SPCS2_HUMAN
ID SPCS2_HUMAN Reviewed; 226 AA.
AC Q15005; Q15507; Q3KQT0; Q641R4; Q6FG65; Q6IRX0; Q6P1P4; Q96HU9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Signal peptidase complex subunit 2;
DE AltName: Full=Microsomal signal peptidase 25 kDa subunit;
DE Short=SPase 25 kDa subunit;
GN Name=SPCS2; Synonyms=KIAA0102, SPC25;
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=Lung, Pancreas, Skin, and 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-37.
RA Hartmann E.;
RT "5'-end of human signal peptidase 25kDa subunit mRNA.";
RL Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-226.
RC TISSUE=Bone marrow;
RX PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S.,
RA Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III. The
RT coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:37-43(1995).
RN [4]
RP PROTEIN SEQUENCE OF 2-10; 174-180 AND 196-214, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Lao L., Ryan K.M.;
RL Submitted (MAY-2009) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 104-226.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-169 AND LYS-191, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12] {ECO:0007744|PDB:7P2P, ECO:0007744|PDB:7P2Q}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.9 ANGSTROMS), FUNCTION, IDENTIFICATION
RP IN THE SIGNAL PEPTIDASE COMPLEX, CLEAVAGE OF INITIATOR METHIONINE, AND
RP ACETYLATION AT ALA-2.
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: Component of the signal peptidase complex (SPC) which
CC catalyzes the cleavage of N-terminal signal sequences from nascent
CC proteins as they are translocated into the lumen of the endoplasmic
CC reticulum (PubMed:34388369). Enhances the enzymatic activity of SPC and
CC facilitates the interactions between different components of the
CC translocation site (By similarity). {ECO:0000250|UniProtKB:Q04969,
CC ECO:0000269|PubMed:34388369}.
CC -!- SUBUNIT: Component of the signal peptidase complex paralog A (SPC-A)
CC composed of a catalytic subunit SEC11A and three accessory subunits
CC SPCS1, SPCS2 and SPCS3 (PubMed:34388369). Component of the signal
CC peptidase complex paralog C (SPC-C) composed of a catalytic subunit
CC SEC11C and three accessory subunits SPCS1, SPCS2 and SPCS3
CC (PubMed:34388369). Within the complex, interacts with SEC11A or SEC11C
CC and SPCS1 (PubMed:34388369). The complex induces a local thinning of
CC the ER membrane which is used to measure the length of the signal
CC peptide (SP) h-region of protein substrates (PubMed:34388369). This
CC ensures the selectivity of the complex towards h-regions shorter than
CC 18-20 amino acids (PubMed:34388369). {ECO:0000269|PubMed:34388369}.
CC -!- INTERACTION:
CC Q15005; P0DTC2: S; Xeno; NbExp=2; IntAct=EBI-1043352, EBI-25474821;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q28250}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q28250}.
CC -!- SIMILARITY: Belongs to the SPCS2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH08063.3; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH70276.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH82231.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA03492.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BC008063; AAH08063.3; ALT_INIT; mRNA.
DR EMBL; BC064957; AAH64957.1; -; mRNA.
DR EMBL; BC070276; AAH70276.2; ALT_INIT; mRNA.
DR EMBL; BC082231; AAH82231.2; ALT_INIT; mRNA.
DR EMBL; BC106066; AAI06067.1; -; mRNA.
DR EMBL; L38950; AAA60992.1; -; mRNA.
DR EMBL; D14658; BAA03492.1; ALT_INIT; mRNA.
DR EMBL; CR542233; CAG47029.1; -; mRNA.
DR EMBL; CR542243; CAG47039.1; -; mRNA.
DR CCDS; CCDS44681.1; -.
DR RefSeq; NP_055567.2; NM_014752.2.
DR PDB; 7P2P; EM; 4.90 A; C=1-226.
DR PDB; 7P2Q; EM; 4.90 A; C=1-226.
DR PDBsum; 7P2P; -.
DR PDBsum; 7P2Q; -.
DR AlphaFoldDB; Q15005; -.
DR SMR; Q15005; -.
DR BioGRID; 115133; 142.
DR ComplexPortal; CPX-2847; Signal peptidase complex, SEC11A variant.
DR ComplexPortal; CPX-7205; Signal peptidase complex, SEC11C variant.
DR DIP; DIP-47276N; -.
DR IntAct; Q15005; 51.
DR MINT; Q15005; -.
DR STRING; 9606.ENSP00000263672; -.
DR MEROPS; X44.001; -.
DR GlyGen; Q15005; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q15005; -.
DR PhosphoSitePlus; Q15005; -.
DR SwissPalm; Q15005; -.
DR BioMuta; SPCS2; -.
DR DMDM; 6648110; -.
DR EPD; Q15005; -.
DR jPOST; Q15005; -.
DR MassIVE; Q15005; -.
DR MaxQB; Q15005; -.
DR PaxDb; Q15005; -.
DR PeptideAtlas; Q15005; -.
DR PRIDE; Q15005; -.
DR ProteomicsDB; 60356; -.
DR TopDownProteomics; Q15005; -.
DR Antibodypedia; 2848; 123 antibodies from 20 providers.
DR DNASU; 9789; -.
DR Ensembl; ENST00000263672.11; ENSP00000263672.6; ENSG00000118363.13.
DR GeneID; 9789; -.
DR KEGG; hsa:9789; -.
DR MANE-Select; ENST00000263672.11; ENSP00000263672.6; NM_014752.3; NP_055567.2.
DR UCSC; uc001ovu.2; human.
DR CTD; 9789; -.
DR DisGeNET; 9789; -.
DR GeneCards; SPCS2; -.
DR HGNC; HGNC:28962; SPCS2.
DR HPA; ENSG00000118363; Low tissue specificity.
DR MIM; 619411; gene.
DR neXtProt; NX_Q15005; -.
DR OpenTargets; ENSG00000118363; -.
DR PharmGKB; PA128394559; -.
DR VEuPathDB; HostDB:ENSG00000118363; -.
DR eggNOG; KOG4072; Eukaryota.
DR GeneTree; ENSGT00440000038181; -.
DR InParanoid; Q15005; -.
DR OMA; DMRKYDD; -.
DR OrthoDB; 1395649at2759; -.
DR PhylomeDB; Q15005; -.
DR TreeFam; TF314545; -.
DR BRENDA; 3.4.21.89; 2681.
DR PathwayCommons; Q15005; -.
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; Q15005; -.
DR BioGRID-ORCS; 9789; 574 hits in 1038 CRISPR screens.
DR ChiTaRS; SPCS2; human.
DR GenomeRNAi; 9789; -.
DR Pharos; Q15005; Tdark.
DR PRO; PR:Q15005; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q15005; protein.
DR Bgee; ENSG00000118363; Expressed in ventricular zone and 132 other tissues.
DR ExpressionAtlas; Q15005; baseline and differential.
DR Genevisible; Q15005; 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; IPI:ComplexPortal.
DR GO; GO:0045047; P:protein targeting to ER; IBA:GO_Central.
DR GO; GO:0006465; P:signal peptide processing; IDA:ComplexPortal.
DR InterPro; IPR009582; Spc2/SPCS2.
DR PANTHER; PTHR13085; PTHR13085; 1.
DR Pfam; PF06703; SPC25; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing;
KW Endoplasmic reticulum; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:34388369, ECO:0000269|Ref.4,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..226
FT /note="Signal peptidase complex subunit 2"
FT /id="PRO_0000221158"
FT TOPO_DOM 2..86
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q28250"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..111
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q28250"
FT TRANSMEM 112..132
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q28250"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:34388369, ECO:0000269|Ref.4,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 169
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 191
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CONFLICT 64
FT /note="A -> V (in Ref. 1; AAH64957)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 226 AA; 25003 MW; C1EDF687E9F7A57A CRC64;
MAAAAVQGGR SGGSGGCSGA GGASNCGTGS GRSGLLDKWK IDDKPVKIDK WDGSAVKNSL
DDSAKKVLLE KYKYVENFGL IDGRLTICTI SCFFAIVALI WDYMHPFPES KPVLALCVIS
YFVMMGILTI YTSYKEKSIF LVAHRKDPTG MDPDDIWQLS SSLKRFDDKY TLKLTFISGR
TKQQREAEFT KSIAKFFDHS GTLVMDAYEP EISRLHDSLA IERKIK
