SRP54_HUMAN
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 03-AUG-2022, entry version 170.
DE RecName: Full=Signal recognition particle 54 kDa protein {ECO:0000305};
DE Short=SRP54;
DE EC=3.6.5.- {ECO:0000269|PubMed:28972538, ECO:0000269|PubMed:34020957};
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;
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 -!- CAUTION: Reports suggest defects in the GTPase activity and SRP
CC receptor (SR) interaction of SRP54 variant Glu-226 (PubMed:28972538,
CC PubMed:29914977). Another report, however, shows that SRP54 variant
CC Glu-226 displays basal GTPase activity and stimulates GTPase reactions
CC with SR as efficiently as wild-type SRP (PubMed:34020957). The SRP54
CC variant Glu-226 exhibits faster dissociation rates of the interaction
CC with the SR subunit SRPRA; reduced SR compaction; impaired interaction
CC with SR and impaired detachement from ribosomes (PubMed:34020957).
CC {ECO:0000269|PubMed:28972538, ECO:0000269|PubMed:29914977,
CC ECO:0000269|PubMed:34020957}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Signal recognition particle entry;
CC URL="https://en.wikipedia.org/wiki/Signal_recognition_particle";
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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; CCDS53893.1; -. [P61011-2]
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 SMR; P61011; -.
DR BioGRID; 112607; 117.
DR IntAct; P61011; 27.
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; 1 site, 1 O-linked glycan (1 site).
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; P61011; -.
DR PeptideAtlas; P61011; -.
DR PRIDE; P61011; -.
DR ProteomicsDB; 57247; -. [P61011-1]
DR ProteomicsDB; 57248; -. [P61011-2]
DR Antibodypedia; 23175; 219 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 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; DTAGRHK; -.
DR OrthoDB; 463152at2759; -.
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; 799 hits in 1102 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 203 other tissues.
DR ExpressionAtlas; P61011; baseline and differential.
DR Genevisible; P61011; HS.
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: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 Gene3D; 1.10.260.30; -; 1.
DR Gene3D; 1.20.120.140; -; 1.
DR Gene3D; 3.40.50.300; -; 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 PANTHER; PTHR11564; PTHR11564; 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; SSF47364; 1.
DR SUPFAM; SSF47446; SSF47446; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01425; SRP54_euk; 1.
DR PROSITE; PS00300; SRP54; 1.
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 54 kDa protein"
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 GTPase activity; decreases neutrophil numbers and
FT migration capacity; faster dissociation of the interaction
FT with the SRP receptor subunit SRPRA; reduced SR compaction;
FT impaired interaction with SR; impaired detachment from
FT ribosome)"
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
