ID   ITM2C_PONAB             Reviewed;         267 AA.
AC   Q5NVC3;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   04-JAN-2005, sequence version 1.
DT   03-AUG-2022, entry version 70.
DE   RecName: Full=Integral membrane protein 2C;
DE   Contains:
DE     RecName: Full=CT-BRI3;
GN   Name=ITM2C;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Negative regulator of amyloid-beta peptide production. May
CC       inhibit the processing of APP by blocking its access to alpha- and
CC       beta-secretase. Binding to the beta-secretase-cleaved APP C-terminal
CC       fragment is negligible, suggesting that ITM2C is a poor gamma-secretase
CC       cleavage inhibitor. May play a role in TNF-induced cell death and
CC       neuronal differentiation (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with BACE1. Interacts with APP. Interacts with STMN2
CC       (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250}; Single-pass type
CC       II membrane protein {ECO:0000250}. Cell membrane {ECO:0000250}; Single-
CC       pass type II membrane protein {ECO:0000250}.
CC   -!- PTM: Type I membrane-bound, as well as soluble, furin has a pre-eminent
CC       role in ITM2C proteolytic processing. PCSK7 and PCSK5 may also be
CC       involved although to a lesser extent. The soluble form of PCSK7 is
CC       incapable of processing ITM2C. Fails to undergo shedding by ADAM10 and
CC       intramembrane cleavage by SPPL2B (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the ITM2 family. {ECO:0000305}.
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DR   EMBL; CR926115; CAI29740.1; -; mRNA.
DR   EMBL; CR926009; CAI29647.1; -; mRNA.
DR   RefSeq; NP_001127092.1; NM_001133620.1.
DR   AlphaFoldDB; Q5NVC3; -.
DR   STRING; 9601.ENSPPYP00000024194; -.
DR   Ensembl; ENSPPYT00000015418; ENSPPYP00000014821; ENSPPYG00000013257.
DR   GeneID; 100174123; -.
DR   KEGG; pon:100174123; -.
DR   CTD; 81618; -.
DR   eggNOG; KOG4681; Eukaryota.
DR   GeneTree; ENSGT00950000183115; -.
DR   InParanoid; Q5NVC3; -.
DR   OrthoDB; 1322680at2759; -.
DR   Proteomes; UP000001595; Chromosome 2B.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR   GO; GO:0005524; F:ATP binding; IEA:Ensembl.
DR   GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR   GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR   GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR   InterPro; IPR007084; BRICHOS_dom.
DR   InterPro; IPR040145; ITM2.
DR   PANTHER; PTHR10962; PTHR10962; 1.
DR   Pfam; PF04089; BRICHOS; 1.
DR   SMART; SM01039; BRICHOS; 1.
DR   PROSITE; PS50869; BRICHOS; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Cleavage on pair of basic residues; Disulfide bond;
KW   Glycoprotein; Lysosome; Membrane; Phosphoprotein; Reference proteome;
KW   Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN           1..267
FT                   /note="Integral membrane protein 2C"
FT                   /id="PRO_0000154828"
FT   PEPTIDE         243..267
FT                   /note="CT-BRI3"
FT                   /id="PRO_0000232647"
FT   TRANSMEM        55..75
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          136..230
FT                   /note="BRICHOS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00255"
FT   SITE            242..243
FT                   /note="Cleavage; by furin"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         37
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5PQL7"
FT   CARBOHYD        169
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        163..222
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   267 AA;  30270 MW;  9C022630AEE3253B CRC64;
     MVKISFQPAV AGIKGDKADK ASASAPAPAS ATEILLTPAR EEQLPQHRSK RGSSVGGVCY
     LSMGMVVLLM GLVFASVYIY RYFFLAQLAR DNFFRCGVLY EDSLSSQVRT QMELEEDVKI
     YLDENYERIN VPVPQFGGGD PADIIHDFQR GLTAYHDISL DKCYVIELNT TIVLPPRNFW
     ELLMNVKRGT YLPQTYIIQE EMVVTEHVSD KEALGSFIYH LCNGKDTYRL RRRATRRRIN
     KRGAKNCNAI RHFENTFVVE TLICGVV