ALS2

Protein identityUniProt · HPA

UniProt accession

Q96Q42

Gene

ALS2

Ensembl

ENSG00000003393

Chromosome

2

Canonical length

1657 aa

Protein class

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

Subcellular location

Vesicles,Cytosol

OverviewNCBI Gene

The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

Canonical amino-acid sequenceUniProt

1657 residues, UniProt reviewed canonical sequence.

>Q96Q42|ALS2
     1  MDSKKRSSTE AEGSKERGLV HIWQAGSFPI TPERLPGWGG KTVLQAALGV KHGVLLTEDG
    61  EVYSFGTLPW RSGPVEICPS SPILENALVG QYVITVATGS FHSGAVTDNG VAYMWGENSA
   121  GQCAVANQQY VPEPNPVSIA DSEASPLLAV RILQLACGEE HTLALSISRE IWAWGTGCQL
   181  GLITTAFPVT KPQKVEHLAG RVVLQVACGA FHSLALVQCL PSQDLKPVPE RCNQCSQLLI
   241  TMTDKEDHVI ISDSHCCPLG VTLTESQAEN HASTALSPST ETLDRQEEVF ENTLVANDQS
   301  VATELNAVSA QITSSDAMSS QQNVMGTTEI SSARNIPSYP DTQAVNEYLR KLSDHSVRED
   361  SEHGEKPVPS QPLLEEAIPN LHSPPTTSTS ALNSLVVSCA SAVGVRVAAT YEAGALSLKK
   421  VMNFYSTTPC ETGAQAGSSA IGPEGLKDSR EEQVKQESMQ GKKSSSLVDI REEETEGGSR
   481  RLSLPGLLSQ VSPRLLRKAA RVKTRTVVLT PTYSGEADAL LPSLRTEVWT WGKGKEGQLG
   541  HGDVLPRLQP LCVKCLDGKE VIHLEAGGYH SLALTAKSQV YSWGSNTFGQ LGHSDFPTTV
   601  PRLAKISSEN GVWSIAAGRD YSLFLVDTED FQPGLYYSGR QDPTEGDNLP ENHSGSKTPV
   661  LLSCSKLGYI SRVTAGKDSY LALVDKNIMG YIASLHELAT TERRFYSKLS DIKSQILRPL
   721  LSLENLGTTT TVQLLQEVAS RFSKLCYLIG QHGASLSSFL HGVKEARSLV ILKHSSLFLD
   781  SYTEYCTSIT NFLVMGGFQL LAKPAIDFLN KNQELLQDLS EVNDENTQLM EILNTLFFLP
   841  IRRLHNYAKV LLKLATCFEV ASPEYQKLQD SSSCYECLAL HLGRKRKEAE YTLGFWKTFP
   901  GKMTDSLRKP ERRLLCESSN RALSLQHAGR FSVNWFILFN DALVHAQFST HHVFPLATLW
   961  AEPLSEEAGG VNGLKITTPE EQFTLISSTP QEKTKWLRAI SQAVDQALRG MSDLPPYGSG
  1021  SSVQRQEPPI SRSAKYTFYK DPRLKDATYD GRWLSGKPHG RGVLKWPDGK MYSGMFRNGL
  1081  EDGYGEYRIP NKAMNKEDHY VGHWKEGKMC GQGVYSYASG EVFEGCFQDN MRHGHGLLRS
  1141  GKLTSSSPSM FIGQWVMDKK AGYGVFDDIT RGEKYMGMWQ DDVCQGNGVV VTQFGLYYEG
  1201  NFHLNKMMGN GVLLSEDDTI YEGEFSDDWT LSGKGTLTMP NGDYIEGYFS GEWGSGIKIT
  1261  GTYFKPSLYE SDKDRPKVFR KLGNLAVPAD EKWKAVFDEC WRQLGCEGPG QGEVWKAWDN
  1321  IAVALTTSRR QHRDSPEILS RSQTQTLESL EFIPQHVGAF SVEKYDDIRK YLIKACDTPL
  1381  HPLGRLVETL VAVYRMTYVG VGANRRLLQE AVKEIKSYLK RIFQLVRFLF PELPEEGSTI
  1441  PLSAPLPTER KSFCTGKSDS RSESPEPGYV VTSSGLLLPV LLPRLYPPLF MLYALDNDRE
  1501  EDIYWECVLR LNKQPDIALL GFLGVQRKFW PATLSILGES KKVLPTTKDA CFASAVECLQ
  1561  QISTTFTPSD KLKVIQQTFE EISQSVLASL HEDFLWSMDD LFPVFLYVVL RARIRNLGSE
  1621  VHLIEDLMDP YLQHGEQGIM FTTLKACYYQ IQREKLN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ALS2 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)

0.33

Highest tissue expression

21 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ALS2.

Disease | AllUniProt

Conditions ALS2 is implicated in, by any mechanism.

• Amyotrophic lateral sclerosis 2 (ALS2) MIM:205100
• Juvenile primary lateral sclerosis (JPLS) MIM:606353
• Infantile-onset ascending spastic paralysis (IAHSP) MIM:607225

Disease | GeneticClinVar

119 pathogenic / likely-pathogenic of 1,193 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Infantile-onset ascending hereditary spastic paralysis
• Amyotrophic lateral sclerosis type 2, juvenile
• Juvenile primary lateral sclerosis
• Amyotrophic lateral sclerosis
• Tip-toe gait

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)

0.52

gnomAD pLI

0

gnomAD missense Z

1.9

DepMap mean gene effect

0.01

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

• behavioral fear response
• endosomal transport
• endosome organization
• intracellular protein localization
• locomotory behavior
• lysosomal transport
• neuromuscular junction development
• neuron projection morphogenesis
• positive regulation of GTPase activity
• positive regulation of protein kinase activity
• positive regulation of Rac protein signal transduction
• protein homooligomerization
• receptor recycling
• regulation of endosome size
• regulation of postsynaptic membrane neurotransmitter receptor levels
• response to oxidative stress
• synaptic transmission, glutamatergic

Molecular functions

• GTPase activator activity
• guanyl-nucleotide exchange factor activity
• identical protein binding
• protein homodimerization activity
• protein serine/threonine kinase activator activity
• small GTPase binding

Cellular components

• centrosome
• cytoplasm
• cytosol
• dendrite
• dendritic spine
• early endosome
• glutamatergic synapse
• growth cone
• lamellipodium
• nucleus
• postsynaptic density
• protein-containing complex
• ruffle
• vesicle

Protein domainsUniProt · Pfam · InterPro

• Dbl homology domain
• Regulator of chromosome condensation, RCC1
• VPS9 domain
• MORN repeat
• Regulator of chromosome condensation 1/beta-lactamase-inhibitor protein II
• PH-like domain superfamily
• Dbl homology (DH) domain superfamily
• VPS9 domain superfamily
• Alsin
• Alsin-like, PH-like domain
• Regulator of chromosome condensation (RCC1) repeat
• Vacuolar sorting protein 9 (VPS9) domain
• MORN repeat
• Alsin PH-like domain
• Alsin, helical array domain
• Alsin, DH domain
• Alsin, helical array domain

KeywordsUniProt

• Acetylation
• Amyotrophic lateral sclerosis
• Guanine-nucleotide releasing factor
• Neurodegeneration
• Phosphoprotein
• Repeat

InteractionsUniProt · HPA

Protein binding partners of ALS2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ALS2CL
• YWHAB
• YWHAE
• YWHAG
• YWHAH
• YWHAZ