ASTRA_HUMAN
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 03-AUG-2022, entry version 137.
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}.
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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 AlphaFoldDB; Q96CP6; -.
DR SMR; Q96CP6; -.
DR BioGRID; 121690; 154.
DR IntAct; Q96CP6; 46.
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 EPD; Q96CP6; -.
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; 77 antibodies from 15 providers.
DR DNASU; 57655; -.
DR Ensembl; ENST00000317991.10; ENSP00000441032.1; ENSG00000089351.15. [Q96CP6-1]
DR Ensembl; ENST00000411896.6; ENSP00000439267.1; ENSG00000089351.15. [Q96CP6-2]
DR Ensembl; ENST00000680623.1; ENSP00000505404.1; ENSG00000089351.15. [Q96CP6-3]
DR GeneID; 57655; -.
DR KEGG; hsa:57655; -.
DR MANE-Select; ENST00000317991.10; ENSP00000441032.1; NM_020895.5; NP_065946.2.
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 SignaLink; Q96CP6; -.
DR BioGRID-ORCS; 57655; 91 hits in 1078 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 body of pancreas and 162 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:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
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:0032934; F:sterol binding; IBA:GO_Central.
DR GO; GO:0120015; F:sterol transfer activity; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0071397; P:cellular response to cholesterol; ISS:UniProtKB.
DR GO; GO:0032366; P:intracellular sterol transport; IBA:GO_Central.
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
