STIMA_HUMAN
ID STIMA_HUMAN Reviewed; 294 AA.
AC Q86TL2;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Store-operated calcium entry regulator STIMATE {ECO:0000305|PubMed:26322679};
DE AltName: Full=STIM-activating enhancer encoded by TMEM110 {ECO:0000303|PubMed:26322679};
DE AltName: Full=Transmembrane protein 110 {ECO:0000305};
GN Name=STIMATE {ECO:0000312|HGNC:HGNC:30526};
GN Synonyms=TMEM110 {ECO:0000312|HGNC:HGNC:30526};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY STIM1, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF 241-LYS--ARG-246.
RX PubMed=26322679; DOI=10.1038/ncb3234;
RA Jing J., He L., Sun A., Quintana A., Ding Y., Ma G., Tan P., Liang X.,
RA Zheng X., Chen L., Shi X., Zhang S.L., Zhong L., Huang Y., Dong M.Q.,
RA Walker C.L., Hogan P.G., Wang Y., Zhou Y.;
RT "Proteomic mapping of ER-PM junctions identifies STIMATE as a regulator of
RT Ca(2+) influx.";
RL Nat. Cell Biol. 17:1339-1347(2015).
RN [4]
RP FUNCTION, TOPOLOGY, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=26644574; DOI=10.1073/pnas.1521924112;
RA Quintana A., Rajanikanth V., Farber-Katz S., Gudlur A., Zhang C., Jing J.,
RA Zhou Y., Rao A., Hogan P.G.;
RT "TMEM110 regulates the maintenance and remodeling of mammalian ER-plasma
RT membrane junctions competent for STIM-ORAI signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E7083-E7092(2015).
CC -!- FUNCTION: Acts as a regulator of store-operated Ca(2+) entry (SOCE) at
CC junctional sites that connect the endoplasmic reticulum (ER) and plasma
CC membrane (PM), called ER-plasma membrane (ER-PM) junction or cortical
CC ER (PubMed:26322679, PubMed:26644574). SOCE is a Ca(2+) influx
CC following depletion of intracellular Ca(2+) stores (PubMed:26322679).
CC Acts by interacting with STIM1, promoting STIM1 conformational switch
CC (PubMed:26322679). Involved in STIM1 relocalization to ER-PM junctions
CC (PubMed:26644574). Contributes to the maintenance and reorganization of
CC store-dependent ER-PM junctions (PubMed:26644574).
CC {ECO:0000269|PubMed:26322679, ECO:0000269|PubMed:26644574}.
CC -!- SUBUNIT: Homooligomer (PubMed:26322679). Interacts with STIM1
CC (PubMed:26322679). {ECO:0000269|PubMed:26322679}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:26322679, ECO:0000269|PubMed:26644574}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:26322679,
CC ECO:0000269|PubMed:26644574}. Note=Colocalizes with STIM1 at ER-plasma
CC membrane (ER-PM) junctions, also called cortical endoplasmic reticulum
CC (ER), in store-depleted calcium cells (PubMed:26644574). May
CC translocate to ER-PM junctions in a STIM1-dependent manner in store-
CC depleted cells (Probable). {ECO:0000269|PubMed:26644574,
CC ECO:0000305|PubMed:26322679}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:26322679}.
CC -!- DOMAIN: The GXXXG motif may mediate oligomerization (PubMed:26322679).
CC The C-terminus is necessary for its localization at ER-plasma membrane
CC (ER-PM) junctions as well as for the store-dependent rearrangement of
CC ER-PM junctions (PubMed:26644574). {ECO:0000269|PubMed:26644574,
CC ECO:0000303|PubMed:26322679}.
CC -!- SIMILARITY: Belongs to the STIMATE family. {ECO:0000305}.
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DR EMBL; AC099667; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047015; AAH47015.1; -; mRNA.
DR CCDS; CCDS2866.1; -.
DR RefSeq; NP_940965.1; NM_198563.2.
DR AlphaFoldDB; Q86TL2; -.
DR BioGRID; 131975; 3.
DR IntAct; Q86TL2; 1.
DR MINT; Q86TL2; -.
DR STRING; 9606.ENSP00000347195; -.
DR TCDB; 8.A.65.1.1; the endoplasmic reticulum (er)-plasma membrane (pm) junctional competence regulator (tmem110) family.
DR GlyGen; Q86TL2; 1 site.
DR iPTMnet; Q86TL2; -.
DR PhosphoSitePlus; Q86TL2; -.
DR BioMuta; TMEM110; -.
DR jPOST; Q86TL2; -.
DR MassIVE; Q86TL2; -.
DR PaxDb; Q86TL2; -.
DR PeptideAtlas; Q86TL2; -.
DR PRIDE; Q86TL2; -.
DR ProteomicsDB; 69711; -.
DR Antibodypedia; 55365; 39 antibodies from 14 providers.
DR DNASU; 375346; -.
DR Ensembl; ENST00000355083.11; ENSP00000347195.5; ENSG00000213533.13.
DR GeneID; 375346; -.
DR KEGG; hsa:375346; -.
DR MANE-Select; ENST00000355083.11; ENSP00000347195.5; NM_198563.5; NP_940965.1.
DR UCSC; uc062kra.1; human.
DR CTD; 375346; -.
DR DisGeNET; 375346; -.
DR GeneCards; STIMATE; -.
DR HGNC; HGNC:30526; STIMATE.
DR HPA; ENSG00000213533; Low tissue specificity.
DR neXtProt; NX_Q86TL2; -.
DR OpenTargets; ENSG00000213533; -.
DR PharmGKB; PA142670761; -.
DR VEuPathDB; HostDB:ENSG00000213533; -.
DR eggNOG; ENOG502S1HE; Eukaryota.
DR GeneTree; ENSGT00940000153920; -.
DR HOGENOM; CLU_040321_1_0_1; -.
DR InParanoid; Q86TL2; -.
DR OMA; LQCGAWA; -.
DR OrthoDB; 897391at2759; -.
DR PhylomeDB; Q86TL2; -.
DR TreeFam; TF324457; -.
DR PathwayCommons; Q86TL2; -.
DR SignaLink; Q86TL2; -.
DR BioGRID-ORCS; 375346; 9 hits in 1001 CRISPR screens.
DR GenomeRNAi; 375346; -.
DR Pharos; Q86TL2; Tbio.
DR PRO; PR:Q86TL2; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q86TL2; protein.
DR Bgee; ENSG00000213533; Expressed in right lobe of liver and 101 other tissues.
DR ExpressionAtlas; Q86TL2; baseline and differential.
DR Genevisible; Q86TL2; HS.
DR GO; GO:0032541; C:cortical endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0140268; C:endoplasmic reticulum-plasma membrane contact site; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005246; F:calcium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0032237; P:activation of store-operated calcium channel activity; IDA:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IDA:UniProtKB.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IDA:UniProtKB.
DR InterPro; IPR022127; STIMATE/YPL162C.
DR PANTHER; PTHR31735; PTHR31735; 1.
DR Pfam; PF12400; STIMATE; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..294
FT /note="Store-operated calcium entry regulator STIMATE"
FT /id="PRO_0000243915"
FT TOPO_DOM 1..28
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26322679,
FT ECO:0000305|PubMed:26644574"
FT TRANSMEM 29..49
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..294
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26322679,
FT ECO:0000305|PubMed:26644574"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 227..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..246
FT /note="Required for localization in the endoplasmic
FT reticulum"
FT /evidence="ECO:0000269|PubMed:26322679"
FT MOTIF 149..153
FT /note="GXXXG motif"
FT /evidence="ECO:0000303|PubMed:26322679"
FT COMPBIAS 227..256
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 241..246
FT /note="KVRYRR->QVQYQQ: Induces relocalization to cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:26322679"
SQ SEQUENCE 294 AA; 33187 MW; 8B112BB1CB3478E0 CRC64;
MQGPAGNASR GLPGGPPSTV ASGAGRCESG ALMHSFGIFL QGLLGVVAFS TLMLKRFREP
KHERRPWRIW FLDTSKQAIG MLFIHFANVY LADLTEEDPC SLYLINFLLD ATVGMLLIYV
GVRAVSVLVE WQQWESLRFG EYGDPLQCGA WVGQCALYIV IMIFEKSVVF IVLLILQWKK
VALLNPIENP DLKLAIVMLI VPFFVNALMF WVVDNFLMRK GKTKAKLEER GANQDSRNGS
KVRYRRAASH EESESEILIS ADDEMEESDV EEDLRRLTPL KPVKKKKHRF GLPV