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   27-MAR-2024, entry version 179.
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   EMDB; EMD-13171; -.
DR   EMDB; EMD-13172; -.
DR   SMR; Q15005; -.
DR   BioGRID; 115133; 162.
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; 56.
DR   MINT; Q15005; -.
DR   STRING; 9606.ENSP00000263672; -.
DR   MEROPS; X44.001; -.
DR   GlyCosmos; Q15005; 2 sites, 1 glycan.
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; 9606-ENSP00000263672; -.
DR   PeptideAtlas; Q15005; -.
DR   ProteomicsDB; 60356; -.
DR   Pumba; Q15005; -.
DR   TopDownProteomics; Q15005; -.
DR   Antibodypedia; 2848; 147 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   AGR; HGNC:28962; -.
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; INKWDGT; -.
DR   OrthoDB; 2903540at2759; -.
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; 604 hits in 1116 CRISPR screens.
DR   ChiTaRS; SPCS2; human.
DR   GenomeRNAi; 9789; -.
DR   Pharos; Q15005; Tbio.
DR   PRO; PR:Q15005; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q15005; Protein.
DR   Bgee; ENSG00000118363; Expressed in ventricular zone and 134 other cell types or tissues.
DR   ExpressionAtlas; Q15005; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:ComplexPortal.
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; MICROSOMAL SIGNAL PEPTIDASE 25 KDA SUBUNIT; 1.
DR   PANTHER; PTHR13085:SF0; SIGNAL PEPTIDASE COMPLEX SUBUNIT 2; 1.
DR   Pfam; PF06703; SPC25; 1.
DR   Genevisible; Q15005; HS.
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
//