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PR01887

Identifier
SPECTRNALPHA  [View Relations]  [View Alignment]  
Accession
PR01887
No. of Motifs
3
Creation Date
08-DEC-2004  (UPDATE 08-MAY-2008)
Title
Spectrin alpha chain signature
Database References

PFAM; PF00435 Spectrin
PRODOM; PD000012; PD000066
INTERPRO; IPR001452; IPR002017; IPR002048; IPR011992; IPR013315; IPR014837

PDB; 1PWT
SCOP; 1PWT
CATH; 1PWT
Literature References
1. YAN, Y., WINOGRAD, E., VIEL, A., CRONIN, T., HARRISON, S.C.
AND BRANTON, D.
Crystal structure of the repetitive segments of spectrin.
SCIENCE 262 2027-2030 (1993).
 
2. SPEICHER, D.W. AND MARCHESI, V.T.
Erythrocyte spectrin is comprised of many homologous triple helical 
segments.
NATURE 311 177-180 (1984).
 
3. SPEICHER, D.W., WEGLARZ, L. AND DESILVA, T.M.
Properties of human red cell spectrin heterodimer (side-to-side)
assembly and identification of an essential nucleation site.
J.BIOL.CHEM. 267 14775-14782 (1992).
 
4. PASCUAL, J., PFUHL, M., WALTHER, D., SARASTE, M. AND NILGES, M.
Solution structure of the spectrin repeat: a left-handed antiparallel
triple-helical coiled-coil.
J.MOL.BIOL. 273 740-751 (1997).
 
5. MAILLET, P., ALLOISIO, N., MORLE, L. AND DELAUNAY, J.
Spectrin mutations in hereditary elliptocytosis and hereditary
spherocytosis.
HUM.MUTAT. 8 97-107 (1996).
 
6. FLOYD, P.B., GALLAGHER, P.G., VALENTINO, L.A., DAVIS, M.,
MARCHESI, S.L. AND FORGET, B.G.
Heterogeneity of the molecular basis of hereditary pyropoikilocytosis
and hereditary elliptocytosis associated with increased levels of the
spectrin alpha I/74-kilodalton tryptic peptide.
BLOOD 78 1364-1372 (1991).

Documentation
Spectrin is an elongated protein that belongs to a family of related 
molecules (including dystrophin and alpha-actinin) that contain tandemly 
repeated segments and form resilient cellular meshworks by cross-linking 
actin filaments [1]. The protein is an alpha-beta heterodimer [2] in which 
the alpha and beta monomers associate in an anti-parallel fashion [3]. 
Assembly involves initial contact of complementary nucleation sites on each 
subunit, via four tandem repeat regions [3]. Following nucleation, the 
remainder of the subunits associate rapidly along their full lengths to 
form a dimer by super-coiling around each other, forming a rope-like,
flexible rod [3]. Assembly terminates if either polypeptide is interrupted 
by protease cleavage. Heterozygotic mutations involving either nucleation 
site are predicted to affect allele incorporation into the mature membrane 
skeleton [3]. 
 
The structure of a repeat unit of alpha-spectrin has been determined to 
1.8A resolution by means of X-ray crystallography [1]. This was shown to 
comprise an anti-parallel three-helix bundle separated by two loops, which 
folds into a left-handed coiled coil [4]. At the interface between tandem 
repeats, hydrophobic interactions may constrain intersegment flexibility. 
The interaction between alpha- and beta-subunits is mediated by the 
association of two helices at the C-terminus of the beta-chain and a single 
helix from the N-terminus of the alpha-chain. Mutations that affect these 
critical helix side-chain interactions disrupt spectrin associations that 
sustain the integrity of erythrocyte membranes giving rise to haemolytic 
anaemias [1,4]. These haemolytic syndromes include hereditary ellipto-
cytosis, its aggravated form hereditary pyropoikilocytosis and hereditary
spherocytosis [5,6].
 
SPECTRNALPHA is a 3-element fingerprint that provides a signature for
spectrin alpha chains. The fingerprint was derived from an initial
alignment of 10 sequences: the motifs were drawn from the SH3 domain
in central portion of the alignment, focusing on those sections that
characterise the alpha spectrin SH3 domains and distinguish them from
other closely-related SH3-domain containing proteins. A single 
iteration on SPTR44_27f was required to reach convergence, no further 
sequences being identified beyond the starting set.
 
An update on SPTR55_38f identified a true set comprising 25 sequences.
Summary Information
25 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3252525
2000
123
True Positives
A0JPA2_XENTR  A3FG33_DANRE  A3KGU5_MOUSE  A3KGU7_MOUSE  
A3KGU8_MOUSE A6NG51_HUMAN A8PJH9_BRUMA A8XJE3_CAEBR
Q16EQ1_AEDAE Q21408 Q3KN50_DROME Q4T9R4_TETNG
Q4T9R5_TETNG Q5VYL1_HUMAN Q5VYL2_HUMAN Q6IRK8
Q6XDA1 Q7Q515_ANOGA SPCA_DROME SPCA_HUMAN
SPCA_MOUSE SPCN_CHICK SPCN_HUMAN SPCN_RAT
SPTA2_MOUSE
Sequence Titles
A0JPA2_XENTR LOC100036647 protein - Xenopus tropicalis (Western clawed frog) (Silurana tropicalis). 
A3FG33_DANRE Alpha II-spectrin - Danio rerio (Zebrafish) (Brachydanio rerio).
A3KGU5_MOUSE Spectrin alpha 2 - Mus musculus (Mouse).
A3KGU7_MOUSE Spectrin alpha 2 - Mus musculus (Mouse).
A3KGU8_MOUSE Spectrin alpha 2 - Mus musculus (Mouse).
A6NG51_HUMAN Uncharacterized protein SPTAN1 - Homo sapiens (Human).
A8PJH9_BRUMA Spectrin alpha chain, putative - Brugia malayi (Filarial nematode worm).
A8XJE3_CAEBR Putative uncharacterized protein - Caenorhabditis briggsae.
Q16EQ1_AEDAE Spectrin - Aedes aegypti (Yellowfever mosquito).
Q21408 Spectrin protein 1 - Caenorhabditis elegans.
Q3KN50_DROME RE03775p - Drosophila melanogaster (Fruit fly).
Q4T9R4_TETNG Chromosome undetermined SCAF7505, whole genome shotgun sequence - Tetraodon nigroviridis (Green puffer).
Q4T9R5_TETNG Chromosome undetermined SCAF7505, whole genome shotgun sequence - Tetraodon nigroviridis (Green puffer).
Q5VYL1_HUMAN Spectrin, alpha, erythrocytic 1 (Elliptocytosis 2) - Homo sapiens (Human).
Q5VYL2_HUMAN Spectrin, alpha, erythrocytic 1 (Elliptocytosis 2) - Homo sapiens (Human).
Q6IRK8 Spna2 protein - Rattus norvegicus (Rat).
Q6XDA1 Erythroid spectrin alpha - Rattus norvegicus (Rat).
Q7Q515_ANOGA AGAP006686-PA - Anopheles gambiae str. PEST.
SPCA_DROME Spectrin alpha chain - Drosophila melanogaster (Fruit fly).
SPCA_HUMAN Spectrin alpha chain, erythrocyte (Erythroid alpha-spectrin) - Homo sapiens (Human).
SPCA_MOUSE Spectrin alpha chain, erythrocyte (Erythroid alpha-spectrin) - Mus musculus (Mouse).
SPCN_CHICK Spectrin alpha chain, brain (Spectrin, non-erythroid alpha chain) (Fodrin alpha chain) - Gallus gallus (Chicken).
SPCN_HUMAN Spectrin alpha chain, brain (Spectrin, non-erythroid alpha chain) (Alpha-II spectrin) (Fodrin alpha chain) - Homo sapiens (Human).
SPCN_RAT Spectrin alpha chain, brain (Spectrin, non-erythroid alpha chain) (Alpha-II spectrin) (Fodrin alpha chain) - Rattus norvegicus (Rat).
SPTA2_MOUSE Spectrin alpha chain, brain (Spectrin, non-erythroid alpha chain) (Alpha-II spectrin) (Fodrin alpha chain) - Mus musculus (Mouse).
Scan History
SPTR44_27f 1  140  NSINGLE    
SPTR55_38f 2 150 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
EARVIALYDFEARSRREVSM Q6XDA1 977 977 -
KELVLALYDYQEKSPREVTM Q6IRK8 969 969 -
RDCVLALYDYQEKSPREVSM Q21408 985 985 -
EQRVMALYDFQARSPREVTM SPCA_HUMAN 979 979 -
EARVIALYDFEARSRREVSM SPCA_MOUSE 977 977 -
KECVVALYDYTEKSPREVSM SPCA_DROME 972 972 -
KELVLALYDYQEKSPREVTM SPCN_RAT 969 969 -
KELVLALYDYQEKSPREVTM SPCN_HUMAN 969 969 -
KELVLALYDYQEKSPREVTM Q7Z6M5 969 969 -
KELVLALYDYQEKSPREVTM SPCN_CHICK 969 969 -

Motif 2 width=15
Element Seqn Id St Int Rpt
KKGDILTLLNSTNKD SPCN_RAT 989 0 -
KKGDILTLLNSTNKD Q6IRK8 989 0 -
KKGDVLTLLNASNRD Q21408 1005 0 -
KKNDVLTLLSSINKD Q6XDA1 997 0 -
KKNDVLTLLSSINKD SPCA_MOUSE 997 0 -
KKGDVLTLLNSNNKD SPCA_DROME 992 0 -
KKGDVLTLLSSINKD SPCA_HUMAN 999 0 -
KKGDILTLLNSTNKD SPCN_HUMAN 989 0 -
KKGDILTLLNSTNKD Q7Z6M5 989 0 -
KKGDILTLLNSTNKD SPCN_CHICK 989 0 -

Motif 3 width=22
Element Seqn Id St Int Rpt
WWKVEADDHQGFVPAVYVRKLA Q6XDA1 1012 0 -
WWKVEAADHQGIVPAVYVRRLA SPCA_HUMAN 1014 0 -
WWKVEADDHQGFVPAVYVRKLA SPCA_MOUSE 1012 0 -
WWKVEVNDRQGFVPAAYIKKID SPCA_DROME 1007 0 -
WWKVEVNDRQGFVPAAYVKKLD SPCN_RAT 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD SPCN_HUMAN 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD Q7Z6M5 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD SPCN_CHICK 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD Q6IRK8 1004 0 -
WWKVEVNDRQGFVPAAYVKRIE Q21408 1020 0 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
KELVLALYDYQEKSPREVTM A0JPA2_XENTR 969 969 -
KELVLALYDYQEKSPREVTM SPCN_RAT 969 969 -
KELVLALYDYQEKSPREVTM SPTA2_MOUSE 969 969 -
KELVLALYDYQEKSPREVTM SPCN_HUMAN 969 969 -
KELVLALYDYQEKSPREVTM SPCN_CHICK 969 969 -
KELVLALYDYQEKSPREVTM Q6IRK8 969 969 -
KELVLALYDYQEKSPREVTM A6NG51_HUMAN 969 969 -
KELVLALYDYQEKSPREVTM A3KGU8_MOUSE 969 969 -
KELVLALYDYQEKSPREVTM A3KGU7_MOUSE 969 969 -
KELVLALYDYQEKSPREVTM A3KGU5_MOUSE 969 969 -
KELVLALYDYQEKSPREVTM A3FG33_DANRE 969 969 -
KELVLALYDYQEKSPREVTM Q4T9R5_TETNG 1090 1090 -
KELVLALYDYQEKSPREVTM Q4T9R4_TETNG 1006 1006 -
KECVMALYDYTEKSPREVSM Q16EQ1_AEDAE 972 972 -
KECVVALYDYTEKSPREVSM Q3KN50_DROME 972 972 -
KECVVALYDYTEKSPREVSM SPCA_DROME 972 972 -
KECVMALYDYTEKSPREVSM Q7Q515_ANOGA 972 972 -
RDCVLALYDYQEKSPREVSM A8XJE3_CAEBR 985 985 -
RECVMALYDYTEKSPREVSI A8PJH9_BRUMA 985 985 -
RDCVLALYDYQEKSPREVSM Q21408 985 985 -
EQRVMALYDFQARSPREVTM Q5VYL1_HUMAN 979 979 -
EQRVMALYDFQARSPREVTM SPCA_HUMAN 979 979 -
EQRVMALYDFQARSPREVTM Q5VYL2_HUMAN 979 979 -
EARVIALYDFEARSRREVSM Q6XDA1 977 977 -
EARVIALYDFEARSRREVSM SPCA_MOUSE 977 977 -

Motif 2 width=15
Element Seqn Id St Int Rpt
KKGDILTLLNSTNKD A0JPA2_XENTR 989 0 -
KKGDILTLLNSTNKD SPCN_RAT 989 0 -
KKGDILTLLNSTNKD SPTA2_MOUSE 989 0 -
KKGDILTLLNSTNKD SPCN_HUMAN 989 0 -
KKGDILTLLNSTNKD SPCN_CHICK 989 0 -
KKGDILTLLNSTNKD Q6IRK8 989 0 -
KKGDILTLLNSTNKD A6NG51_HUMAN 989 0 -
KKGDILTLLNSTNKD A3KGU8_MOUSE 989 0 -
KKGDILTLLNSTNKD A3KGU7_MOUSE 989 0 -
KKGDILTLLNSTNKD A3KGU5_MOUSE 989 0 -
KKGDILTLLNSTNKD A3FG33_DANRE 989 0 -
KKGDILTLLNSTNKD Q4T9R5_TETNG 1110 0 -
KKGDILTLLNSTNKV Q4T9R4_TETNG 1026 0 -
KKGDVLTLLNSNNKD Q16EQ1_AEDAE 992 0 -
KKGDVLTLLNSNNKD Q3KN50_DROME 992 0 -
KKGDVLTLLNSNNKD SPCA_DROME 992 0 -
KKNDVLTLLNSNNKD Q7Q515_ANOGA 992 0 -
KKGDVLTLLNASNKD A8XJE3_CAEBR 1005 0 -
KKGDVITLLNSSNKD A8PJH9_BRUMA 1005 0 -
KKGDVLTLLNASNRD Q21408 1005 0 -
KKGDVLTLLSSINKD Q5VYL1_HUMAN 999 0 -
KKGDVLTLLSSINKD SPCA_HUMAN 999 0 -
KKGDVLTLLSSINKD Q5VYL2_HUMAN 999 0 -
KKNDVLTLLSSINKD Q6XDA1 997 0 -
KKNDVLTLLSSINKD SPCA_MOUSE 997 0 -

Motif 3 width=22
Element Seqn Id St Int Rpt
WWKVEVNDRQGFVPAAYVKKLD A0JPA2_XENTR 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD SPCN_RAT 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD SPTA2_MOUSE 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD SPCN_HUMAN 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD SPCN_CHICK 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD Q6IRK8 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD A6NG51_HUMAN 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD A3KGU8_MOUSE 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD A3KGU7_MOUSE 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD A3KGU5_MOUSE 1004 0 -
WWKVEVNDRQGFVPAAYVKKLD A3FG33_DANRE 1004 0 -
WWKVEVNDRLGFVPAAYVKKLD Q4T9R5_TETNG 1125 0 -
WWKVEVNDRQGFVPAAYVKKLD Q4T9R4_TETNG 1082 41 -
WWKVEVNDRQGFVPAAYIKKID Q16EQ1_AEDAE 1007 0 -
WWKVEVNDRQGFVPAAYIKKID Q3KN50_DROME 1007 0 -
WWKVEVNDRQGFVPAAYIKKID SPCA_DROME 1007 0 -
WWKVEVNDRQGFVPAAYIKKID Q7Q515_ANOGA 1007 0 -
WWKVEVNDRQGFVPAAYVKRIE A8XJE3_CAEBR 1020 0 -
WWKVEVNDRQGFVPAAYVKKVE A8PJH9_BRUMA 1020 0 -
WWKVEVNDRQGFVPAAYVKRIE Q21408 1020 0 -
WWKVEAADHQGIVPAVYVRRLA Q5VYL1_HUMAN 1014 0 -
WWKVEAADHQGIVPAVYVRRLA SPCA_HUMAN 1014 0 -
WWKVEAADHQGIVPAVYVRRLA Q5VYL2_HUMAN 1014 0 -
WWKVEADDHQGFVPAVYVRKLA Q6XDA1 1012 0 -
WWKVEADDHQGFVPAVYVRKLA SPCA_MOUSE 1012 0 -