SPP2C_MOUSE
ID SPP2C_MOUSE Reviewed; 690 AA.
AC A2A6C4; Q497R4; Q8BHP0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Signal peptide peptidase-like 2C {ECO:0000250|UniProtKB:Q8IUH8, ECO:0000312|MGI:MGI:3045264};
DE Short=SPP-like 2C {ECO:0000250|UniProtKB:Q8IUH8};
DE Short=SPPL2c {ECO:0000250|UniProtKB:Q8IUH8};
DE EC=3.4.23.-;
DE AltName: Full=Intramembrane protease 5 {ECO:0000250|UniProtKB:Q8IUH8};
DE Short=IMP-5 {ECO:0000250|UniProtKB:Q8IUH8};
DE Flags: Precursor;
GN Name=Sppl2c {ECO:0000250|UniProtKB:Q8IUH8, ECO:0000312|MGI:MGI:3045264};
GN Synonyms=Imp5 {ECO:0000250|UniProtKB:Q8IUH8};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Intramembrane-cleaving aspartic protease (I-CLiP) that may be
CC able to cleave type II membrane signal peptides in the hydrophobic
CC plane of the membrane. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8IUH8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8IUH8}. Membrane
CC {ECO:0000250|UniProtKB:Q8IUH8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8IUH8}; Lumenal side
CC {ECO:0000250|UniProtKB:Q8IUH8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A2A6C4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2A6C4-2; Sequence=VSP_030363, VSP_030364;
CC -!- DOMAIN: The PAL motif is required for normal active site conformation.
CC The catalytic domains embedded in the membrane are in the opposite
CC orientation to that of the presenilin protein family; therefore, it is
CC predicted to cleave type II-oriented substrate peptides like the
CC prototypic protease SPP. {ECO:0000250|UniProtKB:P49768}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P49768}.
CC -!- SIMILARITY: Belongs to the peptidase A22B family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC36625.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC36625.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK077122; BAC36625.1; ALT_SEQ; mRNA.
DR EMBL; AL596383; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC100418; AAI00419.1; -; mRNA.
DR CCDS; CCDS36351.1; -. [A2A6C4-2]
DR CCDS; CCDS36352.1; -. [A2A6C4-1]
DR RefSeq; NP_001076004.1; NM_001082535.1. [A2A6C4-2]
DR RefSeq; NP_950184.2; NM_199019.2. [A2A6C4-1]
DR AlphaFoldDB; A2A6C4; -.
DR STRING; 10090.ENSMUSP00000102613; -.
DR GlyGen; A2A6C4; 1 site.
DR iPTMnet; A2A6C4; -.
DR PhosphoSitePlus; A2A6C4; -.
DR PaxDb; A2A6C4; -.
DR PRIDE; A2A6C4; -.
DR ProteomicsDB; 258728; -. [A2A6C4-1]
DR ProteomicsDB; 258729; -. [A2A6C4-2]
DR Antibodypedia; 17655; 47 antibodies from 16 providers.
DR DNASU; 237958; -.
DR Ensembl; ENSMUST00000059448; ENSMUSP00000091453; ENSMUSG00000049506. [A2A6C4-2]
DR Ensembl; ENSMUST00000107000; ENSMUSP00000102613; ENSMUSG00000049506. [A2A6C4-1]
DR GeneID; 237958; -.
DR KEGG; mmu:237958; -.
DR UCSC; uc007lwd.1; mouse. [A2A6C4-2]
DR UCSC; uc011yfz.1; mouse. [A2A6C4-1]
DR CTD; 162540; -.
DR MGI; MGI:3045264; Sppl2c.
DR VEuPathDB; HostDB:ENSMUSG00000049506; -.
DR eggNOG; KOG2442; Eukaryota.
DR GeneTree; ENSGT00940000163306; -.
DR HOGENOM; CLU_023799_2_1_1; -.
DR InParanoid; A2A6C4; -.
DR OMA; DNWSKDY; -.
DR OrthoDB; 535101at2759; -.
DR PhylomeDB; A2A6C4; -.
DR TreeFam; TF319186; -.
DR BRENDA; 3.4.23.B24; 3474.
DR BioGRID-ORCS; 237958; 4 hits in 71 CRISPR screens.
DR PRO; PR:A2A6C4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; A2A6C4; protein.
DR Bgee; ENSMUSG00000049506; Expressed in testis and 3 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0030660; C:Golgi-associated vesicle membrane; IBA:GO_Central.
DR GO; GO:0071458; C:integral component of cytoplasmic side of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0033619; P:membrane protein proteolysis; IBA:GO_Central.
DR InterPro; IPR007369; Peptidase_A22B_SPP.
DR InterPro; IPR006639; Preselin/SPP.
DR InterPro; IPR033150; SPPL2C.
DR PANTHER; PTHR12174; PTHR12174; 1.
DR PANTHER; PTHR12174:SF38; PTHR12174:SF38; 1.
DR Pfam; PF04258; Peptidase_A22B; 1.
DR SMART; SM00730; PSN; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein; Hydrolase;
KW Membrane; Protease; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000250|UniProtKB:Q8IUH8"
FT CHAIN 29..690
FT /note="Signal peptide peptidase-like 2C"
FT /id="PRO_0000314798"
FT TOPO_DOM 29..192
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IUH8"
FT TRANSMEM 193..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..260
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..283
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 284
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..307
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 308..328
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 329..349
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 350..354
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..373
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 374..384
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..448
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IUH8"
FT TRANSMEM 449..469
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 470..482
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 505..525
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 526..690
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IUH8"
FT DOMAIN 87..166
FT /note="PA"
FT REGION 564..633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 508..510
FT /note="PAL"
FT COMPBIAS 611..628
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 395
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT ACT_SITE 457
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 575..581
FT /note="FEQAVDG -> MPEEDFV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030363"
FT VAR_SEQ 582..690
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030364"
FT CONFLICT 299
FT /note="S -> G (in Ref. 1; BAC36625)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 690 AA; 76266 MW; 70AF4E127EE09E7B CRC64;
MACLGSLHPL GSLLLLFLLL LLSPEARGEY GLVRVVSKNW SKDYCVLYSS DYVNLPRDLH
HAPLLSLHDG TKTPWCPDED SFHQAQDSSP RQRPLHQTTT MVTRGNCSFY AKGWLAQDQG
AQGLLIVSRA RNQQCSDTIS KPQDPSKPWP ALTIPVAVLR YTDMLDIVSH TYGDTDVRVA
MFAPLEPVTD YNMAIIFILA VGTVAAGGYW AGLMEANKLQ RRQAQRGGGL GGHNQQQTVA
AERSQRAWED DDFEDAPMDF TPAMTGAVVT MSCSIMILLY FFYDCFVYVM IGIFSLGAST
GLYSCLAPIL CHLPLWRYQW VLPGQRVSVT WPLLLLAGLC AMVTVLWVIH RNEDHWAWLL
QDTLGVAYCL FVLRRVRLPT FKNCTLFLLA LLAFDVFFVF ITPLFTKTGE SIMVEVASGP
ADSSSHERLP MVLKVPRLSF SALTLCNQPF SILGFGDIVV PGFLVAYCHR FDMQVQSRQV
YYMACTVAYA VGLLVTFVAM ILMQMGQPAL LYLVSSTLLT SLAVATCRQE FTLFWTGQGR
AKIPAEPVAQ PCIASAVGSK MKLEDAKDSR TTNRFEQAVD GESGDLESST GDDMAEMVTL
SEDEATSPEG HSESSEGWSD TNLDPNELPS GSPMALEAML IPLIQPIPHP SELGHIRTQS
RVHDSSLPWM GLHKRKGLKV KKSMSAQAPL
