Reviewed, UniProtKB/Swiss-Prot P35612 (ADDB_HUMAN)

Names and origin

Protein names

Recommended name:
    Beta-adducin
Alternative name(s):
    Erythrocyte adducin subunit beta

Gene names

Name:	ADD2
Synonyms:	ADDB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	726 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin. Calmodulin binds preferentially to the beta subunit.
Subunit structure	Heterodimer of an alpha and a beta subunit.
Subcellular location	Cytoplasm › cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side.
Tissue specificity	Expressed mainly in brain, spleen, kidney cortex and medulla, and heart. Also expressed in human umbilical vein endothelial cells, human vascular smooth muscle cells, kidney tubular cells and K562 cells.
Developmental stage	Fetal kidney expresses isoforms 3, 4, 5, 6 and 7, and fetal liver expresses isoforms 3 and 4.
Domain	Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.
Post-translational modification	The N-terminus is blocked.
Sequence similarities	Belongs to the aldolase class II family. Adducin subfamily.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Actin-binding Calmodulin-binding
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	actin binding Ref.1 Traceable author statement. Source: ProtInc calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Notes: Additional isoforms seem to exist.

Isoform 1 (identifier: P35612-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P35612-2)

Also known as: Adducin 63;

The sequence of this isoform differs from the canonical sequence as follows:
     532-559: STESQLMSKGDEDTKDDSEETVPNPFSQ → VEQRLPLTGGETCLPSGSSVPGAGLQDP
     560-726: Missing.

Isoform 3 (identifier: P35612-3)

Also known as: Beta-4; E;

The sequence of this isoform differs from the canonical sequence as follows:
     581-726: GEKETAPEEP...KSKKKEKVES → ETGQEREPGS...QRRRQRQRAL

Isoform 4 (identifier: P35612-4)

Also known as: Beta-4a;

The sequence of this isoform differs from the canonical sequence as follows:
     581-587: GEKETAP → APGWFSS
     588-726: Missing.

Isoform 5 (identifier: P35612-5)

Also known as: Beta-4b;

The sequence of this isoform differs from the canonical sequence as follows:
     188-493: Missing.
     581-586: GEKETA → ETGQER
     587-726: Missing.

Isoform 6 (identifier: P35612-6)

Also known as: Beta-4c;

The sequence of this isoform differs from the canonical sequence as follows:
     188-493: Missing.
     581-587: GEKETAP → APGWFSS
     588-726: Missing.

Isoform 7 (identifier: P35612-7)

Also known as: Beta-4d;

The sequence of this isoform differs from the canonical sequence as follows:
     78-566: Missing.
     581-587: GEKETAP → APGWFSS
     588-726: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 726	725	Beta-adducin		PRO_0000218533
Regions
	Region	425 – 444	20	Interaction with calmodulin Potential
	Region	704 – 721	18	Interaction with calmodulin Potential
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	55	1	Phosphothreonine; by PKA
	Modified residue	532	1	Phosphoserine By similarity
	Modified residue	535	1	Phosphoserine By similarity
	Modified residue	592	1	Phosphoserine By similarity
	Modified residue	600	1	Phosphoserine By similarity
	Modified residue	688	1	Phosphothreonine By similarity
	Modified residue	703	1	Phosphoserine; by PKC
	Modified residue	713	1	Phosphoserine; by PKA and PKC
Natural variations
	Alternative sequence	78 – 566	489	Missing in isoform 7.		VSP_017241
	Alternative sequence	188 – 493	306	Missing in isoform 5 and isoform 6.		VSP_017242
	Alternative sequence	532 – 559	28	STESQ…NPFSQ → VEQRLPLTGGETCLPSGSSV PGAGLQDP in isoform 2.		VSP_000181
	Alternative sequence	560 – 726	167	Missing in isoform 2.		VSP_000182
	Alternative sequence	581 – 726	146	GEKET…EKVES → ETGQEREPGSGPAVCEFFSV ALHIWSNILERKKLPQKSLA HLQSLHLLLQCRAQRRRQRQ RAL in isoform 3.		VSP_000183
	Alternative sequence	581 – 587	7	GEKETAP → APGWFSS in isoform 4, isoform 6 and isoform 7.		VSP_017244
	Alternative sequence	581 – 586	6	GEKETA → ETGQER in isoform 5.		VSP_017243
	Alternative sequence	587 – 726	140	Missing in isoform 5.		VSP_017245
	Alternative sequence	588 – 726	139	Missing in isoform 4, isoform 6 and isoform 7.		VSP_017246
	Natural variant	28	1	D → N: dbSNP rs4986.		VAR_014866
	Natural variant	335	1	E → D: dbSNP rs4982.		VAR_014867
	Natural variant	439	1	T → A: dbSNP rs17855969.		VAR_025318
	Natural variant	663	1	S → R: dbSNP rs4985.		VAR_014868

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: B07F7303D929DBA4	FASTA	726	80,854
	10 20 30 40 50 60 MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS 70 80 90 100 110 120 PSFREELEGL IQEQMKKGNN SSNIWALRQI ADFMASTSHA VFPTSSMNVS MMTPINDLHT 130 140 150 160 170 180 ADSLNLAKGE RLMRCKISSV YRLLDLYGWA QLSDTYVTLR VSKEQDHFLI SPKGVSCSEV 190 200 210 220 230 240 TASSLIKVNI LGEVVEKGSS CFPVDTTGFC LHSAIYAARP DVRCIIHLHT PATAAVSAMK 250 260 270 280 290 300 WGLLPVSHNA LLVGDMAYYD FNGEMEQEAD RINLQKCLGP TCKILVLRNH GVVALGDTVE 310 320 330 340 350 360 EAFYKIFHLQ AACEIQVSAL SSAGGVENLI LLEQEKHRPH EVGSVQWAGS TFGPMQKSRL 370 380 390 400 410 420 GEHEFEALMR MLDNLGYRTG YTYRHPFVQE KTKHKSEVEI PATVTAFVFE EDGAPVPALR 430 440 450 460 470 480 QHAQKQQKEK TRWLNTPNTY LRVNVADEVQ RSMGSPRPKT TWMKADEVEK SSSGMPIRIE 490 500 510 520 530 540 NPNQFVPLYT DPQEVLEMRN KIREQNRQDV KSAGPQSQLL ASVIAEKSRS PSTESQLMSK 550 560 570 580 590 600 GDEDTKDDSE ETVPNPFSQL TDQELEEYKK EVERKKLELD GEKETAPEEP GSPAKSAPAS 610 620 630 640 650 660 PVQSPAKEAE TKSPLVSPSK SLEEGTKKTE TSKAATTEPE TTQPEGVVVN GREEEQTAEE 670 680 690 700 710 720 ILSKGLSQMT TSADTDVDTS KDKTESVTSG PMSPEGSPSK SPSKKKKKFR TPSFLKKSKK KEKVES
	Isoform 2 (Adducin 63) [UniParc]. Checksum: B62B278AE8F48FD4		559	62,467
	10 20 30 40 50 60 MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS 70 80 90 100 110 120 PSFREELEGL IQEQMKKGNN SSNIWALRQI ADFMASTSHA VFPTSSMNVS MMTPINDLHT 130 140 150 160 170 180 ADSLNLAKGE RLMRCKISSV YRLLDLYGWA QLSDTYVTLR VSKEQDHFLI SPKGVSCSEV 190 200 210 220 230 240 TASSLIKVNI LGEVVEKGSS CFPVDTTGFC LHSAIYAARP DVRCIIHLHT PATAAVSAMK 250 260 270 280 290 300 WGLLPVSHNA LLVGDMAYYD FNGEMEQEAD RINLQKCLGP TCKILVLRNH GVVALGDTVE 310 320 330 340 350 360 EAFYKIFHLQ AACEIQVSAL SSAGGVENLI LLEQEKHRPH EVGSVQWAGS TFGPMQKSRL 370 380 390 400 410 420 GEHEFEALMR MLDNLGYRTG YTYRHPFVQE KTKHKSEVEI PATVTAFVFE EDGAPVPALR 430 440 450 460 470 480 QHAQKQQKEK TRWLNTPNTY LRVNVADEVQ RSMGSPRPKT TWMKADEVEK SSSGMPIRIE 490 500 510 520 530 540 NPNQFVPLYT DPQEVLEMRN KIREQNRQDV KSAGPQSQLL ASVIAEKSRS PVEQRLPLTG 550 GETCLPSGSS VPGAGLQDP
	Isoform 3 (Beta-4) (E) [UniParc]. Checksum: 46A10F1D1278E955		643	72,721
	10 20 30 40 50 60 MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS 70 80 90 100 110 120 PSFREELEGL IQEQMKKGNN SSNIWALRQI ADFMASTSHA VFPTSSMNVS MMTPINDLHT 130 140 150 160 170 180 ADSLNLAKGE RLMRCKISSV YRLLDLYGWA QLSDTYVTLR VSKEQDHFLI SPKGVSCSEV 190 200 210 220 230 240 TASSLIKVNI LGEVVEKGSS CFPVDTTGFC LHSAIYAARP DVRCIIHLHT PATAAVSAMK 250 260 270 280 290 300 WGLLPVSHNA LLVGDMAYYD FNGEMEQEAD RINLQKCLGP TCKILVLRNH GVVALGDTVE 310 320 330 340 350 360 EAFYKIFHLQ AACEIQVSAL SSAGGVENLI LLEQEKHRPH EVGSVQWAGS TFGPMQKSRL 370 380 390 400 410 420 GEHEFEALMR MLDNLGYRTG YTYRHPFVQE KTKHKSEVEI PATVTAFVFE EDGAPVPALR 430 440 450 460 470 480 QHAQKQQKEK TRWLNTPNTY LRVNVADEVQ RSMGSPRPKT TWMKADEVEK SSSGMPIRIE 490 500 510 520 530 540 NPNQFVPLYT DPQEVLEMRN KIREQNRQDV KSAGPQSQLL ASVIAEKSRS PSTESQLMSK 550 560 570 580 590 600 GDEDTKDDSE ETVPNPFSQL TDQELEEYKK EVERKKLELD ETGQEREPGS GPAVCEFFSV 610 620 630 640 ALHIWSNILE RKKLPQKSLA HLQSLHLLLQ CRAQRRRQRQ RAL
	Isoform 4 (Beta-4a) [UniParc]. Checksum: B7ACFE32B2731FB5		587	66,154
	10 20 30 40 50 60 MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS 70 80 90 100 110 120 PSFREELEGL IQEQMKKGNN SSNIWALRQI ADFMASTSHA VFPTSSMNVS MMTPINDLHT 130 140 150 160 170 180 ADSLNLAKGE RLMRCKISSV YRLLDLYGWA QLSDTYVTLR VSKEQDHFLI SPKGVSCSEV 190 200 210 220 230 240 TASSLIKVNI LGEVVEKGSS CFPVDTTGFC LHSAIYAARP DVRCIIHLHT PATAAVSAMK 250 260 270 280 290 300 WGLLPVSHNA LLVGDMAYYD FNGEMEQEAD RINLQKCLGP TCKILVLRNH GVVALGDTVE 310 320 330 340 350 360 EAFYKIFHLQ AACEIQVSAL SSAGGVENLI LLEQEKHRPH EVGSVQWAGS TFGPMQKSRL 370 380 390 400 410 420 GEHEFEALMR MLDNLGYRTG YTYRHPFVQE KTKHKSEVEI PATVTAFVFE EDGAPVPALR 430 440 450 460 470 480 QHAQKQQKEK TRWLNTPNTY LRVNVADEVQ RSMGSPRPKT TWMKADEVEK SSSGMPIRIE 490 500 510 520 530 540 NPNQFVPLYT DPQEVLEMRN KIREQNRQDV KSAGPQSQLL ASVIAEKSRS PSTESQLMSK 550 560 570 580 GDEDTKDDSE ETVPNPFSQL TDQELEEYKK EVERKKLELD APGWFSS
	Isoform 5 (Beta-4b) [UniParc]. Checksum: 851E20275B19D246		280	31,935
	10 20 30 40 50 60 MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS 70 80 90 100 110 120 PSFREELEGL IQEQMKKGNN SSNIWALRQI ADFMASTSHA VFPTSSMNVS MMTPINDLHT 130 140 150 160 170 180 ADSLNLAKGE RLMRCKISSV YRLLDLYGWA QLSDTYVTLR VSKEQDHFLI SPKGVSCSEV 190 200 210 220 230 240 TASSLIKEVL EMRNKIREQN RQDVKSAGPQ SQLLASVIAE KSRSPSTESQ LMSKGDEDTK 250 260 270 280 DDSEETVPNP FSQLTDQELE EYKKEVERKK LELDETGQER
	Isoform 6 (Beta-4c) [UniParc]. Checksum: 1CF4ACF5875DDF12		281	31,967
	10 20 30 40 50 60 MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS 70 80 90 100 110 120 PSFREELEGL IQEQMKKGNN SSNIWALRQI ADFMASTSHA VFPTSSMNVS MMTPINDLHT 130 140 150 160 170 180 ADSLNLAKGE RLMRCKISSV YRLLDLYGWA QLSDTYVTLR VSKEQDHFLI SPKGVSCSEV 190 200 210 220 230 240 TASSLIKEVL EMRNKIREQN RQDVKSAGPQ SQLLASVIAE KSRSPSTESQ LMSKGDEDTK 250 260 270 280 DDSEETVPNP FSQLTDQELE EYKKEVERKK LELDAPGWFS S
	Isoform 7 (Beta-4d) [UniParc]. Checksum: 2FABB44289701D9B		98	11,625
	10 20 30 40 50 60 MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS 70 80 90 PSFREELEGL IQEQMKKEYK KEVERKKLEL DAPGWFSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and domain organization of human alpha and beta adducin." Joshi R.L., Gilligan D.M., Otto E., McLaughlin T., Bennett V.D. J. Cell Biol. 115:665-675(1991) [PubMed: 1840603] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. Tissue: Reticulocyte.
[2]	"Expression analysis of the human adducin gene family and evidence of ADD2 beta4 multiple splicing variants." Citterio L., Tizzoni L., Catalano M., Zerbini G., Bianchi G., Barlassina C. Biochem. Biophys. Res. Commun. 309:359-367(2003) [PubMed: 12951058] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6 AND 7), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Fetal kidney and Umbilical vein endothelial cell.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno F.R. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANT ALA-439. Tissue: Eye.
[6]	"A novel isoform of beta adducin utilizes an alternatively spliced exon near the C-terminus." Sinard J.H., Stewart G.W., Argent A.C., Gilligan D.M., Morrow J.S. Mol. Biol. Cell 6:269-269(1995) Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 332-726 (ISOFORM 3). Tissue: Bone marrow.
[7]	"Genomic organisation and chromosomal localisation of the gene encoding human beta adducin." Tisminetzky S., Devescovi G., Tripodi G., Muro A., Bianchi G., Colombi M., Moro L., Barlati S., Tuteja R., Baralle F.E. Gene 167:313-316(1995) [PubMed: 8566798] [Abstract] Cited for: ALTERNATIVE SPLICING.
[8]	"Adducin regulation. Definition of the calmodulin-binding domain and sites of phosphorylation by protein kinases A and C." Matsuoka Y., Hughes C.A., Bennett V. J. Biol. Chem. 271:25157-25166(1996) [PubMed: 8810272] [Abstract] Cited for: PHOSPHORYLATION AT THR-55; SER-703 AND SER-713, PARTIAL PROTEIN SEQUENCE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X58199 mRNA. Translation: CAA41176.1. AF486420 mRNA. Translation: AAP71863.1. AF486421 mRNA. Translation: AAP71864.1. AF486422 mRNA. Translation: AAP71865.1. AF486423 mRNA. Translation: AAP71866.1. AB209227 mRNA. Translation: BAD92464.1. Different initiation. AC005234 Genomic DNA. Translation: AAD12715.1. AC007395 Genomic DNA. No translation available. BC041666 mRNA. Translation: AAH41666.1. BC051882 mRNA. Translation: AAH51882.1. BC056881 mRNA. Translation: AAH56881.1. BC065525 mRNA. Translation: AAH65525.1. U43959 mRNA. Translation: AAA86421.1. S81079, S81077 Genomic DNA. Translation: AAD14349.1.
PIR	S18208.
RefSeq	NP_001608.1. NP_059522.1.
UniGene	Hs.188528
3D structure databases
DisProt	DP00241.
ModBase	Search...
PTM databases
PhosphoSite	P35612.
Genome annotation databases
Ensembl	ENSG00000075340. Homo sapiens. [Contig view]
GeneID	119.
KEGG	hsa:119.
Organism-specific databases
H-InvDB	HIX0029808.
HGNC	HGNC:244. ADD2.
HPA	CAB009796.
MIM	102681. gene.
PharmGKB	PA24566.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P35612.
Gene expression databases
ArrayExpress	P35612.
GermOnline	ENSG00000075340. Homo sapiens.
Family and domain databases
InterPro	IPR001303. Aldolase_II/adducin_N. [Graphical view]
Gene3D	G3DSA:3.40.225.10. Aldolase_II/adducin_N. 1 hit.
Pfam	PF00596. Aldolase_II. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	469.
SOURCE	Search...

Entry information

Entry name	ADDB_HUMAN
Accession	Primary (citable) accession number: P35612 Secondary accession number(s): Q13482