IQSEC2

Protein identityUniProt · HPA

UniProt accession

Q5JU85

Gene

IQSEC2

Ensembl

ENSG00000124313

Chromosome

X

Canonical length

1488 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Vesicles,Lipid droplets

OverviewNCBI Gene

This gene encodes a guanine nucleotide exchange factor for the ARF family of small GTP-binding proteins. The encoded protein is a component of the postsynaptic density at excitatory synapses, and may play a critical role in cytoskeletal and synaptic organization through the activation of selected ARF substrates including ARF1 and ARF6. Mutations in this gene have been implicated in nonsyndromic X-linked cognitive disability. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

Canonical amino-acid sequenceUniProt

1488 residues, UniProt reviewed canonical sequence.

>Q5JU85|IQSEC2
     1  MEAGSGPPGG PGSESPNRAV EYLLELNNII ESQQQLLETQ RRRIEELEGQ LDQLTQENRD
    61  LREESQLHRG ELHRDPHGAR DSPGRESQYQ NLRETQFHHR ELRESQFHQA ARDVGYPNRE
   121  GAYQNREAVY RDKERDASYP LQDTTGYTAR ERDVAQCHLH HENPALGRER GGREAGPAHP
   181  GREKEAGYSA AVGVGPRPPR ERGQLSRGAS RSSSPGAGGG HSTSTSTSPA TTLQRKSDGE
   241  NSRTVSVEGD APGSDLSTAV DSPGSQPPYR LSQLPPSSSH MGGPPAGVGL PWAQRARLQP
   301  ASVALRKQEE EEIKRSKALS DSYELSTDLQ DKKVEMLERK YGGSFLSRRA ARTIQTAFRQ
   361  YRMNKNFERL RSSASESRMS RRIILSNMRM QFSFEEYEKA QNPAYFEGKP ASLDEGAMAG
   421  ARSHRLERGL PYGGSCGGGI DGGGSSVTTS GEFSNDITEL EDSFSKQVKS LAESIDEALN
   481  CHPSGPMSEE PGSAQLEKRE SKEQQEDSSA TSFSDLPLYL DDTVPQQSPE RLPSTEPPPQ
   541  GRPEFWAPAP LPPVPPPVPS GTREDGSREE GTRRGPGCLE CRDFRLRAAH LPLLTIEPPS
   601  DSSVDLSDRS DRGSVHRQLV YEADGCSPHG TLKHKGPPGR APIPHRHYPA PEGPAPAPPG
   661  PLPPAPNSGT GPSGVAGGRR LGKCEAAGEN SDGGDNESLE SSSNSNETIN CSSGSSSRDS
   721  LREPPATGLC KQTYQRETRH SWDSPAFNND VVQRRHYRIG LNLFNKKPEK GIQYLIERGF
   781  LSDTPVGVAH FILERKGLSR QMIGEFLGNR QKQFNRDVLD CVVDEMDFSS MDLDDALRKF
   841  QSHIRVQGEA QKVERLIEAF SQRYCVCNPA LVRQFRNPDT IFILAFAIIL LNTDMYSPSV
   901  KAERKMKLDD FIKNLRGVDN GEDIPRDLLV GIYQRIQGRE LRTNDDHVSQ VQAVERMIVG
   961  KKPVLSLPHR RLVCCCQLYE VPDPNRPQRL GLHQREVFLF NDLLVVTKIF QKKKILVTYS
  1021  FRQSFPLVEM HMQLFQNSYY QFGIKLLSAV PGGERKVLII FNAPSLQDRL RFTSDLRESI
  1081  AEVQEMEKYR VESELEKQKG MMRPNASQPG GAKDSVNGTM ARSSLEDTYG AGDGLKRGAL
  1141  SSSLRDLSDA GKRGRRNSVG SLDSTIEGSV ISSPRPHQRM PPPPPPPPPE EYKSQRPVSN
  1201  SSSFLGSLFG SKRGKGPFQM PPPPTGQASA SSSSASSTHH HHHHHHHGHS HGGLGVLPDG
  1261  QSKLQALHAQ YCQGPGPAPP PYLPPQQPSL PPPPQQPPPL PQLGSIPPPP ASAPPVGPHR
  1321  HFHAHGPVPG PQHYTLGRPG RAPRRGAGGH PQFAPHGRHP LHQPTSPLPL YSPAPQHPPA
  1381  HKQGPKHFIF SHHPQMMPAA GAAGGPGSRP PGGSYSHPHH PQSPLSPHSP IPPHPSYPPL
  1441  PPPSPHTPHS PLPPTSPHGP LHASGPPGTA NPPSANPKAK PSRISTVV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IQSEC2 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.57

Highest tissue expression

57 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IQSEC2.

Disease | AllUniProt

Conditions IQSEC2 is implicated in, by any mechanism.

• Intellectual developmental disorder, X-linked 1 (XLID1) MIM:309530

Disease | GeneticClinVar

228 pathogenic / likely-pathogenic of 1,513 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, X-linked 1
• Inborn genetic diseases
• NEURODEVELOPMENTAL DISORDER, X-LINKED, WITH POOR OR ABSENT SPEECH AND BEHAVIORAL ABNORMALITIES
• Intellectual disability
• Thyroid cancer, nonmedullary, 1

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)

0.13

gnomAD pLI

1

gnomAD missense Z

5.19

DepMap mean gene effect

0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• actin cytoskeleton organization
• modulation of chemical synaptic transmission
• positive regulation of long-term synaptic depression
• positive regulation of synapse assembly
• positive regulation of synaptic transmission, glutamatergic
• regulation of ARF protein signal transduction
• regulation of neurotransmitter receptor localization to postsynaptic specialization membrane

Molecular functions

• guanyl-nucleotide exchange factor activity

Cellular components

• cytoplasm
• Schaffer collateral - CA1 synapse

Protein domainsUniProt · Pfam · InterPro

• Sec7 domain
• Pleckstrin homology domain
• PH-like domain superfamily
• Sec7, C-terminal domain superfamily
• IQ motif and SEC7 domain-containing protein, PH domain
• Sec7 domain superfamily
• Sec7 domain
• PH domain

KeywordsUniProt

• Coiled coil
• Cytoplasm
• Intellectual disability
• Methylation
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of IQSEC2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CALM1