ADD2

Protein identityUniProt · HPA

UniProt accession

P35612

Gene

ADD2

Ensembl

ENSG00000075340

Chromosome

2

Canonical length

726 aa

Protein class

Predicted intracellular proteins

Subcellular location

Nucleoplasm,Plasma membrane,Cytosol

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 transcript variants have been described. [provided by RefSeq, Jun 2010]

Canonical amino-acid sequenceUniProt

726 residues, UniProt reviewed canonical sequence.

>P35612|ADD2
     1  MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS
    61  PSFREELEGL IQEQMKKGNN SSNIWALRQI ADFMASTSHA VFPTSSMNVS MMTPINDLHT
   121  ADSLNLAKGE RLMRCKISSV YRLLDLYGWA QLSDTYVTLR VSKEQDHFLI SPKGVSCSEV
   181  TASSLIKVNI LGEVVEKGSS CFPVDTTGFC LHSAIYAARP DVRCIIHLHT PATAAVSAMK
   241  WGLLPVSHNA LLVGDMAYYD FNGEMEQEAD RINLQKCLGP TCKILVLRNH GVVALGDTVE
   301  EAFYKIFHLQ AACEIQVSAL SSAGGVENLI LLEQEKHRPH EVGSVQWAGS TFGPMQKSRL
   361  GEHEFEALMR MLDNLGYRTG YTYRHPFVQE KTKHKSEVEI PATVTAFVFE EDGAPVPALR
   421  QHAQKQQKEK TRWLNTPNTY LRVNVADEVQ RSMGSPRPKT TWMKADEVEK SSSGMPIRIE
   481  NPNQFVPLYT DPQEVLEMRN KIREQNRQDV KSAGPQSQLL ASVIAEKSRS PSTESQLMSK
   541  GDEDTKDDSE ETVPNPFSQL TDQELEEYKK EVERKKLELD GEKETAPEEP GSPAKSAPAS
   601  PVQSPAKEAE TKSPLVSPSK SLEEGTKKTE TSKAATTEPE TTQPEGVVVN GREEEQTAEE
   661  ILSKGLSQMT TSADTDVDTS KDKTESVTSG PMSPEGSPSK SPSKKKKKFR TPSFLKKSKK
   721  KEKVES

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADD2 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)

0.49

Highest tissue expression

63 nTPM

Expression across tissuesHPA

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)

0.27

gnomAD pLI

1

gnomAD missense Z

2.1

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

• actin cytoskeleton organization
• actin filament bundle assembly
• barbed-end actin filament capping
• hemopoiesis
• leukocyte migration
• leukocyte tethering or rolling
• protein-containing complex assembly
• synapse assembly

Molecular functions

• actin binding
• actin filament binding
• calmodulin binding
• cytoskeletal anchor activity
• protein dimerization activity
• protein heterodimerization activity
• protein homodimerization activity
• protein kinase binding
• spectrin binding
• structural constituent of cytoskeleton

Cellular components

• cytoplasmic vesicle
• cytoskeleton
• cytosol
• F-actin capping protein complex
• plasma membrane
• plasma membrane raft
• 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

• Actin-binding
• Calmodulin-binding
• Cell membrane
• Cytoplasm
• Cytoskeleton
• Membrane
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of ADD2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SLC2A1
• ACTB