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Q9NQX7 (ITM2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Integral membrane protein 2C
Alternative name(s):
Cerebral protein 14
Transmembrane protein BRI3

Cleaved into the following chain:

  1. CT-BRI3
Gene names
Name:ITM2C
Synonyms:BRI3
ORF Names:hucep-14, NPD018, PSEC0047
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length267 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.14 Ref.16

Subunit structure

Interacts with BACE1. Interacts with APP. Interacts with STMN2. Ref.13 Ref.14 Ref.16

Subcellular location

Lysosome membrane; Single-pass type II membrane protein By similarity. Cell membrane; Single-pass type II membrane protein Ref.15.

Tissue specificity

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. Ref.2 Ref.13

Post-translational modification

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.

Sequence similarities

Belongs to the ITM2 family.

Contains 1 BRICHOS domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NQX7-1)

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.
Isoform 2 (identifier: Q9NQX7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     41-87: Missing.
Isoform 3 (identifier: Q9NQX7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     151-187: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 267267Integral membrane protein 2C
PRO_0000154826
Peptide243 – 26725CT-BRI3
PRO_0000232645

Regions

Transmembrane55 – 7521Helical; Signal-anchor for type II membrane protein; Potential
Domain136 – 23095BRICHOS

Sites

Site242 – 2432Cleavage; by furin

Amino acid modifications

Glycosylation1691N-linked (GlcNAc...) Probable

Natural variations

Alternative sequence41 – 8747Missing in isoform 2.
VSP_013471
Alternative sequence151 – 18737Missing in isoform 3.
VSP_013472
Natural variant531G → S. Ref.1 Ref.6 Ref.7 Ref.10 Ref.12
Corresponds to variant rs2289235 [ dbSNP | Ensembl ].
VAR_022111

Experimental info

Mutagenesis241 – 2422KR → AA: Completely abrogates proteolytic processing. Ref.13
Sequence conflict22 – 3918Missing in BAC03562. Ref.6
Sequence conflict1331V → A in BAD96417. Ref.8
Sequence conflict2051T → A in CAG33489. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 234DDB91B4F282E7

FASTA26730,224
        10         20         30         40         50         60 
MVKISFQPAV AGIKGDKADK ASASAPAPAS ATEILLTPAR EEQPPQHRSK RGGSVGGVCY 

        70         80         90        100        110        120 
LSMGMVVLLM GLVFASVYIY RYFFLAQLAR DNFFRCGVLY EDSLSSQVRT QMELEEDVKI 

       130        140        150        160        170        180 
YLDENYERIN VPVPQFGGGD PADIIHDFQR GLTAYHDISL DKCYVIELNT TIVLPPRNFW 

       190        200        210        220        230        240 
ELLMNVKRGT YLPQTYIIQE EMVVTEHVSD KEALGSFIYH LCNGKDTYRL RRRATRRRIN 

       250        260 
KRGAKNCNAI RHFENTFVVE TLICGVV 

« Hide

Isoform 2 [UniParc].

Checksum: 9C16C85BD37BA9CC
Show »

FASTA22024,956
Isoform 3 [UniParc].

Checksum: 6C8BF583B61C58D0
Show »

FASTA23025,921

References

« Hide 'large scale' references
[1]"Molecular cloning of a gene specifically expressed in human brain."
Yoshimoto M., Yazaki M., Matsumoto K., Takayama K.
Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-53.
Tissue: Brain.
[2]"Sequence, genomic structure and tissue expression of human BRI3, a member of the BRI gene family."
Vidal R., Calero M., Revesz T., Plant G., Ghiso J., Frangione B.
Gene 266:95-102(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]Wu J., Zhang B., Peng X., Yuan J., Qiang B.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Pituitary.
[5]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT SER-53.
Tissue: Amygdala.
[7]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-53.
[8]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[9]"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. expand/collapse author list , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Teratocarcinoma.
[10]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-53.
Tissue: Uterus.
[11]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT SER-53.
Tissue: Brain, Chondrosarcoma and Colon.
[13]"Beta-amyloid protein converting enzyme 1 and brain-specific type II membrane protein BRI3: binding partners processed by furin."
Wickham L., Benjannet S., Marcinkiewicz E., Chretien M., Seidah N.G.
J. Neurochem. 92:93-102(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BACE1, GLYCOSYLATION, CLEAVAGE, TISSUE SPECIFICITY, MUTAGENESIS OF 241-LYS-ARG-242.
[14]"BRI3 associates with SCG10 and attenuates NGF-induced neurite outgrowth in PC12 cells."
Gong Y., Wu J., Qiang H., Liu B., Chi Z., Chen T., Yin B., Peng X., Yuan J.
BMB Rep. 41:287-293(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STMN2.
[15]"Substrate requirements for SPPL2b-dependent regulated intramembrane proteolysis."
Martin L., Fluhrer R., Haass C.
J. Biol. Chem. 284:5662-5670(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ABSENCE OF CLEAVAGE BY ADAM10 AND SPPL2B, SUBCELLULAR LOCATION.
[16]"BRI3 inhibits amyloid precursor protein processing in a mechanistically distinct manner from its homologue dementia gene BRI2."
Matsuda S., Matsuda Y., D'Adamio L.
J. Biol. Chem. 284:15815-15825(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH APP.
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001012532.1. NM_001012514.2.
NP_001012534.1. NM_001012516.2.
NP_001274169.1. NM_001287240.1.
NP_001274170.1. NM_001287241.1.
NP_112188.1. NM_030926.5.
UniGeneHs.111577.

3D structure databases

ProteinModelPortalQ9NQX7.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123553. 4 interactions.
IntActQ9NQX7. 4 interactions.
MINTMINT-4724210.

PTM databases

PhosphoSiteQ9NQX7.

Polymorphism databases

DMDM12585259.

Proteomic databases

PaxDbQ9NQX7.
PRIDEQ9NQX7.

Protocols and materials databases

DNASU81618.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000326407; ENSP00000322100; ENSG00000135916. [Q9NQX7-3]
ENST00000326427; ENSP00000322730; ENSG00000135916. [Q9NQX7-1]
ENST00000335005; ENSP00000335121; ENSG00000135916. [Q9NQX7-2]
GeneID81618.
KEGGhsa:81618.
UCSCuc002vqz.3. human. [Q9NQX7-1]
uc002vra.3. human. [Q9NQX7-2]
uc002vrb.3. human. [Q9NQX7-3]

Organism-specific databases

CTD81618.
GeneCardsGC02P231729.
HGNCHGNC:6175. ITM2C.
MIM609554. gene.
neXtProtNX_Q9NQX7.
PharmGKBPA29972.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG283703.
HOVERGENHBG059373.
InParanoidQ9NQX7.
OMACSGKETY.
PhylomeDBQ9NQX7.
TreeFamTF317770.

Gene expression databases

ArrayExpressQ9NQX7.
BgeeQ9NQX7.
CleanExHS_BRI3.
HS_ITM2C.
GenevestigatorQ9NQX7.

Family and domain databases

InterProIPR007084. BRICHOS_dom.
[Graphical view]
PfamPF04089. BRICHOS. 1 hit.
[Graphical view]
SMARTSM01039. BRICHOS. 1 hit.
[Graphical view]
PROSITEPS50869. BRICHOS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSITM2C. human.
GeneWikiITM2C.
GenomeRNAi81618.
NextBio71968.
PROQ9NQX7.
SOURCESearch...

Entry information

Entry nameITM2C_HUMAN
AccessionPrimary (citable) accession number: Q9NQX7
Secondary accession number(s): B3KPG4 expand/collapse secondary AC list , Q4G0A8, Q53H84, Q6IAE7, Q86VK5, Q8N288, Q8TAW0, Q9BUP8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM