SLN14_HUMAN
ID SLN14_HUMAN Reviewed; 912 AA.
AC P0C7P3; B2RTW9;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 2.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Protein SLFN14 {ECO:0000305};
DE Contains:
DE RecName: Full=C-terminally truncated SLFN14 endoribonuclease {ECO:0000305};
DE EC=3.1.-.- {ECO:0000250|UniProtKB:G1SRW8};
DE AltName: Full=Schlafen family member 14 {ECO:0000312|HGNC:HGNC:32689};
GN Name=SLFN14 {ECO:0000312|HGNC:HGNC:32689};
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 GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-385.
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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=20956525; DOI=10.1074/jbc.m110.151076;
RA Katsoulidis E., Mavrommatis E., Woodard J., Shields M.A., Sassano A.,
RA Carayol N., Sawicki K.T., Munshi H.G., Platanias L.C.;
RT "Role of interferon {alpha} (IFN{alpha})-inducible Schlafen-5 in regulation
RT of anchorage-independent growth and invasion of malignant melanoma cells.";
RL J. Biol. Chem. 285:40333-40341(2010).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, ASSOCIATION WITH RIBOSOMES, AND MUTAGENESIS
RP OF ASP-248 AND ASP-249.
RX PubMed=25996083; DOI=10.1021/acs.biochem.5b00302;
RA Pisareva V.P., Muslimov I.A., Tcherepanov A., Pisarev A.V.;
RT "Characterization of novel ribosome-associated endoribonuclease SLFN14 from
RT rabbit reticulocytes.";
RL Biochemistry 54:3286-3301(2015).
RN [5]
RP INVOLVEMENT IN BDPLT20, VARIANTS BDPLT20 GLU-218; ASN-219 AND ASP-220,
RP CHARACTERIZATION OF VARIANTS BDPLT20 GLU-218; ASN-219 AND ASP-220,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=26280575; DOI=10.1172/jci80347;
RG UK Genotyping and Phenotyping of Platelets study group;
RA Fletcher S.J., Johnson B., Lowe G.C., Bem D., Drake S., Lordkipanidze M.,
RA Guiu I.S., Dawood B., Rivera J., Simpson M.A., Daly M.E., Motwani J.,
RA Collins P.W., Watson S.P., Morgan N.V.;
RT "SLFN14 mutations underlie thrombocytopenia with excessive bleeding and
RT platelet secretion defects.";
RL J. Clin. Invest. 125:3600-3605(2015).
RN [6]
RP FUNCTION, AND VARIANT BDPLT20 TRP-223.
RX PubMed=26769223; DOI=10.1160/th15-11-0884;
RA Marconi C., Di Buduo C.A., Barozzi S., Palombo F., Pardini S.,
RA Zaninetti C., Pippucci T., Noris P., Balduini A., Seri M., Pecci A.;
RT "SLFN14-related thrombocytopenia: identification within a large series of
RT patients with inherited thrombocytopenia.";
RL Thromb. Haemost. 115:1076-1079(2016).
CC -!- FUNCTION: [Protein SLFN14]: Shows no ribosome-associated and
CC endoribonuclease activities. {ECO:0000269|PubMed:25996083}.
CC -!- FUNCTION: [C-terminally truncated SLFN14 endoribonuclease]: Displays
CC polysome-associated endoribonuclease activity towards mRNAs and rRNAs
CC (PubMed:25996083). May play a role in RNA surveillance pathways by
CC recognizing stalled ribosomes and triggering endonucleolytic cleavage
CC of aberrant mRNAs (Probable). Cleaves different types of rRNAs and
CC mRNAs in a magnesium- and manganese-dependent and ATP-independent
CC manner (By similarity). Involved in correct maturation of
CC megakaryocytes and especially important for proplatelet extension.
CC {ECO:0000250|UniProtKB:G1SRW8, ECO:0000269|PubMed:25996083,
CC ECO:0000269|PubMed:26769223, ECO:0000305|PubMed:25996083}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:G1SRW8};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:G1SRW8};
CC Note=C-terminally truncated SLFN14 endoribonuclease requires manganese
CC and magnesium for its endoribonuclease activity.
CC {ECO:0000250|UniProtKB:G1SRW8};
CC -!- SUBUNIT: [C-terminally truncated SLFN14 endoribonuclease]: Associates
CC with ribosomes in an ATP-independent manner (PubMed:25996083).
CC {ECO:0000269|PubMed:25996083}.
CC -!- SUBCELLULAR LOCATION: [Protein SLFN14]: Nucleus
CC {ECO:0000269|PubMed:25996083, ECO:0000269|PubMed:26280575}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P0C7P3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P0C7P3-2; Sequence=VSP_034414;
CC -!- TISSUE SPECIFICITY: Expressed in megakaryocytes and platelets (at
CC protein level) (PubMed:26280575). Weakly expressed in melanocytes and
CC malignant melanoma cells (PubMed:20956525).
CC {ECO:0000269|PubMed:20956525, ECO:0000269|PubMed:26280575}.
CC -!- DISEASE: Bleeding disorder, platelet-type, 20 (BDPLT20) [MIM:616913]: A
CC disorder characterized by increased bleeding tendency due to platelet
CC dysfunction. Clinical features include epistaxis, hematomas, bleeding
CC after tooth extraction, and menorrhagia. BDPLT20 is characterized by
CC moderate thrombocytopenia and platelet secretion defects. Inheritance
CC is autosomal dominant. {ECO:0000269|PubMed:26280575,
CC ECO:0000269|PubMed:26769223}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Schlafen family. Subgroup III subfamily.
CC {ECO:0000305}.
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DR EMBL; AC015911; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC140847; AAI40848.1; -; mRNA.
DR EMBL; BC157877; AAI57878.1; -; mRNA.
DR EMBL; BC157879; AAI57880.1; -; mRNA.
DR CCDS; CCDS45650.1; -. [P0C7P3-1]
DR RefSeq; NP_001123292.1; NM_001129820.1. [P0C7P3-1]
DR RefSeq; XP_016880065.1; XM_017024576.1.
DR RefSeq; XP_016880066.1; XM_017024577.1. [P0C7P3-1]
DR RefSeq; XP_016880067.1; XM_017024578.1. [P0C7P3-1]
DR RefSeq; XP_016880068.1; XM_017024579.1. [P0C7P3-1]
DR AlphaFoldDB; P0C7P3; -.
DR SMR; P0C7P3; -.
DR BioGRID; 131189; 1.
DR IntAct; P0C7P3; 1.
DR STRING; 9606.ENSP00000391101; -.
DR iPTMnet; P0C7P3; -.
DR PhosphoSitePlus; P0C7P3; -.
DR BioMuta; SLFN14; -.
DR DMDM; 288558826; -.
DR MassIVE; P0C7P3; -.
DR MaxQB; P0C7P3; -.
DR PaxDb; P0C7P3; -.
DR PeptideAtlas; P0C7P3; -.
DR PRIDE; P0C7P3; -.
DR ProteomicsDB; 52355; -. [P0C7P3-1]
DR ProteomicsDB; 52356; -. [P0C7P3-2]
DR Antibodypedia; 43976; 73 antibodies from 18 providers.
DR DNASU; 342618; -.
DR Ensembl; ENST00000415846.3; ENSP00000391101.2; ENSG00000236320.4. [P0C7P3-1]
DR Ensembl; ENST00000674182.1; ENSP00000501524.1; ENSG00000236320.4. [P0C7P3-1]
DR GeneID; 342618; -.
DR KEGG; hsa:342618; -.
DR MANE-Select; ENST00000674182.1; ENSP00000501524.1; NM_001129820.2; NP_001123292.1.
DR UCSC; uc010ctu.2; human. [P0C7P3-1]
DR CTD; 342618; -.
DR DisGeNET; 342618; -.
DR GeneCards; SLFN14; -.
DR HGNC; HGNC:32689; SLFN14.
DR HPA; ENSG00000236320; Tissue enriched (bone).
DR MalaCards; SLFN14; -.
DR MIM; 614958; gene.
DR MIM; 616913; phenotype.
DR neXtProt; NX_P0C7P3; -.
DR OpenTargets; ENSG00000236320; -.
DR Orphanet; 466806; Autosomal dominant thrombocytopenia with platelet secretion defect.
DR PharmGKB; PA144596361; -.
DR VEuPathDB; HostDB:ENSG00000236320; -.
DR eggNOG; ENOG502QWKG; Eukaryota.
DR GeneTree; ENSGT00410000025651; -.
DR HOGENOM; CLU_007071_0_0_1; -.
DR InParanoid; P0C7P3; -.
DR OMA; FQVHHAD; -.
DR OrthoDB; 211385at2759; -.
DR PhylomeDB; P0C7P3; -.
DR TreeFam; TF337168; -.
DR PathwayCommons; P0C7P3; -.
DR SignaLink; P0C7P3; -.
DR BioGRID-ORCS; 342618; 3 hits in 1073 CRISPR screens.
DR GenomeRNAi; 342618; -.
DR Pharos; P0C7P3; Tbio.
DR PRO; PR:P0C7P3; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P0C7P3; protein.
DR Bgee; ENSG00000236320; Expressed in monocyte and 26 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0071286; P:cellular response to magnesium ion; ISS:UniProtKB.
DR GO; GO:0071287; P:cellular response to manganese ion; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0036345; P:platelet maturation; IMP:UniProtKB.
DR GO; GO:0090502; P:RNA phosphodiester bond hydrolysis, endonucleolytic; IDA:UniProtKB.
DR GO; GO:0016075; P:rRNA catabolic process; IDA:UniProtKB.
DR Gene3D; 3.30.950.30; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR029684; Schlafen.
DR InterPro; IPR007421; Schlafen_AlbA_2_dom.
DR InterPro; IPR038461; Schlafen_AlbA_2_dom_sf.
DR InterPro; IPR029677; SLFN14.
DR PANTHER; PTHR12155; PTHR12155; 1.
DR PANTHER; PTHR12155:SF30; PTHR12155:SF30; 1.
DR Pfam; PF04326; AlbA_2; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Disease variant; Endonuclease;
KW Hydrolase; Nuclease; Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..912
FT /note="Protein SLFN14"
FT /id="PRO_0000342339"
FT CHAIN 1..?
FT /note="C-terminally truncated SLFN14 endoribonuclease"
FT /id="PRO_0000436153"
FT REGION 206..391
FT /note="Required for endoribonuclease activity"
FT /evidence="ECO:0000269|PubMed:25996083"
FT REGION 392..571
FT /note="Required for ribosome binding"
FT /evidence="ECO:0000269|PubMed:25996083"
FT BINDING 593..600
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT VAR_SEQ 353..368
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_034414"
FT VARIANT 93
FT /note="Q -> R (in dbSNP:rs10512472)"
FT /id="VAR_044177"
FT VARIANT 218
FT /note="K -> E (in BDPLT20; the mutation results in strongly
FT reduced protein stability; dbSNP:rs869320716)"
FT /evidence="ECO:0000269|PubMed:26280575"
FT /id="VAR_075786"
FT VARIANT 219
FT /note="K -> N (in BDPLT20; the mutation results in strongly
FT reduced protein stability; dbSNP:rs869320715)"
FT /evidence="ECO:0000269|PubMed:26280575"
FT /id="VAR_075787"
FT VARIANT 220
FT /note="V -> D (in BDPLT20; the mutation results in weakly
FT reduced protein stability; dbSNP:rs869320714)"
FT /evidence="ECO:0000269|PubMed:26280575"
FT /id="VAR_075788"
FT VARIANT 223
FT /note="R -> W (in BDPLT20; dbSNP:rs757188030)"
FT /evidence="ECO:0000269|PubMed:26769223"
FT /id="VAR_076796"
FT VARIANT 385
FT /note="K -> E (in dbSNP:rs321612)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_044178"
FT VARIANT 870
FT /note="G -> S (in dbSNP:rs1350011)"
FT /id="VAR_044179"
FT VARIANT 880
FT /note="S -> I (in dbSNP:rs1350010)"
FT /id="VAR_044180"
FT VARIANT 905
FT /note="L -> F (in dbSNP:rs9907259)"
FT /id="VAR_044181"
FT VARIANT 912
FT /note="Y -> F (in dbSNP:rs8073060)"
FT /id="VAR_044182"
FT MUTAGEN 248
FT /note="D->A: Reduces endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:25996083"
FT MUTAGEN 249
FT /note="D->A: Abolishes endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:25996083"
FT CONFLICT 356
FT /note="P -> S (in Ref. 2; AAI40848/AAI57878/AAI57880)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 912 AA; 103907 MW; 391054668F58FFAB CRC64;
MESLKTDTEM PYPEVIVDVG RVIFGEENRK KMTNSCLKRS ENSRIIRAIC ALLNSGGGVI
KAEIDDKTYS YQCHGLGQDL ETSFQKLLPS GSQKYLDYMQ QGHNLLIFVK SWSPDVFSLP
LRICSLRSNL YRRDVTSAIN LSASSALELL REKGFRAQRG RPRVKKLHPQ QVLNRCIQEE
EDMRILASEF FKKDKLMYKE KLNFTESTHV EFKRFTTKKV IPRIKEMLPH YVSAFANTQG
GYVLIGVDDK SKEVVGCKWE KVNPDLLKKE IENCIEKLPT FHFCCEKPKV NFTTKILNVY
QKDVLDGYVC VIQVEPFCCV VFAEAPDSWI MKDNSVTRLT AEQWVVMMLD TQSAPPSLVT
DYNSCLISSA SSARKSPGYP IKVHKFKEAL QRHLFPVTQE EVQFKPESLC KKLFSDHKEL
EGLMKTLIHP CSQGIVIFSR SWAGDVGFRK EQNVLCDALL IAVNSPVVLY TILIDPNWPG
GLEYARNTAH QLKQKLQTVG GYTGKVCIIP RLIHLSSTQS RPGEIPLRYP RSYRLADEEE
MEDLLQALVV VSLSSRSLLS DQMGCEFFNL LIMEQSQLLS ESLQKTRELF IYCFPGVRKT
ALAIKIMEKI KDLFHCKPKE ILYVCESDSL KDFVTQQTTC QAVTRKTFMQ GEFLKIKHIV
MDETENFCSK YGNWYMKAKN ITHPKAKGTG SENLHHGILW LFLDPFQIHH ADVNGLPPPS
AQFPRKTITS GIHCALEIAK VMKEEMKRIK ENPPSNMSPD TLALFSETAY EEATCAQALP
GVCETKTNLT TEQIANYVAR KCHSLFQCGY LPKDIAILCR RGEDRGRYRL ALLKAMELIE
THRPSEVVFS PATGVWGSHI VLDSIQQFSG LERTVVFGLS PECDQSEEFH KLCFASRAIK
HLYLLYEKRA AY
