ID IMA5_MOUSE Reviewed; 538 AA.
AC Q60960; Q3TF32;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 27-MAR-2024, entry version 196.
DE RecName: Full=Importin subunit alpha-5;
DE AltName: Full=Importin alpha-S1;
DE AltName: Full=Karyopherin subunit alpha-1;
DE AltName: Full=Nucleoprotein interactor 1;
DE Short=NPI-1;
DE AltName: Full=RAG cohort protein 2;
DE AltName: Full=SRP1-beta;
GN Name=Kpna1; Synonyms=Rch2;
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], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=8631802; DOI=10.1074/jbc.271.13.7654;
RA Prieve M.G., Guttridge K.L., Waterman M.L.;
RT "The nuclear localization signal of lymphoid enhancer factor-1 is
RT recognized by two differentially expressed Srp1-nuclear localization
RT sequence receptor proteins.";
RL J. Biol. Chem. 271:7654-7658(1996).
RN [2]
RP SEQUENCE REVISION TO 83, AND TISSUE SPECIFICITY.
RX PubMed=9369227; DOI=10.1016/s0014-5793(97)01092-2;
RA Tsuji L., Takumi T., Imamoto N., Yoneda Y.;
RT "Identification of novel homologues of mouse importin alpha, the alpha
RT subunit of the nuclear pore-targeting complex, and their tissue-specific
RT expression.";
RL FEBS Lett. 416:30-34(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 NUCLEOTIDE SEQUENCE [MRNA] OF 50-538.
RX PubMed=8052633; DOI=10.1073/pnas.91.16.7633;
RA Cortes P., Ye Z.-S., Baltimore D.;
RT "RAG-1 interacts with the repeated amino acid motif of the human homologue
RT of the yeast protein SRP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7633-7637(1994).
RN [6]
RP INTERACTION WITH ANP32E.
RX PubMed=10692581; DOI=10.1016/s0014-5793(00)01218-7;
RA Matsubae M., Kurihara T., Tachibana T., Imamoto N., Yoneda Y.;
RT "Characterization of the nuclear transport of a novel leucine-rich acidic
RT nuclear protein-like protein.";
RL FEBS Lett. 468:171-175(2000).
RN [7]
RP INTERACTION WITH ZIC3.
RX PubMed=18716025; DOI=10.1093/hmg/ddn239;
RA Hatayama M., Tomizawa T., Sakai-Kato K., Bouvagnet P., Kose S., Imamoto N.,
RA Yokoyama S., Utsunomiya-Tate N., Mikoshiba K., Kigawa T., Aruga J.;
RT "Functional and structural basis of the nuclear localization signal in the
RT ZIC3 zinc finger domain.";
RL Hum. Mol. Genet. 17:3459-3473(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Liver, Pancreas, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP INTERACTION WITH TALDO1.
RX PubMed=27703206; DOI=10.1038/srep34648;
RA Moriyama T., Tanaka S., Nakayama Y., Fukumoto M., Tsujimura K., Yamada K.,
RA Bamba T., Yoneda Y., Fukusaki E., Oka M.;
RT "Two isoforms of TALDO1 generated by alternative translational initiation
RT show differential nucleocytoplasmic distribution to regulate the global
RT metabolic network.";
RL Sci. Rep. 6:34648-34648(2016).
RN [10]
RP INTERACTION WITH ITSN1 ISOFORM 2.
RX PubMed=29599122; DOI=10.1042/bcj20170897;
RA Alvisi G., Paolini L., Contarini A., Zambarda C., Di Antonio V.,
RA Colosini A., Mercandelli N., Timmoneri M., Palu G., Caimi L., Ricotta D.,
RA Radeghieri A.;
RT "Intersectin goes nuclear: secret life of an endocytic protein.";
RL Biochem. J. 475:1455-1472(2018).
CC -!- FUNCTION: Functions in nuclear protein import as an adapter protein for
CC nuclear receptor KPNB1 (PubMed:8631802). Binds specifically and
CC directly to substrates containing either a simple or bipartite NLS
CC motif (PubMed:8631802). Docking of the importin/substrate complex to
CC the nuclear pore complex (NPC) is mediated by KPNB1 through binding to
CC nucleoporin FxFG repeats and the complex is subsequently translocated
CC through the pore by an energy requiring, Ran-dependent mechanism
CC (PubMed:8631802). At the nucleoplasmic side of the NPC, Ran binds to
CC importin-beta and the three components separate and importin-alpha and
CC -beta are re-exported from the nucleus to the cytoplasm where GTP
CC hydrolysis releases Ran from importin (PubMed:8631802). The
CC directionality of nuclear import is thought to be conferred by an
CC asymmetric distribution of the GTP- and GDP-bound forms of Ran between
CC the cytoplasm and nucleus (PubMed:8631802).
CC {ECO:0000269|PubMed:8631802}.
CC -!- SUBUNIT: Heterodimer; with KPNB1 (By similarity). Interacts with NSMF;
CC the interaction occurs in a calcium-independent manner after synaptic
CC NMDA receptor stimulation and is required for nuclear import of NSMF
CC but is competed by CABP1 (By similarity). Interacts with APEX1 (via its
CC N-terminus) (By similarity). Interacts with CTNNBL1 (via its N-
CC terminal) (By similarity). Interacts with AICDA (via its NLS) (By
CC similarity). Interacts with ANP32E (PubMed:10692581). Interacts with
CC ZIC3 (PubMed:18716025). Interacts with SNAI1 (via zinc fingers) (By
CC similarity). Interacts with DCAF8 (By similarity). Interacts with ITSN1
CC isoform 2 (PubMed:29599122). Interacts with TALDO1 isoform 1
CC (PubMed:27703206). Interacts with the AMPK-mediated 'Ser-659'
CC phosphorylated form of ACSS2; this interaction results in nuclear
CC translocation of ACSS2 (By similarity). {ECO:0000250|UniProtKB:P52294,
CC ECO:0000250|UniProtKB:P83953, ECO:0000269|PubMed:10692581,
CC ECO:0000269|PubMed:18716025, ECO:0000269|PubMed:27703206,
CC ECO:0000269|PubMed:29599122}.
CC -!- INTERACTION:
CC Q60960; Q15637: SF1; Xeno; NbExp=3; IntAct=EBI-8573008, EBI-744603;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:8631802}. Nucleus
CC {ECO:0000305|PubMed:8631802}.
CC -!- TISSUE SPECIFICITY: Low levels in all tissues examined.
CC {ECO:0000269|PubMed:8631802, ECO:0000269|PubMed:9369227}.
CC -!- DOMAIN: Consists of an N-terminal hydrophilic region, a hydrophobic
CC central region composed of 10 repeats, and a short hydrophilic C-
CC terminus. The N-terminal hydrophilic region contains the importin beta
CC binding domain (IBB domain), which is sufficient for binding importin
CC beta and essential for nuclear protein import.
CC {ECO:0000250|UniProtKB:P52294}.
CC -!- DOMAIN: The IBB domain is thought to act as an intrasteric
CC autoregulatory sequence by interacting with the internal autoinhibitory
CC NLS. Binding of KPNB1 probably overlaps the internal NLS and
CC contributes to a high affinity for cytoplasmic NLS-containing cargo
CC substrates. After dissociation of the importin/substrate complex in the
CC nucleus the internal autohibitory NLS contributes to a low affinity for
CC nuclear NLS-containing proteins (By similarity).
CC {ECO:0000250|UniProtKB:P52293}.
CC -!- DOMAIN: The major and minor NLS binding sites are mainly involved in
CC recognition of simple or bipartite NLS motifs. Structurally located
CC within in a helical surface groove they contain several conserved Trp
CC and Asn residues of the corresponding third helices (H3) of ARM repeats
CC which mainly contribute to binding (By similarity).
CC {ECO:0000250|UniProtKB:P52293}.
CC -!- PTM: Polyubiquitinated in the presence of RAG1 (in vitro).
CC {ECO:0000250|UniProtKB:P52294}.
CC -!- SIMILARITY: Belongs to the importin alpha family. {ECO:0000305}.
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DR EMBL; U34228; AAC52450.1; -; mRNA.
DR EMBL; AK028259; BAC25847.1; -; mRNA.
DR EMBL; AK028307; BAC25872.1; -; mRNA.
DR EMBL; AK154800; BAE32838.1; -; mRNA.
DR EMBL; AK169311; BAE41066.1; -; mRNA.
DR EMBL; AK169348; BAE41098.1; -; mRNA.
DR EMBL; BC006771; AAH06771.1; -; mRNA.
DR EMBL; U20619; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS28144.1; -.
DR RefSeq; NP_032491.2; NM_008465.5.
DR RefSeq; XP_006521877.1; XM_006521814.3.
DR AlphaFoldDB; Q60960; -.
DR SMR; Q60960; -.
DR BioGRID; 201006; 20.
DR ComplexPortal; CPX-1056; Importin complex, KPNA1 variant.
DR DIP; DIP-48614N; -.
DR IntAct; Q60960; 5.
DR MINT; Q60960; -.
DR STRING; 10090.ENSMUSP00000004054; -.
DR GlyGen; Q60960; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q60960; -.
DR PhosphoSitePlus; Q60960; -.
DR EPD; Q60960; -.
DR jPOST; Q60960; -.
DR MaxQB; Q60960; -.
DR PaxDb; 10090-ENSMUSP00000004054; -.
DR PeptideAtlas; Q60960; -.
DR ProteomicsDB; 267240; -.
DR Pumba; Q60960; -.
DR Antibodypedia; 32899; 421 antibodies from 39 providers.
DR DNASU; 16646; -.
DR Ensembl; ENSMUST00000004054.13; ENSMUSP00000004054.7; ENSMUSG00000022905.13.
DR GeneID; 16646; -.
DR KEGG; mmu:16646; -.
DR UCSC; uc007zcb.1; mouse.
DR AGR; MGI:103560; -.
DR CTD; 3836; -.
DR MGI; MGI:103560; Kpna1.
DR VEuPathDB; HostDB:ENSMUSG00000022905; -.
DR eggNOG; KOG0166; Eukaryota.
DR GeneTree; ENSGT01050000244950; -.
DR HOGENOM; CLU_018084_6_0_1; -.
DR InParanoid; Q60960; -.
DR OMA; GGFHETQ; -.
DR OrthoDB; 916229at2759; -.
DR PhylomeDB; Q60960; -.
DR TreeFam; TF354205; -.
DR Reactome; R-MMU-140342; Apoptosis induced DNA fragmentation.
DR Reactome; R-MMU-68616; Assembly of the ORC complex at the origin of replication.
DR Reactome; R-MMU-909733; Interferon alpha/beta signaling.
DR BioGRID-ORCS; 16646; 0 hits in 76 CRISPR screens.
DR ChiTaRS; Kpna1; mouse.
DR PRO; PR:Q60960; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q60960; Protein.
DR Bgee; ENSMUSG00000022905; Expressed in triceps brachii and 276 other cell types or tissues.
DR ExpressionAtlas; Q60960; baseline and differential.
DR Genevisible; Q60960; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0042564; C:NLS-dependent protein nuclear import complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0061608; F:nuclear import signal receptor activity; ISO:MGI.
DR GO; GO:0008139; F:nuclear localization sequence binding; ISO:MGI.
DR GO; GO:0006607; P:NLS-bearing protein import into nucleus; IMP:MGI.
DR GO; GO:0099527; P:postsynapse to nucleus signaling pathway; IDA:SynGO.
DR GO; GO:0006606; P:protein import into nucleus; ISS:ComplexPortal.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:MGI.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IMP:MGI.
DR GO; GO:0014901; P:satellite cell activation involved in skeletal muscle regeneration; IMP:MGI.
DR GO; GO:0014841; P:skeletal muscle satellite cell proliferation; IMP:MGI.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IMP:MGI.
DR Gene3D; 1.20.5.690; Importin-alpha, importin-beta-binding domain; 1.
DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR032413; Arm_3.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR002652; Importin-a_IBB.
DR InterPro; IPR036975; Importin-a_IBB_sf.
DR InterPro; IPR024931; Importin_alpha.
DR PANTHER; PTHR23316; IMPORTIN ALPHA; 1.
DR PANTHER; PTHR23316:SF3; IMPORTIN SUBUNIT ALPHA-5; 1.
DR Pfam; PF00514; Arm; 8.
DR Pfam; PF16186; Arm_3; 1.
DR Pfam; PF01749; IBB; 1.
DR PIRSF; PIRSF005673; Importin_alpha; 1.
DR SMART; SM00185; ARM; 8.
DR SUPFAM; SSF48371; ARM repeat; 1.
DR PROSITE; PS50176; ARM_REPEAT; 3.
DR PROSITE; PS51214; IBB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transport; Ubl conjugation.
FT CHAIN 1..538
FT /note="Importin subunit alpha-5"
FT /id="PRO_0000120720"
FT DOMAIN 1..57
FT /note="IBB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00561"
FT REPEAT 77..117
FT /note="ARM 1; truncated"
FT REPEAT 118..161
FT /note="ARM 2"
FT REPEAT 162..206
FT /note="ARM 3"
FT REPEAT 207..245
FT /note="ARM 4"
FT REPEAT 246..290
FT /note="ARM 5"
FT REPEAT 291..330
FT /note="ARM 6"
FT REPEAT 331..372
FT /note="ARM 7"
FT REPEAT 373..412
FT /note="ARM 8"
FT REPEAT 413..457
FT /note="ARM 9"
FT REPEAT 460..504
FT /note="ARM 10; atypical"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 149..241
FT /note="NLS binding site (major)"
FT /evidence="ECO:0000250|UniProtKB:P52293"
FT REGION 245..437
FT /note="Binding to RAG1"
FT /evidence="ECO:0000250|UniProtKB:P52294"
FT REGION 318..406
FT /note="NLS binding site (minor)"
FT /evidence="ECO:0000250|UniProtKB:P52293"
FT MOTIF 42..51
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P52293"
FT COMPBIAS 10..41
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P52294"
FT MOD_RES 3
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P52294"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P52294"
FT CONFLICT 83
FT /note="I -> T (in Ref. 1; AAC52450)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 538 AA; 60183 MW; 8FE16ACA99F2BA4F CRC64;
MSTPGKENFR LKSYKNKSLN PDEMRRRREE EGLQLRKQKR EEQLFKRRNV ATAEEETEEE
VMSDGGFHEA QINNMEMAPG GVITSDMTDM IFSNSPEQQL SATQKFRKLL SKEPNPPIDE
VINTPGVVAR FVEFLKRKEN CTLQFESAWV LTNIASGNSL QTRNVIQAGA VPIFIELLSS
EFEDVQEQAV WALGNIAGDS TMCRDYVLNC NILPPLLQLF SKQNRLTMTR NAVWALSNLC
RGKSPPPEFA KVSPCLNVLS WLLFVSDTDV LADACWALSY LSDGPNDKIQ AVIDAGVCRR
LVELLMHNDY KVVSPALRAV GNIVTGDDIQ TQVILNCSAL QSLLHLLSSP KESIKKEACW
TISNITAGNR AQIQTVIDAN MFPALISILQ TAEFRTRKEA AWAITNATSG GSAEQIKYLV
ELGCIKPLCD LLTVMDAKIV QVALNGLENI LRLGEQEAKR NGSGINPYCA LIEEAYGLDK
IEFLQSHENQ EIYQKAFDLI EHYFGTEDED SSIAPQVDLS QQQYIFQQCE APMEGFQL
//
