P42167 (LAP2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lamina-associated polypeptide 2, isoforms beta/gamma

Alternative name(s):
Thymopoietin, isoforms beta/gamma
Short name=TP beta/gamma
Thymopoietin-related peptide isoforms beta/gamma
Short name=TPRP isoforms beta/gamma

Cleaved into the following 2 chains:

1. Thymopoietin
   Short name=TP
   Alternative name(s):
   Splenin
2. Thymopentin
   Alternative name(s):
   TP5

Gene names

Name:	TMPO
Synonyms:	LAP2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	454 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May help direct the assembly of the nuclear lamina and thereby help maintain the structural organization of the nuclear envelope. Possible receptor for attachment of lamin filaments to the inner nuclear membrane. May be involved in the control of initiation of DNA replication through its interaction with NAKAP95. TP and TP5 may play a role in T-cell development and function. TP5 is an immunomodulating pentapeptide.
Subunit structure	Interacts with LMNB1, LMNB2, BANF1, AKAP8L, GMCL and chromosomes By similarity. Ref.5 Ref.6
Subcellular location	Nucleus inner membrane; Single-pass type II membrane protein. Note: Tightly associated with the nuclear lamina.
Tissue specificity	Expressed in many tissues. Most abundant in adult thymus and fetal liver.
Domain	Has two structurally independent, non-interacting domains: LEM-like (also called LAP2-N or LEM-D) and LEM (also called LAP2-C or LEM-B). LEM-like binds DNA while LEM interacts with BANF1.
Post-translational modification	Mitosis-specific phosphorylation specifically abolishes its binding to lamin B and chromosomes By similarity.
Pharmaceutical use	TP5 is available under the names Timunox (Cilag), Sintomodulina (Italofarmaco) and Mepentil (Recordati). Used in primary and secondary immune deficiencies, autoimmunity, infections and cancer.
Sequence similarities	Belongs to the LEM family. Contains 1 LEM domain. Contains 1 LEM-like domain.

Ontologies

Keywords
Cellular component	Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	Complete proteome Pharmaceutical Reference proteome
Gene Ontology (GO)
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nuclear envelope Traceable author statement Ref.4. Source: ProtInc nuclear inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW lamin binding Traceable author statement Ref.4. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-455283,EBI-389883

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform Beta (identifier: P42167-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Alpha (identifier: P42166-1)

The sequence of this isoform can be found in the external entry P42166.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Isoform Gamma (identifier: P42167-2)

The sequence of this isoform differs from the canonical sequence as follows:
     222-330: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 454	454	Lamina-associated polypeptide 2, isoforms beta/gamma		PRO_0000045841
	Peptide	1 – 50	50	Thymopoietin		PRO_0000017677
	Peptide	33 – 37	5	Thymopentin		PRO_0000017678
Regions
	Transmembrane	411 – 434	24	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	435 – 454	20	Lumenal Potential
	Domain	5 – 48	44	LEM-like
	Domain	109 – 153	45	LEM
	Region	1 – 410	410	Nucleoplasmic Potential
	Region	49 – 108	60	Linker
	Region	138 – 243	106	NAKAP95-binding N
	Region	299 – 371	73	Binds lamins B
	Region	300 – 374	75	NAKAP95-binding C
Amino acid modifications
	Modified residue	66	1	Phosphoserine By similarity
	Modified residue	67	1	Phosphoserine By similarity
	Modified residue	74	1	Phosphothreonine By similarity
	Modified residue	156	1	Phosphoserine By similarity
	Modified residue	160	1	Phosphothreonine By similarity
	Modified residue	177	1	Phosphoserine Ref.13
	Modified residue	180	1	Phosphoserine Ref.13
	Modified residue	184	1	Phosphoserine Ref.17
	Modified residue	208	1	Phosphothreonine Ref.15
	Modified residue	211	1	Phosphothreonine Ref.15
	Modified residue	265	1	Phosphoserine Ref.15
	Modified residue	292	1	Phosphoserine Ref.14
	Modified residue	306	1	Phosphoserine Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
	Modified residue	312	1	Phosphothreonine Ref.15
	Modified residue	315	1	Phosphoserine Ref.11 Ref.13 Ref.15
	Modified residue	362	1	Phosphoserine Ref.13
	Modified residue	385	1	Phosphoserine Ref.13
Natural variations
	Alternative sequence	222 – 330	109	Missing in isoform Gamma.		VSP_004456
	Natural variant	287	1	A → P. Corresponds to variant rs7133258 [ dbSNP | Ensembl ].		VAR_049779
	Natural variant	427	1	L → F. Corresponds to variant rs1058288 [ dbSNP | Ensembl ].		VAR_014786

Sequences

	Sequence		Length	Mass (Da)
	Isoform Beta [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 03277C5723117909	FASTA	454	50,670
	10 20 30 40 50 60 MPEFLEDPSV LTKDKLKSEL VANNVTLPAG EQRKDVYVQL YLQHLTARNR PPLPAGTNSK 70 80 90 100 110 120 GPPDFSSDEE REPTPVLGSG AAAAGRSRAA VGRKATKKTD KPRQEDKDDL DVTELTNEDL 130 140 150 160 170 180 LDQLVKYGVN PGPIVGTTRK LYEKKLLKLR EQGTESRSST PLPTISSSAE NTRQNGSNDS 190 200 210 220 230 240 DRYSDNEEDS KIELKLEKRE PLKGRAKTPV TLKQRRVEHN QSYSQAGITE TEWTSGSSKG 250 260 270 280 290 300 GPLQALTRES TRGSRRTPRK RVETSEHFRI DGPVISESTP IAETIMASSN ESLVVNRVTG 310 320 330 340 350 360 NFKHASPILP ITEFSDIPRR APKKPLTRAE VGEKTEERRV ERDILKEMFP YEASTPTGIS 370 380 390 400 410 420 ASCRRPIKGA AGRPLELSDF RMEESFSSKY VPKYVPLADV KSEKTKKGRS IPVWIKILLF 430 440 450 VVVAVFLFLV YQAMETNQVN PFSNFLHVDP RKSN
	Isoform Alpha [UniParc]. See P42166.		–	–
	Isoform Gamma [UniParc]. Checksum: F0669D9AEF97B32E	FASTA	345	38,738
	10 20 30 40 50 60 MPEFLEDPSV LTKDKLKSEL VANNVTLPAG EQRKDVYVQL YLQHLTARNR PPLPAGTNSK 70 80 90 100 110 120 GPPDFSSDEE REPTPVLGSG AAAAGRSRAA VGRKATKKTD KPRQEDKDDL DVTELTNEDL 130 140 150 160 170 180 LDQLVKYGVN PGPIVGTTRK LYEKKLLKLR EQGTESRSST PLPTISSSAE NTRQNGSNDS 190 200 210 220 230 240 DRYSDNEEDS KIELKLEKRE PLKGRAKTPV TLKQRRVEHN QVGEKTEERR VERDILKEMF 250 260 270 280 290 300 PYEASTPTGI SASCRRPIKG AAGRPLELSD FRMEESFSSK YVPKYVPLAD VKSEKTKKGR 310 320 330 340 SIPVWIKILL FVVVAVFLFL VYQAMETNQV NPFSNFLHVD PRKSN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Three distinct human thymopoietins are derived from alternatively spliced mRNAs." Harris C.A., Andryuk P.J., Cline S.W., Chan H.K., Natarajan A., Siekierka J.J., Goldstein G. Proc. Natl. Acad. Sci. U.S.A. 91:6283-6287(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA). Tissue: Thymus.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA). Tissue: Eye.
[3]	Yu W., Gibbs R.A. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA). Tissue: Brain.
[4]	"Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO beta to rat lamin-associated polypeptide 2." Harris C.A., Andryuk P.J., Cline S.W., Siekierka J.J., Goldstein G. Genomics 28:198-205(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-237 AND 313-454 (ISOFORMS BETA AND GAMMA).
[5]	"Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin." Furukawa K., Kondo T. Eur. J. Biochem. 251:729-733(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LMNB1.
[6]	"HA95 and LAP2 beta mediate a novel chromatin-nuclear envelope interaction implicated in initiation of DNA replication." Martins S., Eikvar S., Furukawa K., Collas P. J. Cell Biol. 160:177-188(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AKAP8L.
[7]	"Review: lamina-associated polypeptide 2 isoforms and related proteins in cell cycle-dependent nuclear structure dynamics." Dechat T., Vlcek S., Foisner R. J. Struct. Biol. 129:335-345(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction." Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R. Mol. Cell. Proteomics 6:1952-1967(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[11]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306 AND SER-315, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177; SER-180; SER-306; SER-315; SER-362 AND SER-385, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292 AND SER-306, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-208; THR-211; SER-265; SER-306; THR-312 AND SER-315, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184, MASS SPECTROMETRY.
[18]	"Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA." Cai M., Huang Y., Ghirlando R., Wilson K.L., Craigie R., Clore G.M. EMBO J. 20:4399-4407(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-169.
[19]	"Structural characterization of the LEM motif common to three human inner nuclear membrane proteins." Laguri C., Gilquin B., Wolff N., Romi-Lebrun R., Courchay K., Callebaut I., Worman H.J., Zinn-Justin S. Structure 9:503-511(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-57 AND 103-159.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U09087 mRNA. Translation: AAB60330.1. U09088 mRNA. Translation: AAB60331.1. BC053675 mRNA. Translation: AAH53675.1. AF070631 mRNA. Translation: AAC25390.1. U18269 , U18266, U18267, U18268, U18270 Genomic DNA. Translation: AAB60434.1. U18271 Genomic DNA. Translation: AAB60435.1.
IPI	IPI00030131. IPI00181409.
PIR	B55741. C55741.
RefSeq	NP_001027454.1. NM_001032283.2. NP_001027455.1. NM_001032284.2.
UniGene	Hs.11355.
3D structure databases
ProteinModelPortal	P42167.
ModBase	Search...
Protein-protein interaction databases
IntAct	P42167. 7 interactions.
MINT	MINT-2839042.
PTM databases
PhosphoSite	P42167.
Polymorphism databases
DMDM	1174690.
Proteomic databases
PeptideAtlas	P42167.
PRIDE	P42167.
Protocols and materials databases
DNASU	7112.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000393053; ENSP00000376773; ENSG00000120802. ENST00000556029; ENSP00000450627; ENSG00000120802.
GeneID	7112.
KEGG	hsa:7112.
UCSC	uc001tfj.3. human. uc001tfk.3. human.
Organism-specific databases
CTD	7112.
GeneCards	GC12P098909.
HGNC	HGNC:11875. TMPO.
HPA	CAB009847. HPA008150.
MIM	188380. gene.
neXtProt	NX_P42167.
PharmGKB	PA36576.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HOG000113280.
HOVERGEN	HBG000166.
OMA	TGNFKHA.
Gene expression databases
ArrayExpress	P42167.
Bgee	P42167.
CleanEx	HS_TMPO.
Genevestigator	P42167.
GermOnline	ENSG00000120802. Homo sapiens.
Family and domain databases
Gene3D	1.10.720.40. 2 hits.
InterPro	IPR013146. LEM-like_dom. IPR011015. LEM/LEM-like_dom. IPR003887. LEM_dom. [Graphical view]
Pfam	PF03020. LEM. 1 hit. PF08198. Thymopoietin. 1 hit. [Graphical view]
SMART	SM00540. LEM. 1 hit. [Graphical view]
SUPFAM	SSF63451. LEM_like. 2 hits.
PROSITE	PS50954. LEM. 1 hit. PS50955. LEM_LIKE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TMPO. human.
GenomeRNAi	7112.
NextBio	27839.
PMAP-CutDB	P42167.
SOURCE	Search...

Entry information

Entry name

LAP2B_HUMAN

Accession

Primary (citable) accession number: P42167
Secondary accession number(s): Q14861

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 138 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.