ID ASTRA_HUMAN Reviewed; 724 AA. AC Q96CP6; A6NKY7; Q8NC77; Q9P1Z5; DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 16-MAY-2006, sequence version 2. DT 05-DEC-2018, entry version 115. DE RecName: Full=Protein Aster-A {ECO:0000250|UniProtKB:Q8VEF1}; DE AltName: Full=GRAM domain-containing protein 1A {ECO:0000305}; GN Name=GRAMD1A {ECO:0000312|HGNC:HGNC:29305}; Synonyms=KIAA1533; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full- RT length human cDNAs encoding secretion or membrane proteins from oligo- RT capped cDNA libraries."; RL DNA Res. 12:117-126(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 71-724 (ISOFORM 3). RC TISSUE=Brain; RX PubMed=10819331; DOI=10.1093/dnares/7.2.143; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 7:143-150(2000). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263 AND SER-267, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [9] RP INDUCTION, TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=27585821; DOI=10.1038/srep31963; RA Fu B., Meng W., Zhao H., Zhang B., Tang H., Zou Y., Yao J., Li H., RA Zhang T.; RT "GRAM domain-containing protein 1A (GRAMD1A) promotes the expansion of RT hepatocellular carcinoma stem cell and hepatocellular carcinoma growth RT through STAT5."; RL Sci. Rep. 6:31963-31963(2016). RN [10] RP SUBCELLULAR LOCATION, AND DOMAIN GRAM. RX PubMed=29469807; DOI=10.7554/eLife.31019; RA Besprozvannaya M., Dickson E., Li H., Ginburg K.S., Bers D.M., RA Auwerx J., Nunnari J.; RT "GRAM domain proteins specialize functionally distinct ER-PM contact RT sites in human cells."; RL Elife 7:0-0(2018). CC -!- FUNCTION: Cholesterol transporter that mediates non-vesicular CC transport of cholesterol from the plasma membrane (PM) to the CC endoplasmic reticulum (ER) (By similarity). Contains unique CC domains for binding cholesterol and the PM, thereby serving as a CC molecular bridge for the transfer of cholesterol from the PM to CC the ER (By similarity). Plays a crucial role in cholesterol CC homeostasis and has the unique ability to localize to the PM based CC on the level of membrane cholesterol (By similarity). In lipid- CC poor conditions localizes to the ER membrane and in response to CC excess cholesterol in the PM is recruited to the endoplasmic CC reticulum-plasma membrane contact sites (EPCS) which is mediated CC by the GRAM domain (By similarity). At the EPCS, the sterol- CC binding VASt/ASTER domain binds to the cholesterol in the PM and CC facilitates its transfer from the PM to ER (By similarity). May CC play a role in tumor progression (By similarity). CC {ECO:0000250|UniProtKB:Q8VEF1}. CC -!- INTERACTION: CC Q53SE7:FLJ13057; NbExp=3; IntAct=EBI-1384139, EBI-10172181; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:29469807}; Single-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:29469807}; CC Single-pass membrane protein {ECO:0000255}. Note=In lipid-poor CC conditions localizes to the ER membrane and is recruited to CC endoplasmic reticulum-plasma membrane contact sites (EPCS) in CC response to excess cholesterol in the PM (By similarity). CC Localizes to distinct EPCS than GRAMD2A and ESYT2/3 CC (PubMed:29469807). {ECO:0000250|UniProtKB:Q8VEF1, CC ECO:0000269|PubMed:29469807}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96CP6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96CP6-2; Sequence=VSP_025465, VSP_025466; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q96CP6-3; Sequence=VSP_025466; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in liver. CC {ECO:0000269|PubMed:27585821}. CC -!- INDUCTION: Up-regulated in hepatocellular carcinoma tissues. CC {ECO:0000269|PubMed:27585821}. CC -!- DOMAIN: GRAM domain binds phosphatidylserine in the PM and CC mediates protein recruitment to endoplasmic reticulum-plasma CC membrane contact sites (EPCS) in response to excess cholesterol in CC the PM. {ECO:0000269|PubMed:29469807}. CC -!- DOMAIN: VASt (VAD1 Analog of StAR-related lipid transfer) domain, CC also known as ASTER (Greek for star) domain is a sterol-binding CC domain. {ECO:0000250|UniProtKB:Q8VEF1}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK074914; BAC11289.1; -; mRNA. DR EMBL; AC020907; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC014077; AAH14077.2; -; mRNA. DR EMBL; AB040966; BAA96057.1; -; mRNA. DR CCDS; CCDS42546.1; -. [Q96CP6-1] DR CCDS; CCDS46046.1; -. [Q96CP6-2] DR RefSeq; NP_001129671.1; NM_001136199.2. [Q96CP6-2] DR RefSeq; NP_001306963.1; NM_001320034.1. [Q96CP6-3] DR RefSeq; NP_001306964.1; NM_001320035.1. DR RefSeq; NP_001306965.1; NM_001320036.1. DR RefSeq; NP_065946.2; NM_020895.4. [Q96CP6-1] DR UniGene; Hs.515351; -. DR ProteinModelPortal; Q96CP6; -. DR SMR; Q96CP6; -. DR BioGrid; 121690; 41. DR IntAct; Q96CP6; 10. DR MINT; Q96CP6; -. DR STRING; 9606.ENSP00000441032; -. DR iPTMnet; Q96CP6; -. DR PhosphoSitePlus; Q96CP6; -. DR BioMuta; GRAMD1A; -. DR DMDM; 121944494; -. DR EPD; Q96CP6; -. DR MaxQB; Q96CP6; -. DR PaxDb; Q96CP6; -. DR PeptideAtlas; Q96CP6; -. DR PRIDE; Q96CP6; -. DR ProteomicsDB; 76203; -. DR ProteomicsDB; 76204; -. [Q96CP6-2] DR ProteomicsDB; 76205; -. [Q96CP6-3] DR DNASU; 57655; -. DR Ensembl; ENST00000317991; ENSP00000441032; ENSG00000089351. [Q96CP6-1] DR Ensembl; ENST00000411896; ENSP00000439267; ENSG00000089351. [Q96CP6-2] DR GeneID; 57655; -. DR KEGG; hsa:57655; -. DR UCSC; uc002nxk.3; human. [Q96CP6-1] DR CTD; 57655; -. DR EuPathDB; HostDB:ENSG00000089351.14; -. DR GeneCards; GRAMD1A; -. DR HGNC; HGNC:29305; GRAMD1A. DR HPA; HPA008852; -. DR HPA; HPA012570; -. DR neXtProt; NX_Q96CP6; -. DR OpenTargets; ENSG00000089351; -. DR PharmGKB; PA134869487; -. DR eggNOG; KOG1032; Eukaryota. DR eggNOG; ENOG410XRQQ; LUCA. DR GeneTree; ENSGT00940000161007; -. DR HOVERGEN; HBG062004; -. DR InParanoid; Q96CP6; -. DR PhylomeDB; Q96CP6; -. DR TreeFam; TF327695; -. DR ChiTaRS; GRAMD1A; human. DR GenomeRNAi; 57655; -. DR PRO; PR:Q96CP6; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000089351; Expressed in 178 organ(s), highest expression level in blood. DR CleanEx; HS_GRAMD1A; -. DR ExpressionAtlas; Q96CP6; baseline and differential. DR Genevisible; Q96CP6; HS. DR GO; GO:0140268; C:endoplasmic reticulum-plasma membrane contact site; ISS:UniProtKB. 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:0015485; F:cholesterol binding; ISS:UniProtKB. DR GO; GO:0120020; F:intermembrane cholesterol transfer activity; ISS:UniProtKB. DR GO; GO:0071397; P:cellular response to cholesterol; ISS:UniProtKB. DR Gene3D; 2.30.29.30; -; 1. DR InterPro; IPR004182; GRAM. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR031968; VASt. DR Pfam; PF02893; GRAM; 1. DR Pfam; PF16016; VASt; 1. DR SMART; SM00568; GRAM; 1. DR PROSITE; PS51778; VAST; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Complete proteome; KW Endoplasmic reticulum; Lipid transport; Lipid-binding; Membrane; KW Phosphoprotein; Reference proteome; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1 724 Protein Aster-A. FT /FTId=PRO_0000287446. FT TRANSMEM 610 630 Helical. {ECO:0000255}. FT DOMAIN 91 158 GRAM. {ECO:0000255}. FT DOMAIN 367 538 VASt. {ECO:0000255|PROSITE- FT ProRule:PRU01114}. FT MOD_RES 263 263 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 267 267 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 271 271 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8VEF1}. FT MOD_RES 415 415 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT VAR_SEQ 74 80 Missing (in isoform 2). FT {ECO:0000303|PubMed:16303743}. FT /FTId=VSP_025465. FT VAR_SEQ 615 618 Missing (in isoform 2 and isoform 3). FT {ECO:0000303|PubMed:10819331, FT ECO:0000303|PubMed:16303743}. FT /FTId=VSP_025466. FT CONFLICT 439 439 S -> P (in Ref. 1; BAC11289). FT {ECO:0000305}. FT CONFLICT 477 477 H -> R (in Ref. 1; BAC11289). FT {ECO:0000305}. SQ SEQUENCE 724 AA; 80680 MW; 39D988FAD1327D14 CRC64; MFDTTPHSGR STPSSSPSLR KRLQLLPPSR PPPEPEPGTM VEKGSDSSSE KGGVPGTPST QSLGSRNFIR NSKKMQSWYS MLSPTYKQRN EDFRKLFSKL PEAERLIVDY SCALQREILL QGRLYLSENW ICFYSNIFRW ETTISIQLKE VTCLKKEKTA KLIPNAIQIC TESEKHFFTS FGARDRCFLL IFRLWQNALL EKTLSPRELW HLVHQCYGSE LGLTSEDEDY VSPLQLNGLG TPKEVGDVIA LSDITSSGAA DRSQEPSPVG SRRGHVTPNL SRASSDADHG AEEDKEEQVD SQPDASSSQT VTPVAEPPST EPTQPDGPTT LGPLDLLPSE ELLTDTSNSS SSTGEEADLA ALLPDLSGRL LINSVFHVGA ERLQQMLFSD SPFLQGFLQQ CKFTDVTLSP WSGDSKCHQR RVLTYTIPIS NPLGPKSASV VETQTLFRRG PQAGGCVVDS EVLTQGIPYQ DYFYTAHRYC ILGLARNKAR LRVSSEIRYR KQPWSLVKSL IEKNSWSGIE DYFHHLEREL AKAEKLSLEE GGKDARGLLS GLRRRKRPLS WRAHGDGPQH PDPDPCARAG IHTSGSLSSR FSEPSVDQGP GAGIPSALVL ISIVICVSLI ILIALNVLLF YRLWSLERTA HTFESWHSLA LAKGKFPQTA TEWAEILALQ KQFHSVEVHK WRQILRASVE LLDEMKFSLE KLHQGITVSD PPFDTQPRPD DSFS //