Q9NQX7 (ITM2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	267 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Lysosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	induction of programmed cell death Inferred from electronic annotation. Source: Compara negative regulation of neuron projection development Inferred from direct assay Ref.14. Source: UniProtKB neuron differentiation Inferred from direct assay Ref.14. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from direct assay. Source: LIFEdb integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosome Inferred from direct assay PubMed 14592447. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay Ref.14. Source: UniProtKB plasma membrane Inferred from direct assay Ref.15. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: Compara beta-amyloid binding Inferred from physical interaction PubMed 19849849. Source: BHF-UCL
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 267	267	Integral membrane protein 2C		PRO_0000154826
	Peptide	243 – 267	25	CT-BRI3		PRO_0000232645
Regions
	Transmembrane	55 – 75	21	Helical; Signal-anchor for type II membrane protein; Potential
	Domain	136 – 230	95	BRICHOS
Sites
	Site	242 – 243	2	Cleavage; by furin
Amino acid modifications
	Modified residue	37	1	Phosphothreonine By similarity
	Glycosylation	169	1	N-linked (GlcNAc...) Probable
Natural variations
	Alternative sequence	41 – 87	47	Missing in isoform 2.		VSP_013471
	Alternative sequence	151 – 187	37	Missing in isoform 3.		VSP_013472
	Natural variant	53	1	G → S. Ref.1 Ref.6 Ref.7 Ref.10 Ref.12 Corresponds to variant rs2289235 [ dbSNP | Ensembl ].		VAR_022111
Experimental info
	Mutagenesis	241 – 242	2	KR → AA: Completely abrogates proteolytic processing. Ref.13
	Sequence conflict	22 – 39	18	Missing in BAC03562. Ref.6
	Sequence conflict	133	1	V → A in BAD96417. Ref.8
	Sequence conflict	205	1	T → A in CAG33489. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 234DDB91B4F282E7	FASTA	267	30,224
	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
	Isoform 2 [UniParc]. Checksum: 9C16C85BD37BA9CC	FASTA	220	24,956
	10 20 30 40 50 60 MVKISFQPAV AGIKGDKADK ASASAPAPAS ATEILLTPAR LARDNFFRCG VLYEDSLSSQ 70 80 90 100 110 120 VRTQMELEED VKIYLDENYE RINVPVPQFG GGDPADIIHD FQRGLTAYHD ISLDKCYVIE 130 140 150 160 170 180 LNTTIVLPPR NFWELLMNVK RGTYLPQTYI IQEEMVVTEH VSDKEALGSF IYHLCNGKDT 190 200 210 220 YRLRRRATRR RINKRGAKNC NAIRHFENTF VVETLICGVV
	Isoform 3 [UniParc]. Checksum: 6C8BF583B61C58D0	FASTA	230	25,921
	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 RGTYLPQTYI IQEEMVVTEH VSDKEALGSF 190 200 210 220 230 IYHLCNGKDT YRLRRRATRR RINKRGAKNC NAIRHFENTF VVETLICGVV

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.
IPI	IPI00016014. IPI00290583. IPI00384327.
RefSeq	NP_001012532.1. NM_001012514.1. NP_001012534.1. NM_001012516.1. NP_112188.1. NM_030926.4.
UniGene	Hs.111577.
3D structure databases
ProteinModelPortal	Q9NQX7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NQX7. 3 interactions.
PTM databases
PhosphoSite	Q9NQX7.
Polymorphism databases
DMDM	12585259.
Proteomic databases
PaxDb	Q9NQX7.
PRIDE	Q9NQX7.
Protocols and materials databases
DNASU	81618.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000326407; ENSP00000322100; ENSG00000135916. ENST00000326427; ENSP00000322730; ENSG00000135916. ENST00000335005; ENSP00000335121; ENSG00000135916.
GeneID	81618.
KEGG	hsa:81618.
UCSC	uc002vqz.3. human. uc002vra.3. human. uc002vrb.3. human.
Organism-specific databases
CTD	81618.
GeneCards	GC02P231693.
HGNC	HGNC:6175. ITM2C.
MIM	609554. gene.
neXtProt	NX_Q9NQX7.
PharmGKB	PA29972.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG283703.
HOVERGEN	HBG059373.
InParanoid	Q9NQX7.
OMA	IIQEEMI.
OrthoDB	EOG40ZQZG.
Gene expression databases
ArrayExpress	Q9NQX7.
Bgee	Q9NQX7.
CleanEx	HS_BRI3. HS_ITM2C.
Genevestigator	Q9NQX7.
GermOnline	ENSG00000135916. Homo sapiens.
Family and domain databases
InterPro	IPR007084. BRICHOS_dom. [Graphical view]
Pfam	PF04089. BRICHOS. 1 hit. [Graphical view]
SMART	SM01039. BRICHOS. 1 hit. [Graphical view]
PROSITE	PS50869. BRICHOS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ITM2C. human.
GenomeRNAi	81618.
NextBio	71968.
SOURCE	Search...

Entry information

Entry name

ITM2C_HUMAN

Accession

Primary (citable) accession number: Q9NQX7
Secondary accession number(s): B3KPG4 , 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 3, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.