Seroatlas · Human Serome Atlas

ANKLE2

Ankyrin repeat and LEM domain-containing protein 2

Also known as: ANKL2_HUMAN, KIAA0692, Lem4, LEMD7

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q86XL3
Gene: ANKLE2
Ensembl: ENSG00000176915
Chromosome: 12
Canonical length: 938 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Endoplasmic reticulum,Plasma membrane

OverviewNCBI Gene

This gene encodes a member of the LEM family of inner nuclear membrane proteins. The encoded protein functions as a mitotic regulator through postmitotic formation of the nuclear envelope. Mutations in this gene cause morphology defects in the nuclear envelope and BAF hyperphosphorylation. [provided by RefSeq, Mar 2014]

Canonical amino-acid sequenceUniProt

938 residues, UniProt reviewed canonical sequence.

>Q86XL3|ANKLE2
     1  MLWPRLAAAE WAALAWELLG ASVLLIAVRW LVRRLGPRPG GLGRSGTPVP PPSAAAAPAS
    61  GEMTMDALLA RLKLLNPDDL REEIVKAGLK CGPITSTTRF IFEKKLAQAL LEQGGRLSSF
   121  YHHEAGVTAL SQDPQRILKP AEGNPTDQAG FSEDRDFGYS VGLNPPEEEA VTSKTCSVPP
   181  SDTDTYRAGA TASKEPPLYY GVCPVYEDVP ARNERIYVYE NKKEALQAVK MIKGSRFKAF
   241  STREDAEKFA RGICDYFPSP SKTSLPLSPV KTAPLFSNDR LKDGLCLSES ETVNKERANS
   301  YKNPRTQDLT AKLRKAVEKG EEDTFSDLIW SNPRYLIGSG DNPTIVQEGC RYNVMHVAAK
   361  ENQASICQLT LDVLENPDFM RLMYPDDDEA MLQKRIRYVV DLYLNTPDKM GYDTPLHFAC
   421  KFGNADVVNV LSSHHLIVKN SRNKYDKTPE DVICERSKNK SVELKERIRE YLKGHYYVPL
   481  LRAEETSSPV IGELWSPDQT AEASHVSRYG GSPRDPVLTL RAFAGPLSPA KAEDFRKLWK
   541  TPPREKAGFL HHVKKSDPER GFERVGRELA HELGYPWVEY WEFLGCFVDL SSQEGLQRLE
   601  EYLTQQEIGK KAQQETGERE ASCRDKATTS GSNSISVRAF LDEDDMSLEE IKNRQNAARN
   661  NSPPTVGAFG HTRCSAFPLE QEADLIEAAE PGGPHSSRNG LCHPLNHSRT LAGKRPKAPR
   721  GEEAHLPPVS DLTVEFDKLN LQNIGRSVSK TPDESTKTKD QILTSRINAV ERDLLEPSPA
   781  DQLGNGHRRT ESEMSARIAK MSLSPSSPRH EDQLEVTREP ARRLFLFGEE PSKLDQDVLA
   841  ALECADVDPH QFPAVHRWKS AVLCYSPSDR QSWPSPAVKG RFKSQLPDLS GPHSYSPGRN
   901  SVAGSNPAKP GLGSPGRYSP VHGSQLRRMA RLAELAAL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ANKLE2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Other membrane
Secreted: No
Transmembrane segments: 1
Mean surface accessibility (rSASA): 0.48
Highest tissue expression: 53 nTPM

Expression across tissuesHPA

Tissue

testis: 53 nTPM
spleen: 37 nTPM
bone marrow: 36 nTPM
adrenal gland: 36 nTPM
skin: 36 nTPM
esophagus: 33 nTPM

Single-cell type

late primary spermatocytes: 345 nCPM
urothelial cells: 217 nCPM
ocular epithelial cells: 189 nCPM
endometrial glandular cells: 167 nCPM
esophageal apical cells: 166 nCPM
endometrial secretory cells: 155 nCPM

Immune cell

eosinophil: 4.5 nTPM
memory CD8 T-cell: 2.8 nTPM
naive B-cell: 2.8 nTPM
NK-cell: 2.8 nTPM
memory B-cell: 2.7 nTPM
memory CD4 T-cell: 2.7 nTPM

Brain region

choroid plexus: 38 nTPM
cerebral cortex: 26 nTPM
cerebellum: 23 nTPM
thalamus: 22 nTPM
hypothalamus: 21 nTPM
hippocampal formation: 20 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ANKLE2.

Disease | AllUniProt

Conditions ANKLE2 is implicated in, by any mechanism.

Microcephaly 16, primary, autosomal recessive (MCPH16) MIM:616681

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 375 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Microcephaly 16, primary, autosomal recessive
Microcephaly
Intellectual disability
Vanishing white matter disease
Hypotonia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.85
gnomAD pLI: 0
gnomAD missense Z: 0.34
DepMap mean gene effect: -2.26
DepMap dependency class: pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

Ankyrin repeat
LEM domain
LEM/LEM-like domain superfamily
Ribonuclease H1, N-terminal
Ankyrin repeat-containing domain superfamily
Ribonuclease H1, N-terminal domain superfamily
Ankyrin repeat
Ribonuclease H1 N-terminal domain
LEM domain
Ankyrin repeat and LEM domain-containing protein 2, LEM domain
ANKLE2, third alpha/beta domain
ANKLE2 third alpha/beta domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ANKLE2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ANKLE2 as an antibody target. Whether an autoantibody or antibody against ANKLE2 could matter depends on whether native ANKLE2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ANKLE2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label ANKLE2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Loading the interactive Seroatlas protein explorer...