ID SRP54_HUMAN Reviewed; 504 AA. AC P61011; B2R759; B4DUW6; P13624; DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 26-APR-2004, sequence version 1. DT 27-MAR-2024, entry version 179. DE RecName: Full=Signal recognition particle subunit SRP54; DE EC=3.6.5.4 {ECO:0000269|PubMed:28972538, ECO:0000269|PubMed:34020957}; DE AltName: Full=Signal recognition particle 54 kDa protein {ECO:0000305}; GN Name=SRP54 {ECO:0000312|HGNC:HGNC:11301}; 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]. RC TISSUE=Placenta; RX PubMed=8722571; DOI=10.3109/10425179609010204; RA Patel S., Austen B.; RT "Sequence of the highly conserved gene encoding the human 54kDa subunit of RT signal recognition particle."; RL DNA Seq. 6:167-170(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9511762; DOI=10.1016/s0378-1119(97)00627-6; RA Gowda K., Black S.D., Moeller I., Sakakibara Y., Liu M.C., Zwieb C.; RT "Protein SRP54 of human signal recognition particle: cloning, expression, RT and comparative analysis of functional sites."; RL Gene 207:197-207(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Trachea; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Eye, and Placenta; 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 [6] RP INTERACTION WITH RNPS1, AND SUBCELLULAR LOCATION. RX PubMed=14729963; DOI=10.1128/mcb.24.3.1174-1187.2004; RA Sakashita E., Tatsumi S., Werner D., Endo H., Mayeda A.; RT "Human RNPS1 and its associated factors: a versatile alternative pre-mRNA RT splicing regulator in vivo."; RL Mol. Cell. Biol. 24:1174-1187(2004). RN [7] 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 [8] RP IDENTIFICATION BY MASS SPECTROMETRY [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 [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). 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 IDENTIFICATION BY MASS SPECTROMETRY [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] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 326-432. RX PubMed=10497032; DOI=10.1006/jmbi.1999.3090; RA Clemons W.M. Jr., Gowda K., Black S.D., Zwieb C., Ramakrishnan V.; RT "Crystal structure of the conserved subdomain of human protein SRP54M at RT 2.1 A resolution: evidence for the mechanism of signal peptide binding."; RL J. Mol. Biol. 292:697-705(1999). RN [13] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 323-441 IN COMPLEX WITH SRP19 AND RP 7SL RNA. RX PubMed=12244299; DOI=10.1038/nsb843; RA Kuglstatter A., Oubridge C., Nagai K.; RT "Induced structural changes of 7SL RNA during the assembly of human signal RT recognition particle."; RL Nat. Struct. Biol. 9:740-744(2002). RN [14] RP VARIANTS SCN8 ALA-115; THR-117 DEL AND GLU-226, CHARACTERIZATION OF RP VARIANTS SCN8 ALA-115; THR-117 DEL AND GLU-226, CATALYTIC ACTIVITY, AND RP FUNCTION. RX PubMed=28972538; DOI=10.1172/jci92876; RA Carapito R., Konantz M., Paillard C., Miao Z., Pichot A., Leduc M.S., RA Yang Y., Bergstrom K.L., Mahoney D.H., Shardy D.L., Alsaleh G., Naegely L., RA Kolmer A., Paul N., Hanauer A., Rolli V., Mueller J.S., Alghisi E., RA Sauteur L., Macquin C., Morlon A., Sancho C.S., Amati-Bonneau P., RA Procaccio V., Mosca-Boidron A.L., Marle N., Osmani N., Lefebvre O., RA Goetz J.G., Unal S., Akarsu N.A., Radosavljevic M., Chenard M.P., RA Rialland F., Grain A., Bene M.C., Eveillard M., Vincent M., Guy J., RA Faivre L., Thauvin-Robinet C., Thevenon J., Myers K., Fleming M.D., RA Shimamura A., Bottollier-Lemallaz E., Westhof E., Lengerke C., Isidor B., RA Bahram S.; RT "Mutations in signal recognition particle SRP54 cause syndromic neutropenia RT with Shwachman-Diamond-like features."; RL J. Clin. Invest. 127:4090-4103(2017). RN [15] RP FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, VARIANTS SCN8 ARG-113; RP THR-117 DEL; TYR-118; TYR-136; ASP-223; GLU-226 AND ASP-274, AND RP CHARACTERIZATION OF VARIANTS SCN8 THR-117 DEL; TYR-118; TYR-136 AND RP ASP-223. RX PubMed=29914977; DOI=10.1182/blood-2017-12-820308; RA Bellanne-Chantelot C., Schmaltz-Panneau B., Marty C., Fenneteau O., RA Callebaut I., Clauin S., Docet A., Damaj G.L., Leblanc T., Pellier I., RA Stoven C., Souquere S., Antony-Debre I., Beaupain B., Aladjidi N., RA Barlogis V., Bauduer F., Bensaid P., Boespflug-Tanguy O., Berger C., RA Bertrand Y., Carausu L., Fieschi C., Galambrun C., Schmidt A., Journel H., RA Mazingue F., Nelken B., Quah T.C., Oksenhendler E., Ouachee M., Pasquet M., RA Saada V., Suarez F., Pierron G., Vainchenker W., Plo I., Donadieu J.; RT "Mutations in the SRP54 gene cause severe congenital neutropenia as well as RT Shwachman-Diamond-like syndrome."; RL Blood 132:1318-1331(2018). RN [16] {ECO:0007744|PDB:7NFX} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) OF SIGNAL RECOGNITION RP PARTICLE IN COMPLEX WITH RIBOSOME NASCENT CHAIN COMPLEX AND THE SRP RP RECEPTOR, FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SRPRA, RP CHARACTERIZATION OF VARIANT SCN8 GLU-226, AND DOMAIN. RX PubMed=34020957; DOI=10.1126/sciadv.abg0942; RA Lee J.H., Jomaa A., Jomaa A., Chung S., Hwang Fu Y.H., Qian R., Sun X., RA Hsieh H.H., Chandrasekar S., Bi X., Mattei S., Boehringer D., Weiss S., RA Ban N., Shan S.O.; RT "Receptor compaction and GTPase rearrangement drive SRP-mediated RT cotranslational protein translocation into the ER."; RL Sci. Adv. 7:942-942(2021). CC -!- FUNCTION: Component of the signal recognition particle (SRP) complex, a CC ribonucleoprotein complex that mediates the cotranslational targeting CC of secretory and membrane proteins to the endoplasmic reticulum (ER) CC (PubMed:34020957). As part of the SRP complex, associates with the SRP CC receptor (SR) component SRPRA to target secretory proteins to the CC endoplasmic reticulum membrane (PubMed:34020957). Binds to the signal CC sequence of presecretory proteins when they emerge from the ribosomes CC (PubMed:34020957). Displays basal GTPase activity, and stimulates CC reciprocal GTPase activation of the SR subunit SRPRA (PubMed:28972538, CC PubMed:34020957). Forms a guanosine 5'-triphosphate (GTP)-dependent CC complex with the SR subunit SRPRA (PubMed:34020957). SR compaction and CC GTPase mediated rearrangement of SR drive SRP-mediated cotranslational CC protein translocation into the ER (PubMed:34020957). Requires the CC presence of SRP9/SRP14 and/or SRP19 to stably interact with RNA (By CC similarity). Plays a role in proliferation and differentiation of CC granulocytic cells, neutrophils migration capacity and exocrine CC pancreas development (PubMed:28972538, PubMed:29914977). CC {ECO:0000250|UniProtKB:P61010, ECO:0000269|PubMed:28972538, CC ECO:0000269|PubMed:29914977, ECO:0000269|PubMed:34020957}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.4; CC Evidence={ECO:0000269|PubMed:28972538}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000269|PubMed:28972538}; CC -!- SUBUNIT: Component of a signal recognition particle (SRP) complex that CC consists of a 7SL RNA molecule of 300 nucleotides and six protein CC subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9 (PubMed:12244299). CC Interacts with RNPS1 (PubMed:14729963). Interacts with the SRP receptor CC subunit SRPRA (PubMed:34020957). {ECO:0000269|PubMed:12244299, CC ECO:0000269|PubMed:14729963, ECO:0000269|PubMed:34020957}. CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:14729963}. CC Cytoplasm {ECO:0000269|PubMed:14729963, ECO:0000269|PubMed:29914977}. CC Endoplasmic reticulum {ECO:0000269|PubMed:29914977}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P61011-1; Sequence=Displayed; CC Name=2; CC IsoId=P61011-2; Sequence=VSP_043696; CC -!- DEVELOPMENTAL STAGE: up-regulated during granulocytic differentiation. CC {ECO:0000269|PubMed:29914977}. CC -!- DOMAIN: The NG domain, also named G domain, is a special guanosine CC triphosphatase (GTPase) domain, which binds GTP and forms a guanosine CC 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in CC the SRP receptor subunit SRPRA (PubMed:34020957). The two NG domains CC undergo cooperative rearrangements upon their assembly, which culminate CC in the reciprocal activation of the GTPase activity of one another CC (PubMed:34020957). SRP receptor compaction upon binding with cargo- CC loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational CC protein translocation into the ER (PubMed:34020957). CC {ECO:0000269|PubMed:34020957}. CC -!- DOMAIN: The M domain binds the 7SL RNA in presence of SRP19 and binds CC the signal sequence of presecretory proteins. CC {ECO:0000269|PubMed:34020957}. CC -!- DISEASE: Neutropenia, severe congenital 8, autosomal dominant (SCN8) CC [MIM:618752]: A form of severe congenital neutropenia, a disorder of CC hematopoiesis characterized by maturation arrest of granulopoiesis at CC the level of promyelocytes with peripheral blood absolute neutrophil CC counts below 0.5 x 10(9)/l and early onset of severe bacterial CC infections. {ECO:0000269|PubMed:28972538, ECO:0000269|PubMed:29914977, CC ECO:0000269|PubMed:34020957}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the GTP-binding SRP family. SRP54 subfamily. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Signal recognition particle entry; CC URL="https://en.wikipedia.org/wiki/Signal_recognition_particle"; 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; X86373; CAA60132.1; -; Genomic_DNA. DR EMBL; U51920; AAC50994.1; -; mRNA. DR EMBL; AK300824; BAG62478.1; -; mRNA. DR EMBL; AK312853; BAG35706.1; -; mRNA. DR EMBL; AL049776; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000652; AAH00652.1; -; mRNA. DR EMBL; BC003389; AAH03389.1; -; mRNA. DR CCDS; CCDS9652.1; -. [P61011-1] DR PIR; S54143; S54143. DR RefSeq; NP_001139754.1; NM_001146282.1. [P61011-2] DR RefSeq; NP_003127.1; NM_003136.3. [P61011-1] DR RefSeq; XP_011535408.1; XM_011537106.1. [P61011-1] DR PDB; 1MFQ; X-ray; 3.10 A; C=323-441. DR PDB; 1QB2; X-ray; 2.10 A; A/B=326-434. DR PDB; 5L3Q; X-ray; 3.20 A; A/C=1-436. DR PDB; 6Y2Z; X-ray; 2.15 A; A/B=1-296. DR PDB; 6Y30; X-ray; 2.65 A; A/B=1-296. DR PDB; 6Y31; X-ray; 4.00 A; A/B/C/D=1-296. DR PDB; 6Y32; X-ray; 2.60 A; A/C/E/G=1-296. DR PDB; 7NFX; EM; 3.20 A; x=1-504. DR PDB; 7QWQ; EM; 2.83 A; x=1-504. DR PDBsum; 1MFQ; -. DR PDBsum; 1QB2; -. DR PDBsum; 5L3Q; -. DR PDBsum; 6Y2Z; -. DR PDBsum; 6Y30; -. DR PDBsum; 6Y31; -. DR PDBsum; 6Y32; -. DR PDBsum; 7NFX; -. DR PDBsum; 7QWQ; -. DR AlphaFoldDB; P61011; -. DR EMDB; EMD-12303; -. DR EMDB; EMD-14191; -. DR SMR; P61011; -. DR BioGRID; 112607; 167. DR ComplexPortal; CPX-2652; Signal recognition particle. DR IntAct; P61011; 30. DR MINT; P61011; -. DR STRING; 9606.ENSP00000451818; -. DR ChEMBL; CHEMBL4295786; -. DR TCDB; 3.A.5.9.1; the general secretory pathway (sec) family. DR CarbonylDB; P61011; -. DR GlyGen; P61011; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P61011; -. DR MetOSite; P61011; -. DR PhosphoSitePlus; P61011; -. DR SwissPalm; P61011; -. DR BioMuta; SRP54; -. DR DMDM; 46577650; -. DR EPD; P61011; -. DR jPOST; P61011; -. DR MassIVE; P61011; -. DR MaxQB; P61011; -. DR PaxDb; 9606-ENSP00000451818; -. DR PeptideAtlas; P61011; -. DR ProteomicsDB; 57247; -. [P61011-1] DR ProteomicsDB; 57248; -. [P61011-2] DR Pumba; P61011; -. DR Antibodypedia; 23175; 238 antibodies from 29 providers. DR DNASU; 6729; -. DR Ensembl; ENST00000216774.11; ENSP00000216774.6; ENSG00000100883.13. [P61011-1] DR Ensembl; ENST00000556994.5; ENSP00000451818.1; ENSG00000100883.13. [P61011-1] DR Ensembl; ENST00000677647.1; ENSP00000504673.1; ENSG00000100883.13. [P61011-1] DR Ensembl; ENST00000678963.1; ENSP00000504518.1; ENSG00000100883.13. [P61011-1] DR GeneID; 6729; -. DR KEGG; hsa:6729; -. DR MANE-Select; ENST00000216774.11; ENSP00000216774.6; NM_003136.4; NP_003127.1. DR UCSC; uc001wso.4; human. [P61011-1] DR AGR; HGNC:11301; -. DR CTD; 6729; -. DR DisGeNET; 6729; -. DR GeneCards; SRP54; -. DR GeneReviews; SRP54; -. DR HGNC; HGNC:11301; SRP54. DR HPA; ENSG00000100883; Low tissue specificity. DR MalaCards; SRP54; -. DR MIM; 604857; gene. DR MIM; 618752; phenotype. DR neXtProt; NX_P61011; -. DR OpenTargets; ENSG00000100883; -. DR Orphanet; 486; Autosomal dominant severe congenital neutropenia. DR Orphanet; 811; Shwachman-Diamond syndrome. DR PharmGKB; PA36125; -. DR VEuPathDB; HostDB:ENSG00000100883; -. DR eggNOG; KOG0780; Eukaryota. DR GeneTree; ENSGT00550000074824; -. DR InParanoid; P61011; -. DR OMA; GMTGQDA; -. DR OrthoDB; 1110531at2759; -. DR PhylomeDB; P61011; -. DR TreeFam; TF106249; -. DR PathwayCommons; P61011; -. DR Reactome; R-HSA-1799339; SRP-dependent cotranslational protein targeting to membrane. DR SignaLink; P61011; -. DR SIGNOR; P61011; -. DR BioGRID-ORCS; 6729; 827 hits in 1184 CRISPR screens. DR ChiTaRS; SRP54; human. DR EvolutionaryTrace; P61011; -. DR GenomeRNAi; 6729; -. DR Pharos; P61011; Tbio. DR PRO; PR:P61011; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P61011; Protein. DR Bgee; ENSG00000100883; Expressed in body of pancreas and 205 other cell types or tissues. DR ExpressionAtlas; P61011; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005786; C:signal recognition particle, endoplasmic reticulum targeting; IDA:UniProtKB. DR GO; GO:0008312; F:7S RNA binding; IDA:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0030942; F:endoplasmic reticulum signal peptide binding; IDA:UniProtKB. DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB. DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB. DR GO; GO:0003924; F:GTPase activity; IMP:UniProtKB. DR GO; GO:0043021; F:ribonucleoprotein complex binding; IDA:MGI. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0031017; P:exocrine pancreas development; ISS:UniProtKB. DR GO; GO:0030851; P:granulocyte differentiation; IMP:UniProtKB. DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB. DR GO; GO:0045047; P:protein targeting to ER; IMP:UniProtKB. DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; IC:MGI. DR GO; GO:0006617; P:SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition; ISS:UniProtKB. DR GO; GO:0006616; P:SRP-dependent cotranslational protein targeting to membrane, translocation; ISS:UniProtKB. DR CDD; cd17875; SRP54_G; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 1.20.120.140; Signal recognition particle SRP54, nucleotide-binding domain; 1. DR Gene3D; 1.10.260.30; Signal recognition particle, SRP54 subunit, M-domain; 1. DR HAMAP; MF_00306; SRP54; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR036891; Signal_recog_part_SRP54_M_sf. DR InterPro; IPR013822; Signal_recog_particl_SRP54_hlx. DR InterPro; IPR004125; Signal_recog_particle_SRP54_M. DR InterPro; IPR036225; SRP/SRP_N. DR InterPro; IPR022941; SRP54. DR InterPro; IPR006325; SRP54_euk. DR InterPro; IPR000897; SRP54_GTPase_dom. DR InterPro; IPR042101; SRP54_N_sf. DR NCBIfam; TIGR01425; SRP54_euk; 1. DR PANTHER; PTHR11564:SF5; SIGNAL RECOGNITION PARTICLE 54 KDA PROTEIN; 1. DR PANTHER; PTHR11564; SIGNAL RECOGNITION PARTICLE 54K PROTEIN SRP54; 1. DR Pfam; PF00448; SRP54; 1. DR Pfam; PF02881; SRP54_N; 1. DR Pfam; PF02978; SRP_SPB; 1. DR SMART; SM00382; AAA; 1. DR SMART; SM00962; SRP54; 1. DR SMART; SM00963; SRP54_N; 1. DR SUPFAM; SSF47364; Domain of the SRP/SRP receptor G-proteins; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF47446; Signal peptide-binding domain; 1. DR PROSITE; PS00300; SRP54; 1. DR Genevisible; P61011; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; KW Endoplasmic reticulum; GTP-binding; Hydrolase; Nucleotide-binding; Nucleus; KW Reference proteome; Ribonucleoprotein; RNA-binding; KW Signal recognition particle. FT CHAIN 1..504 FT /note="Signal recognition particle subunit SRP54" FT /id="PRO_0000101192" FT REGION 1..295 FT /note="NG domain" FT /evidence="ECO:0000303|PubMed:34020957" FT REGION 296..504 FT /note="M-domain" FT /evidence="ECO:0000303|PubMed:34020957" FT BINDING 108..115 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT BINDING 190..194 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT BINDING 248..251 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT VAR_SEQ 1..57 FT /note="MVLADLGRKITSALRSLSNATIINEEVLNAMLKEVCTALLEADVNIKLVKQL FT RENVK -> MPPLSMKR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043696" FT VARIANT 113 FT /note="G -> R (in SCN8)" FT /evidence="ECO:0000269|PubMed:29914977" FT /id="VAR_083566" FT VARIANT 115 FT /note="T -> A (in SCN8; decreases expression levels; FT decreases GTPase activity; decreases neutrophil numbers and FT migration capacity)" FT /evidence="ECO:0000269|PubMed:28972538" FT /id="VAR_083567" FT VARIANT 117 FT /note="Missing (in SCN8; decreases expression levels; FT slightly decreases GTPase activity; decreases neutrophil FT numbers and migration capacity; decreased granulocyte FT proliferation; delayed granulocytic differentiation; FT impaired signaling; increased apoptosis; induced FT autophagy)" FT /evidence="ECO:0000269|PubMed:28972538, FT ECO:0000269|PubMed:29914977" FT /id="VAR_083568" FT VARIANT 118 FT /note="C -> Y (in SCN8; decreased granulocyte FT proliferation; increased apoptosis)" FT /evidence="ECO:0000269|PubMed:29914977" FT /id="VAR_083569" FT VARIANT 136 FT /note="C -> Y (in SCN8; decreased granulocyte FT proliferation; delayed granulocytic differentiation; FT impaired signaling; induced autophagy)" FT /evidence="ECO:0000269|PubMed:29914977" FT /id="VAR_083570" FT VARIANT 223 FT /note="A -> D (in SCN8; decreased granulocyte FT proliferation; induced autophagy)" FT /evidence="ECO:0000269|PubMed:29914977" FT /id="VAR_083571" FT VARIANT 226 FT /note="G -> E (in SCN8; decreases expression levels; FT decreases neutrophil numbers and migration capacity; faster FT dissociation of the interaction with the SRP receptor FT subunit SRPRA; reduced SR compaction; impaired interaction FT with SR; impaired detachment from ribosome; effects on FT enzymatic activity are unclear as both normal and reduced FT GTPase activity have been reported)" FT /evidence="ECO:0000269|PubMed:28972538, FT ECO:0000269|PubMed:29914977, ECO:0000269|PubMed:34020957" FT /id="VAR_083572" FT VARIANT 274 FT /note="G -> D (in SCN8)" FT /evidence="ECO:0000269|PubMed:29914977" FT /id="VAR_083573" FT HELIX 4..19 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 25..40 FT /evidence="ECO:0007829|PDB:6Y2Z" FT TURN 41..43 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 46..59 FT /evidence="ECO:0007829|PDB:6Y2Z" FT TURN 62..64 FT /evidence="ECO:0007829|PDB:6Y32" FT HELIX 71..86 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 102..108 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 114..127 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 132..136 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 143..155 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:6Y30" FT HELIX 168..181 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 185..190 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 198..212 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 215..222 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 223..228 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 229..237 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 241..248 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 251..254 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 256..265 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 270..274 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 276..278 FT /evidence="ECO:0007829|PDB:6Y2Z" FT STRAND 282..284 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 287..295 FT /evidence="ECO:0007829|PDB:6Y2Z" FT HELIX 329..341 FT /evidence="ECO:0007829|PDB:1QB2" FT HELIX 343..351 FT /evidence="ECO:0007829|PDB:1QB2" FT TURN 357..360 FT /evidence="ECO:0007829|PDB:1QB2" FT HELIX 365..379 FT /evidence="ECO:0007829|PDB:1QB2" FT HELIX 384..388 FT /evidence="ECO:0007829|PDB:1QB2" FT TURN 390..392 FT /evidence="ECO:0007829|PDB:1QB2" FT HELIX 393..398 FT /evidence="ECO:0007829|PDB:1QB2" FT HELIX 401..409 FT /evidence="ECO:0007829|PDB:1QB2" FT HELIX 414..430 FT /evidence="ECO:0007829|PDB:1QB2" SQ SEQUENCE 504 AA; 55705 MW; 7D7630A43BC5EC2C CRC64; MVLADLGRKI TSALRSLSNA TIINEEVLNA MLKEVCTALL EADVNIKLVK QLRENVKSAI DLEEMASGLN KRKMIQHAVF KELVKLVDPG VKAWTPTKGK QNVIMFVGLQ GSGKTTTCSK LAYYYQRKGW KTCLICADTF RAGAFDQLKQ NATKARIPFY GSYTEMDPVI IASEGVEKFK NENFEIIIVD TSGRHKQEDS LFEEMLQVAN AIQPDNIVYV MDASIGQACE AQAKAFKDKV DVASVIVTKL DGHAKGGGAL SAVAATKSPI IFIGTGEHID DFEPFKTQPF ISKLLGMGDI EGLIDKVNEL KLDDNEALIE KLKHGQFTLR DMYEQFQNIM KMGPFSQILG MIPGFGTDFM SKGNEQESMA RLKKLMTIMD SMNDQELDST DGAKVFSKQP GRIQRVARGS GVSTRDVQEL LTQYTKFAQM VKKMGGIKGL FKGGDMSKNV SQSQMAKLNQ QMAKMMDPRV LHHMGGMAGL QSMMRQFQQG AAGNMKGMMG FNNM //