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Q96BY9

- SARAF_HUMAN

UniProt

Q96BY9 - SARAF_HUMAN

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Protein

Store-operated calcium entry-associated regulatory factor

Gene

SARAF

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Biological processi

  1. calcium ion transport Source: UniProtKB-KW
  2. regulation of store-operated calcium entry Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Names & Taxonomyi

Protein namesi
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 namesi
Name:SARAF
Synonyms:TMEM66, XTP3
ORF Names:HSPC035, NPD003, PSEC0019, UNQ1967/PRO4499
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:28789. SARAF.

Subcellular locationi

Endoplasmic reticulum membrane 1 Publication; Single-pass type I membrane protein 1 Publication
Note: Translocates to the endoplasmic reticulum-plasma membrane (ER-PM) region in a STIM1-dependent manner following cytosolic Ca2+ elevation.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini31 – 173143LumenalSequence AnalysisAdd
BLAST
Transmembranei174 – 19421HelicalSequence AnalysisAdd
BLAST
Topological domaini195 – 339145CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of endoplasmic reticulum membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi148 – 1481E → A: Dominant-negative mutant; leading to impair inhibition of SOCE. 1 Publication

Organism-specific databases

PharmGKBiPA142670779.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 30301 PublicationAdd
BLAST
Chaini31 – 339309Store-operated calcium entry-associated regulatory factorPRO_0000045485Add
BLAST

Proteomic databases

MaxQBiQ96BY9.
PaxDbiQ96BY9.
PeptideAtlasiQ96BY9.
PRIDEiQ96BY9.

PTM databases

PhosphoSiteiQ96BY9.

Expressioni

Tissue specificityi

Highly expressed in macrophages.1 Publication

Gene expression databases

BgeeiQ96BY9.
CleanExiHS_TMEM66.
ExpressionAtlasiQ96BY9. baseline and differential.
GenevestigatoriQ96BY9.

Interactioni

Subunit structurei

Interacts with STIM1.1 Publication

Protein-protein interaction databases

BioGridi119672. 13 interactions.
IntActiQ96BY9. 13 interactions.
MINTiMINT-1380432.
STRINGi9606.ENSP00000256255.

Structurei

3D structure databases

ProteinModelPortaliQ96BY9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The cytoplasmic C-terminal region mediates interaction with STIM1, while the N-terminal lumenal region mediates regulation of SOCE activity.1 Publication

Sequence similaritiesi

Belongs to the SARAF family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG85111.
GeneTreeiENSGT00390000013419.
HOGENOMiHOG000154648.
HOVERGENiHBG059843.
InParanoidiQ96BY9.
OrthoDBiEOG7QG462.
PhylomeDBiQ96BY9.
TreeFamiTF314811.

Family and domain databases

InterProiIPR009567. DUF1183_TMEM66.
[Graphical view]
PANTHERiPTHR15929. PTHR15929. 1 hit.
PfamiPF06682. DUF1183. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q96BY9-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MAAACGPGAA GYCLLLGLHL FLLTAGPALG WNDPDRMLLR DVKALTLHYD
60 70 80 90 100
RYTTSRRLDP IPQLKCVGGT AGCDSYTPKV IQCQNKGWDG YDVQWECKTD
110 120 130 140 150
LDIAYKFGKT VVSCEGYESS EDQYVLRGSC GLEYNLDYTE LGLQKLKESG
160 170 180 190 200
KQHGFASFSD YYYKWSSADS CNMSGLITIV VLLGIAFVVY KLFLSDGQYS
210 220 230 240 250
PPPYSEYPPF SHRYQRFTNS AGPPPPGFKS EFTGPQNTGH GATSGFGSAF
260 270 280 290 300
TGQQGYENSG PGFWTGLGTG GILGYLFGSN RAATPFSDSW YYPSYPPSYP
310 320 330
GTWNRAYSPL HGGSGSYSVC SNSDTKTRTA SGYGGTRRR
Length:339
Mass (Da):36,975
Last modified:December 1, 2001 - v1
Checksum:i83CC0517AB635FE9
GO
Isoform 2 (identifier: Q96BY9-2) [UniParc]FASTAAdd to Basket

Also known as: Short

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

Show »
Length:167
Mass (Da):17,876
Checksum:i19AD430329A55D3E
GO

Sequence cautioni

The sequence AAD44487.1 differs from that shown. Reason: Frameshift at position 28. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti57 – 582RL → SW in AAO85460. 1 PublicationCurated
Sequence conflicti57 – 582RL → SW in AAD43012. (PubMed:11042152)Curated
Sequence conflicti57 – 571R → K in AAD44487. 1 PublicationCurated
Sequence conflicti145 – 1451K → E in BAG52116. (PubMed:16303743)Curated
Sequence conflicti231 – 2311E → G in BAD96352. 1 PublicationCurated
Sequence conflicti267 – 2671L → S in BAD96352. 1 PublicationCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti78 – 781P → T.
Corresponds to variant rs11538828 [ dbSNP | Ensembl ].
VAR_054042

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 172172Missing in isoform 2. 2 PublicationsVSP_043773Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6074.1. [Q96BY9-1]
CCDS64866.1. [Q96BY9-2]
RefSeqiNP_001271168.1. NM_001284239.1. [Q96BY9-2]
NP_057211.4. NM_016127.5. [Q96BY9-1]
UniGeneiHs.521487.

Genome annotation databases

EnsembliENST00000256255; ENSP00000256255; ENSG00000133872. [Q96BY9-1]
ENST00000545648; ENSP00000441351; ENSG00000133872. [Q96BY9-2]
GeneIDi51669.
KEGGihsa:51669.
UCSCiuc003xhs.3. human. [Q96BY9-1]
uc003xhv.3. human. [Q96BY9-2]

Polymorphism databases

DMDMi74731293.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSi CCDS6074.1. [Q96BY9-1 ]
CCDS64866.1. [Q96BY9-2 ]
RefSeqi NP_001271168.1. NM_001284239.1. [Q96BY9-2 ]
NP_057211.4. NM_016127.5. [Q96BY9-1 ]
UniGenei Hs.521487.

3D structure databases

ProteinModelPortali Q96BY9.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 119672. 13 interactions.
IntActi Q96BY9. 13 interactions.
MINTi MINT-1380432.
STRINGi 9606.ENSP00000256255.

PTM databases

PhosphoSitei Q96BY9.

Polymorphism databases

DMDMi 74731293.

Proteomic databases

MaxQBi Q96BY9.
PaxDbi Q96BY9.
PeptideAtlasi Q96BY9.
PRIDEi Q96BY9.

Protocols and materials databases

DNASUi 51669.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000256255 ; ENSP00000256255 ; ENSG00000133872 . [Q96BY9-1 ]
ENST00000545648 ; ENSP00000441351 ; ENSG00000133872 . [Q96BY9-2 ]
GeneIDi 51669.
KEGGi hsa:51669.
UCSCi uc003xhs.3. human. [Q96BY9-1 ]
uc003xhv.3. human. [Q96BY9-2 ]

Organism-specific databases

CTDi 51669.
GeneCardsi GC08M029920.
HGNCi HGNC:28789. SARAF.
MIMi 614768. gene.
neXtProti NX_Q96BY9.
PharmGKBi PA142670779.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG85111.
GeneTreei ENSGT00390000013419.
HOGENOMi HOG000154648.
HOVERGENi HBG059843.
InParanoidi Q96BY9.
OrthoDBi EOG7QG462.
PhylomeDBi Q96BY9.
TreeFami TF314811.

Miscellaneous databases

GeneWikii TMEM66.
GenomeRNAii 51669.
NextBioi 35531222.
PROi Q96BY9.
SOURCEi Search...

Gene expression databases

Bgeei Q96BY9.
CleanExi HS_TMEM66.
ExpressionAtlasi Q96BY9. baseline and differential.
Genevestigatori Q96BY9.

Family and domain databases

InterProi IPR009567. DUF1183_TMEM66.
[Graphical view ]
PANTHERi PTHR15929. PTHR15929. 1 hit.
Pfami PF06682. DUF1183. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiSARAF_HUMAN
AccessioniPrimary (citable) accession number: Q96BY9
Secondary accession number(s): B3KQQ4
, B7Z9J1, D3DSU7, H9MHJ8, H9MHJ9, Q53HE8, Q9UNZ3, Q9Y683
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: December 1, 2001
Last modified: October 29, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3