ID   LAP2B_HUMAN    STANDARD;      PRT;   453 AA.
AC   P42167; Q14861;
DT   01-NOV-1995 (Rel. 32, Created)
DT   01-NOV-1995 (Rel. 32, Last sequence update)
DT   24-JAN-2006 (Rel. 49, Last annotation update)
DE   Lamina-associated polypeptide 2, isoforms beta/gamma (Thymopoietin,
DE   isoforms beta/gamma) (TP beta/gamma) (Thymopoietin-related peptide
DE   isoforms beta/gamma) (TPRP isoforms beta/gamma) [Contains:
DE   Thymopoietin (TP) (Splenin); Thymopentin (TP5)].
GN   Name=TMPO; Synonyms=LAP2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE (ISOFORMS ALPHA; BETA AND GAMMA).
RC   TISSUE=Thymus;
RX   MEDLINE=94294366; PubMed=7517549;
RA   Harris C.A., Andryuk P.J., Cline S.W., Chan H.K., Natarajan A.,
RA   Siekierka J.J., Goldstein G.;
RT   "Three distinct human thymopoietins are derived from alternatively
RT   spliced mRNAs.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:6283-6287(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
RC   TISSUE=Eye;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA).
RC   TISSUE=Brain;
RA   Yu W., Gibbs R.A.;
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE OF 1-236 AND 312-453 (ISOFORMS BETA AND GAMMA).
RX   MEDLINE=96015047; PubMed=8530026;
RA   Harris C.A., Andryuk P.J., Cline S.W., Siekierka J.J., Goldstein G.;
RT   "Structure and mapping of the human thymopoietin (TMPO) gene and
RT   relationship of human TMPO beta to rat lamin-associated polypeptide
RT   2.";
RL   Genomics 28:198-205(1995).
RN   [5]
RP   INTERACTION WITH LMNB1.
RX   PubMed=9490046;
RA   Furukawa K., Kondo T.;
RT   "Identification of the lamina-associated-polypeptide-2-binding domain
RT   of B-type lamin.";
RL   Eur. J. Biochem. 251:729-733(1998).
RN   [6]
RP   INTERACTION WITH NAKAP95.
RX   PubMed=12538639; DOI=10.1083/jcb.200210026;
RA   Martins S., Eikvar S., Furukawa K., Collas P.;
RT   "HA95 and LAP2 beta mediate a novel chromatin-nuclear envelope
RT   interaction implicated in initiation of DNA replication.";
RL   J. Cell Biol. 160:177-188(2003).
RN   [7]
RP   TOPOLOGY.
RX   PubMed=10806084; DOI=10.1006/jsbi.2000.4212;
RA   Dechat T., Vlcek S., Foisner R.;
RT   "Review: lamina-associated polypeptide 2 isoforms and related proteins
RT   in cell cycle-dependent nuclear structure dynamics.";
RL   J. Struct. Biol. 129:335-345(2000).
RN   [8]
RP   STRUCTURE BY NMR OF 1-168.
RX   PubMed=11500367; DOI=10.1093/emboj/20.16.4399;
RA   Cai M., Huang Y., Ghirlando R., Wilson K.L., Craigie R., Clore G.M.;
RT   "Solution structure of the constant region of nuclear envelope protein
RT   LAP2 reveals two LEM-domain structures: one binds BAF and the other
RT   binds DNA.";
RL   EMBO J. 20:4399-4407(2001).
RN   [9]
RP   STRUCTURE BY NMR OF 1-56 AND 102-158.
RX   MEDLINE=21345418; PubMed=11435115; DOI=10.1016/S0969-2126(01)00611-6;
RA   Laguri C., Gilquin B., Wolff N., Romi-Lebrun R., Courchay K.,
RA   Callebaut I., Worman H.J., Zinn-Justin S.;
RT   "Structural characterization of the LEM motif common to three human
RT   inner nuclear membrane proteins.";
RL   Structure 9:503-511(2001).
CC   -!- FUNCTION: May help direct the assembly of the nuclear lamina and
CC       thereby help maintain the structural organization of the nuclear
CC       envelope. Possible receptor for attachment of lamin filaments to
CC       the inner nuclear membrane. May be involved in the control of
CC       initiation of DNA replication through its interaction with
CC       NAKAP95.
CC   -!- FUNCTION: TP and TP5 may play a role in T-cell development and
CC       function. TP5 is an immunomodulating pentapeptide.
CC   -!- SUBUNIT: Interacts with LMNB1, LMNB2, BANF1, NAKAP95, GMCL and
CC       chromosomes (By similarity).
CC   -!- SUBCELLULAR LOCATION: Type II integral membrane; inner nuclear
CC       membrane. Tightly associated with the nuclear lamina.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC         Comment=Additional isoforms seem to exist;
CC       Name=Beta;
CC         IsoId=P42167-1; Sequence=Displayed;
CC       Name=Alpha;
CC         IsoId=P42166-1; Sequence=External;
CC       Name=Gamma;
CC         IsoId=P42167-2; Sequence=VSP_004456;
CC   -!- TISSUE SPECIFICITY: Expressed in many tissues. Most abundant in
CC       adult thymus and fetal liver.
CC   -!- DOMAIN: Has two structurally independent, non-interacting domains:
CC       LEM-like (also called LAP2-N or LEM-D) and LEM (also called LAP2-C
CC       or LEM-B). LEM-like binds DNA while LEM interacts with BANF1.
CC   -!- PTM: Mitosis-specific phosphorylation specifically abolishes its
CC       binding to lamin B and chromosomes (By similarity).
CC   -!- PHARMACEUTICAL: TP5 is available under the names Timunox (Cilag),
CC       Sintomodulina (Italofarmaco) and Mepentil (Recordati). Used in
CC       primary and secondary immune deficiencies, autoimmunity,
CC       infections and cancer.
CC   -!- SIMILARITY: Belongs to the LEM family.
CC   -!- SIMILARITY: Contains 1 LEM domain.
CC   -!- SIMILARITY: Contains 1 LEM-like domain.
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DR   EMBL; U09087; AAB60330.1; -; mRNA.
DR   EMBL; U09088; AAB60331.1; -; mRNA.
DR   EMBL; BC053675; AAH53675.1; -; mRNA.
DR   EMBL; AF070631; AAC25390.1; -; mRNA.
DR   EMBL; U18269; AAB60434.1; -; Genomic_DNA.
DR   EMBL; U18266; AAB60434.1; JOINED; Genomic_DNA.
DR   EMBL; U18267; AAB60434.1; JOINED; Genomic_DNA.
DR   EMBL; U18268; AAB60434.1; JOINED; Genomic_DNA.
DR   EMBL; U18270; AAB60434.1; JOINED; Genomic_DNA.
DR   EMBL; U18271; AAB60435.1; -; Genomic_DNA.
DR   PIR; B55741; B55741.
DR   PIR; C55741; C55741.
DR   PDB; 1GJJ; NMR; -.
DR   PDB; 1H9E; NMR; -.
DR   PDB; 1H9F; NMR; -.
DR   SMR; P42167; 1-56, 102-158.
DR   Ensembl; ENSG00000120802; Homo sapiens.
DR   HGNC; HGNC:11875; TMPO.
DR   MIM; 188380; -.
DR   LinkHub; P42167; -.
DR   GO; GO:0005635; C:nuclear membrane; TAS.
DR   GO; GO:0005521; F:lamin binding; TAS.
DR   InterPro; IPR003887; LEM.
DR   Pfam; PF03020; LEM; 1.
DR   ProDom; PD004209; LEM; 2.
DR   SMART; SM00540; LEM; 1.
DR   PROSITE; PS50954; LEM; 1.
DR   PROSITE; PS50955; LEM_LIKE; 1.
KW   3D-structure; Alternative splicing; Chromosomal protein; DNA-binding;
KW   Membrane; Nuclear protein; Pharmaceutical; Phosphorylation;
KW   Polymorphism; Signal-anchor; Transmembrane.
FT   INIT_MET      0      0       By similarity.
FT   PEPTIDE       1     49       Thymopoietin.
FT                                /FTId=PRO_0000017677.
FT   PEPTIDE      32     36       Thymopentin.
FT                                /FTId=PRO_0000017678.
FT   TRANSMEM    410    433       Signal-anchor for type II membrane
FT                                protein (Potential).
FT   TOPO_DOM    434    453       Lumenal (Potential).
FT   DOMAIN        4     47       LEM-like.
FT   DOMAIN      108    152       LEM.
FT   REGION        1    409       Nucleoplasmic (Potential).
FT   REGION       48    107       Linker.
FT   REGION      137    242       NAKAP95-binding N.
FT   REGION      298    370       Binds lamins B.
FT   REGION      299    373       NAKAP95-binding C.
FT   VARSPLIC    221    329       Missing (in isoform Gamma).
FT                                /FTId=VSP_004456.
FT   VARIANT     426    426       L -> F (in dbSNP:1058288).
FT                                /FTId=VAR_014786.
SQ   SEQUENCE   453 AA;  50539 MW;  CFD007EDB21C31FE CRC64;
     PEFLEDPSVL TKDKLKSELV ANNVTLPAGE QRKDVYVQLY LQHLTARNRP PLPAGTNSKG
     PPDFSSDEER EPTPVLGSGA AAAGRSRAAV GRKATKKTDK PRQEDKDDLD VTELTNEDLL
     DQLVKYGVNP GPIVGTTRKL YEKKLLKLRE QGTESRSSTP LPTISSSAEN TRQNGSNDSD
     RYSDNEEDSK IELKLEKREP LKGRAKTPVT LKQRRVEHNQ SYSQAGITET EWTSGSSKGG
     PLQALTREST RGSRRTPRKR VETSEHFRID GPVISESTPI AETIMASSNE SLVVNRVTGN
     FKHASPILPI TEFSDIPRRA PKKPLTRAEV GEKTEERRVE RDILKEMFPY EASTPTGISA
     SCRRPIKGAA GRPLELSDFR MEESFSSKYV PKYVPLADVK SEKTKKGRSI PVWIKILLFV
     VVAVFLFLVY QAMETNQVNP FSNFLHVDPR KSN
//