GET1_HUMAN
ID GET1_HUMAN Reviewed; 174 AA.
AC O00258; A8KAP8; A8MQ44; D3DSH9; O60740;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Guided entry of tail-anchored proteins factor 1 {ECO:0000312|HGNC:HGNC:12790};
DE AltName: Full=Congenital heart disease 5 protein;
DE AltName: Full=Tail-anchored protein insertion receptor WRB;
DE AltName: Full=Tryptophan-rich basic protein;
GN Name=GET1 {ECO:0000312|HGNC:HGNC:12790};
GN Synonyms=CHD5 {ECO:0000312|HGNC:HGNC:12790},
GN WRB {ECO:0000312|HGNC:HGNC:12790};
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] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=9544840; DOI=10.1007/s004390050693;
RA Egeo A., Mazzocco M., Sotgia F., Arrigo P., Oliva R., Bergonon S.,
RA Nizetic D., Rasore-Quartino A., Scartezzini P.;
RT "Identification and characterization of a new human cDNA from chromosome
RT 21q22.3 encoding a basic nuclear protein.";
RL Hum. Genet. 102:289-293(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
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 FUNCTION, TOPOLOGY, INTERACTION WITH GET3, AND SUBCELLULAR LOCATION.
RX PubMed=21444755; DOI=10.1242/jcs.084277;
RA Vilardi F., Lorenz H., Dobberstein B.;
RT "WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored
RT proteins into the ER membrane.";
RL J. Cell Sci. 124:1301-1307(2011).
RN [7]
RP FUNCTION, IDENTIFICATION IN GET COMPLEX, INTERACTION WITH CAMLG, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23041287; DOI=10.1016/j.molcel.2012.08.028;
RA Yamamoto Y., Sakisaka T.;
RT "Molecular machinery for insertion of tail-anchored membrane proteins into
RT the endoplasmic reticulum membrane in mammalian cells.";
RL Mol. Cell 48:387-397(2012).
RN [8]
RP FUNCTION, AND INTERACTION WITH CALMG AND GET3.
RX PubMed=24392163; DOI=10.1371/journal.pone.0085033;
RA Vilardi F., Stephan M., Clancy A., Janshoff A., Schwappach B.;
RT "WRB and CAML are necessary and sufficient to mediate tail-anchored protein
RT targeting to the ER membrane.";
RL PLoS ONE 9:e85033-e85033(2014).
RN [9]
RP FUNCTION.
RX PubMed=27226539; DOI=10.1074/jbc.m115.707752;
RA Colombo S.F., Cardani S., Maroli A., Vitiello A., Soffientini P.,
RA Crespi A., Bram R.F., Benfante R., Borgese N.;
RT "Tail-anchored protein insertion in mammals: function and reciprocal
RT interactions of the two subunits of the TRC40 receptor.";
RL J. Biol. Chem. 291:15292-15306(2016).
RN [10]
RP FUNCTION, AND INTERACTION WITH CAMLG.
RX PubMed=31417168; DOI=10.1038/s41598-019-48363-2;
RA Carvalho H.J.F., Del Bondio A., Maltecca F., Colombo S.F., Borgese N.;
RT "The WRB Subunit of the Get3 Receptor is Required for the Correct
RT Integration of its Partner CAML into the ER.";
RL Sci. Rep. 9:11887-11887(2019).
RN [11]
RP FUNCTION, AND INTERACTION WITH CAMLG.
RX PubMed=32187542; DOI=10.1016/j.celrep.2020.02.084;
RA Inglis A.J., Page K.R., Guna A., Voorhees R.M.;
RT "Differential Modes of Orphan Subunit Recognition for the WRB/CAML
RT Complex.";
RL Cell Rep. 30:3691-3698(2020).
RN [12]
RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) OF THE GET COMPLEX.
RX PubMed=32910895; DOI=10.1016/j.molcel.2020.08.012;
RA McDowell M.A., Heimes M., Fiorentino F., Mehmood S., Farkas A.,
RA Coy-Vergara J., Wu D., Bolla J.R., Schmid V., Heinze R., Wild K.,
RA Flemming D., Pfeffer S., Schwappach B., Robinson C.V., Sinning I.;
RT "Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET
RT Insertase Complex.";
RL Mol. Cell 80:72-86(2020).
CC -!- FUNCTION: Required for the post-translational delivery of tail-anchored
CC (TA) proteins to the endoplasmic reticulum (ER) (PubMed:21444755,
CC PubMed:23041287, PubMed:24392163, PubMed:27226539). Together with
CC CAMLG/GET2, acts as a membrane receptor for soluble GET3/TRC40, which
CC recognizes and selectively binds the transmembrane domain of TA
CC proteins in the cytosol (PubMed:21444755, PubMed:23041287,
CC PubMed:24392163, PubMed:27226539). Required to ensure correct topology
CC and ER insertion of CAMLG (PubMed:31417168, PubMed:32187542).
CC {ECO:0000269|PubMed:21444755, ECO:0000269|PubMed:23041287,
CC ECO:0000269|PubMed:24392163, ECO:0000269|PubMed:27226539,
CC ECO:0000269|PubMed:31417168, ECO:0000269|PubMed:32187542}.
CC -!- SUBUNIT: Component of the Golgi to ER traffic (GET) complex, which is
CC composed of GET1/WRB, CAMLG/GET2 and GET3/TRC40 (PubMed:21444755,
CC PubMed:23041287, PubMed:24392163, PubMed:32910895). Within the complex,
CC GET1 and CAMLG form a heterotetramer which is stabilized by
CC phosphatidylinositol binding and which binds to the GET3 homodimer
CC (PubMed:32910895). Interacts with CAMLG (via C-terminus)
CC (PubMed:23041287, PubMed:31417168, PubMed:32187542). GET3 shows a
CC higher affinity for CAMLG than for GET1 (PubMed:24392163).
CC {ECO:0000269|PubMed:21444755, ECO:0000269|PubMed:23041287,
CC ECO:0000269|PubMed:24392163, ECO:0000269|PubMed:31417168,
CC ECO:0000269|PubMed:32187542, ECO:0000269|PubMed:32910895}.
CC -!- INTERACTION:
CC O00258; Q8WTS1: ABHD5; NbExp=3; IntAct=EBI-18908258, EBI-2813554;
CC O00258; P02652: APOA2; NbExp=3; IntAct=EBI-18908258, EBI-1171525;
CC O00258; Q9BQE5: APOL2; NbExp=3; IntAct=EBI-18908258, EBI-4290634;
CC O00258; P29972: AQP1; NbExp=3; IntAct=EBI-18908258, EBI-745213;
CC O00258; P49069: CAMLG; NbExp=3; IntAct=EBI-18908258, EBI-1748958;
CC O00258; Q8NHW4: CCL4L2; NbExp=3; IntAct=EBI-18908258, EBI-10271156;
CC O00258; Q8IX05: CD302; NbExp=3; IntAct=EBI-18908258, EBI-14259393;
CC O00258; P19397: CD53; NbExp=3; IntAct=EBI-18908258, EBI-6657396;
CC O00258; P51798: CLCN7; NbExp=3; IntAct=EBI-18908258, EBI-4402346;
CC O00258; P21964: COMT; NbExp=3; IntAct=EBI-18908258, EBI-372265;
CC O00258; Q5RI15: COX20; NbExp=3; IntAct=EBI-18908258, EBI-2834035;
CC O00258; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-18908258, EBI-711490;
CC O00258; P30519: HMOX2; NbExp=3; IntAct=EBI-18908258, EBI-712096;
CC O00258; Q9BUP3-3: HTATIP2; NbExp=3; IntAct=EBI-18908258, EBI-12937691;
CC O00258; Q8N138: ORMDL3; NbExp=3; IntAct=EBI-18908258, EBI-721750;
CC O00258; Q5VZY2: PLPP4; NbExp=3; IntAct=EBI-18908258, EBI-10485931;
CC O00258; P43378: PTPN9; NbExp=3; IntAct=EBI-18908258, EBI-742898;
CC O00258; Q8IV61: RASGRP3; NbExp=3; IntAct=EBI-18908258, EBI-1047876;
CC O00258; Q5QGT7: RTP2; NbExp=3; IntAct=EBI-18908258, EBI-10244780;
CC O00258; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-18908258, EBI-749270;
CC O00258; Q9BZV2: SLC19A3; NbExp=3; IntAct=EBI-18908258, EBI-3923779;
CC O00258; Q7Z769: SLC35E3; NbExp=3; IntAct=EBI-18908258, EBI-13389236;
CC O00258; P30825: SLC7A1; NbExp=3; IntAct=EBI-18908258, EBI-4289564;
CC O00258; Q969W0: SPTSSA; NbExp=3; IntAct=EBI-18908258, EBI-723396;
CC O00258; P32856-2: STX2; NbExp=3; IntAct=EBI-18908258, EBI-11956649;
CC O00258; Q9NZ01: TECR; NbExp=3; IntAct=EBI-18908258, EBI-2877718;
CC O00258; P02786: TFRC; NbExp=3; IntAct=EBI-18908258, EBI-355727;
CC O00258; Q96DZ7: TM4SF19; NbExp=3; IntAct=EBI-18908258, EBI-6448756;
CC O00258; Q69YG0: TMEM42; NbExp=3; IntAct=EBI-18908258, EBI-12038591;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:21444755}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00258-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00258-2; Sequence=VSP_043081;
CC -!- SIMILARITY: Belongs to the WRB/GET1 family. {ECO:0000305}.
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DR EMBL; Y12478; CAA73081.1; -; mRNA.
DR EMBL; AK293113; BAF85802.1; -; mRNA.
DR EMBL; AK299144; BAG61196.1; -; mRNA.
DR EMBL; AF064861; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF121781; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL163279; CAB90454.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09645.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09647.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09649.1; -; Genomic_DNA.
DR EMBL; BC012415; AAH12415.1; -; mRNA.
DR CCDS; CCDS13664.1; -. [O00258-1]
DR CCDS; CCDS54485.1; -. [O00258-2]
DR RefSeq; NP_001139690.1; NM_001146218.1. [O00258-2]
DR RefSeq; NP_004618.2; NM_004627.4. [O00258-1]
DR PDB; 6SO5; EM; 4.20 A; C/D=1-174.
DR PDBsum; 6SO5; -.
DR AlphaFoldDB; O00258; -.
DR SMR; O00258; -.
DR BioGRID; 113322; 53.
DR ComplexPortal; CPX-6464; GET complex.
DR IntAct; O00258; 35.
DR STRING; 9606.ENSP00000327716; -.
DR TCDB; 3.A.19.1.1; the guided entry of tail anchored protein (get) family.
DR iPTMnet; O00258; -.
DR PhosphoSitePlus; O00258; -.
DR BioMuta; WRB; -.
DR EPD; O00258; -.
DR jPOST; O00258; -.
DR MassIVE; O00258; -.
DR MaxQB; O00258; -.
DR PaxDb; O00258; -.
DR PeptideAtlas; O00258; -.
DR PRIDE; O00258; -.
DR ProteomicsDB; 47813; -. [O00258-1]
DR ProteomicsDB; 47814; -. [O00258-2]
DR Antibodypedia; 3116; 145 antibodies from 21 providers.
DR DNASU; 7485; -.
DR Ensembl; ENST00000380708.5; ENSP00000370084.1; ENSG00000182093.16. [O00258-2]
DR Ensembl; ENST00000398753.5; ENSP00000381737.1; ENSG00000182093.16. [O00258-2]
DR Ensembl; ENST00000649170.1; ENSP00000496813.1; ENSG00000182093.16. [O00258-1]
DR Ensembl; ENST00000650376.1; ENSP00000497103.1; ENSG00000182093.16. [O00258-2]
DR GeneID; 7485; -.
DR KEGG; hsa:7485; -.
DR MANE-Select; ENST00000649170.1; ENSP00000496813.1; NM_004627.6; NP_004618.2.
DR UCSC; uc002yxs.4; human. [O00258-1]
DR CTD; 7485; -.
DR DisGeNET; 7485; -.
DR GeneCards; GET1; -.
DR HGNC; HGNC:12790; GET1.
DR HPA; ENSG00000182093; Low tissue specificity.
DR MIM; 602915; gene.
DR neXtProt; NX_O00258; -.
DR OpenTargets; ENSG00000182093; -.
DR VEuPathDB; HostDB:ENSG00000182093; -.
DR eggNOG; KOG4253; Eukaryota.
DR GeneTree; ENSGT00390000008610; -.
DR InParanoid; O00258; -.
DR OMA; WFGPLTW; -.
DR OrthoDB; 1508713at2759; -.
DR PhylomeDB; O00258; -.
DR TreeFam; TF314708; -.
DR PathwayCommons; O00258; -.
DR Reactome; R-HSA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR SignaLink; O00258; -.
DR BioGRID-ORCS; 7485; 388 hits in 1087 CRISPR screens.
DR ChiTaRS; WRB; human.
DR GenomeRNAi; 7485; -.
DR Pharos; O00258; Tbio.
DR PRO; PR:O00258; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; O00258; protein.
DR Bgee; ENSG00000182093; Expressed in bronchial epithelial cell and 205 other tissues.
DR ExpressionAtlas; O00258; baseline and differential.
DR Genevisible; O00258; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IC:ComplexPortal.
DR GO; GO:0043529; C:GET complex; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0045048; P:protein insertion into ER membrane; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0071816; P:tail-anchored membrane protein insertion into ER membrane; IDA:UniProtKB.
DR Gene3D; 1.10.287.660; -; 1.
DR InterPro; IPR028945; Get1.
DR InterPro; IPR029012; Helix_hairpin_bin_sf.
DR Pfam; PF04420; CHD5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Endoplasmic reticulum;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..174
FT /note="Guided entry of tail-anchored proteins factor 1"
FT /id="PRO_0000065979"
FT TOPO_DOM 1..8
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..99
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 121..148
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 170..174
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 39..97
FT /note="Interaction with GET3/TRC40"
FT COILED 39..94
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..34
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043081"
FT VARIANT 110
FT /note="V -> I (in dbSNP:rs35946782)"
FT /id="VAR_051491"
FT CONFLICT 31
FT /note="F -> I (in Ref. 1; CAA73081)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 174 AA; 19780 MW; A01F11CC564EAB6E CRC64;
MSSAAADHWA WLLVLSFVFG CNVLRILLPS FSSFMSRVLQ KDAEQESQMR AEIQDMKQEL
STVNMMDEFA RYARLERKIN KMTDKLKTHV KARTAQLAKI KWVISVAFYV LQAALMISLI
WKYYSVPVAV VPSKWITPLD RLVAFPTRVA GGVGITCWIL VCNKVVAIVL HPFS
