Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Integral membrane protein 2C

Gene

ITM2C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Negative regulator of beta amyloid 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

  • ATP binding Source: Ensembl
  • beta-amyloid binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135916-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Integral membrane protein 2C
Alternative 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:6175. ITM2C.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei55 – 75Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • Golgi apparatus Source: LIFEdb
  • integral component of membrane Source: UniProtKB-KW
  • lysosomal membrane Source: UniProtKB-SubCell
  • lysosome Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi241 – 242KR → AA: Completely abrogates proteolytic processing. 1 Publication2

Organism-specific databases

DisGeNETi81618.
OpenTargetsiENSG00000135916.
PharmGKBiPA29972.

Polymorphism and mutation databases

BioMutaiITM2C.
DMDMi12585259.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001548261 – 267Integral membrane protein 2CAdd BLAST267
PeptideiPRO_0000232645243 – 267CT-BRI3Add BLAST25

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei37PhosphothreonineBy similarity1
Disulfide bondi163 ↔ 222By similarity
Glycosylationi169N-linked (GlcNAc...)1 Publication1

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 intramembanaire cleavage by SPPL2B.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei242 – 243Cleavage; by furin2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9NQX7.
MaxQBiQ9NQX7.
PaxDbiQ9NQX7.
PeptideAtlasiQ9NQX7.
PRIDEiQ9NQX7.

PTM databases

iPTMnetiQ9NQX7.
PhosphoSitePlusiQ9NQX7.
SwissPalmiQ9NQX7.

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

BgeeiENSG00000135916.
CleanExiHS_BRI3.
HS_ITM2C.
ExpressionAtlasiQ9NQX7. baseline and differential.
GenevisibleiQ9NQX7. HS.

Interactioni

Subunit structurei

Interacts with BACE1. Interacts with APP. Interacts with STMN2.3 Publications

Protein-protein interaction databases

BioGridi123553. 7 interactors.
IntActiQ9NQX7. 12 interactors.
MINTiMINT-4724210.
STRINGi9606.ENSP00000322730.

Structurei

3D structure databases

ProteinModelPortaliQ9NQX7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini136 – 230BRICHOSPROSITE-ProRule annotationAdd BLAST95

Sequence similaritiesi

Belongs to the ITM2 family.Curated
Contains 1 BRICHOS domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4681. Eukaryota.
ENOG410XRNN. LUCA.
GeneTreeiENSGT00390000005162.
HOVERGENiHBG059373.
InParanoidiQ9NQX7.
KOiK18265.
OMAiNYEKITV.
OrthoDBiEOG091G0E78.
PhylomeDBiQ9NQX7.
TreeFamiTF317770.

Family and domain databases

InterProiIPR007084. BRICHOS_dom.
[Graphical view]
PfamiPF04089. BRICHOS. 1 hit.
[Graphical view]
SMARTiSM01039. BRICHOS. 1 hit.
[Graphical view]
PROSITEiPS50869. BRICHOS. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NQX7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:267
Mass (Da):30,224
Last modified:October 1, 2000 - v1
Checksum:i234DDB91B4F282E7
GO
Isoform 2 (identifier: Q9NQX7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     41-87: Missing.

Show »
Length:220
Mass (Da):24,956
Checksum:i9C16C85BD37BA9CC
GO
Isoform 3 (identifier: Q9NQX7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     151-187: Missing.

Note: No experimental confirmation available.
Show »
Length:230
Mass (Da):25,921
Checksum:i6C8BF583B61C58D0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22 – 39Missing in BAC03562 (PubMed:14702039).CuratedAdd BLAST18
Sequence conflicti133V → A in BAD96417 (Ref. 8) Curated1
Sequence conflicti205T → A in CAG33489 (Ref. 7) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02211153G → S.5 PublicationsCorresponds to variant rs2289235dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01347141 – 87Missing in isoform 2. 2 PublicationsAdd BLAST47
Alternative sequenceiVSP_013472151 – 187Missing in isoform 3. 1 PublicationAdd BLAST37

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.
CCDSiCCDS2479.1. [Q9NQX7-1]
CCDS33395.1. [Q9NQX7-3]
CCDS33396.1. [Q9NQX7-2]
RefSeqiNP_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]
UniGeneiHs.111577.

Genome annotation databases

EnsembliENST00000326407; ENSP00000322100; ENSG00000135916. [Q9NQX7-3]
ENST00000326427; ENSP00000322730; ENSG00000135916. [Q9NQX7-1]
ENST00000335005; ENSP00000335121; ENSG00000135916. [Q9NQX7-2]
GeneIDi81618.
KEGGihsa:81618.
UCSCiuc002vqz.5. human. [Q9NQX7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS2479.1. [Q9NQX7-1]
CCDS33395.1. [Q9NQX7-3]
CCDS33396.1. [Q9NQX7-2]
RefSeqiNP_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]
UniGeneiHs.111577.

3D structure databases

ProteinModelPortaliQ9NQX7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123553. 7 interactors.
IntActiQ9NQX7. 12 interactors.
MINTiMINT-4724210.
STRINGi9606.ENSP00000322730.

PTM databases

iPTMnetiQ9NQX7.
PhosphoSitePlusiQ9NQX7.
SwissPalmiQ9NQX7.

Polymorphism and mutation databases

BioMutaiITM2C.
DMDMi12585259.

Proteomic databases

EPDiQ9NQX7.
MaxQBiQ9NQX7.
PaxDbiQ9NQX7.
PeptideAtlasiQ9NQX7.
PRIDEiQ9NQX7.

Protocols and materials databases

DNASUi81618.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000326407; ENSP00000322100; ENSG00000135916. [Q9NQX7-3]
ENST00000326427; ENSP00000322730; ENSG00000135916. [Q9NQX7-1]
ENST00000335005; ENSP00000335121; ENSG00000135916. [Q9NQX7-2]
GeneIDi81618.
KEGGihsa:81618.
UCSCiuc002vqz.5. human. [Q9NQX7-1]

Organism-specific databases

CTDi81618.
DisGeNETi81618.
GeneCardsiITM2C.
HGNCiHGNC:6175. ITM2C.
MIMi609554. gene.
neXtProtiNX_Q9NQX7.
OpenTargetsiENSG00000135916.
PharmGKBiPA29972.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4681. Eukaryota.
ENOG410XRNN. LUCA.
GeneTreeiENSGT00390000005162.
HOVERGENiHBG059373.
InParanoidiQ9NQX7.
KOiK18265.
OMAiNYEKITV.
OrthoDBiEOG091G0E78.
PhylomeDBiQ9NQX7.
TreeFamiTF317770.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135916-MONOMER.

Miscellaneous databases

ChiTaRSiITM2C. human.
GeneWikiiITM2C.
GenomeRNAii81618.
PROiQ9NQX7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135916.
CleanExiHS_BRI3.
HS_ITM2C.
ExpressionAtlasiQ9NQX7. baseline and differential.
GenevisibleiQ9NQX7. HS.

Family and domain databases

InterProiIPR007084. BRICHOS_dom.
[Graphical view]
PfamiPF04089. BRICHOS. 1 hit.
[Graphical view]
SMARTiSM01039. BRICHOS. 1 hit.
[Graphical view]
PROSITEiPS50869. BRICHOS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiITM2C_HUMAN
AccessioniPrimary (citable) accession number: Q9NQX7
Secondary accession number(s): B3KPG4
, Q4G0A8, Q53H84, Q6IAE7, Q86VK5, Q8N288, Q8TAW0, Q9BUP8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: October 1, 2000
Last modified: November 2, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.