ID IMA2_HUMAN STANDARD; PRT; 529 AA. AC P52292; Q9BRU5; DT 01-OCT-1996 (Rel. 34, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 01-OCT-2004 (Rel. 45, Last annotation update) DE Importin alpha-2 subunit (Karyopherin alpha-2 subunit) (SRP1-alpha) DE (RAG cohort protein 1). GN Name=KPNA2; Synonyms=RCH1, SRP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=95273975; PubMed=7754385; RA Weis K., Mattaj I.W., Lamond A.I.; RT "Identification of hSRP1 alpha as a functional receptor for nuclear RT localization sequences."; RL Science 268:1049-1053(1995). RN [2] RP SEQUENCE FROM N.A., AND VARIANT ARG-165. RX MEDLINE=21592389; PubMed=11735022; DOI=10.1007/s004390100605; RA Doerr S., Schlicker M., Hansmann I.; RT "Genomic structure of karyopherin alpha2 (KPNA2) within a low-copy RT repeat on chromosome 17q23-q24 and mutation analysis in patients with RT Russell-Silver syndrome."; RL Hum. Genet. 109:479-486(2001). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Bone marrow; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP SEQUENCE OF 33-529 FROM N.A. RC TISSUE=Cervical carcinoma; RX MEDLINE=94286596; PubMed=8016130; RA Cuomo C.A., Kirch S.A., Gyuris J., Brent R., Oettinger M.A.; RT "Rch1, a protein that specifically interacts with the RAG-1 RT recombination-activating protein."; RL Proc. Natl. Acad. Sci. U.S.A. 91:6156-6160(1994). RN [5] RP FUNCTIONAL SUBSTITUTION OF ALPHA-1 BY ALPHA-2 SUBUNIT. RX MEDLINE=95327681; PubMed=7604027; RA Moroianu J., Hijikata M., Blobel G., Radu A.; RT "Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: RT alpha 1 or alpha 2 subunit binds nuclear localization signal and beta RT subunit interacts with peptide repeat-containing nucleoporins."; RL Proc. Natl. Acad. Sci. U.S.A. 92:6532-6536(1995). RN [6] RP IDENTIFICATION OF IBB DOMAIN. RX MEDLINE=96203102; PubMed=8617227; RA Weis K., Ryder U., Lamond A.I.; RT "The conserved amino-terminal domain of hSRP1 alpha is essential for RT nuclear protein import."; RL EMBO J. 15:1818-1825(1996). RN [7] RP INTERACTION WITH CSEIL. RX PubMed=9786944; RA Herold A., Truant R., Wiegand H., Cullen B.R.; RT "Determination of the functional domain organization of the importin RT alpha nuclear import factor."; RL J. Cell Biol. 143:309-318(1998). RN [8] RP MASS SPECTROMETRY. RC TISSUE=Breast cancer; RX MEDLINE=21829512; PubMed=11840567; RX DOI=10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H; RA Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., RA Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., RA Zvelebil M.J.; RT "Cluster analysis of an extensive human breast cancer cell line RT protein expression map database."; RL Proteomics 2:212-223(2002). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 11-54. RX PubMed=10353244; DOI=10.1038/20367; RA Cingolani G., Petosa C., Weis K., Muller C.W.; RT "Structure of importin-beta bound to the IBB domain of importin- RT alpha."; RL Nature 399:221-229(1999). CC -!- FUNCTION: Functions in nuclear protein import as an adapter CC protein for nuclear receptor KPNB1. Binds specifically and CC directly to substrates containing either a simple or bipartite NLS CC motif. Docking of the importin/substrate complex to the nuclear CC pore complex (NPC) is mediated by KPNB1 through binding to CC nucleoporin FxFG repeats and the complex is subsequently CC translocated through the pore by an energy requiring, Ran- CC dependent mechanism. At the nucleoplasmic side of the NPC, Ran CC binds to importin-beta and the three components separate and CC importin-alpha and -beta are re-exported from the nucleus to the CC cytoplasm where GTP hydrolysis releases Ran from importin. 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 CC between the cytoplasm and nucleus. CC -!- SUBUNIT: Forms a complex with importin beta-1 subunit. Interacts CC with CSEIL. CC -!- SUBCELLULAR LOCATION: Cytoplasmic and nuclear. CC -!- TISSUE SPECIFICITY: Expressed ubiquitously. CC -!- DOMAIN: Consists of an N-terminal hydrophilic region, a CC hydrophobic central region composed of 10 repeats, and a short CC hydrophilic C-terminus. The N-terminal hydrophilic region contains CC the importin beta binding domain (IBB domain), which is sufficient CC for binding importin beta and essential for nuclear protein CC import. CC -!- DOMAIN: The IBB domain is thought to act as an intrasteric CC autoregulatory sequence by interacting with the internal CC autoinhibitory NLS. Binding of KPNB1 probably overlaps the CC internal NLS and contributes to a high affinity for cytoplasmic CC NLS-containing cargo substrates. After dissociation of the CC importin/substrate complex in the nucleus the internal CC autohibitory NLS contributes to a low affinity for nuclear NLS- CC containing proteins (By similarity). CC -!- DOMAIN: The major and minor NLS binding sites are mainly involved CC in recognition of simple or bipartite NLS motifs. Structurally CC located within in a helical surface groove they contain several CC conserved Trp and Asn residues of the corresponding third helices CC (H3) of ARM repeats which mainly contribute to binding (By CC similarity). CC -!- MASS SPECTROMETRY: MW=57861.92; METHOD=MALDI; RANGE=1-529; CC NOTE=Ref.8. CC -!- SIMILARITY: Belongs to the importin alpha family. CC -!- SIMILARITY: Contains 10 ARM repeats. 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; U28386; AAA69957.1; -. DR EMBL; AJ303086; CAC83080.1; -. DR EMBL; BC005978; AAH05978.1; -. DR EMBL; U09559; AAA65700.1; -. DR PIR; A56516; A56516. DR PDB; 1EFX; X-ray; C=204-212. DR PDB; 1QGK; X-ray; B=11-54. DR PDB; 1QGR; X-ray; B=28-54. DR IntAct; P52292; -. DR SWISS-2DPAGE; P52292; HUMAN. DR Genew; HGNC:6395; KPNA2. DR MIM; 600685; -. DR GO; GO:0005737; C:cytoplasm; TAS. DR GO; GO:0005654; C:nucleoplasm; TAS. DR GO; GO:0008139; F:nuclear localization sequence binding; TAS. DR GO; GO:0005515; F:protein binding; TAS. DR GO; GO:0006259; P:DNA metabolism; TAS. DR GO; GO:0000085; P:G2 phase of mitotic cell cycle; TAS. DR GO; GO:0000072; P:M-phase specific microtubule process; TAS. DR GO; GO:0006607; P:NLS-bearing substrate-nucleus import; TAS. DR GO; GO:0000018; P:regulation of DNA recombination; TAS. DR InterPro; IPR008938; ARM. DR InterPro; IPR000225; Armadillo. DR InterPro; IPR002652; ImportinA_B. DR Pfam; PF00514; Arm; 8. DR Pfam; PF01749; IBB; 1. DR PROSITE; PS50176; ARM_REPEAT; 5. KW 3D-structure; Nuclear protein; Polymorphism; Protein transport; KW Repeat; Transport. FT DOMAIN 13 53 IBB. FT DOMAIN 45 54 Nuclear localization signal (By FT similarity). FT DOMAIN 142 238 NLS binding site (Major) (By similarity). FT DOMAIN 315 403 NLS binding site (Minor) (By similarity). FT REPEAT 71 111 ARM 1 (incomplete). FT REPEAT 112 151 ARM 2. FT REPEAT 152 193 ARM 3. FT REPEAT 200 244 ARM 4. FT REPEAT 246 282 ARM 5. FT REPEAT 283 322 ARM 6. FT REPEAT 325 364 ARM 7. FT REPEAT 367 409 ARM 8. FT REPEAT 410 456 ARM 9. FT REPEAT 457 496 ARM 10 (atypical). FT DOMAIN 28 31 Poly-Arg. FT DOMAIN 499 502 Poly-Glu. FT VARIANT 165 165 P -> R. FT /FTId=VAR_013137. FT VARIANT 430 430 T -> P (in dbSNP:1059538). FT /FTId=VAR_014453. FT CONFLICT 157 157 A -> V (in Ref. 3). FT CONFLICT 453 453 K -> N (in Ref. 3). FT HELIX 30 48 FT TURN 49 50 SQ SEQUENCE 529 AA; 57861 MW; B0F94A0475B80EED CRC64; MSTNENANTP AARLHRFKNK GKDSTEMRRR RIEVNVELRK AKKDDQMLKR RNVSSFPDDA TSPLQENRNN QGTVNWSVDD IVKGINSSNV ENQLQATQAA RKLLSREKQP PIDNIIRAGL IPKFVSFLGR TDCSPIQFES AWALTNIASG TSEQTKAVVD GGAIPAFISL LASPHAHISE QAVWALGNIA GDGSVFRDLV IKYGAVDPLL ALLAVPDMSS LACGYLRNLT WTLSNLCRNK NPAPPIDAVE QILPTLVRLL HHDDPEVLAD TCWAISYLTD GPNERIGMVV KTGVVPQLVK LLGASELPIV TPALRAIGNI VTGTDEQTQV VIDAGALAVF PSLLTNPKTN IQKEATWTMS NITAGRQDQI QQVVNHGLVP FLVSVLSKAD FKTQKEAVWA VTNYTSGGTV EQIVYLVHCG IIEPLMNLLT AKDTKIILVI LDAISNIFQA AEKLGETEKL SIMIEECGGL DKIEALQNHE NESVYKASLS LIEKYFSVEE EEDQNVVPET TSEGYTFQVQ DGAPGTFNF //