IR3IP_HUMAN
ID IR3IP_HUMAN Reviewed; 82 AA.
AC Q9Y5U9;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Immediate early response 3-interacting protein 1 {ECO:0000305};
GN Name=IER3IP1 {ECO:0000303|PubMed:15276200, ECO:0000312|HGNC:HGNC:18550};
GN ORFNames=HSPC039 {ECO:0000303|PubMed:11042152};
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Liver {ECO:0000312|EMBL:AAK53816.1};
RX PubMed=15276200; DOI=10.1016/j.gene.2004.04.033;
RA Yiu W.H., Poon J.W.M., Tsui S.K.W., Fung K.P., Waye M.M.Y.;
RT "Cloning and characterization of a novel endoplasmic reticulum localized G-
RT patch domain protein, IER3IP1.";
RL Gene 337:37-44(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood {ECO:0000312|EMBL:AAD39917.1};
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland {ECO:0000312|EMBL:AAF80762.1};
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5] {ECO:0000312|EMBL:CAG38519.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow {ECO:0000312|EMBL:AAH17391.1}, and
RC Brain {ECO:0000312|EMBL:AAH10888.1};
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=33122427; DOI=10.1126/science.abb5390;
RA Esk C., Lindenhofer D., Haendeler S., Wester R.A., Pflug F., Schroeder B.,
RA Bagley J.A., Elling U., Zuber J., von Haeseler A., Knoblich J.A.;
RT "A human tissue screen identifies a regulator of ER secretion as a brain-
RT size determinant.";
RL Science 370:935-941(2020).
RN [9]
RP VARIANTS MEDS1 GLY-21 AND PRO-78.
RX PubMed=21835305; DOI=10.1016/j.ajhg.2011.07.006;
RA Poulton C.J., Schot R., Kia S.K., Jones M., Verheijen F.W., Venselaar H.,
RA de Wit M.C., de Graaff E., Bertoli-Avella A.M., Mancini G.M.;
RT "Microcephaly with simplified gyration, epilepsy, and infantile diabetes
RT linked to inappropriate apoptosis of neural progenitors.";
RL Am. J. Hum. Genet. 89:265-276(2011).
RN [10]
RP VARIANT MEDS1 PRO-78.
RX PubMed=22991235; DOI=10.1002/ajmg.a.35583;
RA Abdel-Salam G.M., Schaffer A.E., Zaki M.S., Dixon-Salazar T., Mostafa I.S.,
RA Afifi H.H., Gleeson J.G.;
RT "A homozygous IER3IP1 mutation causes microcephaly with simplified gyral
RT pattern, epilepsy, and permanent neonatal diabetes syndrome (MEDS).";
RL Am. J. Med. Genet. A 158A:2788-2796(2012).
RN [11]
RP VARIANT MEDS1 GLY-21.
RX PubMed=24138066; DOI=10.1111/pedi.12086;
RA Shalev S.A., Tenenbaum-Rakover Y., Horovitz Y., Paz V.P., Ye H.,
RA Carmody D., Highland H.M., Boerwinkle E., Hanis C.L., Muzny D.M.,
RA Gibbs R.A., Bell G.I., Philipson L.H., Greeley S.A.;
RT "Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous
RT mutations in IER3IP1: insights into the natural history of a rare
RT disorder.";
RL Pediatr. Diabetes 15:252-256(2014).
CC -!- FUNCTION: Regulator of endoplasmic reticulum secretion that acts as a
CC key determinant of brain size (PubMed:33122427). Required for secretion
CC of extracellular matrix proteins (PubMed:33122427). Required for
CC correct brain development by depositing sufficient extracellular matrix
CC proteins for tissue integrity and the proliferation of neural
CC progenitors (PubMed:33122427). Acts as a regulator of the unfolded
CC protein response (UPR) (By similarity). {ECO:0000250|UniProtKB:Q9CR20,
CC ECO:0000269|PubMed:33122427}.
CC -!- INTERACTION:
CC Q9Y5U9; Q9NVV5-2: AIG1; NbExp=3; IntAct=EBI-725665, EBI-11957045;
CC Q9Y5U9; Q8NEA5: C19orf18; NbExp=3; IntAct=EBI-725665, EBI-18323646;
CC Q9Y5U9; O14735: CDIPT; NbExp=3; IntAct=EBI-725665, EBI-358858;
CC Q9Y5U9; Q96G23: CERS2; NbExp=3; IntAct=EBI-725665, EBI-1057080;
CC Q9Y5U9; Q9HA82: CERS4; NbExp=3; IntAct=EBI-725665, EBI-2622997;
CC Q9Y5U9; P01037: CST1; NbExp=3; IntAct=EBI-725665, EBI-1056240;
CC Q9Y5U9; Q9P2X0-2: DPM3; NbExp=3; IntAct=EBI-725665, EBI-10962476;
CC Q9Y5U9; Q15125: EBP; NbExp=3; IntAct=EBI-725665, EBI-3915253;
CC Q9Y5U9; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-725665, EBI-18535450;
CC Q9Y5U9; Q7Z2K6: ERMP1; NbExp=3; IntAct=EBI-725665, EBI-10976398;
CC Q9Y5U9; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-725665, EBI-18938272;
CC Q9Y5U9; P08034: GJB1; NbExp=3; IntAct=EBI-725665, EBI-17565645;
CC Q9Y5U9; O14653: GOSR2; NbExp=3; IntAct=EBI-725665, EBI-4401517;
CC Q9Y5U9; O15529: GPR42; NbExp=3; IntAct=EBI-725665, EBI-18076404;
CC Q9Y5U9; Q9BSE4: HERPUD2; NbExp=3; IntAct=EBI-725665, EBI-2868124;
CC Q9Y5U9; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-725665, EBI-10266796;
CC Q9Y5U9; Q09470: KCNA1; NbExp=3; IntAct=EBI-725665, EBI-8286599;
CC Q9Y5U9; O75425: MOSPD3; NbExp=3; IntAct=EBI-725665, EBI-12179105;
CC Q9Y5U9; O00623: PEX12; NbExp=3; IntAct=EBI-725665, EBI-594836;
CC Q9Y5U9; P57054: PIGP; NbExp=3; IntAct=EBI-725665, EBI-17630288;
CC Q9Y5U9; P60201-2: PLP1; NbExp=3; IntAct=EBI-725665, EBI-12188331;
CC Q9Y5U9; Q9H5K3: POMK; NbExp=3; IntAct=EBI-725665, EBI-11337900;
CC Q9Y5U9; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-725665, EBI-17247926;
CC Q9Y5U9; O14863: SLC30A4; NbExp=3; IntAct=EBI-725665, EBI-13918058;
CC Q9Y5U9; Q96CE8: TM4SF18; NbExp=3; IntAct=EBI-725665, EBI-13351685;
CC Q9Y5U9; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-725665, EBI-10694905;
CC Q9Y5U9; Q9Y6G1: TMEM14A; NbExp=3; IntAct=EBI-725665, EBI-2800360;
CC Q9Y5U9; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-725665, EBI-8638294;
CC Q9Y5U9; Q8TBQ9: TMEM167A; NbExp=5; IntAct=EBI-725665, EBI-13383218;
CC Q9Y5U9; Q96Q45-2: TMEM237; NbExp=5; IntAct=EBI-725665, EBI-10982110;
CC Q9Y5U9; P61165: TMEM258; NbExp=3; IntAct=EBI-725665, EBI-12019210;
CC Q9Y5U9; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-725665, EBI-11742770;
CC Q9Y5U9; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-725665, EBI-2548832;
CC Q9Y5U9; Q6ZT21: TMPPE; NbExp=3; IntAct=EBI-725665, EBI-11724433;
CC Q9Y5U9; Q9Y320: TMX2; NbExp=3; IntAct=EBI-725665, EBI-6447886;
CC Q9Y5U9; P34981: TRHR; NbExp=3; IntAct=EBI-725665, EBI-18055230;
CC Q9Y5U9; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-725665, EBI-741480;
CC Q9Y5U9; Q9BSR8: YIPF4; NbExp=3; IntAct=EBI-725665, EBI-751253;
CC Q9Y5U9; Q5T4F4: ZFYVE27; NbExp=3; IntAct=EBI-725665, EBI-3892947;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15276200, ECO:0000305|PubMed:33122427}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highest levels in heart, skeletal muscle, and
CC kidney. {ECO:0000269|PubMed:15276200}.
CC -!- DISEASE: Microcephaly, epilepsy, and diabetes syndrome 1 (MEDS1)
CC [MIM:614231]: An autosomal recessive disorder characterized by
CC microcephaly, simplified gyral pattern, severe epilepsy, and infantile
CC diabetes. {ECO:0000269|PubMed:21835305, ECO:0000269|PubMed:22991235,
CC ECO:0000269|PubMed:24138066}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the YOS1 family. {ECO:0000305}.
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DR EMBL; AF371963; AAK53816.1; -; mRNA.
DR EMBL; AF125100; AAD39917.1; -; mRNA.
DR EMBL; AF164798; AAF80762.1; -; mRNA.
DR EMBL; AL136667; CAB66602.1; -; mRNA.
DR EMBL; CR533488; CAG38519.1; -; mRNA.
DR EMBL; BC010888; AAH10888.1; -; mRNA.
DR EMBL; BC017391; AAH17391.1; -; mRNA.
DR CCDS; CCDS11933.1; -.
DR RefSeq; NP_057181.1; NM_016097.4.
DR AlphaFoldDB; Q9Y5U9; -.
DR SMR; Q9Y5U9; -.
DR BioGRID; 119311; 61.
DR IntAct; Q9Y5U9; 50.
DR MINT; Q9Y5U9; -.
DR STRING; 9606.ENSP00000256433; -.
DR iPTMnet; Q9Y5U9; -.
DR PhosphoSitePlus; Q9Y5U9; -.
DR BioMuta; IER3IP1; -.
DR DMDM; 74735295; -.
DR EPD; Q9Y5U9; -.
DR jPOST; Q9Y5U9; -.
DR MassIVE; Q9Y5U9; -.
DR MaxQB; Q9Y5U9; -.
DR PaxDb; Q9Y5U9; -.
DR PeptideAtlas; Q9Y5U9; -.
DR PRIDE; Q9Y5U9; -.
DR ProteomicsDB; 86512; -.
DR TopDownProteomics; Q9Y5U9; -.
DR Antibodypedia; 2445; 22 antibodies from 12 providers.
DR DNASU; 51124; -.
DR Ensembl; ENST00000256433.6; ENSP00000256433.3; ENSG00000134049.6.
DR GeneID; 51124; -.
DR KEGG; hsa:51124; -.
DR MANE-Select; ENST00000256433.6; ENSP00000256433.3; NM_016097.5; NP_057181.1.
DR UCSC; uc002lcu.4; human.
DR CTD; 51124; -.
DR DisGeNET; 51124; -.
DR GeneCards; IER3IP1; -.
DR HGNC; HGNC:18550; IER3IP1.
DR HPA; ENSG00000134049; Low tissue specificity.
DR MalaCards; IER3IP1; -.
DR MIM; 609382; gene.
DR MIM; 614231; phenotype.
DR neXtProt; NX_Q9Y5U9; -.
DR OpenTargets; ENSG00000134049; -.
DR Orphanet; 306558; Primary microcephaly-epilepsy-permanent neonatal diabetes syndrome.
DR PharmGKB; PA134899219; -.
DR VEuPathDB; HostDB:ENSG00000134049; -.
DR eggNOG; KOG4779; Eukaryota.
DR GeneTree; ENSGT00510000047648; -.
DR HOGENOM; CLU_152125_3_0_1; -.
DR InParanoid; Q9Y5U9; -.
DR OMA; WASWQNV; -.
DR OrthoDB; 1624874at2759; -.
DR PhylomeDB; Q9Y5U9; -.
DR TreeFam; TF300263; -.
DR PathwayCommons; Q9Y5U9; -.
DR SignaLink; Q9Y5U9; -.
DR BioGRID-ORCS; 51124; 126 hits in 1073 CRISPR screens.
DR ChiTaRS; IER3IP1; human.
DR GeneWiki; IER3IP1; -.
DR GenomeRNAi; 51124; -.
DR Pharos; Q9Y5U9; Tbio.
DR PRO; PR:Q9Y5U9; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q9Y5U9; protein.
DR Bgee; ENSG00000134049; Expressed in oocyte and 195 other tissues.
DR ExpressionAtlas; Q9Y5U9; baseline and differential.
DR Genevisible; Q9Y5U9; HS.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0030173; C:integral component of Golgi membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0007420; P:brain development; IDA:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0035265; P:organ growth; IDA:UniProtKB.
DR GO; GO:0003331; P:positive regulation of extracellular matrix constituent secretion; IMP:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:2000269; P:regulation of fibroblast apoptotic process; IMP:UniProtKB.
DR InterPro; IPR013880; Yos1.
DR PANTHER; PTHR15858; PTHR15858; 1.
DR Pfam; PF08571; Yos1; 1.
PE 1: Evidence at protein level;
KW Diabetes mellitus; Disease variant; Endoplasmic reticulum; Epilepsy;
KW Membrane; Protein transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..82
FT /note="Immediate early response 3-interacting protein 1"
FT /id="PRO_0000257961"
FT TRANSMEM 2..22
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 62..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 21
FT /note="V -> G (in MEDS1; dbSNP:rs387907011)"
FT /evidence="ECO:0000269|PubMed:21835305,
FT ECO:0000269|PubMed:24138066"
FT /id="VAR_066569"
FT VARIANT 78
FT /note="L -> P (in MEDS1; dbSNP:rs387907012)"
FT /evidence="ECO:0000269|PubMed:21835305,
FT ECO:0000269|PubMed:22991235"
FT /id="VAR_066570"
SQ SEQUENCE 82 AA; 8969 MW; 2015B211F0AFF580 CRC64;
MAFTLYSLLQ AALLCVNAIA VLHEERFLKN IGWGTDQGIG GFGEEPGIKS QLMNLIRSVR
TVMRVPLIIV NSIAIVLLLL FG
