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Protein

Lamina-associated polypeptide 2, isoform alpha

Gene

TMPO

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • DNA binding Source: UniProtKB-KW
  • lamin binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

DNA-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
Alternative name(s):
TP5
Gene namesi
Name:TMPO
Synonyms:LAP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11875. TMPO.

Subcellular locationi

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • chromatin Source: MGI
  • endoplasmic reticulum membrane Source: Ensembl
  • nuclear envelope Source: ProtInc
  • nuclear inner membrane Source: Ensembl
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, dilated 1T (CMD1T)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
See also OMIM:613740
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049778690R → C in CMD1T; affects the interaction with LMNA. 1 PublicationCorresponds to variant rs17028450dbSNPEnsembl.1

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, Disease mutation

Organism-specific databases

DisGeNETi7112.
MalaCardsiTMPO.
MIMi613740. phenotype.
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.

PTM databases

iPTMnetiP42166.
SwissPalmiP42166.

Miscellaneous databases

PMAP-CutDBP42166.

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.3 Publications

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • lamin binding Source: ProtInc

Protein-protein interaction databases

BioGridi112967. 105 interactors.
IntActiP42166. 37 interactors.
MINTiMINT-2863664.
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
Contains 1 LEM domain.PROSITE-ProRule annotation
Contains 1 LEM-like domain.PROSITE-ProRule annotation

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.
InterProiIPR021623. LAP2alpha.
IPR013146. LEM-like_dom.
IPR011015. LEM/LEM-like_dom.
IPR003887. LEM_dom.
[Graphical view]
PfamiPF11560. LAP2alpha. 1 hit.
PF03020. LEM. 1 hit.
PF08198. Thymopoietin. 1 hit.
[Graphical view]
SMARTiSM00540. LEM. 1 hit.
SM01261. Thymopoietin. 1 hit.
[Graphical view]
SUPFAMiSSF63451. SSF63451. 2 hits.
PROSITEiPS50954. LEM. 1 hit.
PS50955. LEM_LIKE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049773238L → R.Corresponds to variant rs35998138dbSNPEnsembl.1
Natural variantiVAR_049774293S → A.Corresponds to variant rs35645287dbSNPEnsembl.1
Natural variantiVAR_049775317T → S.Corresponds to variant rs35969221dbSNPEnsembl.1
Natural variantiVAR_049776416K → E.Corresponds to variant rs11838270dbSNPEnsembl.1
Natural variantiVAR_049777478K → N.Corresponds to variant rs35761089dbSNPEnsembl.1
Natural variantiVAR_005635599Q → E.1 PublicationCorresponds to variant rs17459334dbSNPEnsembl.1
Natural variantiVAR_049778690R → C in CMD1T; affects the interaction with LMNA. 1 PublicationCorresponds to variant rs17028450dbSNPEnsembl.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

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi112967. 105 interactors.
IntActiP42166. 37 interactors.
MINTiMINT-2863664.
STRINGi9606.ENSP00000266732.

PTM databases

iPTMnetiP42166.
SwissPalmiP42166.

Polymorphism and mutation databases

BioMutaiDLC1.
DMDMi1174689.

Proteomic databases

EPDiP42166.
PaxDbiP42166.
PeptideAtlasiP42166.
PRIDEiP42166.

Protocols and materials databases

DNASUi7112.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7112.
DisGeNETi7112.
GeneCardsiTMPO.
GeneReviewsiTMPO.
HGNCiHGNC:11875. TMPO.
HPAiCAB009847.
MalaCardsiTMPO.
MIMi188380. gene.
613740. phenotype.
neXtProtiNX_P42166.
OpenTargetsiENSG00000120802.
Orphaneti154. Familial isolated dilated cardiomyopathy.
PharmGKBiPA36576.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IT7C. Eukaryota.
ENOG4111J0N. LUCA.
GeneTreeiENSGT00510000048934.
HOGENOMiHOG000060228.
HOVERGENiHBG081890.
InParanoidiP42166.
OrthoDBiEOG091G03A8.
PhylomeDBiP42166.
TreeFamiTF328426.

Miscellaneous databases

ChiTaRSiTMPO. human.
EvolutionaryTraceiP42166.
GeneWikiiThymopoietin.
GenomeRNAii7112.
PMAP-CutDBP42166.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000120802.
CleanExiHS_TMPO.
ExpressionAtlasiP42166. baseline and differential.
GenevisibleiP42166. HS.

Family and domain databases

Gene3Di1.10.720.40. 2 hits.
InterProiIPR021623. LAP2alpha.
IPR013146. LEM-like_dom.
IPR011015. LEM/LEM-like_dom.
IPR003887. LEM_dom.
[Graphical view]
PfamiPF11560. LAP2alpha. 1 hit.
PF03020. LEM. 1 hit.
PF08198. Thymopoietin. 1 hit.
[Graphical view]
SMARTiSM00540. LEM. 1 hit.
SM01261. Thymopoietin. 1 hit.
[Graphical view]
SUPFAMiSSF63451. SSF63451. 2 hits.
PROSITEiPS50954. LEM. 1 hit.
PS50955. LEM_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLAP2A_HUMAN
AccessioniPrimary (citable) accession number: P42166
Secondary accession number(s): P08918
, P08919, Q14860, Q16295
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 179 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.