ASTRA_MOUSE
ID ASTRA_MOUSE Reviewed; 722 AA.
AC Q8VEF1; Q3U914; Q3UD89; Q69ZH2; Q8BNF1;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Protein Aster-A {ECO:0000303|PubMed:30220461};
DE AltName: Full=GRAM domain-containing protein 1A {ECO:0000305};
GN Name=Gramd1a {ECO:0000312|MGI:MGI:105490}; Synonyms=D7Bwg0611e, Kiaa1533;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, and Spinal ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-722 (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 293-722 (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265; SER-269 AND SER-273, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP 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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 334-562 IN COMPLEX WITH
RP 25-HYDROXYCHOLESTEROL, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DOMAINS GRAM AND VAST/ASTER, AND GENE STRUCTURE.
RX PubMed=30220461; DOI=10.1016/j.cell.2018.08.033;
RA Sandhu J., Li S., Fairall L., Pfisterer S.G., Gurnett J.E., Xiao X.,
RA Weston T.A., Vashi D., Ferrari A., Orozco J.L., Hartman C.L.,
RA Strugatsky D., Lee S.D., He C., Hong C., Jiang H., Bentolila L.A.,
RA Gatta A.T., Levine T.P., Ferng A., Lee R., Ford D.A., Young S.G.,
RA Ikonen E., Schwabe J.W.R., Tontonoz P.;
RT "Aster proteins facilitate nonvesicular plasma membrane to ER cholesterol
RT transport in mammalian cells.";
RL Cell 175:514-529(2018).
CC -!- FUNCTION: Cholesterol transporter that mediates non-vesicular transport
CC of cholesterol from the plasma membrane (PM) to the endoplasmic
CC reticulum (ER) (PubMed:30220461). 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 (PubMed:30220461). Plays
CC a crucial role in cholesterol homeostasis and has the unique ability to
CC localize to the PM based on the level of membrane cholesterol
CC (PubMed:30220461). In lipid-poor conditions localizes to the ER
CC membrane and in response to excess cholesterol in the PM is recruited
CC to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which
CC is mediated by the GRAM domain (PubMed:30220461). At the EPCS, the
CC sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and
CC facilitates its transfer from the PM to ER (PubMed:30220461). May play
CC a role in tumor progression (PubMed:27585821). Plays a role in
CC autophagy regulation and is required for biogenesis of the
CC autophagosome. This function in autophagy requires its cholesterol-
CC transfer activity (By similarity). {ECO:0000250|UniProtKB:Q96CP6,
CC ECO:0000269|PubMed:27585821, ECO:0000269|PubMed:30220461}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:30220461}; Single-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:30220461}; Single-pass
CC membrane protein {ECO:0000255}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q96CP6}. Note=In lipid-poor conditions localizes
CC to the ER membrane and in response to excess cholesterol in the PM is
CC recruited to the endoplasmic reticulum-plasma membrane contact sites
CC (EPCS) (PubMed:30220461). Localizes to distinct EPCS than GRAMD2A and
CC ESYT2/3 (By similarity). {ECO:0000250|UniProtKB:Q96CP6,
CC ECO:0000269|PubMed:30220461}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8VEF1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VEF1-2; Sequence=VSP_025467;
CC Name=3;
CC IsoId=Q8VEF1-3; Sequence=VSP_025468;
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain.
CC {ECO:0000269|PubMed:30220461}.
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:30220461}.
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:0000269|PubMed:30220461}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH18554.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD32472.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=BAE29255.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE29372.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE29897.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE30853.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE31103.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE32853.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK083837; BAC39036.1; -; mRNA.
DR EMBL; AK150032; BAE29255.1; ALT_INIT; mRNA.
DR EMBL; AK150196; BAE29372.1; ALT_INIT; mRNA.
DR EMBL; AK150837; BAE29897.1; ALT_INIT; mRNA.
DR EMBL; AK151987; BAE30853.1; ALT_INIT; mRNA.
DR EMBL; AK152294; BAE31103.1; ALT_INIT; mRNA.
DR EMBL; AK154821; BAE32853.1; ALT_INIT; mRNA.
DR EMBL; BC018554; AAH18554.1; ALT_INIT; mRNA.
DR EMBL; AK173194; BAD32472.1; ALT_SEQ; Transcribed_RNA.
DR CCDS; CCDS52189.1; -. [Q8VEF1-1]
DR RefSeq; NP_082174.3; NM_027898.3. [Q8VEF1-1]
DR PDB; 6GQF; X-ray; 2.90 A; A/B/C/D=334-562.
DR PDBsum; 6GQF; -.
DR AlphaFoldDB; Q8VEF1; -.
DR SMR; Q8VEF1; -.
DR BioGRID; 206857; 4.
DR IntAct; Q8VEF1; 1.
DR STRING; 10090.ENSMUSP00000001280; -.
DR iPTMnet; Q8VEF1; -.
DR PhosphoSitePlus; Q8VEF1; -.
DR EPD; Q8VEF1; -.
DR MaxQB; Q8VEF1; -.
DR PaxDb; Q8VEF1; -.
DR PeptideAtlas; Q8VEF1; -.
DR PRIDE; Q8VEF1; -.
DR ProteomicsDB; 271090; -. [Q8VEF1-1]
DR ProteomicsDB; 271091; -. [Q8VEF1-2]
DR ProteomicsDB; 271092; -. [Q8VEF1-3]
DR Antibodypedia; 2264; 77 antibodies from 15 providers.
DR DNASU; 52857; -.
DR Ensembl; ENSMUST00000001280; ENSMUSP00000001280; ENSMUSG00000001248. [Q8VEF1-1]
DR Ensembl; ENSMUST00000186634; ENSMUSP00000140195; ENSMUSG00000001248. [Q8VEF1-2]
DR GeneID; 52857; -.
DR KEGG; mmu:52857; -.
DR UCSC; uc009gif.1; mouse. [Q8VEF1-1]
DR CTD; 57655; -.
DR MGI; MGI:105490; Gramd1a.
DR VEuPathDB; HostDB:ENSMUSG00000001248; -.
DR eggNOG; KOG1032; Eukaryota.
DR GeneTree; ENSGT00940000161007; -.
DR HOGENOM; CLU_015189_1_2_1; -.
DR InParanoid; Q8VEF1; -.
DR OMA; LIVYSCA; -.
DR OrthoDB; 944155at2759; -.
DR PhylomeDB; Q8VEF1; -.
DR TreeFam; TF327695; -.
DR BioGRID-ORCS; 52857; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Gramd1a; mouse.
DR PRO; PR:Q8VEF1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8VEF1; protein.
DR Bgee; ENSMUSG00000001248; Expressed in embryonic brain and 251 other tissues.
DR ExpressionAtlas; Q8VEF1; baseline and differential.
DR Genevisible; Q8VEF1; MM.
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; ISO:MGI.
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:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0044232; C:organelle membrane contact site; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0015485; F:cholesterol binding; IDA:UniProtKB.
DR GO; GO:0120020; F:cholesterol transfer activity; IMP: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; IDA: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 3D-structure; Alternative splicing; Autophagy; Cell membrane;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Lipid transport; Lipid-binding;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..722
FT /note="Protein Aster-A"
FT /id="PRO_0000287447"
FT TRANSMEM 609..629
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 93..160
FT /note="GRAM"
FT /evidence="ECO:0000255"
FT DOMAIN 369..540
FT /note="VASt"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01114"
FT REGION 1..62
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 561..600
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..62
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 575..597
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 273
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 417
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96CP6"
FT VAR_SEQ 495..722
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_025467"
FT VAR_SEQ 495..528
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_025468"
FT CONFLICT 37
FT /note="P -> S (in Ref. 2; AAH18554)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="V -> M (in Ref. 2; AAH18554)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="G -> SQ (in Ref. 2; AAH18554)"
FT /evidence="ECO:0000305"
FT CONFLICT 705
FT /note="T -> A (in Ref. 1; BAE29897/BAE31103/BAE30853)"
FT /evidence="ECO:0000305"
FT STRAND 369..380
FT /evidence="ECO:0007829|PDB:6GQF"
FT HELIX 382..389
FT /evidence="ECO:0007829|PDB:6GQF"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:6GQF"
FT HELIX 394..402
FT /evidence="ECO:0007829|PDB:6GQF"
FT STRAND 406..410
FT /evidence="ECO:0007829|PDB:6GQF"
FT STRAND 421..430
FT /evidence="ECO:0007829|PDB:6GQF"
FT STRAND 433..436
FT /evidence="ECO:0007829|PDB:6GQF"
FT STRAND 438..450
FT /evidence="ECO:0007829|PDB:6GQF"
FT HELIX 452..454
FT /evidence="ECO:0007829|PDB:6GQF"
FT STRAND 458..469
FT /evidence="ECO:0007829|PDB:6GQF"
FT TURN 470..474
FT /evidence="ECO:0007829|PDB:6GQF"
FT STRAND 475..487
FT /evidence="ECO:0007829|PDB:6GQF"
FT STRAND 490..503
FT /evidence="ECO:0007829|PDB:6GQF"
FT HELIX 507..533
FT /evidence="ECO:0007829|PDB:6GQF"
SQ SEQUENCE 722 AA; 80699 MW; 323B29510A77F409 CRC64;
MFDTTPHSGR SSPSSSPSLR KRLQLLPPIR PPPASEPEPG TMVEKGSDSS SEKSGVSGTL
STQSLGSRNF IRNSKKMQSW YSMLCPTYKQ RNEDFRKLFS KLPEAERLIV DYSCALQREI
LLQGRLYLSE NWICFYSNIF RWETTISIQL KEVTCLKKEK TAKLIPNAIQ ICTESEKHFF
TSFGARDRCF LLIFRLWQNA LLEKTLSPRE LWHLVHQCYG SELGLTSEDE DYVCPLQLNG
LGSPKEVGDV IALSDISPSG AADHSQEPSP VGSRRGRVTP NLSRASSDAD HGAEEDKEEQ
TDGLDASSSQ TVTPVAEPLS SEPTPPDGPT SSLGPLDLLS REELLTDTSN SSSSTGEEGD
LAALLPDLSG RLLINSVFHM GAERLQQMLF SDSPFLQGFL QQRKFTDVTL SPWSSDSKCH
QRRVLTYTIP ISNQLGPKSA SVVETQTLFR RGPQAGGCVV DSEVLTQGIP YQDYFYTAHR
YCILGLARNK ARLRVSSEIR YRKQPWSLVK SLIEKNSWSG IEDYFHHLDR ELAKAEKLSL
EEGGKDTRGL LSGLRRRKRP LSWRGHRDGP QHPDPDPCTQ TSMHTSGSLS SRFSEPSVDQ
GPGAGIPSAL VLISIVLIVL IALNALLFYR LWSLERTAHT FESWHSLALA KGKFPQTATE
WAEILALQKH FHSVEVHKWR QILRASVELL DEMKFSLEKL HQGITVPDPP LDTQPQPDDS
FP
