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UniProtKB - P42166 (LAP2A_HUMAN)

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Protein

Lamina-associated polypeptide 2, isoform alpha

Gene

TMPO

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

May be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly. Plays an important role, together with LMNA, in the nuclear anchorage of RB1.
TP and TP5 may play a role in T-cell development and function. TP5 is an immunomodulating pentapeptide.

Caution

TMPO was originally considered a good candidate for dilated cardiomyopathy, and variant Cys-290 has been reported to be a likely pathogenic mutation (PubMed:16247757). However, Cys-290 has a high allele frequency and individuals homozygous for the variant have been reported in ExAC database. Therefore, this variant has been reclassified as a likely benign polymorphism (PubMed:27896284).1 Publication1 Publication

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • DNA binding Source: UniProtKB-KW
  • lamin binding Source: ProtInc
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Lamina-associated polypeptide 2, isoform alpha
Alternative name(s):
Thymopoietin isoform alpha
Short name:
TP alpha
Thymopoietin-related peptide isoform alpha
Short name:
TPRP isoform alpha
Cleaved into the following 2 chains:
Thymopoietin
Short name:
TP
Alternative name(s):
Splenin
Thymopentin
Alternative name(s):
TP5
Gene namesi
Name:TMPO
Synonyms:LAP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000120802.13
HGNCiHGNC:11875 TMPO
MIMi188380 gene
neXtProtiNX_P42166

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Pharmaceutical usei

TP5 is available under the names Timunox (Cilag), Sintomodulina (Italofarmaco) and Mepentil (Recordati). Used in primary and secondary immune deficiencies, autoimmunity, infections and cancer.

Keywords - Diseasei

Cardiomyopathy

Organism-specific databases

DisGeNETi7112
GeneReviewsiTMPO
MalaCardsiTMPO
OpenTargetsiENSG00000120802
Orphaneti154 Familial isolated dilated cardiomyopathy
PharmGKBiPA36576

Polymorphism and mutation databases

BioMutaiDLC1
DMDMi1174689

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000176742 – 694Lamina-associated polypeptide 2, isoform alphaAdd BLAST693
PeptideiPRO_00000176752 – 50ThymopoietinAdd BLAST49
PeptideiPRO_000001767633 – 37Thymopentin5

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57PhosphothreonineCombined sources1
Modified residuei59PhosphoserineCombined sources1
Modified residuei66PhosphoserineCombined sources1
Modified residuei67PhosphoserineCombined sources1
Modified residuei74PhosphothreonineCombined sources1
Modified residuei79PhosphoserineCombined sources1
Modified residuei86Omega-N-methylarginineBy similarity1
Modified residuei88Omega-N-methylarginineBy similarity1
Modified residuei154PhosphothreonineCombined sources1
Modified residuei156PhosphoserineCombined sources1
Modified residuei159PhosphoserineBy similarity1
Modified residuei160PhosphothreonineCombined sources1
Modified residuei164PhosphothreonineCombined sources1
Modified residuei166PhosphoserineBy similarity1
Modified residuei168PhosphoserineCombined sources1
Modified residuei272PhosphoserineCombined sources1
Modified residuei312PhosphoserineCombined sources1
Modified residuei351PhosphoserineCombined sources1
Modified residuei354PhosphoserineCombined sources1
Modified residuei370PhosphoserineCombined sources1
Modified residuei424PhosphoserineCombined sources1
Modified residuei656N6-acetyllysineCombined sources1

Post-translational modificationi

Phosphorylated in a mitose-specific manner.1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiP42166
PaxDbiP42166
PeptideAtlasiP42166
PRIDEiP42166
ProteomicsDBi55488

PTM databases

iPTMnetiP42166
SwissPalmiP42166

Miscellaneous databases

PMAP-CutDBiP42166

Expressioni

Tissue specificityi

Expressed in many tissues. Most abundant in adult thymus and fetal liver.

Gene expression databases

BgeeiENSG00000120802
CleanExiHS_TMPO
ExpressionAtlasiP42166 baseline and differential
GenevisibleiP42166 HS

Organism-specific databases

HPAiCAB009847

Interactioni

Subunit structurei

Interacts with LMNA, BANF1 and RB1 and with chromosomes. Associates directly or indirectly with lamins at specific cell-cycle stages. Interacts with CMTM6 (PubMed:28813417).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LMNAP025454EBI-395393,EBI-351935

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • lamin binding Source: ProtInc
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112967, 117 interactors
IntActiP42166, 39 interactors
MINTiP42166
STRINGi9606.ENSP00000266732

Structurei

Secondary structure

1694
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 11Combined sources4
Helixi13 – 22Combined sources10
Beta strandi29 – 31Combined sources3
Helixi34 – 39Combined sources6
Turni40 – 42Combined sources3
Beta strandi43 – 45Combined sources3
Turni46 – 48Combined sources3
Beta strandi113 – 115Combined sources3
Helixi117 – 122Combined sources6
Beta strandi123 – 125Combined sources3
Turni126 – 128Combined sources3
Beta strandi136 – 138Combined sources3
Helixi139 – 145Combined sources7
Helixi147 – 152Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GJJNMR-A1-168[»]
1H9ENMR-A2-57[»]
1H9FNMR-A103-159[»]
ProteinModelPortaliP42166
SMRiP42166
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42166

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 48LEM-likePROSITE-ProRule annotationAdd BLAST44
Domaini109 – 153LEMPROSITE-ProRule annotationAdd BLAST45

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni49 – 108LinkerAdd BLAST60

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili558 – 657By similarityAdd BLAST100

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi190 – 196Nuclear localization signalSequence analysis7

Domaini

The N-terminal part contains 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.
The C-terminal domain forms a four-stranded coiled coil.By similarity

Sequence similaritiesi

Belongs to the LEM family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IT7C Eukaryota
ENOG4111J0N LUCA
GeneTreeiENSGT00510000048934
HOGENOMiHOG000060228
HOVERGENiHBG081890
InParanoidiP42166
OrthoDBiEOG091G03A8
PhylomeDBiP42166
TreeFamiTF328426

Family and domain databases

Gene3Di1.10.720.40, 2 hits
InterProiView protein in InterPro
IPR021623 LAP2alpha_C
IPR013146 LEM-like_dom
IPR011015 LEM/LEM-like_dom_sf
IPR003887 LEM_dom
PfamiView protein in Pfam
PF11560 LAP2alpha, 1 hit
PF03020 LEM, 1 hit
PF08198 Thymopoietin, 1 hit
SMARTiView protein in SMART
SM00540 LEM, 1 hit
SM01261 Thymopoietin, 1 hit
SUPFAMiSSF63451 SSF63451, 2 hits
PROSITEiView protein in PROSITE
PS50954 LEM, 1 hit
PS50955 LEM_LIKE, 1 hit

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform Alpha (identifier: P42166-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPEFLEDPSV LTKDKLKSEL VANNVTLPAG EQRKDVYVQL YLQHLTARNR 
        60         70         80         90        100
PPLPAGTNSK GPPDFSSDEE REPTPVLGSG AAAAGRSRAA VGRKATKKTD 
       110        120        130        140        150
KPRQEDKDDL DVTELTNEDL LDQLVKYGVN PGPIVGTTRK LYEKKLLKLR 
       160        170        180        190        200
EQGTESRSST PLPTISSSAE NTRQNGSNDS DRYSDNEEGK KKEHKKVKST 
       210        220        230        240        250
RDIVPFSELG TTPSGGGFFQ GISFPEISTR PPLGSTELQA AKKVHTSKGD 
       260        270        280        290        300
LPREPLVATN LPGRGQLQKL ASERNLFISC KSSHDRCLEK SSSSSSQPEH 
       310        320        330        340        350
SAMLVSTAAS PSLIKETTTG YYKDIVENIC GREKSGIQPL CPERSHISDQ 
       360        370        380        390        400
SPLSSKRKAL EESESSQLIS PPLAQAIRDY VNSLLVQGGV GSLPGTSNSM 
       410        420        430        440        450
PPLDVENIQK RIDQSKFQET EFLSPPRKVP RLSEKSVEER DSGSFVAFQN 
       460        470        480        490        500
IPGSELMSSF AKTVVSHSLT TLGLEVAKQS QHDKIDASEL SFPFHESILK 
       510        520        530        540        550
VIEEEWQQVD RQLPSLACKY PVSSREATQI LSVPKVDDEI LGFISEATPL 
       560        570        580        590        600
GGIQAASTES CNQQLDLALC RAYEAAASAL QIATHTAFVA KAMQADISQA 
       610        620        630        640        650
AQILSSDPSR THQALGILSK TYDAASYICE AAFDEVKMAA HTMGNATVGR 
       660        670        680        690 
RYLWLKDCKI NLASKNKLAS TPFKGGTLFG GEVCKVIKKR GNKH
Length:694
Mass (Da):75,492
Last modified:January 23, 2007 - v2
Checksum:i1B514B0FB61D0D75
GO
Isoform Beta (identifier: P42167-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P42167.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:454
Mass (Da):50,670
GO
Isoform Gamma (identifier: P42167-2) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P42167.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:345
Mass (Da):38,738
GO
Isoform Zeta (identifier: P42167-3) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P42167.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Inhibits LAP2beta-mediated repression.
Length:248
Mass (Da):27,388
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049773238L → R. Corresponds to variant dbSNP:rs35998138EnsemblClinVar.1
Natural variantiVAR_049774293S → A. Corresponds to variant dbSNP:rs35645287EnsemblClinVar.1
Natural variantiVAR_049775317T → S. Corresponds to variant dbSNP:rs35969221EnsemblClinVar.1
Natural variantiVAR_049776416K → E. Corresponds to variant dbSNP:rs11838270EnsemblClinVar.1
Natural variantiVAR_049777478K → N. Corresponds to variant dbSNP:rs35761089EnsemblClinVar.1
Natural variantiVAR_005635599Q → E1 PublicationCorresponds to variant dbSNP:rs17459334EnsemblClinVar.1
Natural variantiVAR_049778690R → C Polymorphism; affects the interaction with LMNA. 1 PublicationCorresponds to variant dbSNP:rs17028450EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09086 mRNA Translation: AAB60329.1
U18270
, U18266, U18267, U18268 Genomic DNA Translation: AAB60433.1
S76736 mRNA Translation: AAB33958.1
CCDSiCCDS9064.1 [P42166-1]
PIRiG01161
RefSeqiNP_003267.1, NM_003276.2 [P42166-1]
UniGeneiHs.11355

Genome annotation databases

EnsembliENST00000266732; ENSP00000266732; ENSG00000120802 [P42166-1]
GeneIDi7112
UCSCiuc001tfh.3 human [P42166-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLAP2A_HUMAN
AccessioniPrimary (citable) accession number: P42166
Secondary accession number(s): P08918
, P08919, Q14860, Q16295
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 194 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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