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   05-OCT-2010, entry version 62.
DE   RecName: Full=TIMELESS-interacting protein;
GN   Name=TIPIN;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA   Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA   Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA   Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA   Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA   Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA   Nusbaum C.;
RT   "Analysis of the DNA sequence and duplication history of human
RT   chromosome 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   IDENTIFICATION, AND VARIANT PRO-53.
RX   MEDLINE=22758615; 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   SUBCELLULAR LOCATION, INTERACTION WITH TIMELESS; MCM6 AND MCM7, AND
RP   FUNCTION.
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   SUBCELLULAR LOCATION, INTERACTION WITH TIMELESS, AND FUNCTION.
RX   PubMed=17102137; DOI=10.1074/jbc.M605596200;
RA   Yoshizawa-Sugata N., Masai H.;
RT   "Human Tim/Timeless-interacting protein, Tipin, is required for
RT   efficient 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.,
RA   Cordeiro-Stone M., Sancar A., Kaufmann W.K.;
RT   "The human Tim/Tipin complex coordinates an Intra-S checkpoint
RT   response to UV that slows replication fork displacement.";
RL   Mol. Cell. Biol. 27:3131-3142(2007).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-222, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Embryonic kidney;
RX   PubMed=17525332; DOI=10.1126/science.1140321;
RA   Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA   Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA   Lerenthal Y., Shiloh Y., 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 MASS
RP   SPECTROMETRY.
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-233, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
CC   -!- FUNCTION: Required for normal progression of S-phase. Important
CC       for cell survival after DNA damage or replication stress. May be
CC       specifically required for the ATR-CHK1 pathway in the replication
CC       checkpoint induced by hydroxyurea or ultraviolet light.
CC   -!- SUBUNIT: Interacts with TIMELESS, which impairs TIMELESS self-
CC       association. Interacts with RPA2, PRDX2, MCM6 and MCM7.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC   -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
CC   -!- SIMILARITY: Belongs to the CSM3 family.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/tipin/";
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
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   IPI; IPI00306452; -.
DR   RefSeq; NP_060328.2; -.
DR   UniGene; Hs.572318; -.
DR   IntAct; Q9BVW5; 4.
DR   STRING; Q9BVW5; -.
DR   PhosphoSite; Q9BVW5; -.
DR   PRIDE; Q9BVW5; -.
DR   Ensembl; ENST00000261881; ENSP00000261881; ENSG00000075131.
DR   GeneID; 54962; -.
DR   KEGG; hsa:54962; -.
DR   UCSC; uc002apr.2; human.
DR   CTD; 54962; -.
DR   GeneCards; GC15M066629; -.
DR   H-InvDB; HIX0012362; -.
DR   HGNC; HGNC:30750; TIPIN.
DR   MIM; 610716; gene.
DR   eggNOG; prNOG08943; -.
DR   HOGENOM; HBG277865; -.
DR   HOVERGEN; HBG061130; -.
DR   InParanoid; Q9BVW5; -.
DR   NextBio; 58172; -.
DR   ArrayExpress; Q9BVW5; -.
DR   Bgee; Q9BVW5; -.
DR   CleanEx; HS_TIPIN; -.
DR   Genevestigator; Q9BVW5; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0000790; C:nuclear chromatin; IDA:HGNC.
DR   GO; GO:0005515; F:protein binding; IPI:HGNC.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0000076; P:DNA replication checkpoint; IMP:HGNC.
DR   GO; GO:0031573; P:intra-S DNA damage checkpoint; IMP:HGNC.
DR   GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR   GO; GO:0008284; P:positive regulation of cell proliferation; IMP:HGNC.
DR   GO; GO:0033262; P:regulation of DNA replication involved in S...; TAS:HGNC.
DR   GO; GO:0048478; P:replication fork protection; IEA:InterPro.
DR   InterPro; IPR012923; Swi3.
DR   Pfam; PF07962; Swi3; 1.
DR   ProDom; PD089639; Swi3; 1.
PE   1: Evidence at protein level;
KW   Cell cycle; Cell division; Complete proteome; Cytoplasm; DNA damage;
KW   Mitosis; Nucleus; Phosphoprotein; Polymorphism.
FT   CHAIN         1    301       TIMELESS-interacting protein.
FT                                /FTId=PRO_0000305253.
FT   REGION       67    143       Interaction with TIMELESS.
FT   MOD_RES     194    194       Phosphoserine.
FT   MOD_RES     222    222       Phosphoserine.
FT   MOD_RES     233    233       Phosphothreonine.
FT   VARIANT      53     53       R -> P (in dbSNP:rs9806123).
FT                                /FTId=VAR_035194.
FT   VARIANT     111    111       A -> G (in dbSNP:rs2063690).
FT                                /FTId=VAR_035195.
FT   VARIANT     260    260       L -> P (in dbSNP:rs3759787).
FT                                /FTId=VAR_053952.
FT   VARIANT     267    267       A -> S (in dbSNP:rs3759786).
FT                                /FTId=VAR_035196.
FT   VARIANT     270    270       N -> D (in dbSNP:rs34848112).
FT                                /FTId=VAR_062207.
FT   VARIANT     270    270       N -> S.
FT                                /FTId=VAR_054483.
FT   CONFLICT    201    201       Q -> R (in Ref. 1; BAA91229).
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
//