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Reviewed, UniProtKB/Swiss-Prot Q13586 (STIM1_HUMAN)

Last modified June 16, 2009. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Stromal interaction molecule 1
Gene names
Name: STIM1
Synonyms: GOK
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length685 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Plays a role in mediating Ca2+ influx following depletion of intracellular Ca2+ stores. Acts as Ca2+ sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca2+ depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca2+ release-activated Ca2+ (CRAC) channel subunit, TMEM142A/ORAI1. Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17

Subunit structure

Forms homooligomers and heterooligomers with STIM2. Ref.6 Ref.7

Subcellular location

Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Note: Translocates from the endoplasmic reticulum to the cell membrane in response to a depletion of intracellular calcium. Ref.9 Ref.11 Ref.5

Tissue specificity

Ubiquitously expressed in various human primary cells and tumor cell lines. Ref.6 Ref.5

Post-translational modification

Glycosylation is required for cell surface expression.

Phosphorylated predominantly on Ser residues. Ref.5 Ref.12 Ref.18 Ref.19 Ref.20 Ref.21

Involvement in disease

Defects in STIM1 may cause rhabdomyosarcoma and rhabdoid tumors. Ref.4

Sequence similarities

Contains 1 EF-hand domain.

Contains 1 SAM (sterile alpha motif) domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

STIM2Q9P2462EBI-448878,EBI-448891

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 685663Stromal interaction molecule 1
PRO_0000033326

Regions

Topological domain23 – 213191Extracellular Potential
Transmembrane214 – 23421 Potential
Topological domain235 – 685451Cytoplasmic Potential
Domain63 – 9836EF-hand
Domain132 – 20069SAM
Calcium binding76 – 8712 Potential
Coiled coil248 – 388141 Potential
Compositional bias270 – 33667Glu-rich
Compositional bias600 – 62930Pro/Ser-rich
Compositional bias672 – 68514Lys-rich

Amino acid modifications

Modified residue2571Phosphoserine By similarity
Modified residue4201Phosphothreonine Ref.19
Modified residue5191Phosphoserine By similarity
Modified residue5241Phosphoserine By similarity
Modified residue5751Phosphoserine Ref.12 Ref.18 Ref.20 Ref.21
Modified residue6081Phosphoserine Ref.12 Ref.21
Modified residue6601Phosphoserine Ref.21
Modified residue6651Phosphothreonine By similarity
Modified residue6681Phosphoserine Ref.21
Glycosylation1311N-linked (GlcNAc...) Ref.7
Glycosylation1711N-linked (GlcNAc...) Ref.7 Ref.8 Ref.15

Experimental info

Mutagenesis761D → A or N: Increases Ca(2+) influx even when Ca(2+) stores are not depleted. Ref.9 Ref.13
Mutagenesis781D → N: Increases Ca(2+) influx even when Ca(2+) stores are not depleted. Ref.13
Mutagenesis871E → A or Q: Increases Ca(2+) influx through activation of CRAC channels, even when Ca(2+) stores are not depleted. Ref.13 Ref.17
Sequence conflict5561S → R in AAC51627. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q13586-1 [UniParc].

Last modified October 14, 2008. Version 3.
Checksum: FFB5E7CB3D68A7A6

FASTA68577,423
        10         20         30         40         50         60 
MDVCVRLALW LLWGLLLHQG QSLSHSHSEK ATGTSSGANS EESTAAEFCR IDKPLCHSED 

        70         80         90        100        110        120 
EKLSFEAVRN IHKLMDDDAN GDVDVEESDE FLREDLNYHD PTVKHSTFHG EDKLISVEDL 

       130        140        150        160        170        180 
WKAWKSSEVY NWTVDEVVQW LITYVELPQY EETFRKLQLS GHAMPRLAVT NTTMTGTVLK 

       190        200        210        220        230        240 
MTDRSHRQKL QLKALDTVLF GPPLLTRHNH LKDFMLVVSI VIGVGGCWFA YIQNRYSKEH 

       250        260        270        280        290        300 
MKKMMKDLEG LHRAEQSLHD LQERLHKAQE EHRTVEVEKV HLEKKLRDEI NLAKQEAQRL 

       310        320        330        340        350        360 
KELREGTENE RSRQKYAEEE LEQVREALRK AEKELESHSS WYAPEALQKW LQLTHEVEVQ 

       370        380        390        400        410        420 
YYNIKKQNAE KQLLVAKEGA EKIKKKRNTL FGTFHVAHSS SLDDVDHKIL TAKQALSEVT 

       430        440        450        460        470        480 
AALRERLHRW QQIEILCGFQ IVNNPGIHSL VAALNIDPSW MGSTRPNPAH FIMTDDVDDM 

       490        500        510        520        530        540 
DEEIVSPLSM QSPSLQSSVR QRLTEPQHGL GSQRDLTHSD SESSLHMSDR QRVAPKPPQM 

       550        560        570        580        590        600 
SRAADEALNA MTSNGSHRLI EGVHPGSLVE KLPDSPALAK KALLALNHGL DKAHSLMELS 

       610        620        630        640        650        660 
PSAPPGGSPH LDSSRSHSPS SPDPDTPSPV GDSRALQASR NTRIPHLAGK KAVAEEDNGS 

       670        680 
IGEETDSSPG RKKFPLKIFK KPLKK 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of a novel human gene (D11S4896E) at chromosomal region 11p15.5."
Parker N.J., Begley C.G., Smith P.J., Fox R.M.
Genomics 37:253-256(1996) [PubMed: 8921403] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal liver and Placenta.
[2]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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[4]"GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development."
Sabbioni S., Barbanti-Brodano G., Croce C.M., Negrini M.
Cancer Res. 57:4493-4497(1997) [PubMed: 9377559] [Abstract]
Cited for: DISEASE.
[5]"STIM1: a novel phosphoprotein located at the cell surface."
Manji S.S., Parker N.J., Williams R.T., van Stekelenburg L., Pearson R.B., Dziadek M., Smith P.J.
Biochim. Biophys. Acta 1481:147-155(2000) [PubMed: 11004585] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, PHOSPHORYLATION.
[6]"Identification and characterization of the STIM (stromal interaction molecule) gene family: coding for a novel class of transmembrane proteins."
Williams R.T., Manji S.S.M., Parker N.J., Hancock M.S., van Stekelenburg L., Eid J.-P., Senior P.V., Kazenwadel J.S., Shandala T., Saint R., Smith P.J., Dziadek M.A.
Biochem. J. 357:673-685(2001) [PubMed: 11463338] [Abstract]
Cited for: SUBUNIT, TISSUE SPECIFICITY.
[7]"Stromal interaction molecule 1 (STIM1), a transmembrane protein with growth suppressor activity, contains an extracellular SAM domain modified by N-linked glycosylation."
Williams R.T., Senior P.V., van Stekelenburg L., Layton J.E., Smith P.J., Dziadek M.A.
Biochim. Biophys. Acta 1596:131-137(2002) [PubMed: 11983428] [Abstract]
Cited for: SUBUNIT, GLYCOSYLATION AT ASN-131 AND ASN-171.
[8]"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
Zhang H., Li X.-J., Martin D.B., Aebersold R.
Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract]
Cited for: GLYCOSYLATION AT ASN-171.
[9]"STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx."
Liou J., Kim M.L., Heo W.D., Jones J.T., Myers J.W., Ferrell J.E. Jr., Meyer T.
Curr. Biol. 15:1235-1241(2005) [PubMed: 16005298] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-76.
[10]"STIM1, an essential and conserved component of store-operated Ca2+ channel function."
Roos J., DiGregorio P.J., Yeromin A.V., Ohlsen K., Lioudyno M., Zhang S., Safrina O., Kozak J.A., Wagner S.L., Cahalan M.D., Velicelebi G., Stauderman K.A.
J. Cell Biol. 169:435-445(2005) [PubMed: 15866891] [Abstract]
Cited for: FUNCTION.
[11]"STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane."
Zhang S.L., Yu Y., Roos J., Kozak J.A., Deerinck T.J., Ellisman M.H., Stauderman K.A., Cahalan M.D.
Nature 437:902-905(2005) [PubMed: 16208375] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-575 AND SER-608, MASS SPECTROMETRY.
Tissue: Epithelium.
[13]"Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1."
Mercer J.C., Dehaven W.I., Smyth J.T., Wedel B., Boyles R.R., Bird G.S., Putney J.W. Jr.
J. Biol. Chem. 281:24979-24990(2006) [PubMed: 16807233] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-76; ASP-78 AND GLU-87.
[14]"Orai1 and STIM reconstitute store-operated calcium channel function."
Soboloff J., Spassova M.A., Tang X.D., Hewavitharana T., Xu W., Gill D.L.
J. Biol. Chem. 281:20661-20665(2006) [PubMed: 16766533] [Abstract]
Cited for: FUNCTION.
[15]"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
Lewandrowski U., Moebius J., Walter U., Sickmann A.
Mol. Cell. Proteomics 5:226-233(2006) [PubMed: 16263699] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-171, MASS SPECTROMETRY.
Tissue: Platelet.
[16]"Amplification of CRAC current by STIM1 and CRACM1 (Orai1)."
Peinelt C., Vig M., Koomoa D.L., Beck A., Nadler M.J.S., Koblan-Huberson M., Lis A., Fleig A., Penner R., Kinet J.-P.
Nat. Cell Biol. 8:771-773(2006) [PubMed: 16733527] [Abstract]
Cited for: FUNCTION.
[17]"STIM1 has a plasma membrane role in the activation of store-operated Ca(2+) channels."
Spassova M.A., Soboloff J., He L.-P., Xu W., Dziadek M.A., Gill D.L.
Proc. Natl. Acad. Sci. U.S.A. 103:4040-4045(2006) [PubMed: 16537481] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLU-87.
[18]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.
J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-575, MASS SPECTROMETRY.
Tissue: Epithelium.
[19]"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.
Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-420, MASS SPECTROMETRY.
[20]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-575, MASS SPECTROMETRY.
Tissue: Platelet.
[21]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-575; SER-608; SER-660 AND SER-668, MASS SPECTROMETRY.
[22]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[23]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-171, MASS SPECTROMETRY.
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

U52426 mRNA. Translation: AAC51627.1.
CH471158 Genomic DNA. Translation: EAX02581.1.
BC021300 mRNA. Translation: AAH21300.1.
IPIIPI00299063.
RefSeqNP_003147.2.
UniGeneHs.501735

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2K60NMR-A58-201[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ13586. 1 interaction.

Protein family/group databases

TCDB1.A.52.1.1. Ca2+ release-activated Ca2+ (CRAC) channel (CRAC-C) family.

PTM databases

PhosphoSiteQ13586.

Proteomic databases

PRIDEQ13586.

Genome annotation databases

EnsemblENSG00000167323. Homo sapiens. [Contig view]
GeneID6786.
KEGGhsa:6786.

Organism-specific databases

GeneCardsGC11P003833.
H-InvDBHIX0009379.
HGNCHGNC:11386. STIM1.
HPAHPA011088.
HPA012123.
MIM605921. gene.
PharmGKBPA36195.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ13586.
HOVERGENQ13586.
OMAQ13586. MAPKPPQ.

Enzyme and pathway databases

Pathway_Interaction_DBtcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Gene expression databases

ArrayExpressQ13586.
BgeeQ13586.
CleanExHS_STIM1.

Family and domain databases

InterProIPR018247. EF_HAND_1.
IPR001660. SAM.
IPR011510. SAM_2.
[Graphical view]
PfamPF07647. SAM_2. 1 hit.
[Graphical view]
SMARTSM00454. SAM. 1 hit.
[Graphical view]
PROSITEPS00018. EF_HAND_1. False negative.
PS50222. EF_HAND_2. False negative.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio26496.
SOURCESearch...

Entry information

Entry nameSTIM1_HUMAN
AccessionPrimary (citable) accession number: Q13586
Secondary accession number(s): Q8N382
Entry history
Integrated into UniProtKB/Swiss-Prot: November 2, 2001
Last sequence update: October 14, 2008
Last modified: June 16, 2009
This is version 87 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents