ADD3

Protein identityUniProt · HPA

UniProt accession

Q9UEY8

Gene

ADD3

Ensembl

ENSG00000148700

Chromosome

10

Canonical length

706 aa

Protein class

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

Subcellular location

Plasma membrane

OverviewNCBI Gene

Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma. The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues. Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta. Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension. Heterodimers consisting of alpha and gamma subunits have also been described. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced adducin gamma transcripts encoding different isoforms have been described. The functions of the different isoforms are not known. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

706 residues, UniProt reviewed canonical sequence.

>Q9UEY8|ADD3
     1  MSSDASQGVI TTPPPPSMPH KERYFDRINE NDPEYIRERN MSPDLRQDFN MMEQRKRVTQ
    61  ILQSPAFRED LECLIQEQMK KGHNPTGLLA LQQIADYIMA NSFSGFSSPP LSLGMVTPIN
   121  DLPGADTSSY VKGEKLTRCK LASLYRLVDL FGWAHLANTY ISVRISKEQD HIIIIPRGLS
   181  FSEATASNLV KVNIIGEVVD QGSTNLKIDH TGFSPHAAIY STRPDVKCVI HIHTLATAAV
   241  SSMKCGILPI SQESLLLGDV AYYDYQGSLE EQEERIQLQK VLGPSCKVLV LRNHGVVALG
   301  ETLEEAFHYI FNVQLACEIQ VQALAGAGGV DNLHVLDFQK YKAFTYTVAA SGGGGVNMGS
   361  HQKWKVGEIE FEGLMRTLDN LGYRTGYAYR HPLIREKPRH KSDVEIPATV TAFSFEDDTV
   421  PLSPLKYMAQ RQQREKTRWL NSPNTYMKVN VPEESRNGET SPRTKITWMK AEDSSKVSGG
   481  TPIKIEDPNQ FVPLNTNPNE VLEKRNKIRE QNRYDLKTAG PQSQLLAGIV VDKPPSTMQF
   541  EDDDHGPPAP PNPFSHLTEG ELEEYKRTIE RKQQGLEDAE QELLSDDASS VSQIQSQTQS
   601  PQNVPEKLEE NHELFSKSFI SMEVPVMVVN GKDDMHDVED ELAKRVSRLS TSTTIENIEI
   661  TIKSPEKIEE VLSPEGSPSK SPSKKKKKFR TPSFLKKNKK KEKVEA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADD3 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.48

Highest tissue expression

108 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ADD3.

Disease | AllUniProt

Conditions ADD3 is implicated in, by any mechanism.

• Cerebral palsy, spastic quadriplegic 3 (CPSQ3) MIM:617008

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 264 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cerebral palsy
• Cerebral palsy, spastic quadriplegic, 3

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)

0.25

gnomAD pLI

1

gnomAD missense Z

0.33

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• barbed-end actin filament capping
• positive regulation of cytoskeleton organization
• positive regulation of vasoconstriction
• response to xenobiotic stimulus

Molecular functions

• actin filament binding
• calmodulin binding
• protein kinase C binding
• structural constituent of cytoskeleton

Cellular components

• brush border
• cell cortex
• cell-cell junction
• condensed nuclear chromosome
• cytoskeleton
• cytosol
• membrane
• plasma membrane
• postsynaptic density

Protein domainsUniProt · Pfam · InterPro

• Class II aldolase/adducin N-terminal
• Class II aldolase/adducin N-terminal domain superfamily
• Aldolase class II Adducin subfamily
• Class II Aldolase and Adducin N-terminal domain

KeywordsUniProt

• Acetylation
• Actin-binding
• Calmodulin-binding
• Cell membrane
• Cytoplasm
• Cytoskeleton
• Isopeptide bond
• Membrane
• Phosphoprotein
• Ubl conjugation