SPP2C_HUMAN
ID SPP2C_HUMAN Reviewed; 684 AA.
AC Q8IUH8; Q8TC67; Q8WVZ6;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Signal peptide peptidase-like 2C {ECO:0000303|PubMed:15385547};
DE Short=SPP-like 2C {ECO:0000303|PubMed:15385547};
DE Short=SPPL2c {ECO:0000303|PubMed:15385547};
DE EC=3.4.23.-;
DE AltName: Full=Intramembrane protease 5 {ECO:0000303|PubMed:12139484};
DE Short=IMP-5 {ECO:0000303|PubMed:12139484};
DE Flags: Precursor;
GN Name=SPPL2C {ECO:0000303|PubMed:15385547};
GN Synonyms=IMP5 {ECO:0000303|PubMed:12139484};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-303.
RX PubMed=12139484; DOI=10.1023/a:1016365227942;
RA Grigorenko A.P., Moliaka Y.K., Korovaitseva G.I., Rogaev E.I.;
RT "Novel class of polytopic proteins with domains associated with putative
RT protease activity.";
RL Biochemistry (Mosc.) 67:826-834(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-303 AND VAL-626.
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).
RN [4]
RP GLYCOSYLATION, TOPOLOGY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15385547; DOI=10.1074/jbc.m407898200;
RA Friedmann E., Lemberg M.K., Weihofen A., Dev K.K., Dengler U., Rovelli G.,
RA Martoglio B.;
RT "Consensus analysis of signal peptide peptidase and homologous human
RT aspartic proteases reveals opposite topology of catalytic domains compared
RT with presenilins.";
RL J. Biol. Chem. 279:50790-50798(2004).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=16829952; DOI=10.1038/ncb1440;
RA Friedmann E., Hauben E., Maylandt K., Schleeger S., Vreugde S.,
RA Lichtenthaler S.F., Kuhn P.H., Stauffer D., Rovelli G., Martoglio B.;
RT "SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in
RT activated dendritic cells to trigger IL-12 production.";
RL Nat. Cell Biol. 8:843-848(2006).
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 -!- INTERACTION:
CC Q8IUH8; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-14064968, EBI-3867333;
CC Q8IUH8; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-14064968, EBI-22310682;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16829952}; Multi-pass membrane protein
CC {ECO:0000305}. Membrane {ECO:0000269|PubMed:15385547,
CC ECO:0000269|PubMed:16829952}; Multi-pass membrane protein
CC {ECO:0000305}; Lumenal side {ECO:0000269|PubMed:15385547}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:15385547}.
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:0000269|PubMed:15385547}.
CC -!- SIMILARITY: Belongs to the peptidase A22B family. {ECO:0000305}.
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DR EMBL; AY169316; AAO12541.1; -; Genomic_DNA.
DR EMBL; AC003662; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC217770; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC217771; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022041; AAH22041.2; -; mRNA.
DR EMBL; BC025401; AAH25401.1; -; mRNA.
DR CCDS; CCDS32673.1; -.
DR RefSeq; NP_787078.2; NM_175882.2.
DR AlphaFoldDB; Q8IUH8; -.
DR BioGRID; 127824; 4.
DR IntAct; Q8IUH8; 3.
DR STRING; 9606.ENSP00000332488; -.
DR MEROPS; A22.006; -.
DR GlyGen; Q8IUH8; 1 site.
DR iPTMnet; Q8IUH8; -.
DR PhosphoSitePlus; Q8IUH8; -.
DR BioMuta; SPPL2C; -.
DR DMDM; 269849676; -.
DR jPOST; Q8IUH8; -.
DR MassIVE; Q8IUH8; -.
DR PaxDb; Q8IUH8; -.
DR PeptideAtlas; Q8IUH8; -.
DR PRIDE; Q8IUH8; -.
DR ProteomicsDB; 70575; -.
DR Antibodypedia; 17655; 47 antibodies from 16 providers.
DR DNASU; 162540; -.
DR Ensembl; ENST00000329196.7; ENSP00000332488.5; ENSG00000185294.7.
DR GeneID; 162540; -.
DR KEGG; hsa:162540; -.
DR MANE-Select; ENST00000329196.7; ENSP00000332488.5; NM_175882.3; NP_787078.2.
DR UCSC; uc010wka.3; human.
DR CTD; 162540; -.
DR DisGeNET; 162540; -.
DR GeneCards; SPPL2C; -.
DR HGNC; HGNC:28902; SPPL2C.
DR HPA; ENSG00000185294; Tissue enriched (testis).
DR MIM; 608284; gene.
DR neXtProt; NX_Q8IUH8; -.
DR OpenTargets; ENSG00000185294; -.
DR VEuPathDB; HostDB:ENSG00000185294; -.
DR eggNOG; KOG2442; Eukaryota.
DR GeneTree; ENSGT00940000163306; -.
DR HOGENOM; CLU_023799_2_1_1; -.
DR InParanoid; Q8IUH8; -.
DR OMA; DNWSKDY; -.
DR OrthoDB; 535101at2759; -.
DR PhylomeDB; Q8IUH8; -.
DR TreeFam; TF319186; -.
DR BRENDA; 3.4.23.B24; 2681.
DR PathwayCommons; Q8IUH8; -.
DR SignaLink; Q8IUH8; -.
DR BioGRID-ORCS; 162540; 15 hits in 1058 CRISPR screens.
DR GenomeRNAi; 162540; -.
DR Pharos; Q8IUH8; Tbio.
DR PRO; PR:Q8IUH8; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8IUH8; protein.
DR Bgee; ENSG00000185294; Expressed in right testis and 27 other tissues.
DR Genevisible; Q8IUH8; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA: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; IDA:UniProtKB.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; IDA: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; IDA: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 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Membrane; Protease;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:15385547"
FT CHAIN 22..684
FT /note="Signal peptide peptidase-like 2C"
FT /id="PRO_0000314797"
FT TOPO_DOM 22..186
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:15385547"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 208..253
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 254..274
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 275..276
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 277..297
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 298..319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 320..340
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 341..346
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 366..376
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 398..439
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:15385547"
FT TRANSMEM 440..460
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 461..472
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 473..493
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 494..495
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 496..516
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 517..684
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15385547"
FT DOMAIN 83..163
FT /note="PA"
FT REGION 216..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 548..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 499..501
FT /note="PAL"
FT COMPBIAS 592..606
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 386
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT ACT_SITE 448
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:15385547"
FT VARIANT 123
FT /note="R -> Q (in dbSNP:rs17763658)"
FT /id="VAR_038048"
FT VARIANT 303
FT /note="R -> H (in dbSNP:rs242944)"
FT /evidence="ECO:0000269|PubMed:12139484,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_038049"
FT VARIANT 461
FT /note="R -> P (in dbSNP:rs12185233)"
FT /id="VAR_038050"
FT VARIANT 471
FT /note="I -> V (in dbSNP:rs12185268)"
FT /id="VAR_038051"
FT VARIANT 601
FT /note="S -> P (in dbSNP:rs12373123)"
FT /id="VAR_038052"
FT VARIANT 620
FT /note="G -> R (in dbSNP:rs12373139)"
FT /id="VAR_038053"
FT VARIANT 626
FT /note="M -> V (in dbSNP:rs17852270)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060590"
FT VARIANT 643
FT /note="P -> R (in dbSNP:rs12373142)"
FT /id="VAR_038054"
FT VARIANT 659
FT /note="T -> I (in dbSNP:rs16940694)"
FT /id="VAR_057147"
SQ SEQUENCE 684 AA; 74503 MW; 578DA60509765667 CRC64;
MACLGFLLPV GFLLLISTVA GGKYGVAHVV SENWSKDYCI LFSSDYITLP RDLHHAPLLP
LYDGTKAPWC PGEDSPHQAQ LRSPSQRPLR QTTAMVMRGN CSFHTKGWLA QGQGAHGLLI
VSRVSDQQCS DTTLAPQDPR QPLADLTIPV AMLHYADMLD ILSHTRGEAV VRVAMYAPPE
PIIDYNMLVI FILAVGTVAA GGYWAGLTEA NRLQRRRARR GGGSGGHHQL QEAAAAEGAQ
KEDNEDIPVD FTPAMTGVVV TLSCSLMLLL YFFYDHFVYV TIGIFGLGAG IGLYSCLSPL
VCRLSLRQYQ RPPHSLWASL PLPLLLLASL CATVIIFWVA YRNEDRWAWL LQDTLGISYC
LFVLHRVRLP TLKNCSSFLL ALLAFDVFFV FVTPFFTKTG ESIMAQVALG PAESSSHERL
PMVLKVPRLR VSALTLCSQP FSILGFGDIV VPGFLVAYCC RFDVQVCSRQ IYFVACTVAY
AVGLLVTFMA MVLMQMGQPA LLYLVSSTLL TSLAVAACRQ ELSLFWTGQG RAKMCGLGCA
PSAGSRQKQE GAADAHTAST LERGTSRGAG DLDSNPGEDT TEIVTISENE ATNPEDRSDS
SEGWSDAHLD PNELPFIPPG ASEELMPLMP MAMLIPLMPL MPPPSELGHV HAQAQAHETG
LPWAGLHKRK GLKVRKSMST QAPL
