Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q96BY9 (SARAF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length339 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Ref.13
Chain31 – 339309Store-operated calcium entry-associated regulatory factor
PRO_0000045485

Regions

Topological domain31 – 173143Lumenal Potential
Transmembrane174 – 19421Helical; Potential
Topological domain195 – 339145Cytoplasmic Potential

Natural variations

Alternative sequence1 – 172172Missing in isoform 2.
VSP_043773
Natural variant781P → T.
Corresponds to variant rs11538828 [ dbSNP | Ensembl ].
VAR_054042

Experimental info

Mutagenesis1481E → A: Dominant-negative mutant; leading to impair inhibition of SOCE. Ref.1
Sequence conflict57 – 582RL → SW in AAO85460. Ref.3
Sequence conflict57 – 582RL → SW in AAD43012. Ref.4
Sequence conflict571R → K in AAD44487. Ref.12
Sequence conflict1451K → E in BAG52116. Ref.6
Sequence conflict2311E → G in BAD96352. Ref.8
Sequence conflict2671L → S in BAD96352. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 83CC0517AB635FE9

FASTA33936,975
        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 

« Hide

Isoform 2 (Short) [UniParc].

Checksum: 19AD430329A55D3E
Show »

FASTA16717,876

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
RefSeqNP_001271168.1. NM_001284239.1.
NP_057211.4. NM_016127.5.
UniGeneHs.521487.

3D structure databases

ProteinModelPortalQ96BY9.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119672. 8 interactions.
IntActQ96BY9. 13 interactions.
MINTMINT-1380432.
STRING9606.ENSP00000256255.

PTM databases

PhosphoSiteQ96BY9.

Polymorphism databases

DMDM74731293.

Proteomic databases

PaxDbQ96BY9.
PeptideAtlasQ96BY9.
PRIDEQ96BY9.

Protocols and materials databases

DNASU51669.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256255; ENSP00000256255; ENSG00000133872. [Q96BY9-1]
ENST00000536273; ENSP00000441723; ENSG00000133872. [Q96BY9-2]
ENST00000545648; ENSP00000441351; ENSG00000133872. [Q96BY9-2]
GeneID51669.
KEGGhsa:51669.
UCSCuc003xhs.3. human. [Q96BY9-1]
uc003xhv.3. human. [Q96BY9-2]

Organism-specific databases

CTD51669.
GeneCardsGC08M029920.
HGNCHGNC:28789. TMEM66.
MIM614768. gene.
neXtProtNX_Q96BY9.
PharmGKBPA142670779.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG85111.
HOGENOMHOG000154648.
HOVERGENHBG059843.
InParanoidQ96BY9.
OrthoDBEOG7QG462.
PhylomeDBQ96BY9.
TreeFamTF314811.

Gene expression databases

ArrayExpressQ96BY9.
BgeeQ96BY9.
CleanExHS_TMEM66.
GenevestigatorQ96BY9.

Family and domain databases

InterProIPR009567. DUF1183_TMEM66.
[Graphical view]
PANTHERPTHR15929. PTHR15929. 1 hit.
PfamPF06682. DUF1183. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTMEM66.
GenomeRNAi51669.
NextBio35531222.
PROQ96BY9.
SOURCESearch...

Entry information

Entry nameSARAF_HUMAN
AccessionPrimary (citable) accession number: Q96BY9
Secondary accession number(s): B3KQQ4 expand/collapse secondary AC list , 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: April 16, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM