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Protein

Ankyrin repeat and LEM domain-containing protein 2

Gene

ANKLE2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in mitotic nuclear envelope reassembly by promoting dephosphorylation of BAF/BANF1 during mitotic exit. Coordinates the control of BAF/BANF1 dephosphorylation by inhibiting VRK1 kinase and promoting dephosphorylation of BAF/BANF1 by protein phosphatase 2A (PP2A), thereby facilitating nuclear envelope assembly. It is unclear whether it acts as a real PP2A regulatory subunit or whether it is involved in recruitment of the PP2A complex. Involved in brain development (PubMed:25259927).2 Publications

GO - Molecular functioni

  • protein phosphatase 2A binding Source: UniProtKB
  • protein phosphatase type 2A regulator activity Source: UniProtKB

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • central nervous system development Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB-KW
  • mitotic nuclear envelope reassembly Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of phosphorylation Source: UniProtKB
  • positive regulation of protein dephosphorylation Source: UniProtKB
  • regulation of catalytic activity Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Enzyme and pathway databases

ReactomeiR-HSA-2995383. Initiation of Nuclear Envelope Reformation.
SIGNORiQ86XL3.

Names & Taxonomyi

Protein namesi
Recommended name:
Ankyrin repeat and LEM domain-containing protein 2
Alternative name(s):
LEM domain-containing protein 4
Gene namesi
Name:ANKLE2
Synonyms:KIAA0692, LEM4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:29101. ANKLE2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 12LumenalSequence analysisAdd BLAST12
Transmembranei13 – 32Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST20
Topological domaini33 – 938CytoplasmicSequence analysisAdd BLAST906

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: Reactome
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Microcephaly 16, primary, autosomal recessive (MCPH16)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small.
See also OMIM:616681
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076205573L → V in MCPH16. 1 Publication1

Keywords - Diseasei

Disease mutation, Primary microcephaly

Organism-specific databases

DisGeNETi23141.
MIMi616681. phenotype.
OpenTargetsiENSG00000176915.
PharmGKBiPA162376532.

Polymorphism and mutation databases

BioMutaiANKLE2.
DMDMi269849748.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002802421 – 938Ankyrin repeat and LEM domain-containing protein 2Add BLAST938

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei259PhosphoserineCombined sources1
Modified residuei268PhosphoserineCombined sources1
Modified residuei488PhosphoserineCombined sources1
Modified residuei496PhosphoserineCombined sources1
Modified residuei512PhosphoserineCombined sources1
Modified residuei528PhosphoserineCombined sources1
Modified residuei662PhosphoserineCombined sources1
Modified residuei804PhosphoserineCombined sources1
Modified residuei896PhosphoserineCombined sources1
Modified residuei914PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ86XL3.
MaxQBiQ86XL3.
PaxDbiQ86XL3.
PeptideAtlasiQ86XL3.
PRIDEiQ86XL3.

PTM databases

iPTMnetiQ86XL3.
PhosphoSitePlusiQ86XL3.

Expressioni

Gene expression databases

BgeeiENSG00000176915.
CleanExiHS_ANKLE2.
ExpressionAtlasiQ86XL3. baseline and differential.
GenevisibleiQ86XL3. HS.

Organism-specific databases

HPAiHPA003602.

Interactioni

Subunit structurei

Interacts with BAF/BANF1. Interacts with protein phosphatase 2A (PP2A) components PPP2C (PPP2CA or PPP2CB) and PPP2R1A.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
vrk-1Q198482EBI-1773621,EBI-2414048From a different organism.

GO - Molecular functioni

  • protein phosphatase 2A binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116758. 35 interactors.
IntActiQ86XL3. 22 interactors.
MINTiMINT-1187128.
STRINGi9606.ENSP00000350686.

Structurei

3D structure databases

ProteinModelPortaliQ86XL3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini69 – 113LEMPROSITE-ProRule annotationAdd BLAST45
Repeati411 – 440ANKAdd BLAST30

Sequence similaritiesi

Belongs to the ANKLE2 family.Curated
Contains 1 ANK repeat.Curated
Contains 1 LEM domain.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IE4A. Eukaryota.
ENOG410XRMS. LUCA.
GeneTreeiENSGT00390000016767.
HOGENOMiHOG000234326.
HOVERGENiHBG096073.
InParanoidiQ86XL3.
OMAiCYIVDLY.
OrthoDBiEOG091G05GX.
PhylomeDBiQ86XL3.
TreeFamiTF317729.

Family and domain databases

Gene3Di1.10.720.40. 1 hit.
1.25.40.20. 1 hit.
3.40.970.10. 1 hit.
InterProiIPR020683. Ankyrin_rpt-contain_dom.
IPR011015. LEM/LEM-like_dom.
IPR003887. LEM_dom.
IPR011320. RNase_H1_N.
[Graphical view]
PfamiPF01693. Cauli_VI. 1 hit.
PF03020. LEM. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 2 hits.
SSF63451. SSF63451. 1 hit.
PROSITEiPS50954. LEM. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86XL3-1) [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
MLWPRLAAAE WAALAWELLG ASVLLIAVRW LVRRLGPRPG GLGRSGTPVP
60 70 80 90 100
PPSAAAAPAS GEMTMDALLA RLKLLNPDDL REEIVKAGLK CGPITSTTRF
110 120 130 140 150
IFEKKLAQAL LEQGGRLSSF YHHEAGVTAL SQDPQRILKP AEGNPTDQAG
160 170 180 190 200
FSEDRDFGYS VGLNPPEEEA VTSKTCSVPP SDTDTYRAGA TASKEPPLYY
210 220 230 240 250
GVCPVYEDVP ARNERIYVYE NKKEALQAVK MIKGSRFKAF STREDAEKFA
260 270 280 290 300
RGICDYFPSP SKTSLPLSPV KTAPLFSNDR LKDGLCLSES ETVNKERANS
310 320 330 340 350
YKNPRTQDLT AKLRKAVEKG EEDTFSDLIW SNPRYLIGSG DNPTIVQEGC
360 370 380 390 400
RYNVMHVAAK ENQASICQLT LDVLENPDFM RLMYPDDDEA MLQKRIRYVV
410 420 430 440 450
DLYLNTPDKM GYDTPLHFAC KFGNADVVNV LSSHHLIVKN SRNKYDKTPE
460 470 480 490 500
DVICERSKNK SVELKERIRE YLKGHYYVPL LRAEETSSPV IGELWSPDQT
510 520 530 540 550
AEASHVSRYG GSPRDPVLTL RAFAGPLSPA KAEDFRKLWK TPPREKAGFL
560 570 580 590 600
HHVKKSDPER GFERVGRELA HELGYPWVEY WEFLGCFVDL SSQEGLQRLE
610 620 630 640 650
EYLTQQEIGK KAQQETGERE ASCRDKATTS GSNSISVRAF LDEDDMSLEE
660 670 680 690 700
IKNRQNAARN NSPPTVGAFG HTRCSAFPLE QEADLIEAAE PGGPHSSRNG
710 720 730 740 750
LCHPLNHSRT LAGKRPKAPR GEEAHLPPVS DLTVEFDKLN LQNIGRSVSK
760 770 780 790 800
TPDESTKTKD QILTSRINAV ERDLLEPSPA DQLGNGHRRT ESEMSARIAK
810 820 830 840 850
MSLSPSSPRH EDQLEVTREP ARRLFLFGEE PSKLDQDVLA ALECADVDPH
860 870 880 890 900
QFPAVHRWKS AVLCYSPSDR QSWPSPAVKG RFKSQLPDLS GPHSYSPGRN
910 920 930
SVAGSNPAKP GLGSPGRYSP VHGSQLRRMA RLAELAAL
Length:938
Mass (Da):104,114
Last modified:November 24, 2009 - v4
Checksum:iED2F25F05E8106F2
GO
Isoform 2 (identifier: Q86XL3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     631-648: GSNSISVRAFLDEDDMSL → VEMRFHRIDQAGLELLTS
     649-938: Missing.

Note: No experimental confirmation available.
Show »
Length:648
Mass (Da):72,641
Checksum:iA98712EBEE04E982
GO
Isoform 3 (identifier: Q86XL3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-645: Missing.

Show »
Length:293
Mass (Da):31,982
Checksum:i018D51B5FEA0E877
GO

Sequence cautioni

The sequence BAG51259 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti266P → Q in AAH43157 (PubMed:15489334).Curated1
Sequence conflicti481L → V in AAH43157 (PubMed:15489334).Curated1
Sequence conflicti647S → N in AAH43157 (PubMed:15489334).Curated1
Sequence conflicti662S → I in BAG52720 (PubMed:14702039).Curated1
Sequence conflicti680E → K in BAG52720 (PubMed:14702039).Curated1
Sequence conflicti863L → P in BAG51259 (PubMed:14702039).Curated1
Sequence conflicti891G → A in BAG52720 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031097122H → Y.1 PublicationCorresponds to variant rs1132375dbSNPEnsembl.1
Natural variantiVAR_031098148Q → E.Corresponds to variant rs7968520dbSNPEnsembl.1
Natural variantiVAR_076205573L → V in MCPH16. 1 Publication1
Natural variantiVAR_031099720R → H.2 PublicationsCorresponds to variant rs10781634dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0441731 – 645Missing in isoform 3. 1 PublicationAdd BLAST645
Alternative sequenceiVSP_023574631 – 648GSNSI…DDMSL → VEMRFHRIDQAGLELLTS in isoform 2. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_023575649 – 938Missing in isoform 2. 1 PublicationAdd BLAST290

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK024061 mRNA. Translation: BAG51259.1. Different initiation.
AK093451 mRNA. Translation: BAG52720.1.
AK293028 mRNA. Translation: BAF85717.1.
AC135586 Genomic DNA. No translation available.
AC136467 Genomic DNA. No translation available.
BC001530 mRNA. Translation: AAH01530.2.
BC025347 mRNA. Translation: AAH25347.1.
BC043157 mRNA. Translation: AAH43157.2.
BC062373 mRNA. Translation: AAH62373.1.
BC082962 mRNA. Translation: AAH82962.1.
AB014592 mRNA. Translation: BAA31667.1.
CCDSiCCDS41869.1. [Q86XL3-1]
PIRiT00354.
RefSeqiNP_055929.1. NM_015114.2. [Q86XL3-1]
XP_011533089.1. XM_011534787.2. [Q86XL3-2]
XP_011533090.1. XM_011534788.1. [Q86XL3-2]
UniGeneiHs.654628.

Genome annotation databases

EnsembliENST00000357997; ENSP00000350686; ENSG00000176915. [Q86XL3-1]
ENST00000542282; ENSP00000437807; ENSG00000176915. [Q86XL3-3]
ENST00000542657; ENSP00000438551; ENSG00000176915. [Q86XL3-3]
GeneIDi23141.
KEGGihsa:23141.
UCSCiuc001ukx.3. human. [Q86XL3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK024061 mRNA. Translation: BAG51259.1. Different initiation.
AK093451 mRNA. Translation: BAG52720.1.
AK293028 mRNA. Translation: BAF85717.1.
AC135586 Genomic DNA. No translation available.
AC136467 Genomic DNA. No translation available.
BC001530 mRNA. Translation: AAH01530.2.
BC025347 mRNA. Translation: AAH25347.1.
BC043157 mRNA. Translation: AAH43157.2.
BC062373 mRNA. Translation: AAH62373.1.
BC082962 mRNA. Translation: AAH82962.1.
AB014592 mRNA. Translation: BAA31667.1.
CCDSiCCDS41869.1. [Q86XL3-1]
PIRiT00354.
RefSeqiNP_055929.1. NM_015114.2. [Q86XL3-1]
XP_011533089.1. XM_011534787.2. [Q86XL3-2]
XP_011533090.1. XM_011534788.1. [Q86XL3-2]
UniGeneiHs.654628.

3D structure databases

ProteinModelPortaliQ86XL3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116758. 35 interactors.
IntActiQ86XL3. 22 interactors.
MINTiMINT-1187128.
STRINGi9606.ENSP00000350686.

PTM databases

iPTMnetiQ86XL3.
PhosphoSitePlusiQ86XL3.

Polymorphism and mutation databases

BioMutaiANKLE2.
DMDMi269849748.

Proteomic databases

EPDiQ86XL3.
MaxQBiQ86XL3.
PaxDbiQ86XL3.
PeptideAtlasiQ86XL3.
PRIDEiQ86XL3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357997; ENSP00000350686; ENSG00000176915. [Q86XL3-1]
ENST00000542282; ENSP00000437807; ENSG00000176915. [Q86XL3-3]
ENST00000542657; ENSP00000438551; ENSG00000176915. [Q86XL3-3]
GeneIDi23141.
KEGGihsa:23141.
UCSCiuc001ukx.3. human. [Q86XL3-1]

Organism-specific databases

CTDi23141.
DisGeNETi23141.
GeneCardsiANKLE2.
H-InvDBHIX0020726.
HGNCiHGNC:29101. ANKLE2.
HPAiHPA003602.
MIMi616062. gene.
616681. phenotype.
neXtProtiNX_Q86XL3.
OpenTargetsiENSG00000176915.
PharmGKBiPA162376532.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE4A. Eukaryota.
ENOG410XRMS. LUCA.
GeneTreeiENSGT00390000016767.
HOGENOMiHOG000234326.
HOVERGENiHBG096073.
InParanoidiQ86XL3.
OMAiCYIVDLY.
OrthoDBiEOG091G05GX.
PhylomeDBiQ86XL3.
TreeFamiTF317729.

Enzyme and pathway databases

ReactomeiR-HSA-2995383. Initiation of Nuclear Envelope Reformation.
SIGNORiQ86XL3.

Miscellaneous databases

ChiTaRSiANKLE2. human.
GenomeRNAii23141.
PROiQ86XL3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000176915.
CleanExiHS_ANKLE2.
ExpressionAtlasiQ86XL3. baseline and differential.
GenevisibleiQ86XL3. HS.

Family and domain databases

Gene3Di1.10.720.40. 1 hit.
1.25.40.20. 1 hit.
3.40.970.10. 1 hit.
InterProiIPR020683. Ankyrin_rpt-contain_dom.
IPR011015. LEM/LEM-like_dom.
IPR003887. LEM_dom.
IPR011320. RNase_H1_N.
[Graphical view]
PfamiPF01693. Cauli_VI. 1 hit.
PF03020. LEM. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 2 hits.
SSF63451. SSF63451. 1 hit.
PROSITEiPS50954. LEM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiANKL2_HUMAN
AccessioniPrimary (citable) accession number: Q86XL3
Secondary accession number(s): A8KAG3
, B3KN97, B3KSF8, O75176, Q6P6A5, Q8TAZ9, Q96DH4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: November 24, 2009
Last modified: November 2, 2016
This is version 123 of the entry and version 4 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

Complete proteome, 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. 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.