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]	"Cloning and identification of human gene 3 transactivated by hepatitis B virus X antigen." Liu Y., Cheng J., Lu Y., Wang G., Zhang L., Chen J., Li L. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." 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. Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Umbilical cord blood.
[5]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." 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. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." 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. DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Amygdala.
[8]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Cerebellum.
[9]	"DNA sequence and analysis of human chromosome 8." 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. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[12]	"Human NPD003 mRNA, complete cds." Huang Q.-H., Zhou J., Song H., Peng J., Zhang Q.-H., Fu G., Dai M., Mao Y., Mao M., Chen Z., Chen J. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-339 (ISOFORM 1). Tissue: Pituitary.
[13]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-45.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	JQ348891 mRNA. Translation: AEZ06361.1. JQ348892 mRNA. Translation: AEZ06362.1. AB028926 mRNA. Translation: BAB82465.1. AF490252 mRNA. Translation: AAO85460.1. AF100748 mRNA. Translation: AAD43012.1. AY359104 mRNA. Translation: AAQ89462.1. AK075340 mRNA. Translation: BAG52116.1. AK315956 mRNA. Translation: BAH14327.1. AK222632 mRNA. Translation: BAD96352.1. AC044849 Genomic DNA. No translation available. CH471080 Genomic DNA. Translation: EAW63471.1. CH471080 Genomic DNA. Translation: EAW63472.1. CH471080 Genomic DNA. Translation: EAW63474.1. BC015012 mRNA. Translation: AAH15012.1. AF078855 mRNA. Translation: AAD44487.1. Frameshift.
IPI	IPI00604763.
RefSeq	NP_057211.4. NM_016127.4.
UniGene	Hs.521487.
3D structure databases
ProteinModelPortal	Q96BY9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96BY9. 13 interactions.
MINT	MINT-1380432.
STRING	9606.ENSP00000256255.
PTM databases
PhosphoSite	Q96BY9.
Polymorphism databases
DMDM	74731293.
Proteomic databases
PaxDb	Q96BY9.
PeptideAtlas	Q96BY9.
PRIDE	Q96BY9.
Protocols and materials databases
DNASU	51669.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000256255; ENSP00000256255; ENSG00000133872. ENST00000536273; ENSP00000441723; ENSG00000133872. ENST00000545648; ENSP00000441351; ENSG00000133872.
GeneID	51669.
KEGG	hsa:51669.
UCSC	uc003xhs.3. human.
Organism-specific databases
CTD	51669.
GeneCards	GC08M029920.
HGNC	HGNC:28789. TMEM66.
MIM	614768. gene.
neXtProt	NX_Q96BY9.
PharmGKB	PA142670779.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG85111.
HOGENOM	HOG000154648.
HOVERGEN	HBG059843.
InParanoid	Q96BY9.
OrthoDB	EOG4GQQ5K.
PhylomeDB	Q96BY9.
Gene expression databases
ArrayExpress	Q96BY9.
Bgee	Q96BY9.
CleanEx	HS_TMEM66.
Genevestigator	Q96BY9.
GermOnline	ENSG00000133872. Homo sapiens.
Family and domain databases
InterPro	IPR009567. DUF1183_TMEM66. [Graphical view]
PANTHER	PTHR15929. PTHR15929. 1 hit.
Pfam	PF06682. DUF1183. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	51669.
NextBio	35531222.
SOURCE	Search...

Entry information

Entry name

SARAF_HUMAN

Accession

Primary (citable) accession number: Q96BY9
Secondary accession number(s): B3KQQ4 , B7Z9J1, D3DSU7, H9MHJ8, H9MHJ9, Q53HE8, Q9UNZ3, Q9Y683

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2006
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.