ID ADDG_HUMAN Reviewed; 706 AA. AC Q9UEY8; D3DRA8; O43243; Q5VU09; Q92773; Q9UEY7; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 188. DE RecName: Full=Gamma-adducin; DE AltName: Full=Adducin-like protein 70; GN Name=ADD3; Synonyms=ADDL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=8893809; DOI=10.1159/000134389; RA Katagiri T., Ozaki K., Fujiwara T., Shimizu F., Kawai A., Okuno S., RA Suzuki M., Nakamura Y., Takahashi E., Hirai Y.; RT "Cloning, expression and chromosome mapping of adducin-like 70 (ADDL), a RT human cDNA highly homologous to human erythrocyte adducin."; RL Cytogenet. Cell Genet. 74:90-95(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Moorthy S., Bennett V.; RT "Cloning in the gamma quadrant."; RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING. RX PubMed=10581174; DOI=10.1006/bbrc.1999.1769; RA Citterio L., Azzani T., Duga S., Bianchi G.; RT "Genomic organization of the human gamma adducin gene."; RL Biochem. Biophys. Res. Commun. 266:110-114(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Endometrium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP SUMOYLATION. RX PubMed=15561718; DOI=10.1074/jbc.m411718200; RA Gocke C.B., Yu H., Kang J.; RT "Systematic identification and analysis of mammalian small ubiquitin-like RT modifier substrates."; RL J. Biol. Chem. 280:5004-5012(2005). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-673, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; SER-423; SER-442; RP SER-673; SER-677 AND SER-681, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-402; SER-423 AND SER-681, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-42; SER-673 AND SER-677, CLEAVAGE OF INITIATOR METHIONINE RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-677 AND SER-681, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [17] RP INVOLVEMENT IN CPSQ3, VARIANT CPSQ3 ASP-367, CHARACTERIZATION OF VARIANT RP CPSQ3 ASP-367, AND FUNCTION. RX PubMed=23836506; DOI=10.1002/ana.23971; RA Kruer M.C., Jepperson T., Dutta S., Steiner R.D., Cottenie E., Sanford L., RA Merkens M., Russman B.S., Blasco P.A., Fan G., Pollock J., Green S., RA Woltjer R.L., Mooney C., Kretzschmar D., Paisan-Ruiz C., Houlden H.; RT "Mutations in gamma adducin are associated with inherited cerebral palsy."; RL Ann. Neurol. 74:805-814(2013). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-64; SER-442; SER-461; RP SER-673; SER-677; SER-681 AND SER-683, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-484, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [21] RP TISSUE SPECIFICITY. RX PubMed=33992672; DOI=10.1016/j.pneurobio.2021.102074; RA Xiong M., Zou L., Meng L., Zhang X., Tian Y., Zhang G., Yang J., Chen G., RA Xiong J., Ye K., Zhang Z.; RT "A gamma-adducin cleavage fragment induces neurite deficits and synaptic RT dysfunction in Alzheimer's disease."; RL Prog. Neurobiol. 203:102074-102074(2021). CC -!- FUNCTION: Membrane-cytoskeleton-associated protein that promotes the CC assembly of the spectrin-actin network. Plays a role in actin filament CC capping (PubMed:23836506). Binds to calmodulin (Probable). Involved in CC myogenic reactivity of the renal afferent arteriole (Af-art), renal CC interlobular arteries and middle cerebral artery (MCA) to increased CC perfusion pressure. Involved in regulation of potassium channels in the CC vascular smooth muscle cells (VSMCs) of the Af-art and MCA ex vivo. CC Involved in regulation of glomerular capillary pressure, glomerular CC filtration rate (GFR) and glomerular nephrin expression in response to CC hypertension. Involved in renal blood flow (RBF) autoregulation. Plays CC a role in podocyte structure and function. Regulates globular monomer CC actin (G-actin) and filamentous polymer actin (F-actin) ratios in the CC primary podocytes affecting actin cytoskeleton organization. Regulates CC expression of synaptopodin, RhoA, Rac1 and CDC42 in the renal cortex CC and the primary podocytes. Regulates expression of nephrin in the CC glomeruli and in the primary podocytes, expression of nephrin and CC podocinin in the renal cortex, and expression of focal adhesion CC proteins integrin alpha-3 and integrin beta-1 in the glomeruli. CC Involved in cell migration and cell adhesion of podocytes, and in CC podocyte foot process effacement. Regulates expression of profibrotics CC markers MMP2, MMP9, TGF beta-1, tubular tight junction protein E- CC cadherin, and mesenchymal markers vimentin and alpha-SMA (By CC similarity). Promotes the growth of neurites (By similarity). CC {ECO:0000250|UniProtKB:Q62847, ECO:0000250|UniProtKB:Q9QYB5, CC ECO:0000269|PubMed:23836506, ECO:0000305}. CC -!- SUBUNIT: Heterodimer of an alpha and a gamma subunit. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:Q62847}. Cell membrane CC {ECO:0000250|UniProtKB:Q62847}; Peripheral membrane protein; CC Cytoplasmic side. Cytoplasm {ECO:0000250|UniProtKB:Q9QYB5}. Note=Full- CC length protein and the cleavage fragment 358-706 localize mainly to the CC cytoplasm, while cleavage fragment 1-357 translocates from the CC cytoplasm to the nucleus. {ECO:0000250|UniProtKB:Q9QYB5}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Additional isoforms seem to exist.; CC Name=2; Synonyms=Long; CC IsoId=Q9UEY8-1; Sequence=Displayed; CC Name=1; Synonyms=Short; CC IsoId=Q9UEY8-2; Sequence=VSP_000188; CC -!- TISSUE SPECIFICITY: [Isoform 1]: ubiquitously expressed. CC {ECO:0000269|PubMed:8893809}. CC -!- TISSUE SPECIFICITY: Cleavage fragment 1-357 is abundantly expressed in CC the brain of patients with Alzheimer disease (AD), but hardly CC detectable in age-matched control individuals (at protein level). CC {ECO:0000269|PubMed:33992672}. CC -!- DOMAIN: Comprised of three regions: a N-terminal protease-resistant CC globular head region, a short connecting subdomain, and a protease- CC sensitive tail region. CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:15561718}. CC -!- PTM: Proteolytically cleaved by asparagine endopeptidase (AEP) into 2 CC fragments. Overexpression of the 1-357 fragment induces neuronal CC apoptosis, and overexpression of either 1-357 or 358-706 fragment CC increases the degeneration of dendritic spines. Overexpression of the CC 1-357 fragment impairs neurite outgrowth by downregulating the CC expression of Rac2, and induces synaptic dysfunction and cognitive CC impairments in tau P301S transgenic mice, a mouse model for Alzheimer CC disease (AD). {ECO:0000250|UniProtKB:Q9QYB5}. CC -!- DISEASE: Cerebral palsy, spastic quadriplegic 3 (CPSQ3) [MIM:617008]: A CC form of cerebral palsy, a group of non-progressive disorders of CC movement and/or posture resulting from defects in the developing CC central nervous system. CPSQ3 is an autosomal recessive CC neurodevelopmental disorder characterized by variable spasticity and CC cognitive impairment. {ECO:0000269|PubMed:23836506}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the aldolase class II family. Adducin subfamily. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/520/ADD3"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D67031; BAA23783.1; -; mRNA. DR EMBL; U37122; AAB17126.1; -; mRNA. DR EMBL; Y14372; CAB51805.1; -; Genomic_DNA. DR EMBL; Y14373; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14374; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14375; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14376; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14377; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14378; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14379; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14380; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14381; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14382; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14383; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14384; CAB51805.1; JOINED; Genomic_DNA. DR EMBL; Y14372; CAB51806.1; -; Genomic_DNA. DR EMBL; Y14373; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14374; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14375; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14376; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14377; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14378; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14379; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14380; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14381; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14382; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; Y14384; CAB51806.1; JOINED; Genomic_DNA. DR EMBL; BX647403; CAI46048.1; -; mRNA. DR EMBL; AL590628; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49573.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49574.1; -; Genomic_DNA. DR EMBL; BC062559; AAH62559.1; -; mRNA. DR CCDS; CCDS7561.1; -. [Q9UEY8-1] DR CCDS; CCDS7562.1; -. [Q9UEY8-2] DR PIR; JC7164; JC7164. DR RefSeq; NP_001112.2; NM_001121.3. [Q9UEY8-2] DR RefSeq; NP_001307520.1; NM_001320591.1. [Q9UEY8-1] DR RefSeq; NP_001307521.1; NM_001320592.1. [Q9UEY8-1] DR RefSeq; NP_001307522.1; NM_001320593.1. [Q9UEY8-1] DR RefSeq; NP_001307523.1; NM_001320594.1. DR RefSeq; NP_058432.1; NM_016824.4. [Q9UEY8-1] DR RefSeq; NP_063968.1; NM_019903.4. [Q9UEY8-2] DR AlphaFoldDB; Q9UEY8; -. DR SMR; Q9UEY8; -. DR BioGRID; 106633; 156. DR ComplexPortal; CPX-2643; Adducin complex, alpha-gamma variant. DR IntAct; Q9UEY8; 53. DR MINT; Q9UEY8; -. DR STRING; 9606.ENSP00000348381; -. DR GlyCosmos; Q9UEY8; 2 sites, 1 glycan. DR GlyGen; Q9UEY8; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q9UEY8; -. DR MetOSite; Q9UEY8; -. DR PhosphoSitePlus; Q9UEY8; -. DR BioMuta; ADD3; -. DR DMDM; 12643881; -. DR EPD; Q9UEY8; -. DR jPOST; Q9UEY8; -. DR MassIVE; Q9UEY8; -. DR MaxQB; Q9UEY8; -. DR PaxDb; 9606-ENSP00000348381; -. DR PeptideAtlas; Q9UEY8; -. DR ProteomicsDB; 84160; -. [Q9UEY8-1] DR ProteomicsDB; 84161; -. [Q9UEY8-2] DR Pumba; Q9UEY8; -. DR Antibodypedia; 4067; 233 antibodies from 32 providers. DR DNASU; 120; -. DR Ensembl; ENST00000277900.12; ENSP00000277900.8; ENSG00000148700.15. [Q9UEY8-2] DR Ensembl; ENST00000356080.9; ENSP00000348381.4; ENSG00000148700.15. [Q9UEY8-1] DR Ensembl; ENST00000360162.7; ENSP00000353286.3; ENSG00000148700.15. [Q9UEY8-2] DR GeneID; 120; -. DR KEGG; hsa:120; -. DR MANE-Select; ENST00000356080.9; ENSP00000348381.4; NM_016824.5; NP_058432.1. DR UCSC; uc001kys.5; human. [Q9UEY8-1] DR AGR; HGNC:245; -. DR CTD; 120; -. DR DisGeNET; 120; -. DR GeneCards; ADD3; -. DR HGNC; HGNC:245; ADD3. DR HPA; ENSG00000148700; Low tissue specificity. DR MalaCards; ADD3; -. DR MIM; 601568; gene. DR MIM; 617008; phenotype. DR neXtProt; NX_Q9UEY8; -. DR OpenTargets; ENSG00000148700; -. DR Orphanet; 210141; Inherited congenital spastic tetraplegia. DR PharmGKB; PA24567; -. DR VEuPathDB; HostDB:ENSG00000148700; -. DR eggNOG; KOG3699; Eukaryota. DR GeneTree; ENSGT00940000155257; -. DR HOGENOM; CLU_006033_9_2_1; -. DR InParanoid; Q9UEY8; -. DR OMA; XVRISKE; -. DR OrthoDB; 45123at2759; -. DR PhylomeDB; Q9UEY8; -. DR TreeFam; TF313003; -. DR PathwayCommons; Q9UEY8; -. DR Reactome; R-HSA-5223345; Miscellaneous transport and binding events. DR Reactome; R-HSA-9013405; RHOD GTPase cycle. DR Reactome; R-HSA-9035034; RHOF GTPase cycle. DR SignaLink; Q9UEY8; -. DR SIGNOR; Q9UEY8; -. DR BioGRID-ORCS; 120; 16 hits in 1164 CRISPR screens. DR ChiTaRS; ADD3; human. DR GeneWiki; ADD3; -. DR GenomeRNAi; 120; -. DR Pharos; Q9UEY8; Tbio. DR PRO; PR:Q9UEY8; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q9UEY8; Protein. DR Bgee; ENSG00000148700; Expressed in secondary oocyte and 213 other cell types or tissues. DR ExpressionAtlas; Q9UEY8; baseline and differential. DR GO; GO:0005903; C:brush border; IEA:Ensembl. DR GO; GO:0005938; C:cell cortex; IEA:Ensembl. DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl. DR GO; GO:0000794; C:condensed nuclear chromosome; IEA:Ensembl. DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central. DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0005080; F:protein kinase C binding; IEA:Ensembl. DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc. DR GO; GO:0051016; P:barbed-end actin filament capping; IBA:GO_Central. DR GO; GO:0051495; P:positive regulation of cytoskeleton organization; IEA:Ensembl. DR GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR Gene3D; 3.40.225.10; Class II aldolase/adducin N-terminal domain; 1. DR InterPro; IPR001303; Aldolase_II/adducin_N. DR InterPro; IPR036409; Aldolase_II/adducin_N_sf. DR PANTHER; PTHR10672; ADDUCIN; 1. DR PANTHER; PTHR10672:SF5; GAMMA-ADDUCIN; 1. DR Pfam; PF00596; Aldolase_II; 1. DR SMART; SM01007; Aldolase_II; 1. DR SUPFAM; SSF53639; AraD/HMP-PK domain-like; 1. DR Genevisible; Q9UEY8; HS. PE 1: Evidence at protein level; KW Acetylation; Actin-binding; Alternative splicing; Calmodulin-binding; KW Cell membrane; Cytoplasm; Cytoskeleton; Disease variant; Isopeptide bond; KW Membrane; Phosphoprotein; Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231" FT CHAIN 2..706 FT /note="Gamma-adducin" FT /id="PRO_0000218536" FT REGION 1..20 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 471..497 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 535..555 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 575..610 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 666..706 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 684..701 FT /note="Interaction with calmodulin" FT /evidence="ECO:0000255" FT COMPBIAS 585..605 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 683..697 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 357 FT /note="Cleavage by asparagine endopeptidase (AEP)" FT /evidence="ECO:0000250|UniProtKB:Q9QYB5" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231" FT MOD_RES 42 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 64 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 402 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 414 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QYB5" FT MOD_RES 423 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 442 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 461 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 585 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QYB5" FT MOD_RES 590 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QYB5" FT MOD_RES 673 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 677 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 679 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QYB5" FT MOD_RES 681 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 683 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 484 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 576..607 FT /note="Missing (in isoform 1)" FT /evidence="ECO:0000303|PubMed:17974005, FT ECO:0000303|PubMed:8893809, ECO:0000303|Ref.2" FT /id="VSP_000188" FT VARIANT 367 FT /note="G -> D (in CPSQ3; decreased actin capping activity; FT increased fibroblast proliferation and migration; decreased FT colocalization with alpha subunit ADD1; dbSNP:rs564185858)" FT /evidence="ECO:0000269|PubMed:23836506" FT /id="VAR_076996" FT CONFLICT 49..50 FT /note="FN -> SS (in Ref. 1; BAA23783)" FT /evidence="ECO:0000305" FT CONFLICT 60 FT /note="Q -> R (in Ref. 1; BAA23783)" FT /evidence="ECO:0000305" FT CONFLICT 362 FT /note="Q -> P (in Ref. 2; AAB17126)" FT /evidence="ECO:0000305" FT CONFLICT 420 FT /note="V -> M (in Ref. 2; AAB17126)" FT /evidence="ECO:0000305" FT CONFLICT 421 FT /note="P -> L (in Ref. 1; BAA23783)" FT /evidence="ECO:0000305" FT CONFLICT 426..433 FT /note="KYMAQRQQ -> QIHGTRGNK (in Ref. 2; AAB17126)" FT /evidence="ECO:0000305" FT CONFLICT 484 FT /note="K -> Q (in Ref. 2; AAB17126)" FT /evidence="ECO:0000305" SQ SEQUENCE 706 AA; 79155 MW; EB8EAF602A4D7B41 CRC64; MSSDASQGVI TTPPPPSMPH KERYFDRINE NDPEYIRERN MSPDLRQDFN MMEQRKRVTQ ILQSPAFRED LECLIQEQMK KGHNPTGLLA LQQIADYIMA NSFSGFSSPP LSLGMVTPIN DLPGADTSSY VKGEKLTRCK LASLYRLVDL FGWAHLANTY ISVRISKEQD HIIIIPRGLS FSEATASNLV KVNIIGEVVD QGSTNLKIDH TGFSPHAAIY STRPDVKCVI HIHTLATAAV SSMKCGILPI SQESLLLGDV AYYDYQGSLE EQEERIQLQK VLGPSCKVLV LRNHGVVALG ETLEEAFHYI FNVQLACEIQ VQALAGAGGV DNLHVLDFQK YKAFTYTVAA SGGGGVNMGS HQKWKVGEIE FEGLMRTLDN LGYRTGYAYR HPLIREKPRH KSDVEIPATV TAFSFEDDTV PLSPLKYMAQ RQQREKTRWL NSPNTYMKVN VPEESRNGET SPRTKITWMK AEDSSKVSGG TPIKIEDPNQ FVPLNTNPNE VLEKRNKIRE QNRYDLKTAG PQSQLLAGIV VDKPPSTMQF EDDDHGPPAP PNPFSHLTEG ELEEYKRTIE RKQQGLEDAE QELLSDDASS VSQIQSQTQS PQNVPEKLEE NHELFSKSFI SMEVPVMVVN GKDDMHDVED ELAKRVSRLS TSTTIENIEI TIKSPEKIEE VLSPEGSPSK SPSKKKKKFR TPSFLKKNKK KEKVEA //