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 27-MAR-2024, entry version 179. 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; P61009: SPCS3; NbExp=5; IntAct=EBI-2855401, EBI-6166040; 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}. 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; 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 EMDB; EMD-13172; -. DR SMR; Q9BY50; -. DR BioGRID; 124756; 60. DR ComplexPortal; CPX-7205; Signal peptidase complex, SEC11C variant. DR IntAct; Q9BY50; 43. DR STRING; 9606.ENSP00000468633; -. DR MEROPS; S26.010; -. DR iPTMnet; Q9BY50; -. DR PhosphoSitePlus; Q9BY50; -. DR SwissPalm; Q9BY50; -. DR BioMuta; SEC11C; -. DR DMDM; 17368701; -. DR EPD; Q9BY50; -. DR jPOST; Q9BY50; -. DR MassIVE; Q9BY50; -. DR MaxQB; Q9BY50; -. DR PaxDb; 9606-ENSP00000468633; -. DR PeptideAtlas; Q9BY50; -. DR ProteomicsDB; 79586; -. DR Pumba; Q9BY50; -. DR Antibodypedia; 22969; 55 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 AGR; HGNC:23400; -. 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; IPVVWFP; -. DR OrthoDB; 1114626at2759; -. 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 1152 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 184 other cell types or tissues. DR ExpressionAtlas; Q9BY50; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:ComplexPortal. 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 Gene3D; 2.10.109.10; Umud Fragment, subunit A; 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 NCBIfam; TIGR02228; sigpep_I_arch; 1. DR PANTHER; PTHR10806; SIGNAL PEPTIDASE COMPLEX CATALYTIC SUBUNIT SEC11; 1. DR PANTHER; PTHR10806:SF12; SIGNAL PEPTIDASE COMPLEX CATALYTIC SUBUNIT SEC11C; 1. DR Pfam; PF00717; Peptidase_S24; 1. DR PRINTS; PR00728; SIGNALPTASE. DR SUPFAM; SSF51306; LexA/Signal peptidase; 1. DR PROSITE; PS00501; SPASE_I_1; 1. DR PROSITE; PS00761; SPASE_I_3; 1. DR Genevisible; Q9BY50; HS. 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 //