SHLD1_HUMAN
ID SHLD1_HUMAN Reviewed; 205 AA.
AC Q8IYI0; A8K9J3; Q5TGA9; Q96LU1;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Shieldin complex subunit 1 {ECO:0000312|HGNC:HGNC:26318};
DE AltName: Full=RINN1-REV7-interacting novel NHEJ regulator 3 {ECO:0000303|PubMed:29656893};
DE AltName: Full=Shield complex subunit 1;
GN Name=SHLD1 {ECO:0000312|HGNC:HGNC:26318};
GN Synonyms=C20orf196 {ECO:0000312|HGNC:HGNC:26318},
GN RINN3 {ECO:0000303|PubMed:29656893};
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] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum, and Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [5]
RP FUNCTION, IDENTIFICATION IN THE SHIELDIN COMPLEX, INTERACTION WITH SHLD2,
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=29656893; DOI=10.1016/j.cell.2018.03.050;
RA Gupta R., Somyajit K., Narita T., Maskey E., Stanlie A., Kremer M.,
RA Typas D., Lammers M., Mailand N., Nussenzweig A., Lukas J., Choudhary C.;
RT "DNA repair network analysis reveals shieldin as a key regulator of NHEJ
RT and PARP inhibitor sensitivity.";
RL Cell 0:0-0(2018).
CC -!- FUNCTION: Component of the shieldin complex, which plays an important
CC role in repair of DNA double-stranded breaks (DSBs). During G1 and S
CC phase of the cell cycle, the complex functions downstream of TP53BP1 to
CC promote non-homologous end joining (NHEJ) and suppress DNA end
CC resection. Mediates various NHEJ-dependent processes including
CC immunoglobulin class-switch recombination, and fusion of unprotected
CC telomeres. {ECO:0000269|PubMed:29656893}.
CC -!- SUBUNIT: Component of the shieldin complex, consisting of SHLD1, SHLD2,
CC SHLD3 and MAD2L2/REV7. Within the complex, SHLD2 forms a scaffold which
CC interacts with a SHLD3-MAD2L2 subcomplex via its N-terminus, and with
CC SHLD1 via its C-terminus. {ECO:0000269|PubMed:29656893}.
CC -!- INTERACTION:
CC Q8IYI0; Q92870-2: APBB2; NbExp=3; IntAct=EBI-2560428, EBI-21535880;
CC Q8IYI0; G5E9A7: DMWD; NbExp=3; IntAct=EBI-2560428, EBI-10976677;
CC Q8IYI0; P04792: HSPB1; NbExp=3; IntAct=EBI-2560428, EBI-352682;
CC Q8IYI0; P42858: HTT; NbExp=3; IntAct=EBI-2560428, EBI-466029;
CC Q8IYI0; O60333-2: KIF1B; NbExp=3; IntAct=EBI-2560428, EBI-10975473;
CC Q8IYI0; D3DTS7: PMP22; NbExp=3; IntAct=EBI-2560428, EBI-25882629;
CC Q8IYI0; P47897: QARS1; NbExp=3; IntAct=EBI-2560428, EBI-347462;
CC Q8IYI0; Q86V20: SHLD2; NbExp=2; IntAct=EBI-2560428, EBI-2560414;
CC Q8IYI0; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-2560428, EBI-5235340;
CC Q8IYI0; O76024: WFS1; NbExp=3; IntAct=EBI-2560428, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:29656893}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IYI0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IYI0-2; Sequence=VSP_025125;
CC -!- MISCELLANEOUS: In BRCA1-deficient cells, function of the shieldin
CC complex is necessary for sensitivity to the PARP inhibitor olaparib.
CC {ECO:0000269|PubMed:29656893}.
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DR EMBL; AK057796; BAB71578.1; -; mRNA.
DR EMBL; AK292708; BAF85397.1; -; mRNA.
DR EMBL; AL035249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL390028; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10412.1; -; Genomic_DNA.
DR EMBL; BC035800; AAH35800.1; -; mRNA.
DR CCDS; CCDS13091.1; -. [Q8IYI0-1]
DR RefSeq; NP_001290406.1; NM_001303477.1. [Q8IYI0-1]
DR RefSeq; NP_001290407.1; NM_001303478.1.
DR RefSeq; NP_001290408.1; NM_001303479.1.
DR RefSeq; NP_689717.2; NM_152504.3. [Q8IYI0-1]
DR RefSeq; XP_016883173.1; XM_017027684.1. [Q8IYI0-1]
DR AlphaFoldDB; Q8IYI0; -.
DR BioGRID; 127244; 12.
DR ComplexPortal; CPX-3481; Shieldin complex.
DR CORUM; Q8IYI0; -.
DR IntAct; Q8IYI0; 15.
DR MINT; Q8IYI0; -.
DR STRING; 9606.ENSP00000305875; -.
DR iPTMnet; Q8IYI0; -.
DR PhosphoSitePlus; Q8IYI0; -.
DR BioMuta; C20orf196; -.
DR MassIVE; Q8IYI0; -.
DR PaxDb; Q8IYI0; -.
DR PeptideAtlas; Q8IYI0; -.
DR PRIDE; Q8IYI0; -.
DR ProteomicsDB; 71178; -. [Q8IYI0-1]
DR ProteomicsDB; 71179; -. [Q8IYI0-2]
DR Antibodypedia; 49253; 69 antibodies from 11 providers.
DR DNASU; 149840; -.
DR Ensembl; ENST00000303142.11; ENSP00000305875.6; ENSG00000171984.15. [Q8IYI0-1]
DR GeneID; 149840; -.
DR KEGG; hsa:149840; -.
DR MANE-Select; ENST00000303142.11; ENSP00000305875.6; NM_152504.4; NP_689717.2.
DR UCSC; uc002wmf.4; human. [Q8IYI0-1]
DR CTD; 149840; -.
DR DisGeNET; 149840; -.
DR GeneCards; SHLD1; -.
DR HGNC; HGNC:26318; SHLD1.
DR HPA; ENSG00000171984; Low tissue specificity.
DR MIM; 618028; gene.
DR neXtProt; NX_Q8IYI0; -.
DR OpenTargets; ENSG00000171984; -.
DR PharmGKB; PA145149476; -.
DR VEuPathDB; HostDB:ENSG00000171984; -.
DR eggNOG; ENOG502SUXK; Eukaryota.
DR GeneTree; ENSGT00390000014969; -.
DR HOGENOM; CLU_090358_0_0_1; -.
DR InParanoid; Q8IYI0; -.
DR OMA; VLRSFQM; -.
DR OrthoDB; 1336753at2759; -.
DR PhylomeDB; Q8IYI0; -.
DR TreeFam; TF336046; -.
DR PathwayCommons; Q8IYI0; -.
DR SignaLink; Q8IYI0; -.
DR BioGRID-ORCS; 149840; 81 hits in 1055 CRISPR screens.
DR ChiTaRS; C20orf196; human.
DR GenomeRNAi; 149840; -.
DR Pharos; Q8IYI0; Tbio.
DR PRO; PR:Q8IYI0; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q8IYI0; protein.
DR Bgee; ENSG00000171984; Expressed in monocyte and 122 other tissues.
DR ExpressionAtlas; Q8IYI0; baseline and differential.
DR Genevisible; Q8IYI0; HS.
DR GO; GO:0000785; C:chromatin; IC:ComplexPortal.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR GO; GO:0045830; P:positive regulation of isotype switching; IDA:UniProtKB.
DR GO; GO:0002208; P:somatic diversification of immunoglobulins involved in immune response; IC:ComplexPortal.
DR GO; GO:0043247; P:telomere maintenance in response to DNA damage; IC:ComplexPortal.
DR InterPro; IPR027821; SHLD1.
DR PANTHER; PTHR36863; PTHR36863; 1.
DR Pfam; PF15021; DUF4521; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromosome; DNA damage; DNA repair;
KW Reference proteome.
FT CHAIN 1..205
FT /note="Shieldin complex subunit 1"
FT /id="PRO_0000286612"
FT VAR_SEQ 142..195
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_025125"
FT VARIANT 23
FT /note="A -> V (in dbSNP:rs237422)"
FT /id="VAR_032144"
SQ SEQUENCE 205 AA; 22938 MW; 4AF85DA351FF5FAF CRC64;
MAARDATSGS LSEESSALDL PSACDIRDYV LQGPSQEANS EAFSSLEFHS FPYSSDVDPD
TSNLNIEQNN SWTAENFWLD PAVKGQSEKE EDDGLRKSLD RFYEMFGHPQ PGSANSLSAS
VCKCLSQKIT QLRGQESQKY ALRSFQMARV IFNRDGCSVL QRHSRDTHFY PLEEGSTSLD
DEKPNPGLSK DITHFLLQQN VMKDL
