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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
 
 
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