RBCC

Full text data of IER3IP1

IER3IP1 [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Immediate early response 3-interacting protein 1

UniProt Q9Y5U9
ID IR3IP_HUMAN Reviewed; 82 AA.
AC Q9Y5U9;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 102.
DE RecName: Full=Immediate early response 3-interacting protein 1;
GN Name=IER3IP1; ORFNames=HSPC039;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Liver;
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
RT localized G-patch domain protein, IER3IP1.";
RL Gene 337:37-44(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
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
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
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.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis 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.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
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, and Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP POSSIBLE FUNCTION, AND VARIANTS MEDS 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.,
RA Venselaar H., de Wit M.C., de Graaff E., Bertoli-Avella A.M.,
RA Mancini G.M.;
RT "Microcephaly with simplified gyration, epilepsy, and infantile
RT diabetes linked to inappropriate apoptosis of neural progenitors.";
RL Am. J. Hum. Genet. 89:265-276(2011).
CC -!- FUNCTION: May be implicated in the regulation of apoptosis. May be
CC involved in protein transport between endoplasmic reticulum and
CC Golgi apparatus (By similarity).
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein.
CC -!- TISSUE SPECIFICITY: Highest levels in heart, skeletal muscle, and
CC kidney.
CC -!- DISEASE: Microcephaly, epilepsy, and diabetes syndrome (MEDS)
CC [MIM:614231]: An autosomal recessive disorder characterized by
CC microcephaly, simplified gyral pattern, severe epilepsy, and
CC infantile diabetes. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the YOS1 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 RefSeq; NP_057181.1; NM_016097.4.
DR UniGene; Hs.130917; -.
DR ProteinModelPortal; Q9Y5U9; -.
DR IntAct; Q9Y5U9; 5.
DR MINT; MINT-5002077; -.
DR STRING; 9606.ENSP00000256433; -.
DR PhosphoSite; Q9Y5U9; -.
DR DMDM; 74735295; -.
DR PaxDb; Q9Y5U9; -.
DR PeptideAtlas; Q9Y5U9; -.
DR PRIDE; Q9Y5U9; -.
DR DNASU; 51124; -.
DR Ensembl; ENST00000256433; ENSP00000256433; ENSG00000134049.
DR GeneID; 51124; -.
DR KEGG; hsa:51124; -.
DR UCSC; uc002lcu.3; human.
DR CTD; 51124; -.
DR GeneCards; GC18M044681; -.
DR HGNC; HGNC:18550; IER3IP1.
DR HPA; HPA010027; -.
DR MIM; 609382; gene.
DR MIM; 614231; phenotype.
DR neXtProt; NX_Q9Y5U9; -.
DR Orphanet; 306558; Primary microcephaly-epilepsy-permanent neonatal diabetes syndrome.
DR PharmGKB; PA134899219; -.
DR eggNOG; NOG329574; -.
DR HOGENOM; HOG000192480; -.
DR HOVERGEN; HBG081806; -.
DR InParanoid; Q9Y5U9; -.
DR OMA; QTVMRMP; -.
DR PhylomeDB; Q9Y5U9; -.
DR ChiTaRS; IER3IP1; human.
DR GeneWiki; IER3IP1; -.
DR GenomeRNAi; 51124; -.
DR NextBio; 53917; -.
DR PRO; PR:Q9Y5U9; -.
DR Bgee; Q9Y5U9; -.
DR CleanEx; HS_IER3IP1; -.
DR Genevestigator; Q9Y5U9; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016021; C:integral to membrane; 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 Complete proteome; Diabetes mellitus; Disease mutation;
KW Endoplasmic reticulum; Epilepsy; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1 82 Immediate early response 3-interacting
FT protein 1.
FT /FTId=PRO_0000257961.
FT TRANSMEM 2 22 Helical; (Potential).
FT TRANSMEM 62 82 Helical; (Potential).
FT VARIANT 21 21 V -> G (in MEDS).
FT /FTId=VAR_066569.
FT VARIANT 78 78 L -> P (in MEDS).
FT /FTId=VAR_066570.
SQ SEQUENCE 82 AA; 8969 MW; 2015B211F0AFF580 CRC64;
MAFTLYSLLQ AALLCVNAIA VLHEERFLKN IGWGTDQGIG GFGEEPGIKS QLMNLIRSVR
TVMRVPLIIV NSIAIVLLLL FG
//

MIM 609382
*RECORD*
*FIELD* NO
609382
*FIELD* TI
*609382 IMMEDIATE-EARLY RESPONSE 3-INTERACTING PROTEIN 1; IER3IP1
*FIELD* TX

CLONING
read more
By large-scale partial sequencing of a human liver cDNA library and EST
database searching, Yiu et al. (2004) identified a novel cDNA encoding a
deduced 82-amino acid protein, which they designated immediate-early
response-3-interacting protein-1 (IER3IP1). IER3IP1 contains a putative
G-patch domain and 2 transmembrane domains. Northern blot analysis
revealed a single 1.5-kb transcript expressed at high levels in heart,
skeletal muscle, and kidney, moderate levels in liver and brain, and low
levels in placenta, lung, and peripheral blood leukocytes. Yiu et al.
(2004) found that the IER3IP1 protein localizes to the endoplasmic
reticulum through its C-terminal transmembrane domain.

GENE STRUCTURE

Yiu et al. (2004) demonstrated that the IER3IP1 gene contains 3 exons.

MAPPING

By somatic cell hybrid analysis, Yiu et al. (2004) mapped the IER3IP1
gene to chromosome 18. They refined the mapping to 18q12 by radiation
hybrid analysis.

GENE FUNCTION

In cultured fibroblasts, Poulton et al. (2011) demonstrated that
expression of IER3IP1 was increased approximately 1.5-fold by TNF-alpha
(191160).

MOLECULAR GENETICS

By homozygosity mapping followed by candidate gene sequencing in 2
consanguineous families with microcephaly, epilepsy, and diabetes
syndrome (MEDS; 614231), Poulton et al. (2011) identified different
homozygous mutations in the IER3IP1 gene (609382.0001 and 609382.0002).
Poulton et al. (2011) concluded that the disorder was due to abnormally
increased apoptosis.

*FIELD* AV
.0001
MICROCEPHALY, EPILEPSY, AND DIABETES SYNDROME
IER3IP1, VAL21GLY

In a patient with microcephaly, epilepsy, and diabetes syndrome (MEDS;
614231), who was born of consanguineous parents of Moroccan origin,
Poulton et al. (2011) identified a homozygous 62T-G transversion in exon
1 of the IER3IP1 gene, resulting in a val21-to-gly (V21G) substitution
in a highly conserved residue in the first hydrophobic domain predicted
to be a signal sequence for targeting to the endoplasmic reticulum. Each
unaffected parent was heterozygous for the mutation, which was not found
in 300 control chromosomes. Patient fibroblasts showed an increased
tendency to undergo apoptosis after stress induction. Similar results
were obtained in control cells after knockdown of IER3IP1, suggesting
that IER3IP1 is needed to protect cells from stress. The patient had
originally been reported by de Wit et al. (2006), and died at age 18
months.

.0002
MICROCEPHALY, EPILEPSY, AND DIABETES SYNDROME
IER3IP1, LEU78PRO

In a patient with MEDS (614231), who was born of consanguineous parents
in Argentina, Poulton et al. (2011) identified a homozygous 233T-C
transition in exon 3 of the IER3IP1 gene, resulting in a leu78-to-pro
(L78P) substitution in a highly conserved residue in the second
hydrophobic transmembrane domain. Each unaffected parent was
heterozygous for the mutation, which was not found in 300 control
chromosomes.

*FIELD* RF
1. de Wit, M. C. Y.; de Coo, I. F. M.; Julier, C.; Delepine, M.; Lequin,
M. H.; van de Laar, I.; Sibbles, B. J.; Bruining, G. J.; Mancini,
G. M. S.: Microcephaly and simplified gyral pattern of the brain
associated with early-onset insulin-dependent diabetes mellitus. Neurogenetics 7:
259-263, 2006.

2. Poulton, C. J.; Schot, R.; Kia, S. K.; Jones, M.; Verheijen, F.
W.; Venselaar, H.; de Wit, M.-C. Y.; de Graaff, E.; Bertoli-Avella,
A. M.; Mancini, G. M. S.: Microcephaly with simplified gyration,
epilepsy, and infantile diabetes linked to inappropriate apoptosis
of neural progenitors. Am. J. Hum. Genet. 89: 265-276, 2011.

3. Yiu, W. H.; Poon, J. W. M.; Tsui, S. K. W.; Fung, K. P.; Waye,
M. M. Y.: Cloning and characterization of a novel endoplasmic reticulum
localized G-patch domain protein, IER3IP1. Gene 337: 37-44, 2004.

*FIELD* CN
Cassandra L. Kniffin - updated: 9/19/2011

*FIELD* CD
Jennifer L. Goldstein: 5/23/2005

*FIELD* ED
carol: 09/19/2011
ckniffin: 9/19/2011
carol: 5/24/2005

MIM 614231
*RECORD*
*FIELD* NO
614231
*FIELD* TI
#614231 MICROCEPHALY, EPILEPSY, AND DIABETES SYNDROME; MEDS
*FIELD* TX
A number sign (#) is used with this entry because microcephaly,
read moreepilepsy, and diabetes syndrome (MEDS) can be caused by homozygous
mutation in the IER3IP1 gene (609382) on chromosome 18q12.

DESCRIPTION

MEDS is an autosomal recessive disorder characterized by microcephaly,
simplified gyral pattern, severe epilepsy, and infantile diabetes
(summary by Poulton et al., 2011).

CLINICAL FEATURES

De Wit et al. (2006) and Poulton et al. (2011) reported a male infant,
born of consanguineous Moroccan parents, with a syndromic form of
microcephaly. His head circumference was 2.5 SD below the mean at birth,
and progressed to 3 SD below the mean at age 2 months. He had
developmental delay, hypotonia, seizures, obesity, diabetes mellitus,
and presumed hypogonadism. Brain MRI showed a simplified gyral pattern
and EEG showed hypsarrhythmia. The diabetes and seizures were difficult
to control and he died at age 18 months. Poulton et al. (2011) reported
another consanguineous family in Argentina with a similar disorder. The
index case had microcephaly with simplified gyral pattern, refractory
seizures, and infantile diabetes mellitus. He died at age 27 months.
Postmortem examination of an older affected sib showed extreme
microcephaly with extreme gyral simplification. Microscopy showed
reduced numbers of neurons in the cortex, hypomyelination, and
apoptosis. The pancreas showed few and small islets with few
insulin-positive beta cells.

INHERITANCE

MEDS is an autosomal recessive disorder (Poulton et al., 2011).

MOLECULAR GENETICS

By homozygosity mapping followed by candidate gene sequencing in 2
consanguineous families with MEDS, Poulton et al. (2011) identified
different homozygous mutations in the IER3IP1 gene (609382.0001 and
609382.0002). Poulton et al. (2011) concluded that the disorder was due
to abnormally increased apoptosis.

*FIELD* RF
1. de Wit, M. C. Y.; de Coo, I. F. M.; Julier, C.; Delepine, M.; Lequin,
M. H.; van de Laar, I.; Sibbles, B. J.; Bruining, G. J.; Mancini,
G. M. S.: Microcephaly and simplified gyral pattern of the brain
associated with early-onset insulin-dependent diabetes mellitus. Neurogenetics 7:
259-263, 2006.

2. Poulton, C. J.; Schot, R.; Kia, S. K.; Jones, M.; Verheijen, F.
W.; Venselaar, H.; de Wit, M.-C. Y.; de Graaff, E.; Bertoli-Avella,
A. M.; Mancini, G. M. S.: Microcephaly with simplified gyration,
epilepsy, and infantile diabetes linked to inappropriate apoptosis
of neural progenitors. Am. J. Hum. Genet. 89: 265-276, 2011.

*FIELD* CS
INHERITANCE:
Autosomal recessive

HEAD AND NECK:
[Head];
Microcephaly (about 3 SD below the mean)

NEUROLOGIC:
[Central nervous system];
Developmental delay, severe;
Hypotonia;
Seizures;
Myoclonic seizures;
Hypsarrhythmia;
Simplified gyral pattern;
Thin corpus callosum;
Delayed myelination;
Apoptosis of neurons

ENDOCRINE FEATURES:
Diabetes mellitus, infantile;
Few and small islets of Langerhans;
Hypogonadism (1 patient)

MISCELLANEOUS:
Two families have been reported (as of September 2011);
Death before age 3 years

MOLECULAR BASIS:
Caused by mutation in the immediate-early response 3-interacting protein
1 (IER3IP1, 609382.0001)

*FIELD* CD
Cassandra L. Kniffin: 9/19/2011

*FIELD* ED
joanna: 10/03/2011
ckniffin: 9/19/2011

*FIELD* CD
Cassandra L. Kniffin: 9/19/2011

*FIELD* ED
carol: 09/19/2011
ckniffin: 9/19/2011

RBCC Red Blood Cell Collection

Full text data of IER3IP1