RBCC

Full text data of EPB42

EPB42 (E42P) [Confidence: high (present in two of the MS resources)]
Erythrocyte membrane protein band 4.2; Erythrocyte protein 4.2; P4.2

hRBCD IPI00028120
IPI00028120 erythrocyte membrane protein band 4.2 erythrocyte membrane protein band 4.2 membrane 9 22 32 29 33 19 34 2 62 14 37 3 5 22 17 1 19 36 25 26 membrane bound n/a found at its expected molecular weight found at molecular weight

Comments
Isoform P16452-2 was detected.

UniProt P16452
ID EPB42_HUMAN Reviewed; 691 AA.
AC P16452; Q4VB97;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 3.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Erythrocyte membrane protein band 4.2;
DE Short=Erythrocyte protein 4.2;
DE Short=P4.2;
GN Name=EPB42; Synonyms=E42P;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RC TISSUE=Reticulocyte;
RX PubMed=2052563; DOI=10.1073/pnas.88.11.4840;
RA Korsgren C., Cohen C.M.;
RT "Organization of the gene for human erythrocyte membrane protein 4.2:
RT structural similarities with the gene for the a subunit of factor
RT XIII.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:4840-4844(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE (ISOFORM
RP SHORT).
RC TISSUE=Reticulocyte;
RX PubMed=2300550; DOI=10.1073/pnas.87.2.613;
RA Korsgren C., Lawler J., Lambert S., Speicher D., Cohen C.M.;
RT "Complete amino acid sequence and homologies of human erythrocyte
RT membrane protein band 4.2.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:613-617(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Reticulocyte;
RX PubMed=1689063; DOI=10.1073/pnas.87.3.955;
RA Sung L.A., Chien S., Chang L.-S., Lambert K., Bliss S.A.,
RA Bouhassira E.E., Nagel R.L., Schwartz R.S., Rybicki A.C.;
RT "Molecular cloning of human protein 4.2: a major component of the
RT erythrocyte membrane.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:955-959(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=1544941;
RA Risinger M.A., Dotimas E.M., Cohen C.M.;
RT "Human erythrocyte protein 4.2, a high copy number membrane protein,
RT is N-myristylated.";
RL J. Biol. Chem. 267:5680-5685(1992).
RN [8]
RP PHOSPHORYLATION AT SER-248.
RX PubMed=8499466; DOI=10.1016/0005-2736(93)90156-T;
RA Dotimas E., Speicher D.W., Guptaroy B., Cohen C.M.;
RT "Structural domain mapping and phosphorylation of human erythrocyte
RT pallidin (band 4.2).";
RL Biochim. Biophys. Acta 1148:19-29(1993).
RN [9]
RP VARIANT SPH5 THR-112.
RX PubMed=1558976;
RA Bouhassira E.E., Schwartz R.S., Yawata Y., Ata K., Kanzaki A.,
RA Qiu J.J.-H., Nagel R.L., Rybicki A.C.;
RT "An alanine-to-threonine substitution in protein 4.2 cDNA is
RT associated with a Japanese form of hereditary hemolytic anemia
RT (protein 4.2 Nippon).";
RL Blood 79:1846-1854(1992).
RN [10]
RP VARIANT SPH5 THR-112.
RX PubMed=7819064; DOI=10.1111/j.1365-2141.1994.tb05069.x;
RA Takaoka Y., Ideguchi H., Matsuda M., Sakamoto N., Takeuchi T.,
RA Fukumaki Y.;
RT "A novel mutation in the erythrocyte protein 4.2 gene of Japanese
RT patients with hereditary spherocytosis (protein 4.2 Fukuoka).";
RL Br. J. Haematol. 88:527-533(1994).
RN [11]
RP VARIANT SPH5 GLN-280.
RX PubMed=7772513;
RA Hayette S., Morle L., Bozon M., Ghanem A., Risinger M., Korsgren C.,
RA Tanner M.J.A., Fattoum S., Cohen C.M., Delaunay J.;
RT "A point mutation in the protein 4.2 gene (allele 4.2 Tozeur)
RT associated with hereditary haemolytic anaemia.";
RL Br. J. Haematol. 89:762-770(1995).
RN [12]
RP VARIANTS SPH5 THR-112 AND CYS-287.
RX PubMed=8547071; DOI=10.1111/j.1365-2141.1995.tb05299.x;
RA Kanzaki A., Yasunaga M., Okamoto N., Inoue T., Yawata A., Wada H.,
RA Andoh A., Hodohara K., Fujiyama Y., Bamba T., Harano T., Harano K.,
RA Yawata Y.;
RT "Band 4.2 Shiga: 317 CGC-->TGC in compound heterozygotes with 142
RT GCT-->ACT results in band 4.2 deficiency and microspherocytosis.";
RL Br. J. Haematol. 91:333-340(1995).
RN [13]
RP VARIANT SPH5 TYR-145.
RX PubMed=8547605; DOI=10.1016/0925-5710(95)00372-Y;
RA Kanzaki A., Yawata Y., Yawata A., Inoue T., Okamoto N., Wada H.,
RA Harano T., Harano K., Wilmotte R., Hayette S., Nakamura Y., Niki T.,
RA Kawamura Y., Nakamura S., Matsuda T.;
RT "Band 4.2 Komatsu: 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band
RT 4.2 gene associated with total deficiency of band 4.2, hemolytic
RT anemia with ovalostomatocytosis and marked disruption of the
RT cytoskeletal network.";
RL Int. J. Hematol. 61:165-178(1995).
RN [14]
RP VARIANT SPH5 THR-112.
RX PubMed=10406914;
RA Perrotta S., Iolascon A., Polito R., d'Urzo G., Conte M.L.,
RA Miraglia del Giudice E.;
RT "4.2 Nippon mutation in a non-Japanese patient with hereditary
RT spherocytosis.";
RL Haematologica 84:660-662(1999).
CC -!- FUNCTION: Probably plays an important role in the regulation of
CC erythrocyte shape and mechanical properties.
CC -!- SUBUNIT: Oligomer. Interacts with the cytoplasmic domain of
CC SLC4A1/band 3 anion transport protein.
CC -!- INTERACTION:
CC P58062:SPINK7; NbExp=3; IntAct=EBI-1182496, EBI-1182445;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side. Cytoplasm, cytoskeleton. Note=Cytoplasmic surface of
CC erythrocyte membranes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Short;
CC IsoId=P16452-1; Sequence=Displayed;
CC Note=Major isoform;
CC Name=Long;
CC IsoId=P16452-2; Sequence=VSP_006416;
CC -!- PTM: Both cAMP-dependent kinase (CAPK) and another kinase present
CC in the red-blood cells seem to be able to phosphorylate EPB42.
CC -!- DISEASE: Spherocytosis 5 (SPH5) [MIM:612690]: Spherocytosis is a
CC hematologic disorder leading to chronic hemolytic anemia and
CC characterized by numerous abnormally shaped erythrocytes which are
CC generally spheroidal. Absence of band 4.2 associated with spur or
CC target erythrocytes has also been reported. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The substitution of an Ala for a Cys in the active
CC site may be responsible for the lack of transglutaminase activity
CC of band 4.2.
CC -!- SIMILARITY: Belongs to the transglutaminase superfamily.
CC Transglutaminase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36401.1; Type=Frameshift; Positions=335, 340;
CC Sequence=AAA36402.1; Type=Frameshift; Positions=335, 340;
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DR EMBL; M60298; AAA74589.1; -; mRNA.
DR EMBL; L06519; AAA52385.1; -; Genomic_DNA.
DR EMBL; L06447; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06448; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06449; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06450; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06511; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06512; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06513; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06515; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06516; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06517; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; L06518; AAA52385.1; JOINED; Genomic_DNA.
DR EMBL; M29399; AAA35798.1; -; mRNA.
DR EMBL; M30647; AAA36401.1; ALT_FRAME; mRNA.
DR EMBL; M30646; AAA36402.1; ALT_FRAME; mRNA.
DR EMBL; AC068724; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471125; EAW92591.1; -; Genomic_DNA.
DR EMBL; BC096093; AAH96093.1; -; mRNA.
DR EMBL; BC096094; AAH96094.1; -; mRNA.
DR PIR; A39707; A39707.
DR RefSeq; NP_000110.2; NM_000119.2.
DR RefSeq; NP_001107606.1; NM_001114134.1.
DR UniGene; Hs.368642; -.
DR ProteinModelPortal; P16452; -.
DR SMR; P16452; 5-689.
DR IntAct; P16452; 3.
DR STRING; 9606.ENSP00000300215; -.
DR PhosphoSite; P16452; -.
DR DMDM; 215274164; -.
DR PaxDb; P16452; -.
DR PRIDE; P16452; -.
DR Ensembl; ENST00000300215; ENSP00000300215; ENSG00000166947.
DR Ensembl; ENST00000441366; ENSP00000396616; ENSG00000166947.
DR GeneID; 2038; -.
DR KEGG; hsa:2038; -.
DR UCSC; uc001zqz.4; human.
DR CTD; 2038; -.
DR GeneCards; GC15M043398; -.
DR HGNC; HGNC:3381; EPB42.
DR HPA; HPA040261; -.
DR MIM; 177070; gene.
DR MIM; 612690; phenotype.
DR neXtProt; NX_P16452; -.
DR Orphanet; 822; Hereditary spherocytosis.
DR PharmGKB; PA27814; -.
DR eggNOG; NOG87163; -.
DR HOGENOM; HOG000231695; -.
DR HOVERGEN; HBG106048; -.
DR InParanoid; P16452; -.
DR OMA; SCFAQED; -.
DR OrthoDB; EOG7Z0JVS; -.
DR GeneWiki; Protein_4.2; -.
DR GenomeRNAi; 2038; -.
DR NextBio; 8277; -.
DR PRO; PR:P16452; -.
DR ArrayExpress; P16452; -.
DR Bgee; P16452; -.
DR CleanEx; HS_EPB42; -.
DR Genevestigator; P16452; -.
DR GO; GO:0030863; C:cortical cytoskeleton; IEA:Ensembl.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; TAS:ProtInc.
DR GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; IEA:InterPro.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0043249; P:erythrocyte maturation; IEA:UniProtKB-KW.
DR GO; GO:0020027; P:hemoglobin metabolic process; IEA:Ensembl.
DR GO; GO:0055072; P:iron ion homeostasis; IEA:Ensembl.
DR GO; GO:0018149; P:peptide cross-linking; IEA:InterPro.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.90.260.10; -; 1.
DR InterPro; IPR023608; Gln_gamma-glutamylTfrase_euk.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002931; Transglutaminase-like.
DR InterPro; IPR008958; Transglutaminase_C.
DR InterPro; IPR013808; Transglutaminase_CS.
DR InterPro; IPR001102; Transglutaminase_N.
DR PANTHER; PTHR11590; PTHR11590; 1.
DR Pfam; PF00927; Transglut_C; 2.
DR Pfam; PF01841; Transglut_core; 1.
DR Pfam; PF00868; Transglut_N; 1.
DR PIRSF; PIRSF000459; TGM_EBP42; 1.
DR SMART; SM00460; TGc; 1.
DR SUPFAM; SSF49309; SSF49309; 2.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS00547; TRANSGLUTAMINASES; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell shape; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease mutation;
KW Erythrocyte maturation; Hereditary hemolytic anemia; Lipoprotein;
KW Membrane; Myristate; Phosphoprotein; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 691 Erythrocyte membrane protein band 4.2.
FT /FTId=PRO_0000213720.
FT REGION 31 39 Band 3 binding (By similarity).
FT MOD_RES 248 248 Phosphoserine; by PKA (Probable).
FT LIPID 2 2 N-myristoyl glycine.
FT VAR_SEQ 3 3 Q -> QGEPSQRSTGLAGLYAAPAASPVFIKGSGMD (in
FT isoform Long).
FT /FTId=VSP_006416.
FT VARIANT 112 112 A -> T (in SPH5; Nippon/Fukuoka;
FT dbSNP:rs28933988).
FT /FTId=VAR_007482.
FT VARIANT 145 145 D -> Y (in SPH5; Komatsu).
FT /FTId=VAR_058099.
FT VARIANT 280 280 R -> Q (in SPH5; Tozeur).
FT /FTId=VAR_012268.
FT VARIANT 287 287 R -> C (in SPH5; Shiga).
FT /FTId=VAR_058100.
FT CONFLICT 350 350 H -> D (in Ref. 1; AAA74589/AAA52385 and
FT 2; AAA35798).
FT CONFLICT 376 376 L -> V (in Ref. 1; AAA74589/AAA52385 and
FT 2; AAA35798).
SQ SEQUENCE 691 AA; 77009 MW; 38225C311E478580 CRC64;
MGQALGIKSC DFQAARNNEE HHTKALSSRR LFVRRGQPFT IILYFRAPVR AFLPALKKVA
LTAQTGEQPS KINRTQATFP ISSLGDRKWW SAVVEERDAQ SWTISVTTPA DAVIGHYSLL
LQVSGRKQLL LGQFTLLFNP WNREDAVFLK NEAQRMEYLL NQNGLIYLGT ADCIQAESWD
FGQFEGDVID LSLRLLSKDK QVEKWSQPVH VARVLGALLH FLKEQRVLPT PQTQATQEGA
LLNKRRGSVP ILRQWLTGRG RPVYDGQAWV LAAVACTVLR CLGIPARVVT TFASAQGTGG
RLLIDEYYNE EGLQNGEGQR GRIWIFQTST ECWMTRPALP QGYDGWQILH PSAPNGGGVL
GSCDLVPVRA VKEGTLGLTP AVSDLFAAIN ASCVVWKCCE DGTLELTDSN TKYVGNNIST
KGVGSDRCED ITQNYKYPEG SLQEKEVLER VEKEKMEREK DNGIRPPSLE TASPLYLLLK
APSSLPLRGD AQISVTLVNH SEQEKAVQLA IGVQAVHYNG VLAAKLWRKK LHLTLSANLE
KIITIGLFFS NFERNPPENT FLRLTAMATH SESNLSCFAQ EDIAICRPHL AIKMPEKAEQ
YQPLTASVSL QNSLDAPMED CVISILGRGL IHRERSYRFR SVWPENTMCA KFQFTPTHVG
LQRLTVEVDC NMFQNLTNYK SVTVVAPELS A
//

MIM 177070
*RECORD*
*FIELD* NO
177070
*FIELD* TI
*177070 PROTEIN 4.2, ERYTHROCYTIC; EPB42
*FIELD* TX

CLONING

Korsgren et al. (1990) cloned and sequenced protein band 4.2 from a
read morehuman reticulocyte cDNA library. The deduced 691-amino acid band 4.2
protein has homology with 2 closely related calcium-dependent
crosslinking proteins, guinea pig liver transglutaminase and the alpha
subunit of human coagulation factor XIII (F13A1; 134570). Within the 5
contiguous consensus residues of the transglutaminase active site, band
4.2 has an amino acid substitution which leads to loss of
transglutaminase activity. Sung et al. (1990) also cloned protein 4.2
and likewise found homology to the 2 transglutaminases, as well as the
lack of the critical residue required for enzymatic crosslinking of
substrates.

Korsgren and Cohen (1991) showed that reticulocytes contain 2 different
sized EPB42 messages; the major, smaller, message is produced by
alternative splicing. They found that the human and murine proteins
share 72% sequence identity.

GENE STRUCTURE

Korsgren and Cohen (1991) showed that the band 4.2 gene is about 20 kb
long and contains 13 exons. Alignment of the band 4.2 amino acid
sequence with that of F13A2 and division of the sequences into exons
showed a remarkable correspondence, and in most cases identity, in the
sizes of the paired exons.

Korsgren and Cohen (1994) found that the organization and size of the
human and mouse EPB42 genes are identical.

MAPPING

Sung et al. (1991) mapped the EPB42 gene to 15q15-q21 by fluorescence in
situ hybridization. Najfeld et al. (1992) assigned the gene to 15q15 by
fluorescence in situ hybridization. White et al. (1992) mapped the Epb42
gene to mouse chromosome 2, which shares an extensive segment of
syntenic homology with human chromosome 15.

By long-range genomic PCR, Grenard et al. (2001) mapped the EPB42 gene
to a 100-kb region of 15q15.2, arranged in tandem with 2 other
transglutaminase genes, TGM5 (603805) and TGM7 (606776). By radiation
hybrid analysis, Grenard et al. (2001) mapped the mouse Epb42, Tgm5, and
Tgm7 genes in close proximity on chromosome 2.

GENE FUNCTION

In the red cell membrane skeleton, protein 4.2 may regulate the
association of protein 3 (109270) with ankyrin (612641) (Davies and Lux,
1989).

Azim et al. (1996) demonstrated that both protein 4.2 and dematin
(125305) are ATP-binding proteins.

Bruce et al. (2002) observed that protein 4.2 and CD47 interact in the
human red cell membrane, which provided further evidence for an
association between the band 3 complex (which includes protein 4.2) and
the Rh complex, and defined a point of attachment between the Rh complex
and the red cell cytoskeleton.

MOLECULAR GENETICS

In 4 unrelated Japanese patients with autosomal recessive hereditary
spherocytosis (612690), Bouhassira et al. (1991, 1992) identified
homozygosity for a mutation in the EPB42 gene (177070.0001).

In a Portuguese woman with recessively transmitted hemolytic anemia,
Hayette et al. (1995) identified a mutation in the EPB42 gene
(177070.0002).

In Tunisian sibs with autosomal recessive hemolytic anemia reported by
Ghanem et al. (1990), Hayette et al. (1995) identified homozygosity for
a mutation in the EPB42 gene (177070.0003).

ANIMAL MODEL

The mouse 'pallid' mutation (see 604310) produces defects in at least 3
subcellular organelles: platelet-dense granules, melanosomes, and kidney
lysosomes. White et al. (1992) noted that the mouse Epb42 gene mapped to
the same region as the pallid mutation in the mouse. Prompted to examine
the Epb42 gene in the pallid mouse, they found changes on Southern blot
analysis suggesting a mutation; Northern blot analysis demonstrated
smaller than normal Epb42 transcripts in affected pallid tissues, such
as kidney and skin. However, Gwynn et al. (1997) and White et al. (1997)
excluded Epb42 as a candidate for the mouse pallid mutation. On Northern
blot analysis of normal and pallid mouse kidney, Gwynn et al. (1997)
observed that the truncated Epb42 protein comigrated with normal Epb42
protein. As the pallid mutation originally arose in a wild M. domesticus
mouse, they concluded that the Epb42 protein characteristic of pallid is
a normal polymorphism and that Epb42 and pallid are distinct loci.

*FIELD* AV
.0001
SPHEROCYTOSIS, TYPE 5, DUE TO PROTEIN 4.2-NIPPON
EPB42, ALA142THR

In 4 unrelated Japanese patients with spherocytosis (612690), Bouhassira
et al. (1991, 1992) identified homozygosity for a G-to-A transition in
the EPB42 gene, resulting in an ala142-to-thr (A142T) substitution. The
abnormality in protein 4.2 results in abnormally shaped and osmotically
fragile RBCs. The mutation occurred in an alternatively spliced exon
that is present in 2 of 4 EPB42 mRNA splicing isoforms. Thus this is a
recessive form of spherocytosis causing hereditary hemolytic anemia.

Iwamoto et al. (1993) identified the same mutation in a 27-year-old
Japanese female with acute hemolytic crisis and in her sister.

Perrotta et al. (1999) described the 4.2-Nippon mutation in a
30-year-old female born in a small mountain village in central Italy.
There was no Japanese ancestry. Splenomegaly and moderate hemolytic
anemia were present from birth.

.0002
SPHEROCYTOSIS, TYPE 5, DUE TO PROTEIN 4.2-LISBOA
EPB42, 1-BP DEL, 264G

Hayette et al. (1995) identified a defect in the EPB42 gene in a
26-year-old Portuguese woman with recessively transmitted hereditary
hemolytic anemia (612690). Protein 4.2 was absent from red cell ghosts
by Western blotting. Nucleotide sequencing disclosed deletion of a
single nucleotide at position 264 (or 265): AAG GTG was changed to AAG
TG in codon 88 (or 89) in exon 2. This change, defining allele 4.2
Lisboa, placed in frame the nonsense TGA triplet that normally overlaps
codons 136 and 137 (GTG ACC). In effect, codon 89 was changed from GTG
(val) to TGA (stop). The mutation was present in homozygous state in the
proband and in heterozygous state in the parents and a brother. Apart
from anemia, the patient was free of clinical manifestations. Hayette et
al. (1995) noted that in this case there were only a few spherocytes and
only a limited decrease in the osmotic resistance.

.0003
SPHEROCYTOSIS, TYPE 5, DUE TO PROTEIN 4.2-TOZEUR
EPB42, ARG310GLN

Using high-sensitivity Western blot analysis, Hayette et al. (1995)
found that the Tunisian sibs with autosomal recessive hemolytic anemia
(612690) originally reported by Ghanem et al. (1990) had trace amounts
of the EPB42 protein. They found that the sibs were homozygous for a
G-to-A transition in exon 7 of the EPB42 gene, resulting in an
arg310-to-gln (R310Q) substitution. The parents were heterozygous for
the mutation, which was absent in 48 control chromosomes of Tunisian
individuals.

.0004
SPHEROCYTOSIS, TYPE 5, DUE TO PROTEIN 4.2-NOTAME
EPB42, IVS6DS, G-A, +1

Protein 4.2 (Notame) was found in a 56-year-old Japanese man being
investigated for chronic hyperbilirubinemia (Matsuda et al., 1995). He
had mild splenomegaly and mild anemia with reticulocytosis as well as
microspherocytosis (612690). Erythrocyte osmotic fragility was
remarkably increased. SDS-PAGE showed complete deficiency of protein
4.2. Direct sequencing and dot-blot hybridization with allele-specific
oligonucleotide probes indicated that the man was a compound
heterozygote for the A142T mutation (177070.0001) and a single
nucleotide substitution (G to A) in the first nucleotide of intron 6 of
the EPB42 gene. RT-PCR analysis using total RNA isolated from
reticulocytes of the proband showed that the intron 6 donor site
mutation caused exon 6 to be spliced out with intron 6. The abnormal
mRNA had a premature termination codon as a result of a frameshift,
which precipitated instability of the protein that led to its
degradation.

.0005
SPHEROCYTOSIS, TYPE 5, DUE TO PROTEIN 4.2-HAMMERSMITH
EPB42, 41-BP DEL, NT1709

Bruce et al. (2002) presented data on a patient of Pakistani origin with
recessive spherocytosis due to absence of protein 4.2 (612690). EPB42
cDNA sequence analysis showed the presence of a 41-bp frameshift
deletion in the 5-prime end of exon 11 of the EPB42 gene that produced a
truncated peptide designated protein 4.2 Hammersmith. Quantitative
RT-PCR indicated that the mutant mRNA was unstable. Sequencing of
genomic DNA showed that the deletion stemmed from aberrant splicing. The
proband was homozygous for a G-to-T substitution at position 1747 that
activated a cryptic acceptor splice site within exon 11 of the EPB42
gene. The proband's mother was heterozygous for this substitution.
Unlike protein 4.2-null mice, the proband's red cells showed no evidence
of abnormal cation permeability. Quantitation of red cell membrane
proteins showed that CD47 (601028) was markedly reduced to about 1% (in
the proband) and 65% (in the mother) of that found in healthy controls.

*FIELD* RF
1. Azim, A. C.; Marfatia, S. M.; Korsgren, C.; Dotimas, E.; Cohen,
C. M.; Chishti, A. H.: Human erythrocyte dematin and protein 4.2
(pallidin) are ATP binding proteins. Biochemistry 35: 3001-3006,
1996.

2. Bouhassira, E. E.; Schwartz, R. S.; Yawata, Y.; Ata, K.; Kanzaki,
A.; Qui, J. J.-H.; Nagel, R. L.; Rybicki, A. C.: An alanine-to-threonine
substitution in protein 4.2 cDNA is associated with a Japanese form
of hereditary hemolytic anemia (protein 4.2-Nippon). Blood 79: 1846-1854,
1992.

3. Bouhassira, E. E.; Schwartz, R. S.; Yawata, Y.; Ata, K.; Nagel,
R. L.; Rybicki, A. C.: An alanine to threonine substitution in protein
4.2 cDNA is associated with a Japanese form of hereditary hemolytic
anemia. (Abstract) Clin. Res. 39: 313A, 1991.

4. Bruce, L. J.; Ghosh, S.; King, M. J.; Layton, D. M.; Mawby, W.
J.; Stewart, G. W.; Oldenborg, P.-A.; Delaunay, J.; Tanner, M. J.
A.: Absence of CD47 in protein 4.2-deficient hereditary spherocytosis
in man: an interaction between the Rh complex and the band 3 complex. Blood 100:
1878-1885, 2002.

5. Davies, K. A.; Lux, S. E.: Hereditary disorders of the red cell
membrane skeleton. Trends Genet. 5: 222-227, 1989.

6. Ghanem, A.; Pothier, B.; Marechal, J.; Ducluzeau, M. T.; Morle,
L.; Alloisio, N.; Feo, C.; Ben Abdeladhim, A.; Fattoum, S.; Delaunay,
J.: A haemolytic syndrome associated with the complete absence of
red cell membrane protein 4.2 in two Tunisian siblings. Brit. J.
Haemat. 75: 414-420, 1990.

7. Grenard, P.; Bates, M. K.; Aeschlimann, D.: Evolution of transglutaminase
genes: identification of a transglutaminase gene cluster on human
chromosome 15q15: structure of the gene encoding transglutaminase
X and a novel gene family member, transglutaminase Z. J. Biol. Chem. 276:
33066-33078, 2001.

8. Gwynn, B.; Korsgren, C.; Cohen, C. M.; Ciciotte, S. L.; Peters,
L. L.: The gene encoding protein 4.2 is distinct from the mouse platelet
storage pool deficiency mutation pallid. Genomics 42: 532-535, 1997.

9. Hayette, S.; Dhermy, D.; dos Santos, M.-E.; Bozon, M.; Drenckhahn,
D.; Alloisio, N.; Texier, P.; Delaunay, J.; Morle, L.: A deletional
frameshift mutation in protein 4.2 gene (allele 4.2 Lisboa) associated
with hereditary hemolytic anemia. Blood 85: 250-256, 1995.

10. Hayette, S.; Morle, L.; Bozon, M.; Ghanem, A.; Risinger, M.; Korsgren,
C.; Tanner, M. J. A.; Fattoum, S.; Cohen, C. M.; Delaunay, J.: A
point mutation in the protein 4.2 gene (allele 4.2 Tozeur) associated
with hereditary haemolytic anaemia. Brit. J. Haemat. 89: 762-770,
1995.

11. Iwamoto, S.; Kajii, E.; Omi, T.; Kamesaki, T.; Akifuji, Y.; Ikemoto,
S.: Point mutation in the band 4.2 gene associated with autosomal
recessively inherited erythrocyte band 4.2 deficiency. Europ. J.
Haemat. 50: 286-291, 1993.

12. Korsgren, C.; Cohen, C. M.: Organization of the gene for human
erythrocyte membrane protein 4.2: structural similarities with the
gene for the A subunit of factor XIII. Proc. Nat. Acad. Sci. 88:
4840-4844, 1991.

13. Korsgren, C.; Cohen, C. M.: cDNA sequence, gene sequence, and
properties of murine pallidin (band 4.2), the protein implicated in
the murine pallid mutation. Genomics 21: 478-485, 1994.

14. Korsgren, C.; Lawler, J.; Lambert, S.; Speicher, D.; Cohen, C.
M.: Complete amino acid sequence and homologies of human erythrocyte
membrane protein band 4.2. Proc. Nat. Acad. Sci. 87: 613-617, 1990.

15. Matsuda, M.; Hatano, N.; Ideguchi, H.; Takahira, H.; Fukumaki,
Y.: A novel mutation causing an aberrant splicing in the protein
4.2 gene associated with hereditary spherocytosis (protein 4.2-Notame). Hum.
Molec. Genet. 4: 1187-1191, 1995.

16. Najfeld, V.; Ballard, S. G.; Menninger, J.; Ward, D. C.; Bouhassira,
E. E.; Schwartz, R. S.; Nagel, R. L.; Rybicki, A. C.: The gene for
human erythrocyte protein 4.2 maps to chromosome 15q15. Am. J. Hum.
Genet. 50: 71-75, 1992.

17. Perrotta, S.; Iolascon, A.; Polito, R.; d'Urzo, G.; Conte, M.
L.; Miraglia del Giudice, E.: 4.2 Nippon mutation in a non-Japanese
patient with hereditary spherocytosis. (Letter) Haematologica 84:
660-662, 1999.

18. Sung, L. A.; Chien, S.; Chang, L.-S.; Lambert, K.; Bliss, S. A.;
Bouhassira, E. E.; Nagel, R. L.; Schwartz, R. S.; Rybicki, A. C.:
Molecular cloning of human protein 4.2: a major component of the erythrocyte
membrane. Proc. Nat. Acad. Sci. 87: 955-959, 1990.

19. Sung, L. A.; Fan, Y. S.; Lambert, K.; Chien, S.; Lin, C.: Mapping
of gene for human erythrocyte protein 4.2 to chromosomal region 15q15-q21.
(Abstract) Cytogenet. Cell Genet. 58: 1996, 1991.

20. White, R. A.; Dowler, L. L.; Hummel, G. S.; Adkison, L. R.: Exclusion
of Epb4.2 as a candidate for the mouse mutant pallid. Mouse Genome 95:
492-494, 1997.

21. White, R. A.; Peters, L. L.; Adkison, L. R.; Korsgren, C.; Cohen,
C. M.; Lux, S. E.: The murine pallid mutation is a platelet storage
pool disease associated with the protein 4.2 (pallidin) gene. Nature
Genet. 2: 80-83, 1992.

*FIELD* CN
Carol A. Bocchini - updated: 3/24/2009
Victor A. McKusick - updated: 10/16/2002
Patricia A. Hartz - updated: 3/25/2002
Victor A. McKusick - updated: 2/26/2001
Anne M. Lopez - updated: 11/23/1999

*FIELD* CD
Victor A. McKusick: 9/27/1989

*FIELD* ED
carol: 03/25/2009
terry: 3/24/2009
carol: 3/24/2009
carol: 2/26/2009
carol: 9/9/2003
tkritzer: 11/1/2002
tkritzer: 10/22/2002
terry: 10/16/2002
carol: 3/25/2002
mcapotos: 3/6/2001
terry: 2/26/2001
carol: 11/23/1999
alopez: 11/23/1999
terry: 8/24/1998
mark: 9/1/1997
terry: 7/7/1997
carol: 10/4/1996
mark: 4/26/1996
terry: 4/24/1996
mark: 7/19/1995
mimadm: 2/25/1995
carol: 2/17/1995
jason: 7/1/1994
carol: 9/22/1993
carol: 3/2/1993

MIM 612690
*RECORD*
*FIELD* NO
612690
*FIELD* TI
#612690 SPHEROCYTOSIS, TYPE 5; SPH5
;;SPHEROCYTOSIS, HEREDITARY, 5; HS5
*FIELD* TX
read moreA number sign (#) is used with this entry because hereditary
spherocytosis type 5 is caused by mutation in the gene encoding protein
4.2 (EPB42; 177070) on chromosome 15q15.

For a general phenotypic description and a discussion of genetic
heterogeneity of hereditary spherocytosis, see SPH1 (182900).

CLINICAL FEATURES

Hereditary spherocytosis type 5, which has been observed predominantly
in Japanese individuals, is an autosomal recessive disorder that results
in a hemolytic anemia associated with abnormally shaped, osmotically
fragile red blood cells (Bouhassira et al., 1992).

Hayashi et al. (1974) described 4 Japanese patients, 3 of whom were
sibs, with hereditary spherocytosis and deficiency of protein 4.2.

Nozawa et al. (1974) reported a severe case of hereditary spherocytosis
in a 6-year-old Japanese girl with protein 4.2 deficiency who showed
improvement with splenectomy.

Rybicki et al. (1988) noted that protein 4.2 is partially or completely
absent in Japanese patients with recessive spherocytosis. In 1 Japanese
patient with protein 4.2 deficiency, Rybicki et al. (1988) found that
ankyrin was much less firmly associated with the membrane skeleton than
normal.

Ideguchi et al. (1990) found deficiency of band 4.2 protein as the cause
of an autosomal recessive form of hereditary spherocytosis in a Japanese
brother and sister.

Ghanem et al. (1990) described complete absence of protein 4.2 in 2
Tunisian sibs. The proposita presented with hemolytic anemia cured by
splenectomy. Her red cells had normal morphology. Her sister also had
hemolytic anemia. The parents were first cousins and were clinically
normal, with morphologically normal red cells which had a normal content
of protein 4.2. This may indicate that the primary defect does not
reside in the 4.2 gene, but rather in another element of the red cell
membrane skeleton essential for stabilization of protein 4.2. This
appears to be the first instance of absent protein 4.2 outside of Japan.

MOLECULAR GENETICS

In 4 unrelated Japanese patients with hereditary spherocytosis,
Bouhassira et al. (1991, 1992) identified homozygosity for a mutation in
the EPB42 gene (177070.0001).

In a Portuguese woman with recessively transmitted hemolytic anemia,
Hayette et al. (1995) identified a mutation in the EPB42 gene
(177070.0002).

In Tunisian sibs with autosomal recessive hemolytic anemia reported by
Ghanem et al. (1990), Hayette et al. (1995) identified homozygosity for
a mutation in the EPB42 gene (177070.0003).

*FIELD* RF
1. Bouhassira, E. E.; Schwartz, R. S.; Yawata, Y.; Ata, K.; Kanzaki,
A.; Qui, J. J.-H.; Nagel, R. L.; Rybicki, A. C.: An alanine-to-threonine
substitution in protein 4.2 cDNA is associated with a Japanese form
of hereditary hemolytic anemia (protein 4.2-Nippon). Blood 79: 1846-1854,
1992.

2. Bouhassira, E. E.; Schwartz, R. S.; Yawata, Y.; Ata, K.; Nagel,
R. L.; Rybicki, A. C.: An alanine to threonine substitution in protein
4.2 cDNA is associated with a Japanese form of hereditary hemolytic
anemia. (Abstract) Clin. Res. 39: 313A, 1991.

3. Ghanem, A.; Pothier, B.; Marechal, J.; Ducluzeau, M. T.; Morle,
L.; Alloisio, N.; Feo, C.; Ben Abdeladhim, A.; Fattoum, S.; Delaunay,
J.: A haemolytic syndrome associated with the complete absence of
red cell membrane protein 4.2 in two Tunisian siblings. Brit. J.
Haemat. 75: 414-420, 1990.

4. Hayashi, S.; Koomoto, R.; Yano, A.; Ishigami, S.; Tsujino, G.;
Saeki, S.; Tanaka, T.: Abnormality in a specific protein of the erythrocyte
membrane in hereditary spherocytosis. Biochem. Biophys. Res. Commun. 57:
1038-1044, 1974.

5. Hayette, S.; Dhermy, D.; dos Santos, M.-E.; Bozon, M.; Drenckhahn,
D.; Alloisio, N.; Texier, P.; Delaunay, J.; Morle, L.: A deletional
frameshift mutation in protein 4.2 gene (allele 4.2 Lisboa) associated
with hereditary hemolytic anemia. Blood 85: 250-256, 1995.

6. Hayette, S.; Morle, L.; Bozon, M.; Ghanem, A.; Risinger, M.; Korsgren,
C.; Tanner, M. J. A.; Fattoum, S.; Cohen, C. M.; Delaunay, J.: A
point mutation in the protein 4.2 gene (allele 4.2 Tozeur) associated
with hereditary haemolytic anaemia. Brit. J. Haemat. 89: 762-770,
1995.

7. Ideguchi, H.; Nishimura, J.; Nawata, H.; Hamasaki, N.: A genetic
defect of erythrocyte band 4.2 protein associated with hereditary
spherocytosis. Brit. J. Haemat. 74: 347-353, 1990.

8. Nozawa, Y.; Hogushi, T.; Iida, H.; Fukushima, H.; Sekiya, T.; Ito,
Y.: Erythrocyte membranes in hereditary spherocytosis: alterations
in surface ultrastructure and membrane proteins as inferred by scanning
electron microscopy and SDS gel electrophoresis. Clin. Chim. Acta 55:
81-85, 1974.

9. Rybicki, A. C.; Heath, R.; Wolf, J. L.; Lubin, B.; Schwartz, R.
S.: Deficiency of protein 4.2 in erythrocytes from a patient with
a Coombs negative hemolytic anemia: evidence for a role of protein
4.2 in stabilizing ankyrin on the membrane. J. Clin. Invest. 81:
893-901, 1988.

*FIELD* CD
Carol A. Bocchini: 3/24/2009

*FIELD* ED
carol: 03/25/2009
carol: 3/24/2009

RBCC Red Blood Cell Collection

Full text data of EPB42