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Protein

Store-operated calcium entry-associated regulatory factor

Gene

SARAF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • calcium ion transport Source: UniProtKB-KW
  • regulation of store-operated calcium entry Source: UniProtKB

Keywordsi

Biological processCalcium transport, Ion transport, Transport
LigandCalcium

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
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000133872.13
HGNCiHGNC:28789 SARAF
MIMi614768 gene
neXtProtiNX_Q96BY9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini31 – 173LumenalSequence analysisAdd BLAST143
Transmembranei174 – 194HelicalSequence analysisAdd BLAST21
Topological domaini195 – 339CytoplasmicSequence analysisAdd BLAST145

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi148E → A: Dominant-negative mutant; leading to impair inhibition of SOCE. 1 Publication1

Organism-specific databases

DisGeNETi51669
OpenTargetsiENSG00000133872
PharmGKBiPA142670779

Polymorphism and mutation databases

BioMutaiTMEM66
DMDMi74731293

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 301 PublicationAdd BLAST30
ChainiPRO_000004548531 – 339Store-operated calcium entry-associated regulatory factorAdd BLAST309

Proteomic databases

EPDiQ96BY9
MaxQBiQ96BY9
PaxDbiQ96BY9
PeptideAtlasiQ96BY9
PRIDEiQ96BY9
ProteomicsDBi76130
76131 [Q96BY9-2]

PTM databases

iPTMnetiQ96BY9
PhosphoSitePlusiQ96BY9

Expressioni

Tissue specificityi

Highly expressed in macrophages.1 Publication

Gene expression databases

BgeeiENSG00000133872 Expressed in 239 organ(s), highest expression level in frontal cortex
CleanExiHS_TMEM66
ExpressionAtlasiQ96BY9 baseline and differential
GenevisibleiQ96BY9 HS

Organism-specific databases

HPAiHPA040400

Interactioni

Subunit structurei

Interacts with STIM1.1 Publication

Protein-protein interaction databases

BioGridi119672, 35 interactors
IntActiQ96BY9, 23 interactors
MINTiQ96BY9
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

eggNOGiENOG410IV9Z Eukaryota
ENOG4111IKY LUCA
GeneTreeiENSGT00390000013419
HOGENOMiHOG000154648
HOVERGENiHBG059843
InParanoidiQ96BY9
PhylomeDBiQ96BY9
TreeFamiTF314811

Family and domain databases

InterProiView protein in InterPro
IPR009567 SARAF
PANTHERiPTHR15929 PTHR15929, 1 hit
PfamiView protein in Pfam
PF06682 SARAF, 1 hit

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. AlignAdd to basket

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YBH7H0YBH7_HUMAN
Store-operated calcium entry-associ...
SARAF
347Annotation score:
H0YAN9H0YAN9_HUMAN
Store-operated calcium entry-associ...
SARAF
218Annotation score:
H0YAZ1H0YAZ1_HUMAN
Store-operated calcium entry-associ...
SARAF
213Annotation score:
E5RFJ9E5RFJ9_HUMAN
Store-operated calcium entry-associ...
SARAF
147Annotation score:
E5RHW0E5RHW0_HUMAN
Store-operated calcium entry-associ...
SARAF
202Annotation score:
E5RK07E5RK07_HUMAN
Store-operated calcium entry-associ...
SARAF
40Annotation score:
E5RJG8E5RJG8_HUMAN
Store-operated calcium entry-associ...
SARAF
36Annotation score:
E5RJV6E5RJV6_HUMAN
Store-operated calcium entry-associ...
SARAF
37Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57 – 58RL → SW in AAO85460 (Ref. 3) Curated2
Sequence conflicti57 – 58RL → SW in AAD43012 (PubMed:11042152).Curated2
Sequence conflicti57R → K in AAD44487 (Ref. 12) Curated1
Sequence conflicti145K → E in BAG52116 (PubMed:16303743).Curated1
Sequence conflicti231E → G in BAD96352 (Ref. 8) Curated1
Sequence conflicti267L → S in BAD96352 (Ref. 8) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05404278P → T. Corresponds to variant dbSNP:rs11538828Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0437731 – 172Missing in isoform 2. 2 PublicationsAdd BLAST172

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.5 human [Q96BY9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

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.
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

3D structure databases

ProteinModelPortaliQ96BY9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119672, 35 interactors
IntActiQ96BY9, 23 interactors
MINTiQ96BY9
STRINGi9606.ENSP00000256255

PTM databases

iPTMnetiQ96BY9
PhosphoSitePlusiQ96BY9

Polymorphism and mutation databases

BioMutaiTMEM66
DMDMi74731293

Proteomic databases

EPDiQ96BY9
MaxQBiQ96BY9
PaxDbiQ96BY9
PeptideAtlasiQ96BY9
PRIDEiQ96BY9
ProteomicsDBi76130
76131 [Q96BY9-2]

Protocols and materials databases

DNASUi51669
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256255; ENSP00000256255; ENSG00000133872 [Q96BY9-1]
ENST00000545648; ENSP00000441351; ENSG00000133872 [Q96BY9-2]
GeneIDi51669
KEGGihsa:51669
UCSCiuc003xhs.5 human [Q96BY9-1]

Organism-specific databases

CTDi51669
DisGeNETi51669
EuPathDBiHostDB:ENSG00000133872.13
GeneCardsiSARAF
HGNCiHGNC:28789 SARAF
HPAiHPA040400
MIMi614768 gene
neXtProtiNX_Q96BY9
OpenTargetsiENSG00000133872
PharmGKBiPA142670779
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IV9Z Eukaryota
ENOG4111IKY LUCA
GeneTreeiENSGT00390000013419
HOGENOMiHOG000154648
HOVERGENiHBG059843
InParanoidiQ96BY9
PhylomeDBiQ96BY9
TreeFamiTF314811

Miscellaneous databases

ChiTaRSiSARAF human
GeneWikiiTMEM66
GenomeRNAii51669
PROiPR:Q96BY9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000133872 Expressed in 239 organ(s), highest expression level in frontal cortex
CleanExiHS_TMEM66
ExpressionAtlasiQ96BY9 baseline and differential
GenevisibleiQ96BY9 HS

Family and domain databases

InterProiView protein in InterPro
IPR009567 SARAF
PANTHERiPTHR15929 PTHR15929, 1 hit
PfamiView protein in Pfam
PF06682 SARAF, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSARAF_HUMAN
AccessioniPrimary (citable) accession number: Q96BY9
Secondary accession number(s): B3KQQ4
, B7Z9J1, D3DSU7, H9MHJ8, H9MHJ9, Q53HE8, Q9UNZ3, Q9Y683
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: December 1, 2001
Last modified: September 12, 2018
This is version 120 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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