ASTRC_HUMAN
ID ASTRC_HUMAN Reviewed; 662 AA.
AC Q8IYS0; A8K9Y1; A8KA99; Q6AW94; Q6UWN1; Q8N6S0; Q9UF46;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Protein Aster-C {ECO:0000250|UniProtKB:Q8CI52};
DE AltName: Full=GRAM domain-containing protein 1C;
GN Name=GRAMD1C; ORFNames=UNQ2543/PRO6095;
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), AND VARIANT PRO-644.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Trachea;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, and Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 318-662.
RC TISSUE=Fetal kidney, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
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).
CC {ECO:0000250|UniProtKB:Q8CI52}.
CC -!- INTERACTION:
CC Q8IYS0; P48509: CD151; NbExp=11; IntAct=EBI-7054335, EBI-10210332;
CC Q8IYS0; P21854: CD72; NbExp=3; IntAct=EBI-7054335, EBI-307924;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8CI52}; Single-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q8CI52}; Single-
CC pass membrane protein {ECO:0000255}. Note=In lipid-poor conditions
CC localizes to the ER membrane and in response to excess cholesterol in
CC the PM is recruited to the endoplasmic reticulum-plasma membrane
CC contact sites (EPCS). {ECO:0000250|UniProtKB:Q8CI52}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IYS0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IYS0-2; Sequence=VSP_025477;
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:Q8CI52}.
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:Q8CI52}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH28972.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY358725; AAQ89087.1; -; mRNA.
DR EMBL; AK292846; BAF85535.1; -; mRNA.
DR EMBL; AK292964; BAF85653.1; -; mRNA.
DR EMBL; AK304142; BAH14115.1; -; mRNA.
DR EMBL; CH471052; EAW79621.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79622.1; -; Genomic_DNA.
DR EMBL; BC028972; AAH28972.1; ALT_INIT; mRNA.
DR EMBL; BC035040; AAH35040.1; -; mRNA.
DR EMBL; AL133661; CAB63774.2; -; mRNA.
DR EMBL; BX648633; CAH10770.1; -; mRNA.
DR CCDS; CCDS33826.1; -. [Q8IYS0-1]
DR CCDS; CCDS54625.1; -. [Q8IYS0-2]
DR PIR; T43471; T43471.
DR RefSeq; NP_001165576.1; NM_001172105.1. [Q8IYS0-2]
DR RefSeq; NP_060047.3; NM_017577.4. [Q8IYS0-1]
DR RefSeq; XP_011511233.1; XM_011512931.1. [Q8IYS0-2]
DR PDB; 6GN5; X-ray; 1.41 A; A=318-504.
DR PDBsum; 6GN5; -.
DR AlphaFoldDB; Q8IYS0; -.
DR SMR; Q8IYS0; -.
DR BioGRID; 120137; 20.
DR IntAct; Q8IYS0; 10.
DR MINT; Q8IYS0; -.
DR STRING; 9606.ENSP00000350881; -.
DR TCDB; 9.B.198.2.7; the membrane-anchored lipid-binding protein (lam) family.
DR iPTMnet; Q8IYS0; -.
DR PhosphoSitePlus; Q8IYS0; -.
DR BioMuta; GRAMD1C; -.
DR DMDM; 147645434; -.
DR EPD; Q8IYS0; -.
DR jPOST; Q8IYS0; -.
DR MassIVE; Q8IYS0; -.
DR MaxQB; Q8IYS0; -.
DR PaxDb; Q8IYS0; -.
DR PeptideAtlas; Q8IYS0; -.
DR PRIDE; Q8IYS0; -.
DR ProteomicsDB; 71218; -. [Q8IYS0-1]
DR ProteomicsDB; 71219; -. [Q8IYS0-2]
DR Antibodypedia; 2647; 14 antibodies from 8 providers.
DR DNASU; 54762; -.
DR Ensembl; ENST00000358160.9; ENSP00000350881.4; ENSG00000178075.20. [Q8IYS0-1]
DR Ensembl; ENST00000440446.2; ENSP00000408135.2; ENSG00000178075.20. [Q8IYS0-2]
DR GeneID; 54762; -.
DR KEGG; hsa:54762; -.
DR MANE-Select; ENST00000358160.9; ENSP00000350881.4; NM_017577.5; NP_060047.3.
DR UCSC; uc003eaq.5; human. [Q8IYS0-1]
DR CTD; 54762; -.
DR DisGeNET; 54762; -.
DR GeneCards; GRAMD1C; -.
DR HGNC; HGNC:25252; GRAMD1C.
DR HPA; ENSG00000178075; Low tissue specificity.
DR neXtProt; NX_Q8IYS0; -.
DR OpenTargets; ENSG00000178075; -.
DR PharmGKB; PA142671709; -.
DR VEuPathDB; HostDB:ENSG00000178075; -.
DR eggNOG; KOG1032; Eukaryota.
DR GeneTree; ENSGT00940000158013; -.
DR HOGENOM; CLU_015189_2_0_1; -.
DR InParanoid; Q8IYS0; -.
DR OMA; VFWGTKI; -.
DR OrthoDB; 944155at2759; -.
DR PhylomeDB; Q8IYS0; -.
DR TreeFam; TF327695; -.
DR PathwayCommons; Q8IYS0; -.
DR SignaLink; Q8IYS0; -.
DR BioGRID-ORCS; 54762; 15 hits in 1071 CRISPR screens.
DR ChiTaRS; GRAMD1C; human.
DR GenomeRNAi; 54762; -.
DR Pharos; Q8IYS0; Tdark.
DR PRO; PR:Q8IYS0; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8IYS0; protein.
DR Bgee; ENSG00000178075; Expressed in jejunal mucosa and 174 other tissues.
DR ExpressionAtlas; Q8IYS0; baseline and differential.
DR Genevisible; Q8IYS0; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0140268; C:endoplasmic reticulum-plasma membrane contact site; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
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: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 3D-structure; Alternative splicing; Cell membrane; Endoplasmic reticulum;
KW Lipid transport; Lipid-binding; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..662
FT /note="Protein Aster-C"
FT /id="PRO_0000287451"
FT TRANSMEM 557..577
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 69..136
FT /note="GRAM"
FT /evidence="ECO:0000255"
FT DOMAIN 326..497
FT /note="VASt"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01114"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 212..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 249..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..266
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 267..284
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..205
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_025477"
FT VARIANT 644
FT /note="L -> P (in dbSNP:rs17853381)"
FT /evidence="ECO:0000269|PubMed:12975309"
FT /id="VAR_032302"
FT CONFLICT 503..506
FT /note="PGKL -> AVHH (in Ref. 4; AAH28972)"
FT /evidence="ECO:0000305"
FT STRAND 325..337
FT /evidence="ECO:0007829|PDB:6GN5"
FT HELIX 339..347
FT /evidence="ECO:0007829|PDB:6GN5"
FT HELIX 351..359
FT /evidence="ECO:0007829|PDB:6GN5"
FT STRAND 362..367
FT /evidence="ECO:0007829|PDB:6GN5"
FT STRAND 378..390
FT /evidence="ECO:0007829|PDB:6GN5"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:6GN5"
FT STRAND 394..405
FT /evidence="ECO:0007829|PDB:6GN5"
FT TURN 411..413
FT /evidence="ECO:0007829|PDB:6GN5"
FT STRAND 414..426
FT /evidence="ECO:0007829|PDB:6GN5"
FT TURN 427..431
FT /evidence="ECO:0007829|PDB:6GN5"
FT STRAND 432..444
FT /evidence="ECO:0007829|PDB:6GN5"
FT STRAND 447..460
FT /evidence="ECO:0007829|PDB:6GN5"
FT HELIX 464..498
FT /evidence="ECO:0007829|PDB:6GN5"
SQ SEQUENCE 662 AA; 76035 MW; 1A0F5471FA1F7CD3 CRC64;
MEGAPTVRQV MNEGDSSLAT DLQEDVEENP SPTVEENNVV VKKQGPNLHN WSGDWSFWIS
SSTYKDRNEE YRRQFTHLPD TERLIADYAC ALQRDILLQG RLYLSENWLC FYSNIFRWET
TISIALKNIT FMTKEKTARL IPNAIQIVTE SEKFFFTSFG ARDRSYLSIF RLWQNVLLDK
SLTRQEFWQL LQQNYGTELG LNAEEMENLS LSIEDVQPRS PGRSSLDDSG ERDEKLSKSI
SFTSESISRV SETESFDGNS SKGGLGKEES QNEKQTKKSL LPTLEKKLTR VPSKSLDLNK
NEYLSLDKSS TSDSVDEENV PEKDLHGRLF INRIFHISAD RMFELLFTSS RFMQKFASSR
NIIDVVSTPW TAELGGDQLR TMTYTIVLNS PLTGKCTAAT EKQTLYKESR EARFYLVDSE
VLTHDVPYHD YFYTVNRYCI IRSSKQKCRL RVSTDLKYRK QPWGLVKSLI EKNSWSSLED
YFKQLESDLL IEESVLNQAI EDPGKLTGLR RRRRTFNRTA ETVPKLSSQH SSGDVGLGAK
GDITGKKKEM ENYNVTLIVV MSIFVLLLVL LNVTLFLKLS KIEHAAQSFY RLRLQEEKSL
NLASDMVSRA ETIQKNKDQA HRLKGVLRDS IVMLEQLKSS LIMLQKTFDL LNKNKTGMAV
ES
