SAR1B_HUMAN
ID SAR1B_HUMAN Reviewed; 198 AA.
AC Q9Y6B6; D3DQA4; Q567T4;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=GTP-binding protein SAR1b {ECO:0000305};
DE AltName: Full=GTP-binding protein B {ECO:0000303|Ref.2};
DE Short=GTBPB {ECO:0000303|Ref.2};
GN Name=SAR1B {ECO:0000303|PubMed:33186557, ECO:0000312|HGNC:HGNC:10535};
GN Synonyms=SARA2 {ECO:0000303|PubMed:17309654}, SARB;
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 [MRNA].
RC TISSUE=Pituitary tumor;
RA Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhou Y., Yu L., Gao J., Zhang P.Z., Wang X.K., Zhao S.Y.;
RT "Cloning of a novel human cDNA homologous to murine GTP-binding protein
RT homologue mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
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].
RC TISSUE=Placenta;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, AND IDENTIFICATION BY
RP 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).
RN [7]
RP FUNCTION, AND INTERACTION WITH SURF4.
RX PubMed=33186557; DOI=10.1016/j.cmet.2020.10.020;
RA Wang X., Wang H., Xu B., Huang D., Nie C., Pu L., Zajac G.J.M., Yan H.,
RA Zhao J., Shi F., Emmer B.T., Lu J., Wang R., Dong X., Dai J., Zhou W.,
RA Wang C., Gao G., Wang Y., Willer C., Lu X., Zhu Y., Chen X.W.;
RT "Receptor-mediated ER export of lipoproteins controls lipid homeostasis in
RT mice and humans.";
RL Cell Metab. 33:350-366(2021).
RN [8]
RP VARIANTS CMRD ARG-37; ASN-137 AND ARG-179, AND TISSUE SPECIFICITY.
RX PubMed=12692552; DOI=10.1038/ng1145;
RA Jones B., Jones E.L., Bonney S.A., Patel H.N., Mensenkamp A.R.,
RA Eichenbaum-Voline S., Rudling M., Myrdal U., Annesi G., Naik S.,
RA Meadows N., Quattrone A., Islam S.A., Naoumova R.P., Angelin B.,
RA Infante R., Levy E., Roy C.C., Freemont P.S., Scott J., Shoulders C.C.;
RT "Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid
RT absorption disorders.";
RL Nat. Genet. 34:29-31(2003).
RN [9]
RP INVOLVEMENT IN CMRD BUT NOT IN MSS.
RX PubMed=17309654; DOI=10.1111/j.1399-0004.2007.00759.x;
RA Annesi G., Aguglia U., Tarantino P., Annesi F., De Marco E.V.,
RA Civitelli D., Torroni A., Quattrone A.;
RT "SIL1 and SARA2 mutations in Marinesco-Sjogren and chylomicron retention
RT diseases.";
RL Clin. Genet. 71:288-289(2007).
RN [10]
RP VARIANTS CMRD ASP-11 AND GLY-75.
RX PubMed=19274794; DOI=10.1097/mpg.0b013e318183188f;
RA Treepongkaruna S., Chongviriyaphan N., Suthutvoravut U., Charoenpipop D.,
RA Choubtum L., Wattanasirichaigoon D.;
RT "Novel missense mutations of SAR1B gene in an infant with chylomicron
RT retention disease.";
RL J. Pediatr. Gastroenterol. Nutr. 48:370-373(2009).
CC -!- FUNCTION: GTP-binding protein involved in transport from the
CC endoplasmic reticulum to the Golgi apparatus (By similarity). Activated
CC by the guanine nucleotide exchange factor PREB (By similarity).
CC Involved in the selection of the protein cargo and the assembly of the
CC COPII coat complex (By similarity). Synergizes with the cargo receptor
CC SURF4 to mediate the export of lipoproteins from the endoplasmic
CC reticulum, thereby regulating lipoprotein delivery and the maintenance
CC of lipid homeostasis (PubMed:33186557). {ECO:0000250|UniProtKB:Q9QVY3,
CC ECO:0000269|PubMed:33186557}.
CC -!- SUBUNIT: Homodimer (By similarity). Binds PREB (By similarity). Part of
CC the COPII coat complex (By similarity). Binds to the cytoplasmic tails
CC of target proteins in the endoplasmic reticulum (By similarity).
CC Interacts with SURF4 (PubMed:33186557). {ECO:0000250|UniProtKB:Q9QVY3,
CC ECO:0000269|PubMed:33186557}.
CC -!- INTERACTION:
CC Q9Y6B6; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-4290665, EBI-7062247;
CC Q9Y6B6; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-4290665, EBI-8638294;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9QVY3}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9QVY3}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000250|UniProtKB:Q9QVY3}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9QVY3}. Note=Associated with the endoplasmic
CC reticulum and Golgi stacks, in particular in the juxta-nuclear Golgi
CC region. {ECO:0000250|UniProtKB:Q9QVY3}.
CC -!- TISSUE SPECIFICITY: Expressed in many tissues including small
CC intestine, liver, muscle and brain. {ECO:0000269|PubMed:12692552}.
CC -!- DISEASE: Chylomicron retention disease (CMRD) [MIM:246700]: An
CC autosomal recessive disorder of severe fat malabsorption associated
CC with failure to thrive in infancy. The condition is characterized by
CC deficiency of fat-soluble vitamins, low blood cholesterol levels, and a
CC selective absence of chylomicrons from blood. Affected individuals
CC accumulate chylomicron-like particles in membrane-bound compartments of
CC enterocytes, which contain large cytosolic lipid droplets.
CC {ECO:0000269|PubMed:12692552, ECO:0000269|PubMed:17309654,
CC ECO:0000269|PubMed:19274794}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. SAR1 family.
CC {ECO:0000305}.
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DR EMBL; AF092130; AAD40372.1; -; mRNA.
DR EMBL; AF087850; AAP97161.1; -; mRNA.
DR EMBL; CH471062; EAW62249.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62250.1; -; Genomic_DNA.
DR EMBL; BC002847; AAH02847.1; -; mRNA.
DR EMBL; BC093034; AAH93034.1; -; mRNA.
DR CCDS; CCDS4177.1; -.
DR RefSeq; NP_001028675.1; NM_001033503.2.
DR RefSeq; NP_057187.1; NM_016103.3.
DR RefSeq; XP_016865010.1; XM_017009521.1.
DR AlphaFoldDB; Q9Y6B6; -.
DR SMR; Q9Y6B6; -.
DR BioGRID; 119315; 97.
DR CORUM; Q9Y6B6; -.
DR IntAct; Q9Y6B6; 11.
DR STRING; 9606.ENSP00000385432; -.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR iPTMnet; Q9Y6B6; -.
DR PhosphoSitePlus; Q9Y6B6; -.
DR SwissPalm; Q9Y6B6; -.
DR BioMuta; SAR1B; -.
DR DMDM; 14285769; -.
DR EPD; Q9Y6B6; -.
DR jPOST; Q9Y6B6; -.
DR MassIVE; Q9Y6B6; -.
DR MaxQB; Q9Y6B6; -.
DR PaxDb; Q9Y6B6; -.
DR PeptideAtlas; Q9Y6B6; -.
DR PRIDE; Q9Y6B6; -.
DR ProteomicsDB; 86646; -.
DR Antibodypedia; 26317; 278 antibodies from 33 providers.
DR DNASU; 51128; -.
DR Ensembl; ENST00000402673.7; ENSP00000385432.2; ENSG00000152700.14.
DR Ensembl; ENST00000439578.5; ENSP00000404997.1; ENSG00000152700.14.
DR GeneID; 51128; -.
DR KEGG; hsa:51128; -.
DR MANE-Select; ENST00000402673.7; ENSP00000385432.2; NM_016103.4; NP_057187.1.
DR UCSC; uc003kzq.4; human.
DR CTD; 51128; -.
DR DisGeNET; 51128; -.
DR GeneCards; SAR1B; -.
DR GeneReviews; SAR1B; -.
DR HGNC; HGNC:10535; SAR1B.
DR HPA; ENSG00000152700; Low tissue specificity.
DR MalaCards; SAR1B; -.
DR MIM; 246700; phenotype.
DR MIM; 607690; gene.
DR neXtProt; NX_Q9Y6B6; -.
DR OpenTargets; ENSG00000152700; -.
DR Orphanet; 71; Chylomicron retention disease.
DR PharmGKB; PA34943; -.
DR VEuPathDB; HostDB:ENSG00000152700; -.
DR eggNOG; KOG0077; Eukaryota.
DR GeneTree; ENSGT00940000160154; -.
DR HOGENOM; CLU_040729_6_0_1; -.
DR InParanoid; Q9Y6B6; -.
DR OMA; FRWVAQY; -.
DR OrthoDB; 1168548at2759; -.
DR PhylomeDB; Q9Y6B6; -.
DR TreeFam; TF312890; -.
DR PathwayCommons; Q9Y6B6; -.
DR Reactome; R-HSA-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF).
DR Reactome; R-HSA-204005; COPII-mediated vesicle transport.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-5694530; Cargo concentration in the ER.
DR Reactome; R-HSA-8963888; Chylomicron assembly.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR SignaLink; Q9Y6B6; -.
DR BioGRID-ORCS; 51128; 12 hits in 1078 CRISPR screens.
DR ChiTaRS; SAR1B; human.
DR GeneWiki; SAR1B; -.
DR GenomeRNAi; 51128; -.
DR Pharos; Q9Y6B6; Tbio.
DR PRO; PR:Q9Y6B6; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9Y6B6; protein.
DR Bgee; ENSG00000152700; Expressed in jejunal mucosa and 200 other tissues.
DR ExpressionAtlas; Q9Y6B6; baseline and differential.
DR Genevisible; Q9Y6B6; HS.
DR GO; GO:0030127; C:COPII vesicle coat; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070971; C:endoplasmic reticulum exit site; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0055088; P:lipid homeostasis; IDA:UniProtKB.
DR GO; GO:0042953; P:lipoprotein transport; IDA:UniProtKB.
DR GO; GO:0061024; P:membrane organization; IBA:GO_Central.
DR GO; GO:0070863; P:positive regulation of protein exit from endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0003400; P:regulation of COPII vesicle coating; IBA:GO_Central.
DR GO; GO:0032368; P:regulation of lipid transport; IDA:UniProtKB.
DR GO; GO:0016050; P:vesicle organization; IBA:GO_Central.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR006689; Small_GTPase_ARF/SAR.
DR InterPro; IPR006687; Small_GTPase_SAR1.
DR PANTHER; PTHR45684; PTHR45684; 1.
DR Pfam; PF00025; Arf; 1.
DR PRINTS; PR00328; SAR1GTPBP.
DR SMART; SM00178; SAR; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51422; SAR1; 1.
PE 1: Evidence at protein level;
KW Disease variant; Endoplasmic reticulum; ER-Golgi transport;
KW Golgi apparatus; GTP-binding; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1..198
FT /note="GTP-binding protein SAR1b"
FT /id="PRO_0000206261"
FT BINDING 34..40
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9QVY3"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9QVY3"
FT BINDING 58
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9QVY3"
FT BINDING 75
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9QVY3"
FT BINDING 75
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9QVY3"
FT BINDING 134..137
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9QVY3"
FT BINDING 180..181
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9QVY3"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 11
FT /note="G -> D (in CMRD)"
FT /evidence="ECO:0000269|PubMed:19274794"
FT /id="VAR_059051"
FT VARIANT 37
FT /note="G -> R (in CMRD; loss of GDP/GTP-binding;
FT dbSNP:rs121917846)"
FT /evidence="ECO:0000269|PubMed:12692552"
FT /id="VAR_016806"
FT VARIANT 75
FT /note="D -> G (in CMRD; dbSNP:rs1254114609)"
FT /evidence="ECO:0000269|PubMed:19274794"
FT /id="VAR_059052"
FT VARIANT 137
FT /note="D -> N (in CMRD; reduced affinity for GDP/GTP;
FT dbSNP:rs28942109)"
FT /evidence="ECO:0000269|PubMed:12692552"
FT /id="VAR_016807"
FT VARIANT 179
FT /note="S -> R (in CMRD; loss of GDP/GTP-binding;
FT dbSNP:rs28942110)"
FT /evidence="ECO:0000269|PubMed:12692552"
FT /id="VAR_016808"
SQ SEQUENCE 198 AA; 22410 MW; 3F567683D7F509E6 CRC64;
MSFIFDWIYS GFSSVLQFLG LYKKTGKLVF LGLDNAGKTT LLHMLKDDRL GQHVPTLHPT
SEELTIAGMT FTTFDLGGHV QARRVWKNYL PAINGIVFLV DCADHERLLE SKEELDSLMT
DETIANVPIL ILGNKIDRPE AISEERLREM FGLYGQTTGK GSISLKELNA RPLEVFMCSV
LKRQGYGEGF RWMAQYID
