Reviewed, UniProtKB/Swiss-Prot P16157 (ANK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Ankyrin-1
Alternative name(s):
    Erythrocyte ankyrin
    Ankyrin-R

Gene names

Name:	ANK1
Synonyms:	ANK

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	1881 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	Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions. In skeletal muscle, isoform Mu17 together with obscurin may provide a molecular link between the sarcoplasmic reticulum and myofibrils.
Subunit structure	Interacts with a number of integral membrane proteins and cytoskeletal proteins. Binds SPTB/spectrin (beta chain) through a 70 AA N-terminal region of the 62 kDa domain, and the C-terminal of SLC4A1/erythrocyte membrane protein band 3 through the ankyrin repeat region. Also interacts with TTN/titin. Isoform Mu17 interacts with OBSCN isoform 3/obscurin.
Subcellular location	Isoform Er1: Cytoplasm › cytoskeleton. Note= Probably the other erythrocyte (Er) isoforms, are located near the surface of erythrocytic plasma membrane. Isoform Mu17: Membrane. Cytoplasm › myofibril › sarcomere › M-band. Note= Colocalizes with OBSCN isoform 3/obscurin at the M line in differentiated skeletal muscle cells. Isoform Mu18: Sarcoplasmic reticulumProbable. Isoform Mu19: Sarcoplasmic reticulumProbable. Isoform Mu20: Sarcoplasmic reticulumProbable.
Tissue specificity	Isoform Mu17, isoform Mu18, isoform Mu19 and isoform Mu20 are expressed in skeletal muscle. Isoform Br21 is expressed in brain.
Domain	The 55 kDa regulatory domain is involved in regulating binding of SPTB/spectrin (beta chain) and SLC4A1/erythrocyte membrane protein band 3. The ANK repeat region forms a spiral around a large central cavity and is involved in binding of ion transporters.
Post-translational modification	Regulated by phosphorylation. Palmitoylated.
Involvement in disease	Defects in ANK1 are a cause of hereditary spherocytosis (HS) [MIM:182900]. Inheritance can be autosomal dominant or recessive.
Sequence similarities	Contains 23 ANK repeats. Contains 1 death domain. Contains 1 ZU5 domain.
Sequence caution	AAB47805.1 sequence differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Membrane Sarcoplasmic reticulum
Coding sequence diversity	Alternative promoter usage Alternative splicing Polymorphism
Disease	Disease mutation Elliptocytosis Hereditary hemolytic anemia
Domain	ANK repeat Repeat
PTM	Lipoprotein Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cytoskeleton organization and biogenesis Ref.4 Non-traceable author statement. Source: UniProtKB exocytosis Non-traceable author statement. Source: UniProtKB maintenance of epithelial cell apical/basal polarity Traceable author statement. Source: UniProtKB
Cellular component	basolateral plasma membrane Non-traceable author statement. Source: UniProtKB cytoskeleton Non-traceable author statement. Source: UniProtKB
Molecular function	cytoskeletal adaptor activity Traceable author statement. Source: UniProtKB enzyme binding Traceable author statement. Source: UniProtKB spectrin binding Ref.13 Non-traceable author statement. Source: UniProtKB structural constituent of cytoskeleton Ref.13 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
OBSCN	Q5VST9-3	5	EBI-941819,EBI-941921

Alternative products

This entry describes 21 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Isoform Er1 (identifier: P16157-1)

Also known as: 1; 2.1;

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.

Notes: Probably the other erythrocyte (Er) isoforms, are located near the surface of erythrocytic plasma membrane. Major erythrocyte-specific isoform. Produced by alternative promoter usage.

Isoform Er2 (identifier: P16157-4)

Also known as: 2; 2.2;

The sequence of this isoform differs from the canonical sequence as follows:
     1514-1675: Missing.

Notes: Predominant form of minor erythrocyte-specific isoforms. Produced by alternative splicing of isoform Er1.

Isoform Er3 (identifier: P16157-5)

Also known as: 3;

The sequence of this isoform differs from the canonical sequence as follows:
     1849-1873: Missing.

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er4 (identifier: P16157-6)

Also known as: 4;

The sequence of this isoform differs from the canonical sequence as follows:
     1514-1675: Missing.
     1849-1873: Missing.

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er5 (identifier: P16157-3)

Also known as: 5;

The sequence of this isoform differs from the canonical sequence as follows:
     1850-1881: TVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP → ELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er6 (identifier: P16157-7)

Also known as: 6;

The sequence of this isoform differs from the canonical sequence as follows:
     1514-1675: Missing.
     1850-1881: TVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP → ELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er7 (identifier: P16157-8)

Also known as: 7;

The sequence of this isoform differs from the canonical sequence as follows:
     1827-1873: Missing.

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er8 (identifier: P16157-9)

Also known as: 8;

The sequence of this isoform differs from the canonical sequence as follows:
     1514-1675: Missing.
     1827-1873: Missing.

Isoform Er9 (identifier: P16157-10)

Also known as: 9;

The sequence of this isoform differs from the canonical sequence as follows:
     1799-1873: Missing.

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er10 (identifier: P16157-11)

Also known as: 10;

The sequence of this isoform differs from the canonical sequence as follows:
     1514-1675: Missing.
     1799-1873: Missing.

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er11 (identifier: P16157-12)

Also known as: 11;

The sequence of this isoform differs from the canonical sequence as follows:
     1874-1881: DHTSTPNP → VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er12 (identifier: P16157-13)

Also known as: 12;

The sequence of this isoform differs from the canonical sequence as follows:
     1514-1675: Missing.
     1874-1881: DHTSTPNP → VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er13 (identifier: P16157-14)

Also known as: 13;

The sequence of this isoform differs from the canonical sequence as follows:
     1874-1881: DHTSTPNP → VLRRPRPWGT...KRASLKRGKQ

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er14 (identifier: P16157-15)

Also known as: 14;

The sequence of this isoform differs from the canonical sequence as follows:
     1514-1675: Missing.
     1874-1881: DHTSTPNP → VLRRPRPWGT...KRASLKRGKQ

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er15 (identifier: P16157-16)

Also known as: 15;

The sequence of this isoform differs from the canonical sequence as follows:
     1827-1881: IIRKVVRQID...SKDHTSTPNP → VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ

Notes: Produced by alternative splicing of isoform Er1.

Isoform Er16 (identifier: P16157-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1513-1874: Missing.
     1875-1875: H → D

Notes: Produced by alternative splicing of isoform Er1.

Isoform Mu17 (identifier: P16157-17)

Also known as: ank1.5; muscle-specific 1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1725: Missing.
     1726-1798: TQGPHSFQGT...AKNTFTQVVQ → MWTFVTQLLV...RVVRRRVFLK
     1850-1881: TVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP → ELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ

Notes: Colocalizes with OBSCN isoform 3/obscurin at the M line in differentiated skeletal muscle cells. Produced by alternative promoter usage.

Isoform Mu18 (identifier: P16157-18)

Also known as: ank1.6; muscle-specific 2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1725: Missing.
     1726-1798: TQGPHSFQGT...AKNTFTQVVQ → MWTFVTQLLV...RVVRRRVFLK
     1827-1881: IIRKVVRQID...SKDHTSTPNP → VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ

Notes: Produced by alternative splicing of isoform Mu17.

Isoform Mu19 (identifier: P16157-19)

Also known as: muscle-specific 3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1725: Missing.
     1726-1798: TQGPHSFQGT...AKNTFTQVVQ → MWTFVTQLLV...RVVRRRVFLK
     1799-1873: Missing.

Notes: Produced by alternative splicing of isoform Mu17.

Isoform Mu20 (identifier: P16157-20)

Also known as: muscle-specific 4;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1725: Missing.
     1726-1798: TQGPHSFQGT...AKNTFTQVVQ → MWTFVTQLLV...LCFVLKHIHQ
     1799-1881: GNEFQNIPGE...SKDHTSTPNP → VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ

Notes: Produced by alternative splicing of isoform Mu17.

Isoform Br21 (identifier: P16157-21)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MPYSVGFRE → MAQAAKQLKKIKDIEAQALQEQKEKEESNRKRRNRSRDRKKK
     820-820: E → EGTAHITIM
     1849-1873: Missing.

Notes: No experimental confirmation available. Produced by alternative splicing of isoform Er1.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 1881	1880	Ankyrin-1
Regions
	Repeat	44 – 73	30	ANK 1
	Repeat	77 – 106	30	ANK 2
	Repeat	110 – 139	30	ANK 3
	Repeat	143 – 172	30	ANK 4
	Repeat	174 – 201	28	ANK 5
	Repeat	205 – 234	30	ANK 6
	Repeat	238 – 267	30	ANK 7
	Repeat	271 – 300	30	ANK 8
	Repeat	304 – 333	30	ANK 9
	Repeat	337 – 366	30	ANK 10
	Repeat	370 – 399	30	ANK 11
	Repeat	403 – 432	30	ANK 12
	Repeat	436 – 465	30	ANK 13
	Repeat	469 – 498	30	ANK 14
	Repeat	502 – 531	30	ANK 15
	Repeat	535 – 564	30	ANK 16
	Repeat	568 – 597	30	ANK 17
	Repeat	601 – 630	30	ANK 18
	Repeat	634 – 663	30	ANK 19
	Repeat	667 – 696	30	ANK 20
	Repeat	700 – 729	30	ANK 21
	Repeat	733 – 762	30	ANK 22
	Repeat	766 – 795	30	ANK 23
	Domain	911 – 1018	108	ZU5
	Domain	1403 – 1487	85	Death
	Region	2 – 827	826	89 kDa domain
	Region	1383 – 1881	499	55 kDa regulatory domain
Amino acid modifications
	Modified residue	856	1	Phosphoserine By similarity
	Modified residue	1073	1	Phosphotyrosine By similarity
	Modified residue	1684	1	Phosphothreonine
	Modified residue	1686	1	Phosphoserine
Natural variations
	Alternative sequence	1 – 1725	1725	Missing in isoform Mu17, isoform Mu18, isoform Mu19 and isoform Mu20.
	Alternative sequence	1 – 9	9	MPYSVGFRE → MAQAAKQLKKIKDIEAQALQ EQKEKEESNRKRRNRSRDRK KK in isoform Br21.
	Alternative sequence	820	1	E → EGTAHITIM in isoform Br21.
	Alternative sequence	1513 – 1874	362	Missing in isoform Er16.
	Alternative sequence	1514 – 1675	162	Missing in isoform Er2, isoform Er4, isoform Er6, isoform Er8, isoform Er10, isoform Er12 and isoform Er14.
	Alternative sequence	1726 – 1798	73	TQGPH…TQVVQ → MWTFVTQLLVTLVLLSFFLV SCQNVMHIVRGSLCFVLKHI HQELDKELGESEGLSDDEET ISPRVVRRRVFLK in isoform Mu17, isoform Mu18 and isoform Mu19.
	Alternative sequence	1726 – 1798	73	TQGPH…TQVVQ → MWTFVTQLLVTLVLLSFFLV SCQNVMHIVRGSLCFVLKHI HQ in isoform Mu20.
	Alternative sequence	1799 – 1881	83	GNEFQ…STPNP → VELRGSGLQPDLIEGRKGAQ IVKRASLKRGKQ in isoform Mu20.
	Alternative sequence	1799 – 1873	75	Missing in isoform Er9, isoform Er10 and isoform Mu19.
	Alternative sequence	1827 – 1881	55	IIRKV…STPNP → VELRGSGLQPDLIEGRKGAQ IVKRASLKRGKQ in isoform Er15 and isoform Mu18.
	Alternative sequence	1827 – 1873	47	Missing in isoform Er7 and isoform Er8.
	Alternative sequence	1849 – 1873	25	Missing in isoform Er3, isoform Er4 and isoform Br21.
	Alternative sequence	1850 – 1881	32	TVEGP…STPNP → ELRGSGLQPDLIEGRKGAQI VKRASLKRGKQ in isoform Er5, isoform Er6 and isoform Mu17.
	Alternative sequence	1874 – 1881	8	DHTSTPNP → VELRGSGLQPDLIEGRKGAQ IVKRASLKRGKQ in isoform Er11 and isoform Er12.
	Alternative sequence	1874 – 1881	8	DHTSTPNP → VLRRPRPWGTQRHHCCLALP GRLHDTSLHSPLYELSLQSL FSLVGSVSAPPCRSFRSSAC VLPVFAICPAFCLCCCLQVE LRGSGLQPDLIEGRKGAQIV KRASLKRGKQ in isoform Er13 and isoform Er14.
	Alternative sequence	1875	1	H → D in isoform Er16.
	Natural variant	21	1	R → T
	Natural variant	332	1	D → H in a breast cancer sample; somatic mutation.
	Natural variant	463	1	V → I in HS.
	Natural variant	619	1	R → H in Brueggen. dbSNP rs2304877.
	Natural variant	733	1	L → I: dbSNP rs11778936.
	Natural variant	750	1	V → A
	Natural variant	845	1	D → E
	Natural variant	991	1	V → L
	Natural variant	1126	1	A → P: dbSNP rs504465.
	Natural variant	1192	1	T → P: dbSNP rs486770.
	Natural variant	1286	1	E → D
	Natural variant	1325	1	M → V: dbSNP rs10093583.
	Natural variant	1392	1	S → T
	Natural variant	1546	1	V → I: dbSNP rs1060130.
	Natural variant	1592	1	D → N in Duesseldorf.
Experimental info
	Mutagenesis	1824	1	T → P: Abolishes interaction with OBSCN (in isoform Mu17)
	Mutagenesis	1826	1	K → E: Abolishes interaction with OBSCN (in isoform Mu17)
	Mutagenesis	1829	1	R → G: Abolishes interaction with OBSCN (in isoform Mu17)
	Mutagenesis	1830	1	K → E: Abolishes interaction with OBSCN (in isoform Mu17)
	Sequence conflict	230	1	A → S in AAA51732.