Protein detail

STIM1

Stromal interaction molecule 1

Entry name STIM1	UniProt ID Q13586	EVMP confidence score 0.47
Supporting publications (n) 15	Transmembrane count 1	Protein classification Disease related genesHuman disease related genesPlasma proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

Stromal interaction molecule 1

Protein Class (7)

Disease related genesHuman disease related genesPlasma proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters

Protein Function (7)

Human disease related genes:Cardiovascular diseases:Hematologic diseases
Predicted intracellular proteins
Potential drug targets
Human disease related genes:Musculoskeletal diseases:Muscular diseases
Human disease related genes:Immune system diseases:Primary immunodeficiency
Transporters:Transporter channels and pores
Disease related genes

Transmembrane

214..234; Helical

Transmembrane Count

Ensembl

ENSG00000167323

Entrez Gene Symbol

STIM1

Gene Synonym (2)

D11S4896EGOK

Gene Description

Stromal interaction molecule 1

Chromosome

Position

3854527-4093210

Supporting publications (n)

EVMP confidence score

0.47

Fluorescence & Localization6

Tissue SpecificliverCell SpecificBreast lactating cellsSingle-Nuclei Brain SpecificBergmann gliaBlood Cell SpecificneutrophilBlood Lineage Specificgranulocytes

Function & Pathway7

Protein Function (7)

Human disease related genes:Cardiovascular diseases:Hematologic diseases
Predicted intracellular proteins
Potential drug targets
Human disease related genes:Musculoskeletal diseases:Muscular diseases
Human disease related genes:Immune system diseases:Primary immunodeficiency
Transporters:Transporter channels and pores
Disease related genes

Cellular Component (7)

Molecular Function (6)

Biological Process (3)

KEGG (2)

Reactome (10)

Mediation Categories (4)

Fusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation

Relations & Evidence60

Enzyme-Mediated Modification (20)

20 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
STIM1	CDK1	P06493	S	668	phosphorylation	Sparser_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:19881501 SIGNOR:19881501
STIM1	MAPK1	P28482	S	575	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:22298426 SIGNOR:22298426
STIM1	MAPK1	P28482	S	608	phosphorylation	PhosphoSitePhosphoSite_ProtMapperProtMapper
STIM1	MAPK1	P28482	S	621	phosphorylation	PhosphoSitePhosphoSite_ProtMapperProtMapper
STIM1	PRKAG2	Q9UGJ0	S	521	phosphorylation	PhosphoSite
STIM1	PRKAG2	Q9UGJ0	S	257	phosphorylation	PhosphoSite
STIM1	PRKAA1	Q13131	S	521	phosphorylation	PhosphoSite
STIM1	PRKAA1	Q13131	S	257	phosphorylation	PhosphoSite
STIM1	PRKACA	P17612	T	389	phosphorylation	PhosphoSite
STIM1	PTK2B	Q14289	Y	361	phosphorylation	Sparser_ProtMapperProtMapperRLIMS-P_ProtMapperREACH_ProtMapperPhosphoSite	ProtMapper:28218251

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Ligand-Receptor Signaling (24)

24 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
extracellular	extracellular	OmniPath	No	No	No	Yes	No
intracellular	intracellular	LOCATE	No	No	No	Yes	No
intracellular	intracellular	ComPPI	No	No	No	Yes	No
intracellular	intracellular	GO_Intercell	No	No	No	Yes	No
intracellular	intracellular	UniProt_location	No	No	No	Yes	No
intracellular	intracellular	OmniPath	No	No	No	Yes	No
transmembrane	transmembrane	UniProt_location	No	No	No	Yes	No
transmembrane	transmembrane	UniProt_topology	No	No	No	Yes	No
transmembrane	transmembrane	UniProt_keyword	No	No	No	Yes	No
transmembrane_predicted	transmembrane	OmniPath	No	No	No	Yes	No

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Regulatory Interaction Network (9)

9 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
FA20C	Q8IXL6	STIM1	Q13586	Yes	Yes	No	SIGNORSparser_ProtMapperProtMapper	SIGNOR:30520731 ProtMapper:30520731
PAK1	Q13153	STIM1	Q13586	Yes	Yes	No	SIGNOR	SIGNOR:29780159
AAKB1	Q9Y478	STIM1	Q13586	Yes	No	Yes	PhosphoSite_norefSIGNORPhosphoSite_ProtMapperProtMapper	SIGNOR:31381180
CDK1	P06493	STIM1	Q13586	Yes	No	Yes	Sparser_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetSIGNORProtMapperSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:19881501 PhosphoSite:22748319 ProtMapper:22298426 SIGNOR:19881501
AAPK1	Q13131	STIM1	Q13586	Yes	No	Yes	SIGNORPhosphoSitePhosphoSite_ProtMapperProtMapper	SIGNOR:31381180 PhosphoSite:31381180
MK01	P28482	STIM1	Q13586	Yes	Yes	No	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetSIGNORProtMapperSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:19881501 ProtMapper:22298426 PhosphoSite:25447552 PhosphoSite:33023909 PhosphoSite:28935720 PhosphoSite:22298426 PhosphoSite:24114840 SIGNOR:22298426
AAKG2	Q9UGJ0	STIM1	Q13586	Yes	No	Yes	SIGNORPhosphoSite_ProtMapperProtMapper	SIGNOR:31381180
FAK2	Q14289	STIM1	Q13586	Yes	No	No	Sparser_ProtMapperProtMapperRLIMS-P_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:30975919 PhosphoSite:28218251 ProtMapper:28218251
KAPCA	P17612	STIM1	Q13586	Yes	No	No	PhosphoSitePhosphoSite_ProtMapperProtMapper	PhosphoSite:29326165 PhosphoSite:25504574

Protein Complex Composition (6)

6 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
STIM1-TRPV4 complex	STIM1 TRPV4	Q13586 Q9HBA0	0:0	CORUM	CORUM:6108	25972993
	OXCT1 PPT1 S100A16 SEC22B SEPTIN11 STIM1 TCOF1 TMED10 TMEM9 TST XRCC1	O75396 P18887 P49755 P50897 P55809 Q13428 Q13586 Q16762 Q96FQ6 Q9NVA2 Q9P0T7	0:0:0:0:0:0:0:0:0:0:0	Havugimana2012	Havugimana2012:C_597
	FERMT2 MAD2L1BP S100A16 SEC22B SEPTIN11 SEPTIN9 STIM1 SUCLG1 SUCLG2	O75396 P53597 Q13586 Q15013 Q96AC1 Q96FQ6 Q96I99 Q9NVA2 Q9UHD8	0:0:0:0:0:0:0:0:0	Havugimana2012	Havugimana2012:C_574
	STIM1	Q13586	2	PDB	PDB:3teqPDB:2majPDB:4o9b
	BRINP3 STIM1 STIM2	Q13586 Q76B58 Q9P246	0:0:0	hu.MAP2
	STIM1 STIM2	Q13586 Q9P246	0:0	hu.MAP2

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationUltrafiltration / Tangential Flow FiltrationSize Exclusion ChromatographyImmunoaffinity Capture	Mass spectrometryWestern blottingFlow cytometry	9	31508500 34071777 39436214 38644352 32795414 26884841 40098346 30760538 40091455

Sequence, Structure & Domains15

Sequences

Length

685

Mass

77,423

Sequence

MDVCVRLALWLLWGLLLHQGQSLSHSHSEKATGTSSGANSEESTAAEFCRIDKPLCHSEDEKLSFEAVRNIHKLMDDDANGDVDVEESDEFLREDLNYHDPTVKHSTFHGEDKLISVEDLWKAWKSSEVYNWTVDEVVQWLITYVELPQYEETFRKLQLSGHAMPRLAVTNTTMTGTVLKMTDRSHRQKLQLKALDTVLFGPPLLTRHNHLKDFMLVVSIVIGVGGCWFAYIQNRYSKEHMKKMMKDLEGLHRAEQSLHDLQERLHKAQEEHRTVEVEKVHLEKKLRDEINLAKQEAQRLKELREGTENERSRQKYAEEELEQVREALRKAEKELESHSSWYAPEALQKWLQLTHEVEVQYYNIKKQNAEKQLLVAKEGAEKIKKKRNTLFGTFHVAHSSSLDDVDHKILTAKQALSEVTAALRERLHRWQQIEILCGFQIVNNPGIHSLVAALNIDPSWMGSTRPNPAHFIMTDDVDDMDEEIVSPLSMQSPSLQSSVRQRLTEPQHGLGSQRDLTHSDSESSLHMSDRQRVAPKPPQMSRAADEALNAMTSNGSHRLIEGVHPGSLVEKLPDSPALAKKALLALNHGLDKAHSLMELSPSAPPGGSPHLDSSRSHSPSSPDPDTPSPVGDSRALQASRNTRIPHLAGKKAVAEEDNGSIGEETDSSPGRKKFPLKIFKKPLKK

Alternative Products

Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q13586-1; Sequence=Displayed; Name=2; IsoId=Q13586-2; Sequence=VSP_055150, VSP_055151

Alternative Sequence

515..540; DLTHSDSESSLHMSDRQRVAPKPPQM -> GSSLKANRLSSKGFDPFRFGVLPPHE (in isoform 2); 541..685; Missing (in isoform 2)

3D Structural Models

Turn

85..90; 272..275

Helix

64..73; 91..95; 102..108; 117..126; 128..131; 134..145; 150..157; 163..167; 171..174; 183..199; 249..271; 276..334; 339..341; 345..391; 393..397; 400..404; 408..437

Beta Strand

80..83; 110..112

3D Structure

NMR spectroscopy (4); X-ray crystallography (2)

Domain & Motif Annotations

Compositional Bias

490..499; Low complexity; 515..532; Basic and acidic residues; 608..620; Low complexity; 655..666; Acidic residues; 670..685; Basic residues

Motif

642..645; Microtubule tip localization signal

Coiled Coil

248..442

Domain (CC)

The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.; DOMAIN: The EF-hand domain is responsible for Ca(2+) sensitivity. It consists of a canonical helix-loop-helix EF motif (alpha1beta1alpha2; EF-hand 1) paired to a second helix-loop-helix EF motif (alpha3beta2alpha4; EF-hand 2). EF-hand 1 binds Ca(2+) whereas EF-hand 2 mediates the interactions with SAM domain.; DOMAIN: The sterile alpha motif (SAM) domain folds into a characteristic 5-helix bundle (alpha6-alpha10) which interacts with the EF-hand pairs enabling concerted folding and stability of EF-hand and SAM domains.; DOMAIN: The STIM1 Orai-activating region/CRAC-activating domain (SOAR/CAD) directly interacts with ORAI1 subunits and mediates CRAC channel gating.; DOMAIN: The polybasic Lys-rich region (residues 672-685) functionally interacts with the Pro-rich region of ORAI1 (residues 3-47) and regulates CRAC channel gating at negative membrane potentials.

Domain (FT)

64..97; EF-hand 1; 102..126; EF-hand 2; 132..200; SAM

Region

344..442; SOAR/CAD; 475..483; Contributes to fast Ca(2+)-dependent inactivation of CRAC channels; 490..542; Disordered; 596..685; Disordered; 672..685; Required for generation of inwardly rectifying CRAC currents

Clinical Relevance6

Disease Involvement

Disease variant

Drugs

VINCRISTINE

Antibody (4)

HPA011088 HPA012123 CAB037128 CAB037288

Interaction Protein (6)

ENSG00000101367ENSG00000109689ENSG00000139514ENSG00000170027ENSG00000198833ENSG00000276045

Interaction Count

Interaction Dataset (3)

intact_biogridintact_biogrid_opencellbiogrid_bioplex

Supporting Publications15

PMID	Title	Abstract
30646616	Preferential Localization of MUC1 Glycoprotein in Exosomes Secreted by Non-Small Cell Lung Carcinoma Cells.	THBS1, ANXA6, HIST1H4A, COL18A1, MDK, SRGN, ENO1, TUBA4A, SLC3A2, GPI, MIF, MUC1, TALDO1, SLC7A5, ICAM1, HSP90AA1, G6PD, and LRP1 were found to be expressed in exosomes at more than 5-fold higher level as compared to total cellular membrane proteins.
32230970	Radiation Exposure of Peripheral Mononuclear Blood Cells Alters the Composition and Function of Secreted Extracellular Vesicles.	No abstract available
32854315	Proteomic Profiling of Extracellular Vesicles Derived from Cerebrospinal Fluid of Alzheimer's Disease Patients: A Pilot Study.	Recent studies have highlighted the importance of Aβ and tau-containing extracellular vesicles (EVs) in AD.
34576246	Burn Injury Induces Proinflammatory Plasma Extracellular Vesicles That Associate with Length of Hospital Stay in Women: CRP and SAA1 as Potential Prognostic Indicators.	No abstract available
35359923	TMT-Based Quantitative Proteomics Analysis of Synovial Fluid-Derived Exosomes in Inflammatory Arthritis.	No abstract available
37204515	Proteomic profiling and functional characterization of serum-derived extracellular vesicles in the mucinous and non-mucinous colon adenocarcinoma.	No abstract available
37322475	Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration.	No abstract available
38113368	In-Depth Proteome Profiling of Small Extracellular Vesicles Isolated from Cancer Cell Lines and Patient Serum.	No abstract available
38207106	Proteomic, Metabolomic, and Fatty Acid Profiling of Small Extracellular Vesicles from Glioblastoma Stem-Like Cells and Their Role in Tumor Heterogeneity.	No abstract available
39207047	The trajectory of vesicular proteomic signatures from HBV-HCC by chitosan-magnetic bead-based separation and DIA-proteomic analysis.	No abstract available

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