SHLD3_HUMAN
ID SHLD3_HUMAN Reviewed; 250 AA.
AC Q6ZNX1;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Shieldin complex subunit 3 {ECO:0000312|HGNC:HGNC:53826};
DE AltName: Full=REV7-interacting novel NHEJ regulator 1 {ECO:0000303|PubMed:29656893};
DE AltName: Full=Shield complex subunit 3;
GN Name=SHLD3 {ECO:0000312|HGNC:HGNC:53826};
GN Synonyms=FLJ26957 {ECO:0000312|HGNC:HGNC:53826},
GN RINN1 {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].
RC TISSUE=Salivary gland;
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=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP FUNCTION, IDENTIFICATION IN THE SHIELDIN COMPLEX, INTERACTION WITH MAD2L2
RP AND SHLD2, SUBCELLULAR LOCATION, MUTAGENESIS OF 53-PRO--PRO-58, AND
RP 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 Q6ZNX1; Q9UI95: MAD2L2; NbExp=7; IntAct=EBI-20209073, EBI-77889;
CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:29656893}.
CC Note=Recruited to sites of chromosomal double-stranded breaks during G1
CC and S phase of the cell cycle. {ECO:0000269|PubMed:29656893}.
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; AK130467; BAC85360.1; -; mRNA.
DR EMBL; AC008560; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 6K07; X-ray; 2.24 A; B=46-74.
DR PDB; 6K08; X-ray; 2.31 A; B=46-74.
DR PDB; 6KTO; X-ray; 3.45 A; C=1-64.
DR PDB; 6M7A; X-ray; 1.90 A; C/D=28-73.
DR PDB; 6M7B; X-ray; 1.77 A; C/D=37-73.
DR PDB; 6VE5; X-ray; 2.00 A; B=41-74.
DR PDB; 6WW9; X-ray; 2.70 A; X/Y=35-58.
DR PDB; 6WWA; X-ray; 3.80 A; X/Y=2-58.
DR PDB; 7L9P; EM; 3.60 A; X/Y=2-58.
DR PDBsum; 6K07; -.
DR PDBsum; 6K08; -.
DR PDBsum; 6KTO; -.
DR PDBsum; 6M7A; -.
DR PDBsum; 6M7B; -.
DR PDBsum; 6VE5; -.
DR PDBsum; 6WW9; -.
DR PDBsum; 6WWA; -.
DR PDBsum; 7L9P; -.
DR AlphaFoldDB; Q6ZNX1; -.
DR SMR; Q6ZNX1; -.
DR ComplexPortal; CPX-3481; Shieldin complex.
DR CORUM; Q6ZNX1; -.
DR IntAct; Q6ZNX1; 39.
DR STRING; 9606.ENSP00000424007; -.
DR BioMuta; -; -.
DR MassIVE; Q6ZNX1; -.
DR PaxDb; Q6ZNX1; -.
DR PeptideAtlas; Q6ZNX1; -.
DR PRIDE; Q6ZNX1; -.
DR Antibodypedia; 76730; 2 antibodies from 1 providers.
DR Ensembl; ENST00000510585.3; ENSP00000424007.2; ENSG00000253251.3.
DR MANE-Select; ENST00000510585.3; ENSP00000424007.2; NM_001365341.2; NP_001352270.1.
DR UCSC; uc010iwu.2; human.
DR GeneCards; SHLD3; -.
DR HGNC; HGNC:53826; SHLD3.
DR HPA; ENSG00000253251; Tissue enhanced (bone).
DR MIM; 618030; gene.
DR neXtProt; NX_Q6ZNX1; -.
DR OpenTargets; ENSG00000253251; -.
DR VEuPathDB; HostDB:ENSG00000253251; -.
DR eggNOG; ENOG502RXK7; Eukaryota.
DR GeneTree; ENSGT00530000065159; -.
DR HOGENOM; CLU_1250328_0_0_1; -.
DR InParanoid; Q6ZNX1; -.
DR OMA; CNATIQR; -.
DR TreeFam; TF343624; -.
DR PathwayCommons; Q6ZNX1; -.
DR SignaLink; Q6ZNX1; -.
DR Pharos; Q6ZNX1; Tbio.
DR PRO; PR:Q6ZNX1; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q6ZNX1; protein.
DR Bgee; ENSG00000253251; Expressed in monocyte and 118 other tissues.
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; IPR039996; Shieldin_RINN1.
DR PANTHER; PTHR41404; PTHR41404; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosome; DNA damage; DNA repair; Reference proteome.
FT CHAIN 1..250
FT /note="Shieldin complex subunit 3"
FT /id="PRO_0000439346"
FT REGION 28..83
FT /note="Sufficient for interaction with MAD2L2"
FT /evidence="ECO:0000269|PubMed:29656893"
FT REGION 108..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 53..58
FT /note="PKRSPP->AKRSPA: Fails to interact with MAD2L2."
FT /evidence="ECO:0000269|PubMed:29656893"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:6KTO"
FT HELIX 19..27
FT /evidence="ECO:0007829|PDB:6KTO"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:6WW9"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:6M7B"
FT HELIX 62..71
FT /evidence="ECO:0007829|PDB:6M7B"
SQ SEQUENCE 250 AA; 28842 MW; 39653DD8AF9CF988 CRC64;
MTTEVILHYR PCESDPTQLP KIAEKAIQDF PTRPLSRFIP WFPYDGSKLP LRPKRSPPVI
SEEAAEDVKQ YLTISEHDAK SHSYDCTVDL LEFQPSLKKQ HLTWSHTLKE QTNSGNLGKQ
SEKGKQHKRR SWSISLPSNN CTKNVSPLSK KLQDSLKALN LHSLYRARWT IEHTICNSQT
LEDIWTKLNQ IIRHNELPSC NATIQRHLGQ IWVFCDIMYC EYVGSLLKGR LALTGKINLF
VHKYGVIFSM
