SC11C_HUMAN
ID SC11C_HUMAN Reviewed; 192 AA.
AC Q9BY50; B2RAA3;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Signal peptidase complex catalytic subunit SEC11C;
DE EC=3.4.21.89 {ECO:0000269|PubMed:34388369};
DE AltName: Full=Microsomal signal peptidase 21 kDa subunit;
DE Short=SPase 21 kDa subunit;
DE AltName: Full=SEC11 homolog C;
DE AltName: Full=SEC11-like protein 3;
DE AltName: Full=SPC21;
GN Name=SEC11C; Synonyms=SEC11L3, SPC21, SPCS4C;
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 [LARGE SCALE MRNA].
RC TISSUE=Liver cancer;
RA Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z.;
RT "A novel gene expressed in human liver cancer tissue.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6] {ECO:0007744|PDB:7P2Q}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.9 ANGSTROMS), FUNCTION, CATALYTIC
RP ACTIVITY, IDENTIFICATION IN THE SIGNAL PEPTIDASE COMPLEX, DOMAIN,
RP PROTEOLYTIC CLEAVAGE, ACTIVE SITE, AND MUTAGENESIS OF SER-68; ARG-109;
RP ASP-128; ASP-133 AND ASP-134.
RX PubMed=34388369; DOI=10.1016/j.molcel.2021.07.031;
RA Liaci A.M., Steigenberger B., Telles de Souza P.C., Tamara S.,
RA Groellers-Mulderij M., Ogrissek P., Marrink S.J., Scheltema R.A.,
RA Foerster F.;
RT "Structure of the human signal peptidase complex reveals the determinants
RT for signal peptide cleavage.";
RL Mol. Cell 81:3934-3948.e11(2021).
CC -!- FUNCTION: Catalytic component of the signal peptidase complex (SPC)
CC which catalyzes the cleavage of N-terminal signal sequences from
CC nascent proteins as they are translocated into the lumen of the
CC endoplasmic reticulum (PubMed:34388369). Specifically cleaves N-
CC terminal signal peptides that contain a hydrophobic alpha-helix (h-
CC region) shorter than 18-20 amino acids (PubMed:34388369).
CC {ECO:0000269|PubMed:34388369}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of hydrophobic, N-terminal signal or leader sequences
CC from secreted and periplasmic proteins.; EC=3.4.21.89;
CC Evidence={ECO:0000269|PubMed:34388369};
CC -!- SUBUNIT: Component of the signal peptidase complex paralog C (SPC-C)
CC composed of a catalytic subunit SEC11C and three accessory subunits
CC SPCS1, SPCS2 and SPCS3 (PubMed:34388369). Within the complex, interacts
CC with SPCS2 and SPCS3 (PubMed:34388369). The complex induces a local
CC thinning of the ER membrane which is used to measure the length of the
CC signal peptide (SP) h-region of protein substrates (PubMed:34388369).
CC This ensures the selectivity of the complex towards h-regions shorter
CC than 18-20 amino acids (PubMed:34388369).
CC {ECO:0000269|PubMed:34388369}.
CC -!- INTERACTION:
CC Q9BY50; Q8WVV5: BTN2A2; NbExp=3; IntAct=EBI-2855401, EBI-8648738;
CC Q9BY50; P06681: C2; NbExp=5; IntAct=EBI-2855401, EBI-2835920;
CC Q9BY50; Q8N126: CADM3; NbExp=3; IntAct=EBI-2855401, EBI-18961338;
CC Q9BY50; P09601: HMOX1; NbExp=3; IntAct=EBI-2855401, EBI-2806151;
CC Q9BY50; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-2855401, EBI-11956541;
CC Q9BY50; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-2855401, EBI-11721828;
CC Q9BY50; O95084: PRSS23; NbExp=3; IntAct=EBI-2855401, EBI-712503;
CC Q9BY50; Q5QGT7: RTP2; NbExp=3; IntAct=EBI-2855401, EBI-10244780;
CC Q9BY50; O00767: SCD; NbExp=3; IntAct=EBI-2855401, EBI-2684237;
CC Q9BY50; Q8WWX9: SELENOM; NbExp=3; IntAct=EBI-2855401, EBI-10277687;
CC Q9BY50; Q9Y6X1: SERP1; NbExp=3; IntAct=EBI-2855401, EBI-10329948;
CC Q9BY50; Q86Y82: STX12; NbExp=3; IntAct=EBI-2855401, EBI-2691717;
CC Q9BY50; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-2855401, EBI-10694905;
CC Q9BY50; Q9BU79: TMEM243; NbExp=3; IntAct=EBI-2855401, EBI-12887458;
CC Q9BY50; Q8TBM7: TMEM254; NbExp=3; IntAct=EBI-2855401, EBI-11956809;
CC Q9BY50; Q69YG0: TMEM42; NbExp=3; IntAct=EBI-2855401, EBI-12038591;
CC Q9BY50; Q9NSU2-1: TREX1; NbExp=3; IntAct=EBI-2855401, EBI-16746122;
CC Q9BY50; A0AVG3: TSNARE1; NbExp=3; IntAct=EBI-2855401, EBI-12003468;
CC Q9BY50; Q9Y385: UBE2J1; NbExp=3; IntAct=EBI-2855401, EBI-988826;
CC Q9BY50; P23763-3: VAMP1; NbExp=3; IntAct=EBI-2855401, EBI-12097582;
CC Q9BY50; O75379: VAMP4; NbExp=3; IntAct=EBI-2855401, EBI-744953;
CC Q9BY50; O95183: VAMP5; NbExp=3; IntAct=EBI-2855401, EBI-10191195;
CC Q9BY50; Q9P0L0: VAPA; NbExp=3; IntAct=EBI-2855401, EBI-1059156;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P13679}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:P13679}.
CC -!- DOMAIN: The C-terminal short (CTS) helix is essential for catalytic
CC activity (PubMed:34388369). It may be accommodated as a transmembrane
CC helix in the thinned membrane environment of the complex, similarly to
CC the signal peptide in the complex substrates (Probable).
CC {ECO:0000269|PubMed:34388369, ECO:0000305|PubMed:34388369}.
CC -!- PTM: May undergo processing at the N-terminus.
CC {ECO:0000269|PubMed:34388369}.
CC -!- SIMILARITY: Belongs to the peptidase S26B family. {ECO:0000305}.
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DR EMBL; AF212233; AAK14919.1; -; mRNA.
DR EMBL; AK314107; BAG36800.1; -; mRNA.
DR EMBL; CH471096; EAW63090.1; -; Genomic_DNA.
DR EMBL; BC009703; AAH09703.1; -; mRNA.
DR CCDS; CCDS11970.1; -.
DR RefSeq; NP_150596.1; NM_033280.3.
DR PDB; 7P2Q; EM; 4.90 A; A=1-192.
DR PDBsum; 7P2Q; -.
DR AlphaFoldDB; Q9BY50; -.
DR SMR; Q9BY50; -.
DR BioGRID; 124756; 57.
DR ComplexPortal; CPX-7205; Signal peptidase complex, SEC11C variant.
DR IntAct; Q9BY50; 42.
DR STRING; 9606.ENSP00000468633; -.
DR MEROPS; S26.010; -.
DR iPTMnet; Q9BY50; -.
DR PhosphoSitePlus; Q9BY50; -.
DR BioMuta; SEC11C; -.
DR DMDM; 17368701; -.
DR EPD; Q9BY50; -.
DR jPOST; Q9BY50; -.
DR MassIVE; Q9BY50; -.
DR MaxQB; Q9BY50; -.
DR PaxDb; Q9BY50; -.
DR PeptideAtlas; Q9BY50; -.
DR PRIDE; Q9BY50; -.
DR ProteomicsDB; 79586; -.
DR Antibodypedia; 22969; 53 antibodies from 15 providers.
DR DNASU; 90701; -.
DR Ensembl; ENST00000587834.6; ENSP00000468633.1; ENSG00000166562.9.
DR GeneID; 90701; -.
DR KEGG; hsa:90701; -.
DR MANE-Select; ENST00000587834.6; ENSP00000468633.1; NM_033280.4; NP_150596.1.
DR UCSC; uc002lht.4; human.
DR CTD; 90701; -.
DR DisGeNET; 90701; -.
DR GeneCards; SEC11C; -.
DR HGNC; HGNC:23400; SEC11C.
DR HPA; ENSG00000166562; Low tissue specificity.
DR neXtProt; NX_Q9BY50; -.
DR OpenTargets; ENSG00000166562; -.
DR PharmGKB; PA162402587; -.
DR VEuPathDB; HostDB:ENSG00000166562; -.
DR eggNOG; KOG3342; Eukaryota.
DR GeneTree; ENSGT00390000015600; -.
DR InParanoid; Q9BY50; -.
DR OMA; PYIGMLT; -.
DR OrthoDB; 1486616at2759; -.
DR PhylomeDB; Q9BY50; -.
DR PathwayCommons; Q9BY50; -.
DR Reactome; R-HSA-1799339; SRP-dependent cotranslational protein targeting to membrane.
DR Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-HSA-400511; Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).
DR Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR SignaLink; Q9BY50; -.
DR BioGRID-ORCS; 90701; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; SEC11C; human.
DR GenomeRNAi; 90701; -.
DR Pharos; Q9BY50; Tdark.
DR PRO; PR:Q9BY50; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q9BY50; protein.
DR Bgee; ENSG00000166562; Expressed in islet of Langerhans and 182 other tissues.
DR ExpressionAtlas; Q9BY50; baseline and differential.
DR Genevisible; Q9BY50; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:ComplexPortal.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005787; C:signal peptidase complex; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0006465; P:signal peptide processing; IDA:UniProtKB.
DR CDD; cd06530; S26_SPase_I; 1.
DR InterPro; IPR036286; LexA/Signal_pep-like_sf.
DR InterPro; IPR019758; Pept_S26A_signal_pept_1_CS.
DR InterPro; IPR019756; Pept_S26A_signal_pept_1_Ser-AS.
DR InterPro; IPR015927; Peptidase_S24_S26A/B/C.
DR InterPro; IPR019533; Peptidase_S26.
DR InterPro; IPR001733; Peptidase_S26B.
DR InterPro; IPR037710; SEC11C.
DR PANTHER; PTHR10806; PTHR10806; 1.
DR PANTHER; PTHR10806:SF12; PTHR10806:SF12; 1.
DR Pfam; PF00717; Peptidase_S24; 1.
DR PRINTS; PR00728; SIGNALPTASE.
DR SUPFAM; SSF51306; SSF51306; 1.
DR TIGRFAMs; TIGR02228; sigpep_I_arch; 1.
DR PROSITE; PS00501; SPASE_I_1; 1.
DR PROSITE; PS00761; SPASE_I_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; Hydrolase; Membrane; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..192
FT /note="Signal peptidase complex catalytic subunit SEC11C"
FT /id="PRO_0000109548"
FT TOPO_DOM 1..28
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13679"
FT TRANSMEM 29..48
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 49..192
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P13679"
FT REGION 177..188
FT /note="C-terminal short (CTS) helix"
FT /evidence="ECO:0000269|PubMed:34388369"
FT ACT_SITE 68
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:34388369"
FT ACT_SITE 108
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:34388369"
FT ACT_SITE 134
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:34388369"
FT MUTAGEN 68
FT /note="S->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:34388369"
FT MUTAGEN 109
FT /note="R->D: Slight reduction in catalytic activity; when
FT associated with R-128."
FT /evidence="ECO:0000269|PubMed:34388369"
FT MUTAGEN 128
FT /note="D->N: Moderate reduction in catalytic activity.
FT Reduces protein stability."
FT /evidence="ECO:0000269|PubMed:34388369"
FT MUTAGEN 128
FT /note="D->R: Slight reduction in catalytic activity; when
FT associated with D-109."
FT /evidence="ECO:0000269|PubMed:34388369"
FT MUTAGEN 133
FT /note="D->N: No effect on catalytic activity or protein
FT stability."
FT /evidence="ECO:0000269|PubMed:34388369"
FT MUTAGEN 134
FT /note="D->N: Loss of catalytic activity. Slight reduction
FT in protein stability."
FT /evidence="ECO:0000269|PubMed:34388369"
SQ SEQUENCE 192 AA; 21542 MW; 74FBC5F765791D9F CRC64;
MVRAGAVGAH LPASGLDIFG DLKKMNKRQL YYQVLNFAMI VSSALMIWKG LIVLTGSESP
IVVVLSGSME PAFHRGDLLF LTNFREDPIR AGEIVVFKVE GRDIPIVHRV IKVHEKDNGD
IKFLTKGDNN EVDDRGLYKE GQNWLEKKDV VGRARGFLPY VGMVTIIMND YPKFKYALLA
VMGAYVLLKR ES
