INCA1_MOUSE
ID INCA1_MOUSE Reviewed; 231 AA.
AC Q6PKN7; Q4VAE2;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Protein INCA1;
DE AltName: Full=Inhibitor of CDK interacting with cyclin A1;
GN Name=Inca1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=15159402; DOI=10.1074/jbc.m401708200;
RA Diederichs S., Baeumer N., Ji P., Metzelder S.K., Idos G.E., Cauvet T.,
RA Wang W., Moeller M., Pierschalski S., Gromoll J., Schrader M.G.,
RA Koeffler H.P., Berdel W.E., Serve H., Mueller-Tidow C.;
RT "Identification of interaction partners and substrates of the cyclin A1-
RT CDK2 complex.";
RL J. Biol. Chem. 279:33727-33741(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Aorta, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N; TISSUE=Liver;
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, DISRUPTION PHENOTYPE, INTERACTION WITH CCNA1, INTERACTION WITH
RP THE CCNA1/CDK2 COMPLEX, AND INDUCTION.
RX PubMed=21540187; DOI=10.1074/jbc.m110.203471;
RA Baeumer N., Tickenbrock L., Tschanter P., Lohmeyer L., Diederichs S.,
RA Baeumer S., Skryabin B.V., Zhang F., Agrawal-Singh S., Koehler G.,
RA Berdel W.E., Serve H., Koschmieder S., Mueller-Tidow C.;
RT "Inhibitor of cyclin-dependent kinase (CDK) interacting with cyclin A1
RT (INCA1) regulates proliferation and is repressed by oncogenic signaling.";
RL J. Biol. Chem. 286:28210-28222(2011).
RN [6]
RP FUNCTION.
RX PubMed=21750715; DOI=10.1371/journal.pone.0021505;
RA Zhang F., Baeumer N., Rode M., Ji P., Zhang T., Berdel W.E.,
RA Mueller-Tidow C.;
RT "The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor
RT for its antiproliferative effects.";
RL PLoS ONE 6:E21505-E21505(2011).
CC -!- FUNCTION: Binds to CDK2-bound cyclins and inhibits the kinase activity
CC of CDK2; binding to cyclins is critical for its function as CDK
CC inhibitor. Inhibits cell growth and proliferation and may play a role
CC in cell cycle control (PubMed:21540187). Required for ING5-mediated
CC regulation of S-phase progression, enhancement of Fas-induced apoptosis
CC and inhibition of cell growth (PubMed:21750715).
CC {ECO:0000269|PubMed:21540187, ECO:0000269|PubMed:21750715}.
CC -!- SUBUNIT: Interacts with CCNA1 (PubMed:21540187). Identified in a
CC complex with CCNA1 and CDK2 (By similarity). Interacts with ZNF16; the
CC interaction inhibits INCA1 activity and induces the cell cycle process
CC (By similarity). Interacts with SPACA9 (By similarity). Interacts with
CC CCNA2, CCNB1 and CCNE1 (By similarity). Interacts with the CCNA1/CDK2
CC complex (PubMed:21540187). Interacts with ING5, DAZAP2, RNF26, USP15,
CC SPOUT1, DPH7, TRIM26 and RAB5C (By similarity).
CC {ECO:0000250|UniProtKB:Q0VD86, ECO:0000269|PubMed:21540187}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q0VD86}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q0VD86}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6PKN7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PKN7-2; Sequence=VSP_033236;
CC -!- INDUCTION: By serum starvation. {ECO:0000269|PubMed:21540187}.
CC -!- PTM: Phosphorylated when part of a complex with CCNA1 and CDK2.
CC {ECO:0000250|UniProtKB:Q0VD86}.
CC -!- DISRUPTION PHENOTYPE: Mice show increased CDK2 activity in spleen with
CC disruption of the splenic architecture. {ECO:0000269|PubMed:21540187}.
CC -!- SIMILARITY: Belongs to the INCA family. {ECO:0000305}.
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DR EMBL; AY601909; AAT09154.1; -; mRNA.
DR EMBL; AY601910; AAT09155.1; -; mRNA.
DR EMBL; AY601911; AAT09156.1; -; mRNA.
DR EMBL; AY601912; AAT09157.1; -; mRNA.
DR EMBL; AK139002; BAE23857.1; -; mRNA.
DR EMBL; AL596117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR933735; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096427; AAH96427.1; -; mRNA.
DR EMBL; BC115572; AAI15573.1; -; mRNA.
DR EMBL; BC115573; AAI15574.1; -; mRNA.
DR CCDS; CCDS24964.1; -. [Q6PKN7-1]
DR CCDS; CCDS56789.1; -. [Q6PKN7-2]
DR RefSeq; NP_001239411.1; NM_001252482.1. [Q6PKN7-1]
DR RefSeq; NP_001239412.1; NM_001252483.1. [Q6PKN7-1]
DR RefSeq; NP_001239413.1; NM_001252484.1. [Q6PKN7-1]
DR RefSeq; NP_001239414.1; NM_001252485.1. [Q6PKN7-2]
DR RefSeq; NP_998894.1; NM_213729.1. [Q6PKN7-1]
DR RefSeq; XP_006531989.1; XM_006531926.3. [Q6PKN7-1]
DR RefSeq; XP_006531991.1; XM_006531928.3. [Q6PKN7-2]
DR RefSeq; XP_006531992.1; XM_006531929.3. [Q6PKN7-2]
DR AlphaFoldDB; Q6PKN7; -.
DR BioGRID; 222180; 2.
DR STRING; 10090.ENSMUSP00000073311; -.
DR PhosphoSitePlus; Q6PKN7; -.
DR PaxDb; Q6PKN7; -.
DR PRIDE; Q6PKN7; -.
DR Antibodypedia; 51738; 136 antibodies from 20 providers.
DR DNASU; 103844; -.
DR Ensembl; ENSMUST00000073625; ENSMUSP00000073311; ENSMUSG00000057054. [Q6PKN7-1]
DR Ensembl; ENSMUST00000108541; ENSMUSP00000104181; ENSMUSG00000057054. [Q6PKN7-1]
DR Ensembl; ENSMUST00000108542; ENSMUSP00000104182; ENSMUSG00000057054. [Q6PKN7-1]
DR Ensembl; ENSMUST00000108543; ENSMUSP00000104183; ENSMUSG00000057054. [Q6PKN7-2]
DR Ensembl; ENSMUST00000126114; ENSMUSP00000118761; ENSMUSG00000057054. [Q6PKN7-1]
DR GeneID; 103844; -.
DR KEGG; mmu:103844; -.
DR UCSC; uc007jwg.2; mouse. [Q6PKN7-1]
DR CTD; 388324; -.
DR MGI; MGI:2144284; Inca1.
DR VEuPathDB; HostDB:ENSMUSG00000057054; -.
DR eggNOG; ENOG502SX61; Eukaryota.
DR GeneTree; ENSGT00390000000242; -.
DR HOGENOM; CLU_103802_0_0_1; -.
DR InParanoid; Q6PKN7; -.
DR OMA; TWMEEQY; -.
DR OrthoDB; 1275701at2759; -.
DR PhylomeDB; Q6PKN7; -.
DR TreeFam; TF343431; -.
DR BioGRID-ORCS; 103844; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Inca1; mouse.
DR PRO; PR:Q6PKN7; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q6PKN7; protein.
DR Bgee; ENSMUSG00000057054; Expressed in left lobe of liver and 114 other tissues.
DR Genevisible; Q6PKN7; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; IDA:MGI.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0097190; P:apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IMP:MGI.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:MGI.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IGI:MGI.
DR InterPro; IPR026238; INCA1.
DR PANTHER; PTHR37341; PTHR37341; 1.
DR Pfam; PF15142; INCA1; 1.
DR PRINTS; PR02102; PROTEININCA1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cytoplasm; Nucleus; Phosphoprotein;
KW Protein kinase inhibitor; Reference proteome.
FT CHAIN 1..231
FT /note="Protein INCA1"
FT /id="PRO_0000331514"
FT REGION 75..99
FT /note="Interaction with CCNA1 and CCNA1/CDK2 complex;
FT essential for CDK2 inhibitory activity"
FT /evidence="ECO:0000269|PubMed:21540187"
FT MOTIF 90..95
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOD_RES 180
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q0VD86"
FT VAR_SEQ 1..35
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033236"
SQ SEQUENCE 231 AA; 26477 MW; B2CEEA4A8F36EC60 CRC64;
MQGQEDGDSI LPFAKCSRVV SRFSPCSLPP QNRRPMPQPY GDAFWENLSQ RSSSNWMVEQ
YIPPILRATD CSRPSLHPLE GLPPPEKLWR RKRKKLHLER MQKGPGSIPA RVRAVTYHLE
DLRRRQGIIN ELKRAQWGSS DATPELPALE EGFELLSTTK YFDVEEERAT YPQKETYSVT
PRDQLLWTPW TPVGQQGTYA SGQLSSLTYS TATARKNPVY DPQAMELESE E
