TIPIN_HUMAN
ID TIPIN_HUMAN Reviewed; 301 AA.
AC Q9BVW5; B2CW64; Q9NWZ6;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=TIMELESS-interacting protein;
GN Name=TIPIN;
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], AND VARIANT PRO-53.
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 [GENOMIC DNA], AND VARIANTS GLY-111; SER-267 AND
RP SER-270.
RG NIEHS SNPs program;
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-53.
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-53.
RC TISSUE=Cervix;
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 IDENTIFICATION, AND VARIANT PRO-53.
RX PubMed=12875843; DOI=10.1016/s0022-2836(03)00633-8;
RA Gotter A.L.;
RT "Tipin, a novel timeless-interacting protein, is developmentally co-
RT expressed with timeless and disrupts its self-association.";
RL J. Mol. Biol. 331:167-176(2003).
RN [7]
RP FUNCTION, INTERACTION WITH TIMELESS; MCM6 AND MCM7, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17116885; DOI=10.1073/pnas.0609251103;
RA Chou D.M., Elledge S.J.;
RT "Tipin and Timeless form a mutually protective complex required for
RT genotoxic stress resistance and checkpoint function.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:18143-18147(2006).
RN [8]
RP FUNCTION, INTERACTION WITH TIMELESS, AND SUBCELLULAR LOCATION.
RX PubMed=17102137; DOI=10.1074/jbc.m605596200;
RA Yoshizawa-Sugata N., Masai H.;
RT "Human Tim/Timeless-interacting protein, Tipin, is required for efficient
RT progression of S phase and DNA replication checkpoint.";
RL J. Biol. Chem. 282:2729-2740(2007).
RN [9]
RP INTERACTION WITH RPA2 AND PRDX2, AND SUBCELLULAR LOCATION.
RX PubMed=17141802; DOI=10.1016/j.jmb.2006.10.097;
RA Gotter A.L., Suppa C., Emanuel B.S.;
RT "Mammalian TIMELESS and Tipin are evolutionarily conserved replication
RT fork-associated factors.";
RL J. Mol. Biol. 366:36-52(2007).
RN [10]
RP INTERACTION WITH TIMELESS AND RPA2, AND FUNCTION.
RX PubMed=17296725; DOI=10.1128/mcb.02190-06;
RA Uensal-Kacmaz K., Chastain P.D., Qu P.-P., Minoo P., Cordeiro-Stone M.,
RA Sancar A., Kaufmann W.K.;
RT "The human Tim/Tipin complex coordinates an Intra-S checkpoint response to
RT UV that slows replication fork displacement.";
RL Mol. Cell. Biol. 27:3131-3142(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP REVIEW.
RX PubMed=20139726; DOI=10.4161/cc.9.4.10676;
RA McFarlane R.J., Mian S., Dalgaard J.Z.;
RT "The many facets of the Tim-Tipin protein families' roles in chromosome
RT biology.";
RL Cell Cycle 9:700-705(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-244, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-222 AND THR-233, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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).
CC -!- FUNCTION: Plays an important role in the control of DNA replication and
CC the maintenance of replication fork stability. Important for cell
CC survival after DNA damage or replication stress. May be specifically
CC required for the ATR-CHEK1 pathway in the replication checkpoint
CC induced by hydroxyurea or ultraviolet light. Forms a complex with
CC TIMELESS and this complex regulates DNA replication processes under
CC both normal and stress conditions, stabilizes replication forks and
CC influences both CHEK1 phosphorylation and the intra-S phase checkpoint
CC in response to genotoxic stress. {ECO:0000269|PubMed:17102137,
CC ECO:0000269|PubMed:17116885, ECO:0000269|PubMed:17296725}.
CC -!- SUBUNIT: Interacts with TIMELESS, which impairs TIMELESS self-
CC association. Interacts with RPA2, PRDX2, MCM6 and MCM7.
CC {ECO:0000269|PubMed:17102137, ECO:0000269|PubMed:17116885,
CC ECO:0000269|PubMed:17141802, ECO:0000269|PubMed:17296725}.
CC -!- INTERACTION:
CC Q9BVW5; O15499: GSC2; NbExp=3; IntAct=EBI-2515360, EBI-19954058;
CC Q9BVW5; P15927: RPA2; NbExp=4; IntAct=EBI-2515360, EBI-621404;
CC Q9BVW5; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-2515360, EBI-5235340;
CC Q9BVW5; Q8IYF3: TEX11; NbExp=3; IntAct=EBI-2515360, EBI-742397;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17102137,
CC ECO:0000269|PubMed:17141802}. Nucleus {ECO:0000269|PubMed:17116885,
CC ECO:0000269|PubMed:17141802}.
CC -!- SIMILARITY: Belongs to the CSM3 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tipin/";
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DR EMBL; AK000523; BAA91229.1; -; mRNA.
DR EMBL; EU551725; ACB21044.1; -; Genomic_DNA.
DR EMBL; AC055855; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77762.1; -; Genomic_DNA.
DR EMBL; BC000870; AAH00870.1; -; mRNA.
DR EMBL; BK001386; DAA01365.1; -; mRNA.
DR CCDS; CCDS10215.1; -.
DR RefSeq; NP_001276915.1; NM_001289986.1.
DR RefSeq; NP_060328.2; NM_017858.2.
DR RefSeq; XP_005254578.1; XM_005254521.2.
DR RefSeq; XP_005254579.1; XM_005254522.4.
DR RefSeq; XP_006720657.1; XM_006720594.3.
DR RefSeq; XP_011520045.1; XM_011521743.1.
DR RefSeq; XP_016877879.1; XM_017022390.1.
DR PDB; 7PFO; EM; 3.20 A; L=1-301.
DR PDB; 7PLO; EM; 2.80 A; L=1-301.
DR PDBsum; 7PFO; -.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; Q9BVW5; -.
DR BMRB; Q9BVW5; -.
DR SMR; Q9BVW5; -.
DR BioGRID; 120300; 44.
DR DIP; DIP-53658N; -.
DR ELM; Q9BVW5; -.
DR IntAct; Q9BVW5; 28.
DR MINT; Q9BVW5; -.
DR STRING; 9606.ENSP00000261881; -.
DR iPTMnet; Q9BVW5; -.
DR PhosphoSitePlus; Q9BVW5; -.
DR BioMuta; TIPIN; -.
DR DMDM; 296452932; -.
DR EPD; Q9BVW5; -.
DR jPOST; Q9BVW5; -.
DR MassIVE; Q9BVW5; -.
DR MaxQB; Q9BVW5; -.
DR PaxDb; Q9BVW5; -.
DR PeptideAtlas; Q9BVW5; -.
DR PRIDE; Q9BVW5; -.
DR ProteomicsDB; 79240; -.
DR Antibodypedia; 26122; 363 antibodies from 25 providers.
DR DNASU; 54962; -.
DR Ensembl; ENST00000261881.9; ENSP00000261881.4; ENSG00000075131.10.
DR GeneID; 54962; -.
DR KEGG; hsa:54962; -.
DR MANE-Select; ENST00000261881.9; ENSP00000261881.4; NM_017858.3; NP_060328.3.
DR UCSC; uc002apr.3; human.
DR CTD; 54962; -.
DR DisGeNET; 54962; -.
DR GeneCards; TIPIN; -.
DR HGNC; HGNC:30750; TIPIN.
DR HPA; ENSG00000075131; Low tissue specificity.
DR MIM; 610716; gene.
DR neXtProt; NX_Q9BVW5; -.
DR OpenTargets; ENSG00000075131; -.
DR PharmGKB; PA147357269; -.
DR VEuPathDB; HostDB:ENSG00000075131; -.
DR eggNOG; KOG3004; Eukaryota.
DR GeneTree; ENSGT00390000005764; -.
DR InParanoid; Q9BVW5; -.
DR OMA; IIHEDFI; -.
DR OrthoDB; 1505397at2759; -.
DR PhylomeDB; Q9BVW5; -.
DR TreeFam; TF313290; -.
DR PathwayCommons; Q9BVW5; -.
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR SignaLink; Q9BVW5; -.
DR BioGRID-ORCS; 54962; 580 hits in 1081 CRISPR screens.
DR ChiTaRS; TIPIN; human.
DR GeneWiki; TIPIN; -.
DR GenomeRNAi; 54962; -.
DR Pharos; Q9BVW5; Tbio.
DR PRO; PR:Q9BVW5; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9BVW5; protein.
DR Bgee; ENSG00000075131; Expressed in calcaneal tendon and 158 other tissues.
DR ExpressionAtlas; Q9BVW5; baseline and differential.
DR Genevisible; Q9BVW5; HS.
DR GO; GO:0000785; C:chromatin; IDA:HGNC-UCL.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR GO; GO:0031298; C:replication fork protection complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0044770; P:cell cycle phase transition; IMP:BHF-UCL.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IMP:HGNC-UCL.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IMP:HGNC-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:HGNC-UCL.
DR GO; GO:0033262; P:regulation of nuclear cell cycle DNA replication; TAS:HGNC-UCL.
DR GO; GO:0043111; P:replication fork arrest; IBA:GO_Central.
DR GO; GO:0048478; P:replication fork protection; IBA:GO_Central.
DR GO; GO:0009411; P:response to UV; IEA:Ensembl.
DR InterPro; IPR012923; Csm3.
DR InterPro; IPR040038; TIPIN/Csm3/Swi3.
DR PANTHER; PTHR13220; PTHR13220; 1.
DR Pfam; PF07962; Swi3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Cytoplasm; DNA damage; Mitosis;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..301
FT /note="TIMELESS-interacting protein"
FT /id="PRO_0000305253"
FT REGION 1..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..143
FT /note="Interaction with TIMELESS"
FT REGION 240..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..256
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 222
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 233
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 244
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VARIANT 53
FT /note="R -> P (in dbSNP:rs9806123)"
FT /evidence="ECO:0000269|PubMed:12875843,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.4"
FT /id="VAR_035194"
FT VARIANT 111
FT /note="A -> G (in dbSNP:rs2063690)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_035195"
FT VARIANT 260
FT /note="L -> P (in dbSNP:rs3759787)"
FT /id="VAR_053952"
FT VARIANT 267
FT /note="A -> S (in dbSNP:rs3759786)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_035196"
FT VARIANT 270
FT /note="N -> D (in dbSNP:rs34848112)"
FT /id="VAR_062207"
FT VARIANT 270
FT /note="N -> S (in dbSNP:rs780014564)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_054483"
FT CONFLICT 201
FT /note="Q -> R (in Ref. 1; BAA91229)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 301 AA; 34555 MW; B0C69117A636CE3A CRC64;
MLEPQENGVI DLPDYEHVED ETFPPFPPPA SPERQDGEGT EPDEESGNGA PVRVPPKRTV
KRNIPKLDAQ RLISERGLPA LRHVFDKAKF KGKGHEAEDL KMLIRHMEHW AHRLFPKLQF
EDFIDRVEYL GSKKEVQTCL KRIRLDLPIL HEDFVSNNDE VAENNEHDVT STELDPFLTN
LSESEMFASE LSRSLTEEQQ QRIERNKQLA LERRQAKLLS NSQTLGNDML MNTPRAHTVE
EVNTDEDQKE ESNGLNEDIL DNPCNDAIAN TLNEEETLLD QSFKNVQQQL DATSRNITEA
R
