P16452 (EPB42_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Erythrocyte membrane protein band 4.2
Short name=Erythrocyte protein 4.2
Short name=P4.2

Gene names

Name:	EPB42
Synonyms:	E42P

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	691 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probably plays an important role in the regulation of erythrocyte shape and mechanical properties.
Subunit structure	Oligomer. Interacts with the cytoplasmic domain of SLC4A1/band 3 anion transport protein.
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side. Cytoplasm › cytoskeleton. Note: Cytoplasmic surface of erythrocyte membranes.
Post-translational modification	Both cAMP-dependent kinase (CAPK) and another kinase present in the red-blood cells seem to be able to phosphorylate EPB42.
Involvement in disease	Spherocytosis 5 (SPH5) [MIM:612690]: Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Absence of band 4.2 associated with spur or target erythrocytes has also been reported. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Miscellaneous	The substitution of an Ala for a Cys in the active site may be responsible for the lack of transglutaminase activity of band 4.2.
Sequence similarities	Belongs to the transglutaminase superfamily. Transglutaminase family.
Sequence caution	The sequence AAA36401.1 differs from that shown. Reason: Frameshift at positions 335 and 340. The sequence AAA36402.1 differs from that shown. Reason: Frameshift at positions 335 and 340.

Ontologies

Keywords
Biological process	Cell shape Erythrocyte maturation
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Hereditary hemolytic anemia
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell morphogenesis Inferred from electronic annotation. Source: Compara erythrocyte maturation Inferred from electronic annotation. Source: UniProtKB-KW hemoglobin metabolic process Inferred from electronic annotation. Source: Compara iron ion homeostasis Inferred from electronic annotation. Source: Compara peptide cross-linking Inferred from electronic annotation. Source: InterPro regulation of cell shape Inferred from electronic annotation. Source: UniProtKB-KW spleen development Inferred from electronic annotation. Source: Compara
Cellular_component	cortical cytoskeleton Inferred from electronic annotation. Source: Compara cytoskeleton Traceable author statement PubMed 1350227. Source: ProtInc plasma membrane Traceable author statement PubMed 1350227. Source: ProtInc
Molecular_function	ATP binding Traceable author statement PubMed 8608138. Source: ProtInc protein-glutamine gamma-glutamyltransferase activity Inferred from electronic annotation. Source: InterPro structural constituent of cytoskeleton Traceable author statement PubMed 1350227. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SPINK7	P58062	3	EBI-1182496,EBI-1182445

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Short (identifier: P16452-1)

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.

Note: Major isoform.

Isoform Long (identifier: P16452-2)

The sequence of this isoform differs from the canonical sequence as follows:
     3-3: Q → QGEPSQRSTGLAGLYAAPAASPVFIKGSGMD

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 691	691	Erythrocyte membrane protein band 4.2		PRO_0000213720
Regions
	Region	31 – 39	9	Band 3 binding By similarity
Amino acid modifications
	Modified residue	248	1	Phosphoserine; by PKA Probable
	Lipidation	2	1	N-myristoyl glycine Ref.7
Natural variations
	Alternative sequence	3	1	Q → QGEPSQRSTGLAGLYAAPAA SPVFIKGSGMD in isoform Long.		VSP_006416
	Natural variant	112	1	A → T in SPH5; Nippon/Fukuoka. Ref.9 Ref.10 Ref.12 Ref.14 Corresponds to variant rs28933988 [ dbSNP | Ensembl ].		VAR_007482
	Natural variant	145	1	D → Y in SPH5; Komatsu. Ref.13		VAR_058099
	Natural variant	280	1	R → Q in SPH5; Tozeur. Ref.11		VAR_012268
	Natural variant	287	1	R → C in SPH5; Shiga. Ref.12		VAR_058100
Experimental info
	Sequence conflict	350	1	H → D in AAA74589. Ref.1
	Sequence conflict	350	1	H → D in AAA52385. Ref.1
	Sequence conflict	350	1	H → D in AAA35798. Ref.2
	Sequence conflict	376	1	L → V in AAA74589. Ref.1
	Sequence conflict	376	1	L → V in AAA52385. Ref.1
	Sequence conflict	376	1	L → V in AAA35798. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Short [UniParc]. Last modified November 25, 2008. Version 3. Checksum: 38225C311E478580	FASTA	691	77,009
	10 20 30 40 50 60 MGQALGIKSC DFQAARNNEE HHTKALSSRR LFVRRGQPFT IILYFRAPVR AFLPALKKVA 70 80 90 100 110 120 LTAQTGEQPS KINRTQATFP ISSLGDRKWW SAVVEERDAQ SWTISVTTPA DAVIGHYSLL 130 140 150 160 170 180 LQVSGRKQLL LGQFTLLFNP WNREDAVFLK NEAQRMEYLL NQNGLIYLGT ADCIQAESWD 190 200 210 220 230 240 FGQFEGDVID LSLRLLSKDK QVEKWSQPVH VARVLGALLH FLKEQRVLPT PQTQATQEGA 250 260 270 280 290 300 LLNKRRGSVP ILRQWLTGRG RPVYDGQAWV LAAVACTVLR CLGIPARVVT TFASAQGTGG 310 320 330 340 350 360 RLLIDEYYNE EGLQNGEGQR GRIWIFQTST ECWMTRPALP QGYDGWQILH PSAPNGGGVL 370 380 390 400 410 420 GSCDLVPVRA VKEGTLGLTP AVSDLFAAIN ASCVVWKCCE DGTLELTDSN TKYVGNNIST 430 440 450 460 470 480 KGVGSDRCED ITQNYKYPEG SLQEKEVLER VEKEKMEREK DNGIRPPSLE TASPLYLLLK 490 500 510 520 530 540 APSSLPLRGD AQISVTLVNH SEQEKAVQLA IGVQAVHYNG VLAAKLWRKK LHLTLSANLE 550 560 570 580 590 600 KIITIGLFFS NFERNPPENT FLRLTAMATH SESNLSCFAQ EDIAICRPHL AIKMPEKAEQ 610 620 630 640 650 660 YQPLTASVSL QNSLDAPMED CVISILGRGL IHRERSYRFR SVWPENTMCA KFQFTPTHVG 670 680 690 LQRLTVEVDC NMFQNLTNYK SVTVVAPELS A
	Isoform Long [UniParc]. Checksum: A1C85B41298A93C0	FASTA	721	79,927
	10 20 30 40 50 60 MGQGEPSQRS TGLAGLYAAP AASPVFIKGS GMDALGIKSC DFQAARNNEE HHTKALSSRR 70 80 90 100 110 120 LFVRRGQPFT IILYFRAPVR AFLPALKKVA LTAQTGEQPS KINRTQATFP ISSLGDRKWW 130 140 150 160 170 180 SAVVEERDAQ SWTISVTTPA DAVIGHYSLL LQVSGRKQLL LGQFTLLFNP WNREDAVFLK 190 200 210 220 230 240 NEAQRMEYLL NQNGLIYLGT ADCIQAESWD FGQFEGDVID LSLRLLSKDK QVEKWSQPVH 250 260 270 280 290 300 VARVLGALLH FLKEQRVLPT PQTQATQEGA LLNKRRGSVP ILRQWLTGRG RPVYDGQAWV 310 320 330 340 350 360 LAAVACTVLR CLGIPARVVT TFASAQGTGG RLLIDEYYNE EGLQNGEGQR GRIWIFQTST 370 380 390 400 410 420 ECWMTRPALP QGYDGWQILH PSAPNGGGVL GSCDLVPVRA VKEGTLGLTP AVSDLFAAIN 430 440 450 460 470 480 ASCVVWKCCE DGTLELTDSN TKYVGNNIST KGVGSDRCED ITQNYKYPEG SLQEKEVLER 490 500 510 520 530 540 VEKEKMEREK DNGIRPPSLE TASPLYLLLK APSSLPLRGD AQISVTLVNH SEQEKAVQLA 550 560 570 580 590 600 IGVQAVHYNG VLAAKLWRKK LHLTLSANLE KIITIGLFFS NFERNPPENT FLRLTAMATH 610 620 630 640 650 660 SESNLSCFAQ EDIAICRPHL AIKMPEKAEQ YQPLTASVSL QNSLDAPMED CVISILGRGL 670 680 690 700 710 720 IHRERSYRFR SVWPENTMCA KFQFTPTHVG LQRLTVEVDC NMFQNLTNYK SVTVVAPELS A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Organization of the gene for human erythrocyte membrane protein 4.2: structural similarities with the gene for the a subunit of factor XIII." Korsgren C., Cohen C.M. Proc. Natl. Acad. Sci. U.S.A. 88:4840-4844(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Reticulocyte.
[2]	"Complete amino acid sequence and homologies of human erythrocyte membrane protein band 4.2." Korsgren C., Lawler J., Lambert S., Speicher D., Cohen C.M. Proc. Natl. Acad. Sci. U.S.A. 87:613-617(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE (ISOFORM SHORT). Tissue: Reticulocyte.
[3]	"Molecular cloning of human protein 4.2: a major component of the erythrocyte membrane." 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. Proc. Natl. Acad. Sci. U.S.A. 87:955-959(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT). Tissue: Reticulocyte.
[4]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
[7]	"Human erythrocyte protein 4.2, a high copy number membrane protein, is N-myristylated." Risinger M.A., Dotimas E.M., Cohen C.M. J. Biol. Chem. 267:5680-5685(1992) [PubMed] [Europe PMC] [Abstract] Cited for: MYRISTOYLATION AT GLY-2.
[8]	"Structural domain mapping and phosphorylation of human erythrocyte pallidin (band 4.2)." Dotimas E., Speicher D.W., Guptaroy B., Cohen C.M. Biochim. Biophys. Acta 1148:19-29(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-248.
[9]	"An alanine-to-threonine substitution in protein 4.2 cDNA is associated with a Japanese form of hereditary hemolytic anemia (protein 4.2 Nippon)." Bouhassira E.E., Schwartz R.S., Yawata Y., Ata K., Kanzaki A., Qiu J.J.-H., Nagel R.L., Rybicki A.C. Blood 79:1846-1854(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPH5 THR-112.
[10]	"A novel mutation in the erythrocyte protein 4.2 gene of Japanese patients with hereditary spherocytosis (protein 4.2 Fukuoka)." Takaoka Y., Ideguchi H., Matsuda M., Sakamoto N., Takeuchi T., Fukumaki Y. Br. J. Haematol. 88:527-533(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPH5 THR-112.
[11]	"A point mutation in the protein 4.2 gene (allele 4.2 Tozeur) associated with hereditary haemolytic anaemia." Hayette S., Morle L., Bozon M., Ghanem A., Risinger M., Korsgren C., Tanner M.J.A., Fattoum S., Cohen C.M., Delaunay J. Br. J. Haematol. 89:762-770(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPH5 GLN-280.
[12]	"Band 4.2 Shiga: 317 CGC-->TGC in compound heterozygotes with 142 GCT-->ACT results in band 4.2 deficiency and microspherocytosis." Kanzaki A., Yasunaga M., Okamoto N., Inoue T., Yawata A., Wada H., Andoh A., Hodohara K., Fujiyama Y., Bamba T., Harano T., Harano K., Yawata Y. Br. J. Haematol. 91:333-340(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SPH5 THR-112 AND CYS-287.
[13]	"Band 4.2 Komatsu: 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band 4.2 gene associated with total deficiency of band 4.2, hemolytic anemia with ovalostomatocytosis and marked disruption of the cytoskeletal network." Kanzaki A., Yawata Y., Yawata A., Inoue T., Okamoto N., Wada H., Harano T., Harano K., Wilmotte R., Hayette S., Nakamura Y., Niki T., Kawamura Y., Nakamura S., Matsuda T. Int. J. Hematol. 61:165-178(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPH5 TYR-145.
[14]	"4.2 Nippon mutation in a non-Japanese patient with hereditary spherocytosis." Perrotta S., Iolascon A., Polito R., d'Urzo G., Conte M.L., Miraglia del Giudice E. Haematologica 84:660-662(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPH5 THR-112.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M60298 mRNA. Translation: AAA74589.1. L06519 , L06447, L06448, L06449, L06450, L06511, L06512, L06513, L06515, L06516, L06517, L06518 Genomic DNA. Translation: AAA52385.1. M29399 mRNA. Translation: AAA35798.1. M30647 mRNA. Translation: AAA36401.1. Frameshift. M30646 mRNA. Translation: AAA36402.1. Frameshift. AC068724 Genomic DNA. No translation available. CH471125 Genomic DNA. Translation: EAW92591.1. BC096093 mRNA. Translation: AAH96093.1. BC096094 mRNA. Translation: AAH96094.1.
IPI	IPI00028120. IPI00827872.
PIR	A39707.
RefSeq	NP_000110.2. NM_000119.2. NP_001107606.1. NM_001114134.1.
UniGene	Hs.368642.
3D structure databases
ProteinModelPortal	P16452.
ModBase	Search...
Protein-protein interaction databases
IntAct	P16452. 3 interactions.
STRING	9606.ENSP00000300215.
PTM databases
PhosphoSite	P16452.
Polymorphism databases
DMDM	215274164.
Proteomic databases
PaxDb	P16452.
PRIDE	P16452.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000300215; ENSP00000300215; ENSG00000166947. ENST00000441366; ENSP00000396616; ENSG00000166947.
GeneID	2038.
KEGG	hsa:2038.
UCSC	uc001zqz.4. human. uc001zrb.4. human.
Organism-specific databases
CTD	2038.
GeneCards	GC15M043398.
HGNC	HGNC:3381. EPB42.
HPA	HPA040261.
MIM	177070. gene. 612690. phenotype.
neXtProt	NX_P16452.
Orphanet	822. Hereditary spherocytosis.
PharmGKB	PA27814.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG87163.
HOGENOM	HOG000231695.
HOVERGEN	HBG106048.
InParanoid	P16452.
OMA	PPENSFL.
Gene expression databases
ArrayExpress	P16452.
Bgee	P16452.
CleanEx	HS_EPB42.
Genevestigator	P16452.
GermOnline	ENSG00000166947. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 3 hits.
InterPro	IPR023608. Gln_gamma-glutamylTfrase_euk. IPR013783. Ig-like_fold. IPR014756. Ig_E-set. IPR002931. Transglutaminase-like. IPR008958. Transglutaminase_C. IPR013808. Transglutaminase_CS. IPR001102. Transglutaminase_N. [Graphical view]
PANTHER	PTHR11590. PTHR11590. 1 hit.
Pfam	PF00927. Transglut_C. 2 hits. PF01841. Transglut_core. 1 hit. PF00868. Transglut_N. 1 hit. [Graphical view]
PIRSF	PIRSF000459. TGM_EBP42. 1 hit.
SMART	SM00460. TGc. 1 hit. [Graphical view]
SUPFAM	SSF81296. Ig_E-set. 1 hit. SSF49309. Transglut_C. 2 hits.
PROSITE	PS00547. TRANSGLUTAMINASES. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	2038.
NextBio	8277.
SOURCE	Search...

Entry information

Entry name

EPB42_HUMAN

Accession

Primary (citable) accession number: P16452
Secondary accession number(s): Q4VB97

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 146 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.