ASTRB_HUMAN
ID ASTRB_HUMAN Reviewed; 738 AA.
AC Q3KR37; B3KXJ5; E7EPH8; Q6UW85; Q9ULL9;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Protein Aster-B {ECO:0000250|UniProtKB:Q80TI0};
DE AltName: Full=GRAM domain-containing protein 1B;
GN Name=GRAMD1B; Synonyms=KIAA1201; ORFNames=UNQ3032/PRO9834;
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).
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Thalamus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-274; TYR-389; SER-581 AND
RP THR-585, AND 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30; SER-274 AND SER-550, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [8]
RP SUBCELLULAR LOCATION.
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) (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 in the adrenal gland and has
CC the unique ability to localize to the PM based on the level of membrane
CC cholesterol (By similarity). In lipid-poor conditions localizes to the
CC ER membrane and in response to excess cholesterol in the PM is
CC recruited to the endoplasmic reticulum-plasma membrane contact sites
CC (EPCS) which is mediated by the GRAM domain (By similarity). At the
CC EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in
CC the PM and facilitates its transfer from the PM to ER (By similarity).
CC {ECO:0000250|UniProtKB:Q80TI0}.
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}. 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). {ECO:0000269|PubMed:30220461}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q3KR37-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3KR37-2; Sequence=VSP_025470;
CC Name=3;
CC IsoId=Q3KR37-3; Sequence=VSP_025469, VSP_025471, VSP_025472;
CC Name=4;
CC IsoId=Q3KR37-4; Sequence=VSP_057573;
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:0000250|UniProtKB:Q80TI0}.
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:Q80TI0}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86515.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB033027; BAA86515.1; ALT_INIT; mRNA.
DR EMBL; AY358924; AAQ89283.1; -; mRNA.
DR EMBL; AK127457; BAG54507.1; -; mRNA.
DR EMBL; AP000841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002765; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC105741; AAI05742.1; -; mRNA.
DR EMBL; BC105932; AAI05933.1; -; mRNA.
DR EMBL; BC105931; AAI05932.1; -; mRNA.
DR EMBL; BC107480; AAI07481.1; -; mRNA.
DR CCDS; CCDS53720.1; -. [Q3KR37-1]
DR CCDS; CCDS66253.1; -. [Q3KR37-4]
DR CCDS; CCDS66254.1; -. [Q3KR37-2]
DR RefSeq; NP_001273492.1; NM_001286563.1. [Q3KR37-4]
DR RefSeq; NP_001273493.1; NM_001286564.1. [Q3KR37-2]
DR RefSeq; NP_065767.1; NM_020716.2. [Q3KR37-1]
DR RefSeq; XP_016873536.1; XM_017018047.1. [Q3KR37-2]
DR RefSeq; XP_016873537.1; XM_017018048.1. [Q3KR37-2]
DR AlphaFoldDB; Q3KR37; -.
DR SMR; Q3KR37; -.
DR BioGRID; 121546; 71.
DR IntAct; Q3KR37; 22.
DR STRING; 9606.ENSP00000402457; -.
DR TCDB; 9.B.198.2.5; the membrane-anchored lipid-binding protein (lam) family.
DR iPTMnet; Q3KR37; -.
DR PhosphoSitePlus; Q3KR37; -.
DR BioMuta; GRAMD1B; -.
DR DMDM; 121942617; -.
DR EPD; Q3KR37; -.
DR jPOST; Q3KR37; -.
DR MassIVE; Q3KR37; -.
DR MaxQB; Q3KR37; -.
DR PaxDb; Q3KR37; -.
DR PeptideAtlas; Q3KR37; -.
DR PRIDE; Q3KR37; -.
DR ProteomicsDB; 17363; -.
DR ProteomicsDB; 61737; -. [Q3KR37-1]
DR ProteomicsDB; 61738; -. [Q3KR37-2]
DR ProteomicsDB; 61739; -. [Q3KR37-3]
DR Antibodypedia; 2247; 67 antibodies from 18 providers.
DR DNASU; 57476; -.
DR Ensembl; ENST00000450171.2; ENSP00000388458.2; ENSG00000023171.20. [Q3KR37-3]
DR Ensembl; ENST00000456860.6; ENSP00000402457.2; ENSG00000023171.20. [Q3KR37-4]
DR Ensembl; ENST00000529432.5; ENSP00000432987.1; ENSG00000023171.20. [Q3KR37-2]
DR Ensembl; ENST00000529750.5; ENSP00000436500.1; ENSG00000023171.20. [Q3KR37-1]
DR GeneID; 57476; -.
DR KEGG; hsa:57476; -.
DR UCSC; uc001pyw.4; human.
DR UCSC; uc001pyx.4; human. [Q3KR37-1]
DR CTD; 57476; -.
DR DisGeNET; 57476; -.
DR GeneCards; GRAMD1B; -.
DR HGNC; HGNC:29214; GRAMD1B.
DR HPA; ENSG00000023171; Tissue enhanced (adrenal gland, retina).
DR neXtProt; NX_Q3KR37; -.
DR OpenTargets; ENSG00000023171; -.
DR PharmGKB; PA142671708; -.
DR VEuPathDB; HostDB:ENSG00000023171; -.
DR eggNOG; KOG1032; Eukaryota.
DR GeneTree; ENSGT00940000156649; -.
DR HOGENOM; CLU_015189_1_0_1; -.
DR InParanoid; Q3KR37; -.
DR OrthoDB; 944155at2759; -.
DR PhylomeDB; Q3KR37; -.
DR TreeFam; TF327695; -.
DR PathwayCommons; Q3KR37; -.
DR SignaLink; Q3KR37; -.
DR BioGRID-ORCS; 57476; 11 hits in 1059 CRISPR screens.
DR ChiTaRS; GRAMD1B; human.
DR GenomeRNAi; 57476; -.
DR Pharos; Q3KR37; Tbio.
DR PRO; PR:Q3KR37; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q3KR37; protein.
DR Bgee; ENSG00000023171; Expressed in adrenal tissue and 173 other tissues.
DR ExpressionAtlas; Q3KR37; baseline and differential.
DR Genevisible; Q3KR37; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0015485; F:cholesterol binding; ISS:UniProtKB.
DR GO; GO:0120020; F:cholesterol transfer activity; ISS:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; ISS:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; 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:0071397; P:cellular response to cholesterol; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; 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; Cell membrane; Endoplasmic reticulum;
KW Lipid transport; Lipid-binding; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..738
FT /note="Protein Aster-B"
FT /id="PRO_0000287449"
FT TRANSMEM 623..643
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 96..163
FT /note="GRAM"
FT /evidence="ECO:0000255"
FT DOMAIN 372..543
FT /note="VASt"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01114"
FT REGION 1..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 254..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 544..566
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..40
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..81
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TI0"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 389
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 550
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 581
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 584
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80TI0"
FT MOD_RES 585
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 587
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80TI0"
FT VAR_SEQ 1..309
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_025469"
FT VAR_SEQ 1..40
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10574462"
FT /id="VSP_025470"
FT VAR_SEQ 78
FT /note="K -> KSHKRLSK (in isoform 4)"
FT /id="VSP_057573"
FT VAR_SEQ 310..361
FT /note="EGDGSLEKELAIDNIMGEKIEMIAPVNSPSLDFNDNEDIPTELSDSSDTHDE
FT -> MPTSSAVLLRVLSIPLLTVLILARDLSALGGCPWGPLPLRCHCLLPDPLFCA (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_025471"
FT VAR_SEQ 631..634
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_025472"
FT CONFLICT 336
FT /note="N -> H (in Ref. 3; BAG54507)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 738 AA; 85400 MW; 96784D4504307393 CRC64;
MKGFKLSCTA SNSNRSTPAC SPILRKRSRS PTPQNQDGDT MVEKGSDHSS DKSPSTPEQG
VQRSCSSQSG RSGGKNSKKS QSWYNVLSPT YKQRNEDFRK LFKQLPDTER LIVDYSCALQ
RDILLQGRLY LSENWICFYS NIFRWETLLT VRLKDICSMT KEKTARLIPN AIQVCTDSEK
HFFTSFGARD RTYMMMFRLW QNALLEKPLC PKELWHFVHQ CYGNELGLTS DDEDYVPPDD
DFNTMGYCEE IPVEENEVND SSSKSSIETK PDASPQLPKK SITNSTLTST GSSEAPVSFD
GLPLEEEALE GDGSLEKELA IDNIMGEKIE MIAPVNSPSL DFNDNEDIPT ELSDSSDTHD
EGEVQAFYED LSGRQYVNEV FNFSVDKLYD LLFTNSPFQR DFMEQRRFSD IIFHPWKKEE
NGNQSRVILY TITLTNPLAP KTATVRETQT MYKASQESEC YVIDAEVLTH DVPYHDYFYT
INRYTLTRVA RNKSRLRVST ELRYRKQPWG LVKTFIEKNF WSGLEDYFRH LESELAKTES
TYLAEMHRQS PKEKASKTTT VRRRKRPHAH LRVPHLEEVM SPVTTPTDED VGHRIKHVAG
STQTRHIPED TPNGFHLQSV SKLLLVISCV ICFSLVLLVI LNMMLFYKLW MLEYTTQTLT
AWQGLRLQER LPQSQTEWAQ LLESQQKYHD TELQKWREII KSSVMLLDQM KDSLINLQNG
IRSRDYTSES EEKRNRYH
