GRM2A_HUMAN
ID GRM2A_HUMAN Reviewed; 354 AA.
AC Q8IUY3; B3KT68;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=GRAM domain-containing protein 2A {ECO:0000305};
GN Name=GRAMD2A {ECO:0000312|HGNC:HGNC:27287}; Synonyms=GRAMD2;
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 MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-354.
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND LIPID-BINDING.
RX PubMed=29469807; DOI=10.7554/elife.31019;
RA Besprozvannaya M., Dickson E., Li H., Ginburg K.S., Bers D.M., Auwerx J.,
RA Nunnari J.;
RT "GRAM domain proteins specialize functionally distinct ER-PM contact sites
RT in human cells.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Participates in the organization of endoplasmic reticulum-
CC plasma membrane contact sites (EPCS) with pleiotropic functions
CC including STIM1 recruitment and calcium homeostasis. Constitutive
CC tether that co-localize with ESYT2/3 tethers at endoplasmic reticulum-
CC plasma membrane contact sites in a phosphatidylinositol lipid-dependent
CC manner. Pre-marks the subset of phosphtidylinositol 4,5-biphosphate
CC (PI(4,5)P2)-enriched EPCS destined for the store operated calcium entry
CC pathway (SOCE). {ECO:0000269|PubMed:29469807}.
CC -!- INTERACTION:
CC Q8IUY3; Q12982: BNIP2; NbExp=3; IntAct=EBI-11984319, EBI-752094;
CC Q8IUY3; P50402: EMD; NbExp=3; IntAct=EBI-11984319, EBI-489887;
CC Q8IUY3; Q9Y228: TRAF3IP3; NbExp=3; IntAct=EBI-11984319, EBI-765817;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:29469807}; Single-pass membrane protein
CC {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:29469807}; Peripheral
CC membrane protein {ECO:0000269|PubMed:29469807}. Note=Localizes to
CC endoplasmic reticulum-plasma membrane contact sites (EPCS). Anchored at
CC the ER, PM binding is mediated via GRAM domain and phosphatidylinositol
CC lipid interaction. Localizes to distinct EPCS than GRAMD1A.
CC {ECO:0000269|PubMed:29469807}.
CC -!- DOMAIN: GRAM domain is required for specific location to endoplasmic
CC reticulum-plasma membrane contact sites (EPCS). Mediates interaction to
CC phosphatidylinositol lipids and binding to plasma membrane.
CC {ECO:0000269|PubMed:29469807}.
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DR EMBL; AK095072; BAG52980.1; -; mRNA.
DR EMBL; DA306775; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH471082; EAW77883.1; -; Genomic_DNA.
DR EMBL; BC038451; AAH38451.1; -; mRNA.
DR CCDS; CCDS32283.1; -.
DR RefSeq; NP_001012660.1; NM_001012642.2.
DR AlphaFoldDB; Q8IUY3; -.
DR SMR; Q8IUY3; -.
DR BioGRID; 128234; 13.
DR IntAct; Q8IUY3; 3.
DR STRING; 9606.ENSP00000311657; -.
DR iPTMnet; Q8IUY3; -.
DR PhosphoSitePlus; Q8IUY3; -.
DR BioMuta; GRAMD2A; -.
DR DMDM; 147644890; -.
DR EPD; Q8IUY3; -.
DR MassIVE; Q8IUY3; -.
DR MaxQB; Q8IUY3; -.
DR PaxDb; Q8IUY3; -.
DR PeptideAtlas; Q8IUY3; -.
DR PRIDE; Q8IUY3; -.
DR ProteomicsDB; 70630; -.
DR Antibodypedia; 26585; 65 antibodies from 17 providers.
DR DNASU; 196996; -.
DR Ensembl; ENST00000309731.12; ENSP00000311657.7; ENSG00000175318.12.
DR GeneID; 196996; -.
DR KEGG; hsa:196996; -.
DR MANE-Select; ENST00000309731.12; ENSP00000311657.7; NM_001012642.3; NP_001012660.1.
DR UCSC; uc002atq.4; human.
DR CTD; 196996; -.
DR DisGeNET; 196996; -.
DR GeneCards; GRAMD2A; -.
DR HGNC; HGNC:27287; GRAMD2A.
DR HPA; ENSG00000175318; Tissue enhanced (epididymis, placenta).
DR neXtProt; NX_Q8IUY3; -.
DR OpenTargets; ENSG00000175318; -.
DR PharmGKB; PA142671710; -.
DR VEuPathDB; HostDB:ENSG00000175318; -.
DR eggNOG; KOG1032; Eukaryota.
DR GeneTree; ENSGT00940000159572; -.
DR HOGENOM; CLU_050698_0_1_1; -.
DR InParanoid; Q8IUY3; -.
DR OMA; CSLNWDG; -.
DR OrthoDB; 944155at2759; -.
DR PhylomeDB; Q8IUY3; -.
DR TreeFam; TF327695; -.
DR PathwayCommons; Q8IUY3; -.
DR SignaLink; Q8IUY3; -.
DR BioGRID-ORCS; 196996; 18 hits in 1067 CRISPR screens.
DR ChiTaRS; GRAMD2; human.
DR GenomeRNAi; 196996; -.
DR Pharos; Q8IUY3; Tbio.
DR PRO; PR:Q8IUY3; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8IUY3; protein.
DR Bgee; ENSG00000175318; Expressed in oviduct epithelium and 111 other tissues.
DR ExpressionAtlas; Q8IUY3; baseline and differential.
DR Genevisible; Q8IUY3; HS.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0044232; C:organelle membrane contact site; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0061817; P:endoplasmic reticulum-plasma membrane tethering; IDA:UniProtKB.
DR GO; GO:2001256; P:regulation of store-operated calcium entry; IDA:UniProtKB.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR004182; GRAM.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR042624; RAMD2A.
DR PANTHER; PTHR46973; PTHR46973; 1.
DR Pfam; PF02893; GRAM; 1.
DR SMART; SM00568; GRAM; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endoplasmic reticulum; Lipid-binding; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..354
FT /note="GRAM domain-containing protein 2A"
FT /id="PRO_0000287454"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 72..139
FT /note="GRAM"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..29
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..46
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 354 AA; 40249 MW; FD517ECB47E90314 CRC64;
MTALSRSEAT EEGGNQQMHR KTASLNSPVS CKEKPDRVEE PPDYSLHWPE GLKGEEIKKC
GREGITLNKY NQQYHKLFKD VPLEEVVLKV CSCALQRDFL LQGRLYISPN WLCFHASLFG
KDIKVVIPVV SVQMIKKHKM ARLLPNGLAI TTNTSQKYIF VSLLSRDSVY DLLRRVCTHL
QPSSKKSLSV REFSGEPESL EVLIPEMKWR KVCPSSRSLS LPDNIPCIPP SSVDSTDSFF
PSRKPPMSEK SRAQVASENG GRWAWPMPGW GPACPKKMPN CSPTAKNAVY EEDELEEEPR
STGELRLWDY RLLKVFFVLI CFLVMSSSYL AFRISRLEQQ LCSLSWDDPV PGHR
