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 29-SEP-2021, entry version 134. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT 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., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., 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 project: RT 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. The RT complete sequences of 100 new cDNA clones from brain which code for large RT 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 BY RP 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 BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT 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 BY RP 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., 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). RN [11] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=31222192; DOI=10.1038/s41589-019-0307-5; RA Laraia L., Friese A., Corkery D.P., Konstantinidis G., Erwin N., Hofer W., RA Karatas H., Klewer L., Brockmeyer A., Metz M., Schoelermann B., Dwivedi M., RA Li L., Rios-Munoz P., Koehn M., Winter R., Vetter I.R., Ziegler S., RA Janning P., Wu Y.W., Waldmann H.; RT "The cholesterol transfer protein GRAMD1A regulates autophagosome RT biogenesis."; RL Nat. Chem. Biol. 15:710-720(2019). CC -!- FUNCTION: Cholesterol transporter that mediates non-vesicular transport CC of cholesterol from the plasma membrane (PM) to the endoplasmic CC reticulum (ER) (By similarity). Contains unique domains for binding CC cholesterol and the PM, thereby serving as a molecular bridge for the CC transfer of cholesterol from the PM to the ER (By similarity). Plays a CC crucial role in cholesterol homeostasis and has the unique ability to CC localize to the PM based on the level of membrane cholesterol (By CC similarity). In lipid-poor conditions localizes to the ER membrane and CC in response to excess cholesterol in the PM is recruited to the CC endoplasmic reticulum-plasma membrane contact sites (EPCS) which is CC mediated 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 play a CC role in tumor progression (By similarity). Plays a role in autophagy CC regulation and is required for biogenesis of the autophagosome CC (PubMed:31222192). This function in autophagy requires its cholesterol- CC transfer activity (PubMed:31222192). {ECO:0000250|UniProtKB:Q8VEF1, CC ECO:0000269|PubMed:31222192}. CC -!- INTERACTION: CC Q96CP6; Q53SE7: FLJ13057; NbExp=3; IntAct=EBI-1384139, EBI-10172181; CC Q96CP6; P21145: MAL; NbExp=3; IntAct=EBI-1384139, EBI-3932027; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:29469807}; Single-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:29469807}; Single-pass CC membrane protein {ECO:0000255}. Cytoplasmic vesicle, autophagosome CC {ECO:0000269|PubMed:31222192}. Note=In lipid-poor conditions localizes CC to the ER membrane and is recruited to endoplasmic reticulum-plasma CC membrane contact sites (EPCS) in response to excess cholesterol in the CC PM (By similarity). 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 Name=3; CC IsoId=Q96CP6-3; Sequence=VSP_025466; CC -!- TISSUE SPECIFICITY: Expressed in liver. {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 mediates CC protein recruitment to endoplasmic reticulum-plasma membrane contact CC sites (EPCS) in response to excess cholesterol in the PM. CC {ECO:0000269|PubMed:29469807}. CC -!- DOMAIN: VASt (VAD1 Analog of StAR-related lipid transfer) domain, also CC known as ASTER (Greek for star) domain is a sterol-binding domain. CC {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 SMR; Q96CP6; -. DR BioGRID; 121690; 96. DR IntAct; Q96CP6; 38. DR MINT; Q96CP6; -. DR STRING; 9606.ENSP00000441032; -. DR TCDB; 9.B.198.2.6; the membrane-anchored lipid-binding protein (lam) family. DR iPTMnet; Q96CP6; -. DR PhosphoSitePlus; Q96CP6; -. DR BioMuta; GRAMD1A; -. DR DMDM; 121944494; -. DR jPOST; Q96CP6; -. DR MassIVE; Q96CP6; -. DR MaxQB; Q96CP6; -. DR PaxDb; Q96CP6; -. DR PeptideAtlas; Q96CP6; -. DR PRIDE; Q96CP6; -. DR ProteomicsDB; 76203; -. [Q96CP6-1] DR ProteomicsDB; 76204; -. [Q96CP6-2] DR ProteomicsDB; 76205; -. [Q96CP6-3] DR Antibodypedia; 2264; 70 antibodies. DR DNASU; 57655; -. DR Ensembl; ENST00000317991; ENSP00000441032; ENSG00000089351. [Q96CP6-1] DR Ensembl; ENST00000411896; ENSP00000439267; ENSG00000089351. [Q96CP6-2] DR Ensembl; ENST00000680623; ENSP00000505404; ENSG00000089351. [Q96CP6-3] DR GeneID; 57655; -. DR KEGG; hsa:57655; -. DR UCSC; uc002nxk.3; human. [Q96CP6-1] DR CTD; 57655; -. DR DisGeNET; 57655; -. DR GeneCards; GRAMD1A; -. DR HGNC; HGNC:29305; GRAMD1A. DR HPA; ENSG00000089351; Low tissue specificity. DR neXtProt; NX_Q96CP6; -. DR OpenTargets; ENSG00000089351; -. DR PharmGKB; PA134869487; -. DR VEuPathDB; HostDB:ENSG00000089351; -. DR eggNOG; KOG1032; Eukaryota. DR GeneTree; ENSGT00940000161007; -. DR HOGENOM; CLU_015189_1_0_1; -. DR InParanoid; Q96CP6; -. DR OMA; LIVYSCA; -. DR OrthoDB; 944155at2759; -. DR PhylomeDB; Q96CP6; -. DR TreeFam; TF327695; -. DR PathwayCommons; Q96CP6; -. DR BioGRID-ORCS; 57655; 86 hits in 1018 CRISPR screens. DR ChiTaRS; GRAMD1A; human. DR GenomeRNAi; 57655; -. DR Pharos; Q96CP6; Tbio. DR PRO; PR:Q96CP6; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q96CP6; protein. DR Bgee; ENSG00000089351; Expressed in blood and 193 other tissues. DR ExpressionAtlas; Q96CP6; baseline and differential. DR Genevisible; Q96CP6; HS. DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; IDA:HPA. 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:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0015485; F:cholesterol binding; ISS:UniProtKB. DR GO; GO:0120020; F:cholesterol transfer activity; ISS:UniProtKB. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. 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; Autophagy; Cell membrane; Cytoplasmic vesicle; KW Endoplasmic reticulum; Lipid transport; Lipid-binding; Membrane; KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1..724 FT /note="Protein Aster-A" FT /id="PRO_0000287446" FT TRANSMEM 610..630 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 91..158 FT /note="GRAM" FT /evidence="ECO:0000255" FT DOMAIN 367..538 FT /note="VASt" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01114" FT REGION 1..66 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 256..336 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 560..579 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..22 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 42..66 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 302..317 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 263 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692" FT MOD_RES 267 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 271 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VEF1" FT MOD_RES 415 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 74..80 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16303743" FT /id="VSP_025465" FT VAR_SEQ 615..618 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10819331, FT ECO:0000303|PubMed:16303743" FT /id="VSP_025466" FT CONFLICT 439 FT /note="S -> P (in Ref. 1; BAC11289)" FT /evidence="ECO:0000305" FT CONFLICT 477 FT /note="H -> R (in Ref. 1; BAC11289)" FT /evidence="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 //