UniProtKB - Q9NQX7 (ITM2C_HUMAN)
Protein
Integral membrane protein 2C
Gene
ITM2C
Organism
Homo sapiens (Human)
Status
Functioni
Negative regulator of amyloid-beta peptide production. May inhibit the processing of APP by blocking its access to alpha- and beta-secretase. Binding to the beta-secretase-cleaved APP C-terminal fragment is negligible, suggesting that ITM2C is a poor gamma-secretase cleavage inhibitor. May play a role in TNF-induced cell death and neuronal differentiation (By similarity).By similarity2 Publications
GO - Molecular functioni
- amyloid-beta binding Source: BHF-UCL
- ATP binding Source: Ensembl
GO - Biological processi
- negative regulation of amyloid precursor protein biosynthetic process Source: GO_Central
- negative regulation of neuron projection development Source: UniProtKB
- neuron differentiation Source: UniProtKB
- positive regulation of extrinsic apoptotic signaling pathway Source: Ensembl
Enzyme and pathway databases
PathwayCommonsi | Q9NQX7 |
Names & Taxonomyi
Protein namesi | Recommended name: Integral membrane protein 2CAlternative name(s): Cerebral protein 14 Transmembrane protein BRI3 Cleaved into the following chain: |
Gene namesi | Name:ITM2C Synonyms:BRI3 ORF Names:hucep-14, NPD018, PSEC0047 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6175, ITM2C |
MIMi | 609554, gene |
neXtProti | NX_Q9NQX7 |
VEuPathDBi | HostDB:ENSG00000135916.15 |
Subcellular locationi
Lysosome
- Lysosome membrane By similarity; Single-pass type II membrane protein By similarity
Plasma membrane
- Cell membrane 1 Publication; Single-pass type II membrane protein 1 Publication
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: LIFEdb
Lysosome
- lysosomal membrane Source: UniProtKB-SubCell
- lysosome Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
- perinuclear region of cytoplasm Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 55 – 75 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Cell membrane, Lysosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 241 – 242 | KR → AA: Completely abrogates proteolytic processing. 1 Publication | 2 |
Organism-specific databases
DisGeNETi | 81618 |
OpenTargetsi | ENSG00000135916 |
PharmGKBi | PA29972 |
Miscellaneous databases
Pharosi | Q9NQX7, Tbio |
Genetic variation databases
BioMutai | ITM2C |
DMDMi | 12585259 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000154826 | 1 – 267 | Integral membrane protein 2CAdd BLAST | 267 | |
PeptideiPRO_0000232645 | 243 – 267 | CT-BRI3Add BLAST | 25 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 37 | PhosphothreonineBy similarity | 1 | |
Disulfide bondi | 163 ↔ 222 | By similarity | ||
Glycosylationi | 169 | N-linked (GlcNAc...) asparagine1 Publication | 1 |
Post-translational modificationi
Type I membrane-bound, as well as soluble, furin has a pre-eminent role in ITM2C proteolytic processing. PCSK7 and PCSK5 may also be involved although to a lesser extent. The soluble form of PCSK7 is incapable of processing ITM2C. Fails to undergo shedding by ADAM10 and intramembrane cleavage by SPPL2B.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 242 – 243 | Cleavage; by furin | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
EPDi | Q9NQX7 |
jPOSTi | Q9NQX7 |
MassIVEi | Q9NQX7 |
MaxQBi | Q9NQX7 |
PaxDbi | Q9NQX7 |
PeptideAtlasi | Q9NQX7 |
PRIDEi | Q9NQX7 |
ProteomicsDBi | 82226 [Q9NQX7-1] 82227 [Q9NQX7-2] 82228 [Q9NQX7-3] |
PTM databases
GlyGeni | Q9NQX7, 1 site |
iPTMneti | Q9NQX7 |
PhosphoSitePlusi | Q9NQX7 |
SwissPalmi | Q9NQX7 |
Expressioni
Tissue specificityi
High levels in the brain, specifically in the cerebral cortex, medulla, amygdala, hippocampus, thalamus, caudate nucleus, cerebellum, olfactory lobe and spinal cord. Very low levels in other organs.2 Publications
Gene expression databases
Bgeei | ENSG00000135916, Expressed in nucleus accumbens and 238 other tissues |
ExpressionAtlasi | Q9NQX7, baseline and differential |
Genevisiblei | Q9NQX7, HS |
Organism-specific databases
HPAi | ENSG00000135916, Group enriched (blood, brain, intestine) |
Interactioni
Subunit structurei
Interacts with BACE1.
Interacts with APP.
Interacts with STMN2.
3 PublicationsBinary interactionsi
Hide detailsIsoform 3 [Q9NQX7-3]
Protein-protein interaction databases
BioGRIDi | 123553, 22 interactors |
IntActi | Q9NQX7, 26 interactors |
MINTi | Q9NQX7 |
STRINGi | 9606.ENSP00000322730 |
Miscellaneous databases
RNActi | Q9NQX7, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 136 – 230 | BRICHOSPROSITE-ProRule annotationAdd BLAST | 95 |
Sequence similaritiesi
Belongs to the ITM2 family.Curated
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4681, Eukaryota |
GeneTreei | ENSGT00950000183115 |
InParanoidi | Q9NQX7 |
OMAi | ERPPYHR |
PhylomeDBi | Q9NQX7 |
TreeFami | TF317770 |
Family and domain databases
InterProi | View protein in InterPro IPR007084, BRICHOS_dom IPR040145, ITM2 |
PANTHERi | PTHR10962, PTHR10962, 1 hit |
Pfami | View protein in Pfam PF04089, BRICHOS, 1 hit |
SMARTi | View protein in SMART SM01039, BRICHOS, 1 hit |
PROSITEi | View protein in PROSITE PS50869, BRICHOS, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9NQX7-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MVKISFQPAV AGIKGDKADK ASASAPAPAS ATEILLTPAR EEQPPQHRSK
60 70 80 90 100
RGGSVGGVCY LSMGMVVLLM GLVFASVYIY RYFFLAQLAR DNFFRCGVLY
110 120 130 140 150
EDSLSSQVRT QMELEEDVKI YLDENYERIN VPVPQFGGGD PADIIHDFQR
160 170 180 190 200
GLTAYHDISL DKCYVIELNT TIVLPPRNFW ELLMNVKRGT YLPQTYIIQE
210 220 230 240 250
EMVVTEHVSD KEALGSFIYH LCNGKDTYRL RRRATRRRIN KRGAKNCNAI
260
RHFENTFVVE TLICGVV
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JG41 | C9JG41_HUMAN | Integral membrane protein 2 | ITM2C | 180 | Annotation score: | ||
B8ZZM6 | B8ZZM6_HUMAN | Integral membrane protein 2 | ITM2C | 205 | Annotation score: | ||
F5H4I5 | F5H4I5_HUMAN | Integral membrane protein 2 | ITM2C | 122 | Annotation score: | ||
E7EUS6 | E7EUS6_HUMAN | Integral membrane protein 2 | ITM2C | 125 | Annotation score: | ||
Q96JS4 | Q96JS4_HUMAN | Cerebral protein-3 | ITM2C hucep-3, hCG_34338 | 166 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 22 – 39 | Missing in BAC03562 (PubMed:14702039).CuratedAdd BLAST | 18 | |
Sequence conflicti | 133 | V → A in BAD96417 (Ref. 8) Curated | 1 | |
Sequence conflicti | 205 | T → A in CAG33489 (Ref. 7) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_022111 | 53 | G → S5 PublicationsCorresponds to variant dbSNP:rs2289235Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_013471 | 41 – 87 | Missing in isoform 2. 2 PublicationsAdd BLAST | 47 | |
Alternative sequenceiVSP_013472 | 151 – 187 | Missing in isoform 3. 1 PublicationAdd BLAST | 37 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB003629 mRNA Translation: BAB46927.1 AF272043 mRNA Translation: AAF89492.1 AY049777 mRNA Translation: AAL15434.1 AF271781 mRNA Translation: AAG44792.1 AL136603 mRNA Translation: CAB66538.1 AK056321 mRNA Translation: BAG51676.1 AK090975 mRNA Translation: BAC03562.1 CR457208 mRNA Translation: CAG33489.1 AK222697 mRNA Translation: BAD96417.1 AK075361 mRNA Translation: BAC11570.1 AL713651 mRNA Translation: CAD28460.1 CH471063 Genomic DNA Translation: EAW70936.1 BC002424 mRNA Translation: AAH02424.1 BC025742 mRNA Translation: AAH25742.1 BC050668 mRNA Translation: AAH50668.1 BC098563 mRNA Translation: AAH98563.1 |
CCDSi | CCDS2479.1 [Q9NQX7-1] CCDS33395.1 [Q9NQX7-3] CCDS33396.1 [Q9NQX7-2] |
RefSeqi | NP_001012532.1, NM_001012514.2 [Q9NQX7-2] NP_001012534.1, NM_001012516.2 [Q9NQX7-3] NP_001274169.1, NM_001287240.1 NP_001274170.1, NM_001287241.1 [Q9NQX7-1] NP_112188.1, NM_030926.5 [Q9NQX7-1] |
Genome annotation databases
Ensembli | ENST00000326407; ENSP00000322100; ENSG00000135916 [Q9NQX7-3] ENST00000326427; ENSP00000322730; ENSG00000135916 [Q9NQX7-1] ENST00000335005; ENSP00000335121; ENSG00000135916 [Q9NQX7-2] |
GeneIDi | 81618 |
KEGGi | hsa:81618 |
UCSCi | uc002vqz.5, human [Q9NQX7-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB003629 mRNA Translation: BAB46927.1 AF272043 mRNA Translation: AAF89492.1 AY049777 mRNA Translation: AAL15434.1 AF271781 mRNA Translation: AAG44792.1 AL136603 mRNA Translation: CAB66538.1 AK056321 mRNA Translation: BAG51676.1 AK090975 mRNA Translation: BAC03562.1 CR457208 mRNA Translation: CAG33489.1 AK222697 mRNA Translation: BAD96417.1 AK075361 mRNA Translation: BAC11570.1 AL713651 mRNA Translation: CAD28460.1 CH471063 Genomic DNA Translation: EAW70936.1 BC002424 mRNA Translation: AAH02424.1 BC025742 mRNA Translation: AAH25742.1 BC050668 mRNA Translation: AAH50668.1 BC098563 mRNA Translation: AAH98563.1 |
CCDSi | CCDS2479.1 [Q9NQX7-1] CCDS33395.1 [Q9NQX7-3] CCDS33396.1 [Q9NQX7-2] |
RefSeqi | NP_001012532.1, NM_001012514.2 [Q9NQX7-2] NP_001012534.1, NM_001012516.2 [Q9NQX7-3] NP_001274169.1, NM_001287240.1 NP_001274170.1, NM_001287241.1 [Q9NQX7-1] NP_112188.1, NM_030926.5 [Q9NQX7-1] |
3D structure databases
SMRi | Q9NQX7 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 123553, 22 interactors |
IntActi | Q9NQX7, 26 interactors |
MINTi | Q9NQX7 |
STRINGi | 9606.ENSP00000322730 |
PTM databases
GlyGeni | Q9NQX7, 1 site |
iPTMneti | Q9NQX7 |
PhosphoSitePlusi | Q9NQX7 |
SwissPalmi | Q9NQX7 |
Genetic variation databases
BioMutai | ITM2C |
DMDMi | 12585259 |
Proteomic databases
EPDi | Q9NQX7 |
jPOSTi | Q9NQX7 |
MassIVEi | Q9NQX7 |
MaxQBi | Q9NQX7 |
PaxDbi | Q9NQX7 |
PeptideAtlasi | Q9NQX7 |
PRIDEi | Q9NQX7 |
ProteomicsDBi | 82226 [Q9NQX7-1] 82227 [Q9NQX7-2] 82228 [Q9NQX7-3] |
Protocols and materials databases
Antibodypediai | 34409, 150 antibodies |
DNASUi | 81618 |
Genome annotation databases
Ensembli | ENST00000326407; ENSP00000322100; ENSG00000135916 [Q9NQX7-3] ENST00000326427; ENSP00000322730; ENSG00000135916 [Q9NQX7-1] ENST00000335005; ENSP00000335121; ENSG00000135916 [Q9NQX7-2] |
GeneIDi | 81618 |
KEGGi | hsa:81618 |
UCSCi | uc002vqz.5, human [Q9NQX7-1] |
Organism-specific databases
CTDi | 81618 |
DisGeNETi | 81618 |
GeneCardsi | ITM2C |
HGNCi | HGNC:6175, ITM2C |
HPAi | ENSG00000135916, Group enriched (blood, brain, intestine) |
MIMi | 609554, gene |
neXtProti | NX_Q9NQX7 |
OpenTargetsi | ENSG00000135916 |
PharmGKBi | PA29972 |
VEuPathDBi | HostDB:ENSG00000135916.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4681, Eukaryota |
GeneTreei | ENSGT00950000183115 |
InParanoidi | Q9NQX7 |
OMAi | ERPPYHR |
PhylomeDBi | Q9NQX7 |
TreeFami | TF317770 |
Enzyme and pathway databases
PathwayCommonsi | Q9NQX7 |
Miscellaneous databases
BioGRID-ORCSi | 81618, 2 hits in 877 CRISPR screens |
ChiTaRSi | ITM2C, human |
GeneWikii | ITM2C |
GenomeRNAii | 81618 |
Pharosi | Q9NQX7, Tbio |
PROi | PR:Q9NQX7 |
RNActi | Q9NQX7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000135916, Expressed in nucleus accumbens and 238 other tissues |
ExpressionAtlasi | Q9NQX7, baseline and differential |
Genevisiblei | Q9NQX7, HS |
Family and domain databases
InterProi | View protein in InterPro IPR007084, BRICHOS_dom IPR040145, ITM2 |
PANTHERi | PTHR10962, PTHR10962, 1 hit |
Pfami | View protein in Pfam PF04089, BRICHOS, 1 hit |
SMARTi | View protein in SMART SM01039, BRICHOS, 1 hit |
PROSITEi | View protein in PROSITE PS50869, BRICHOS, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ITM2C_HUMAN | |
Accessioni | Q9NQX7Primary (citable) accession number: Q9NQX7 Secondary accession number(s): B3KPG4 Q9BUP8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 24, 2001 |
Last sequence update: | October 1, 2000 | |
Last modified: | February 10, 2021 | |
This is version 165 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families