SPIDR_HUMAN
ID SPIDR_HUMAN Reviewed; 915 AA.
AC Q14159; B4DFV2; B4E0Y6; Q96BI5;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=DNA repair-scaffolding protein;
DE AltName: Full=Scaffolding protein involved in DNA repair;
GN Name=SPIDR; Synonyms=KIAA0146;
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] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV. The
RT coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Amygdala, 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 701-915 (ISOFORM 1/2).
RC TISSUE=Melanoma;
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 INDUCTION BY IL4.
RX PubMed=15502879; DOI=10.2119/2004-00024.lee;
RA Lee Y.W., Eum S.Y., Chen K.C., Hennig B., Toborek M.;
RT "Gene expression profile in interleukin-4-stimulated human vascular
RT endothelial cells.";
RL Mol. Med. 10:19-27(2004).
RN [6]
RP INDUCTION BY HUMAN SARS-COV (MICROBIAL INFECTION).
RX PubMed=15858003; DOI=10.1128/jvi.79.10.6180-6193.2005;
RA Tang B.S.F., Chan K.-H., Cheng V.C.C., Woo P.C.Y., Lau S.K.P., Lam C.C.K.,
RA Chan T.-L., Wu A.K.L., Hung I.F.N., Leung S.-Y., Yuen K.-Y.;
RT "Comparative host gene transcription by microarray analysis early after
RT infection of the Huh7 cell line by severe acute respiratory syndrome
RT coronavirus and human coronavirus 229E.";
RL J. Virol. 79:6180-6193(2005).
RN [7]
RP FUNCTION, AND INTERACTION WITH FIGNL1.
RX PubMed=23754376; DOI=10.1073/pnas.1220662110;
RA Yuan J., Chen J.;
RT "FIGNL1-containing protein complex is required for efficient homologous
RT recombination repair.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:10640-10645(2013).
RN [8]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH BLM AND RAD51, INTERACTION WITH
RP BLM AND RAD51, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=23509288; DOI=10.1073/pnas.1220921110;
RA Wan L., Han J., Liu T., Dong S., Xie F., Chen H., Huang J.;
RT "Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase
RT with homologous recombination repair.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:10646-10651(2013).
CC -!- FUNCTION: Plays a role in DNA double-strand break (DBS) repair via
CC homologous recombination (HR). Serves as a scaffolding protein that
CC helps to promote the recruitment of DNA-processing enzymes like the
CC helicase BLM and recombinase RAD51 to site of DNA damage, and hence
CC contributes to maintain genomic integrity.
CC {ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376}.
CC -!- SUBUNIT: Found in a complex, at least composed of BLM, RAD51 and SPIDR;
CC the complex formation is mediated by SPIDR. Interacts (via C-terminal
CC region) with BLM; the interaction is direct. Interacts with RAD51; the
CC interaction is direct. Interacts (via the C-terminal region) with
CC FIGNL1 (via N-terminal one-half region); the interaction is direct.
CC {ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376}.
CC -!- INTERACTION:
CC Q14159; P54132: BLM; NbExp=11; IntAct=EBI-11318692, EBI-621372;
CC Q14159; Q06609: RAD51; NbExp=6; IntAct=EBI-11318692, EBI-297202;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23509288}.
CC Note=Together with BLM, is redistributed in discrete nuclear DNA
CC damage-induced foci following hydroxyurea (HU) or camptothecin (CPT)
CC treatment.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q14159-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14159-2; Sequence=VSP_056652;
CC Name=3;
CC IsoId=Q14159-3; Sequence=VSP_056653, VSP_056654;
CC -!- INDUCTION: Up-regulated in vascular endothelial cells treated with IL4.
CC {ECO:0000269|PubMed:15502879}.
CC -!- INDUCTION: (Microbial infection) Up-regulated upon SARS-CoV infection.
CC {ECO:0000269|PubMed:15858003}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09767.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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; D63480; BAA09767.1; ALT_INIT; mRNA.
DR EMBL; AK294275; BAG57563.1; -; mRNA.
DR EMBL; AK303579; BAG64598.1; -; mRNA.
DR EMBL; AC023991; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC024451; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC024649; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104995; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC142471; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC233269; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015561; AAH15561.2; -; mRNA.
DR CCDS; CCDS43737.1; -. [Q14159-1]
DR CCDS; CCDS64890.1; -. [Q14159-3]
DR CCDS; CCDS64891.1; -. [Q14159-2]
DR RefSeq; NP_001073863.1; NM_001080394.3. [Q14159-1]
DR RefSeq; NP_001269845.1; NM_001282916.1. [Q14159-2]
DR RefSeq; NP_001269848.1; NM_001282919.1. [Q14159-3]
DR RefSeq; XP_016868760.1; XM_017013271.1. [Q14159-3]
DR AlphaFoldDB; Q14159; -.
DR BioGRID; 117061; 18.
DR IntAct; Q14159; 11.
DR MINT; Q14159; -.
DR STRING; 9606.ENSP00000297423; -.
DR iPTMnet; Q14159; -.
DR PhosphoSitePlus; Q14159; -.
DR BioMuta; SPIDR; -.
DR DMDM; 115502235; -.
DR EPD; Q14159; -.
DR MassIVE; Q14159; -.
DR MaxQB; Q14159; -.
DR PaxDb; Q14159; -.
DR PeptideAtlas; Q14159; -.
DR PRIDE; Q14159; -.
DR ProteomicsDB; 4082; -.
DR ProteomicsDB; 5709; -.
DR ProteomicsDB; 59872; -. [Q14159-1]
DR Antibodypedia; 24233; 35 antibodies from 9 providers.
DR DNASU; 23514; -.
DR Ensembl; ENST00000297423.9; ENSP00000297423.4; ENSG00000164808.17. [Q14159-1]
DR Ensembl; ENST00000518074.5; ENSP00000429487.1; ENSG00000164808.17. [Q14159-3]
DR Ensembl; ENST00000541342.2; ENSP00000444061.1; ENSG00000164808.17. [Q14159-2]
DR GeneID; 23514; -.
DR KEGG; hsa:23514; -.
DR MANE-Select; ENST00000297423.9; ENSP00000297423.4; NM_001080394.4; NP_001073863.1.
DR UCSC; uc003xqd.5; human. [Q14159-1]
DR CTD; 23514; -.
DR DisGeNET; 23514; -.
DR GeneCards; SPIDR; -.
DR HGNC; HGNC:28971; SPIDR.
DR HPA; ENSG00000164808; Low tissue specificity.
DR MalaCards; SPIDR; -.
DR MIM; 615384; gene.
DR neXtProt; NX_Q14159; -.
DR OpenTargets; ENSG00000164808; -.
DR Orphanet; 243; 46,XX gonadal dysgenesis.
DR PharmGKB; PA142671636; -.
DR VEuPathDB; HostDB:ENSG00000164808; -.
DR eggNOG; ENOG502S0BG; Eukaryota.
DR GeneTree; ENSGT00390000014654; -.
DR HOGENOM; CLU_013509_0_0_1; -.
DR InParanoid; Q14159; -.
DR OMA; WRHQSIS; -.
DR OrthoDB; 326023at2759; -.
DR PhylomeDB; Q14159; -.
DR TreeFam; TF333292; -.
DR PathwayCommons; Q14159; -.
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR SignaLink; Q14159; -.
DR BioGRID-ORCS; 23514; 17 hits in 1070 CRISPR screens.
DR ChiTaRS; SPIDR; human.
DR GenomeRNAi; 23514; -.
DR Pharos; Q14159; Tbio.
DR PRO; PR:Q14159; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q14159; protein.
DR Bgee; ENSG00000164808; Expressed in right hemisphere of cerebellum and 194 other tissues.
DR ExpressionAtlas; Q14159; baseline and differential.
DR Genevisible; Q14159; HS.
DR GO; GO:0000228; C:nuclear chromosome; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0072757; P:cellular response to camptothecin; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0072711; P:cellular response to hydroxyurea; IDA:UniProtKB.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; IMP:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0070202; P:regulation of establishment of protein localization to chromosome; IDA:UniProtKB.
DR InterPro; IPR028026; DUF4502.
DR InterPro; IPR028032; DUF4503.
DR Pfam; PF14950; DUF4502; 1.
DR Pfam; PF14951; DUF4503; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA damage; DNA recombination; DNA repair; Nucleus;
KW Reference proteome.
FT CHAIN 1..915
FT /note="DNA repair-scaffolding protein"
FT /id="PRO_0000251720"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 56..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 151..450
FT /note="Necessary for interaction with RAD51"
FT /evidence="ECO:0000269|PubMed:23509288"
FT COMPBIAS 83..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..85
FT /note="MPRGSRARGSKRKRSWNTECPSFPGERPLQVRRAGLRTAGAAASLSEAWLRC
FT GEGFQNTSGNPSLTAEEKTITEKHLELCPRPKQ -> MAQVWRRVSEHFWES (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056652"
FT VAR_SEQ 1..63
FT /note="MPRGSRARGSKRKRSWNTECPSFPGERPLQVRRAGLRTAGAAASLSEAWLRC
FT GEGFQNTSGNP -> MAQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056653"
FT VAR_SEQ 851..915
FT /note="LLQRSISSLLRFAAGEDGSYEVKSVLGKEVGLLNCFVQSVTAHPTSCIGLEE
FT IELLSAGGASAEH -> VGARPEHARTPSSLQHSEELRSEECPRKGSGVVKLFCPVRNR
FT PPDQLHWIGGNRASECRRGLCRTLAVAAGSVNFAMWLQGWWWWW (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056654"
SQ SEQUENCE 915 AA; 100316 MW; DA35068B5849135D CRC64;
MPRGSRARGS KRKRSWNTEC PSFPGERPLQ VRRAGLRTAG AAASLSEAWL RCGEGFQNTS
GNPSLTAEEK TITEKHLELC PRPKQETTTS KSTSGLTDIT WSSSGSDLSD EDKTLSQLQR
DELQFIDWEI DSDRAEASDC DEFEDDEGAV EISDCASCAS NQSLTSDEKL SELPKPSSIE
ILEYSSDSEK EDDLENVLLI DSESPHKYHV QFASDARQIM ERLIDPRTKS TETILHTPQK
PTAKFPRTPE NSAKKKLLRG GLAERLNGLQ NRERSAISLW RHQCISYQKT LSGRKSGVLT
VKILELHEEC AMQVAMCEQL LGSPATSSSQ SVAPRPGAGL KVLFTKETAG YLRGRPQDTV
RIFPPWQKLI IPSGSCPVIL NTYFCEKVVA KEDSEKTCEV YCPDIPLPRR SISLAQMFVI
KGLTNNSPEI QVVCSGVATT GTAWTHGHKE AKQRIPTSTP LRDSLLDVVE SQGAASWPGA
GVRVVVQRVY SLPSRDSTRG QQGASSGHTD PAGTRACLLV QDACGMFGEV HLEFTMSKAR
QLEGKSCSLV GMKVLQKVTR GRTAGIFSLI DTLWPPAIPL KTPGRDQPCE EIKTHLPPPA
LCYILTAHPN LGQIDIIDED PIYKLYQPPV TRCLRDILQM NDLGTRCSFY ATVIYQKPQL
KSLLLLEQRE IWLLVTDVTL QTKEERDPRL PKTLLVYVAP LCVLGSEVLE ALAGAAPHSL
FFKDALRDQG RIVCAERTVL LLQKPLLSVV SGASSCELPG PVMLDSLDSA TPVNSICSVQ
GTVVGVDEST AFSWPVCDMC GNGRLEQRPE DRGAFSCGDC SRVVTSPVLK RHLQVFLDCR
SRPQCRVKVK LLQRSISSLL RFAAGEDGSY EVKSVLGKEV GLLNCFVQSV TAHPTSCIGL
EEIELLSAGG ASAEH
