ID   ITM2C_PIG               Reviewed;         269 AA.
AC   Q06AV4;
DT   24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 73.
DE   RecName: Full=Integral membrane protein 2C;
DE   Contains:
DE     RecName: Full=CT-BRI3;
GN   Name=ITM2C;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Liu G.Y.;
RL   Submitted (AUG-2006) 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; DQ917621; ABI97166.1; -; mRNA.
DR   RefSeq; NP_001116603.1; NM_001123131.1.
DR   AlphaFoldDB; Q06AV4; -.
DR   STRING; 9823.ENSSSCP00000017233; -.
DR   PaxDb; Q06AV4; -.
DR   PeptideAtlas; Q06AV4; -.
DR   PRIDE; Q06AV4; -.
DR   Ensembl; ENSSSCT00000087047; ENSSSCP00000060874; ENSSSCG00000016267.
DR   Ensembl; ENSSSCT00015105243; ENSSSCP00015044080; ENSSSCG00015077725.
DR   Ensembl; ENSSSCT00030103979; ENSSSCP00030048125; ENSSSCG00030074146.
DR   Ensembl; ENSSSCT00050091243; ENSSSCP00050039231; ENSSSCG00050066946.
DR   Ensembl; ENSSSCT00055037279; ENSSSCP00055029616; ENSSSCG00055019017.
DR   Ensembl; ENSSSCT00060091625; ENSSSCP00060039608; ENSSSCG00060067098.
DR   Ensembl; ENSSSCT00065109299; ENSSSCP00065049093; ENSSSCG00065078733.
DR   Ensembl; ENSSSCT00070018000; ENSSSCP00070014943; ENSSSCG00070009249.
DR   GeneID; 100144481; -.
DR   KEGG; ssc:100144481; -.
DR   CTD; 81618; -.
DR   VGNC; VGNC:96383; ITM2C.
DR   eggNOG; KOG4681; Eukaryota.
DR   GeneTree; ENSGT00950000183115; -.
DR   HOGENOM; CLU_074596_0_0_1; -.
DR   InParanoid; Q06AV4; -.
DR   OMA; ARTRMEL; -.
DR   OrthoDB; 1322680at2759; -.
DR   TreeFam; TF317770; -.
DR   Proteomes; UP000008227; Chromosome 15.
DR   Proteomes; UP000314985; Chromosome 15.
DR   Bgee; ENSSSCG00000016267; Expressed in prefrontal cortex and 43 other tissues.
DR   ExpressionAtlas; Q06AV4; baseline and differential.
DR   Genevisible; Q06AV4; SS.
DR   GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
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:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0001540; F:amyloid-beta binding; IBA:GO_Central.
DR   GO; GO:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; IBA:GO_Central.
DR   GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
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..269
FT                   /note="Integral membrane protein 2C"
FT                   /id="PRO_0000295290"
FT   PEPTIDE         245..269
FT                   /note="CT-BRI3"
FT                   /id="PRO_0000295291"
FT   TRANSMEM        57..77
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          138..232
FT                   /note="BRICHOS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00255"
FT   SITE            244..245
FT                   /note="Cleavage; by furin"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         39
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5PQL7"
FT   CARBOHYD        171
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        165..224
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   269 AA;  30472 MW;  080A4073B9D21F6B CRC64;
     MVKISFQPAV AGIKGDKADK ASASASAPAP APAAEILLTP AREERPPHHR YKKGSSVGGV
     CYLSMGMVVL LMGLVFASVY IYRYFFLAQL ARDNFFHCGV LYEDSLSSQA RTRMELEEDV
     KIYLEENYER INVPVPQFGG GDPADIIHDF QRGLTAYHDI SLDKCYVIEL NTTIVLPPRN
     FWELLMNVKR GTYLPQTYII QEEMVVTEHV SDKEALGSFI YHLCNGKDTY RLRRRATRRR
     INKRGAKNCN AIRHFENTFV VETLICGVV