Skip Header

Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot P23634 (AT2B4_HUMAN)

Last modified February 9, 2010. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Plasma membrane calcium-transporting ATPase 4
      Short name=PMCA4
    EC=3.6.3.8
Alternative name(s):
    Plasma membrane calcium ATPase isoform 4
    Plasma membrane calcium pump isoform 4
    Matrix-remodeling-associated protein 1
Gene names
Name: ATP2B4
Synonyms: ATP2B2, MXRA1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1241 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.

Catalytic activity

ATP + H2O + Ca2+(Cis) = ADP + phosphate + Ca2+(Trans).

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Isoform XB is the most abundant isoform and is expressed ubiquitously. Isoforms containing segment Z have only been detected in heart, while isoforms containing segment a have been found in heart, stomach and brain cortex.

Sequence similarities

Belongs to the cation transport ATPase (P-type) family. Type IIB subfamily.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Dlg1Q626961EBI-1174437,EBI-389325From a different organism.
Dlg2Q636222EBI-1174437,EBI-396947From a different organism.
Dlg3Q629362EBI-1174437,EBI-349596From a different organism.
Dlg4P310161EBI-1174437,EBI-375655From a different organism.

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]

Note: There is a combination of two alternatively spliced domains at N-terminal site A (X and Z) and at C-terminal site B/C (A, B, D and K). The splice sites have mostly been studied independently. Full isoforms so far detected are isoform XA and isoform XB. Experimental confirmation may be lacking for some isoforms.
Isoform XD (identifier: P23634-1)

Also known as: AIICIV;

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 XA (identifier: P23634-2)

Also known as: AIICII;

The sequence of this isoform differs from the canonical sequence as follows:
     1140-1241: IKVVKAFHSS...SSLQSLETSV → VAVAPVKSSPTTSVPAVSSPPMGNQSGQSVP
Isoform ZA (identifier: P23634-3)

Also known as: AICII;

The sequence of this isoform differs from the canonical sequence as follows:
     301-312: Missing.
     1140-1241: IKVVKAFHSS...SSLQSLETSV → VAVAPVKSSPTTSVPAVSSPPMGNQSGQSVP
Isoform XK (identifier: P23634-4)

Also known as: XG;

The sequence of this isoform differs from the canonical sequence as follows:
     1009-1044: Missing.
     1140-1241: IKVVKAFHSS...SSLQSLETSV → VAVAPVKSSPTTSVPAVSSPPMGNQSGQSVP
Isoform ZK (identifier: P23634-5)

Also known as: ZG;

The sequence of this isoform differs from the canonical sequence as follows:
     301-312: Missing.
     1009-1044: Missing.
     1140-1241: IKVVKAFHSS...SSLQSLETSV → VAVAPVKSSPTTSVPAVSSPPMGNQSGQSVP
Isoform XB (identifier: P23634-6)

Also known as: AIICI;

The sequence of this isoform differs from the canonical sequence as follows:
     1104-1139: Missing.
Isoform ZB (identifier: P23634-7)

Also known as: AICI;

The sequence of this isoform differs from the canonical sequence as follows:
     301-312: Missing.
     1104-1139: Missing.
Isoform ZD (identifier: P23634-8)

Also known as: AICIV;

The sequence of this isoform differs from the canonical sequence as follows:
     301-312: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12411241Plasma membrane calcium-transporting ATPase 4
PRO_0000046220

Regions

Topological domain1 – 9292Cytoplasmic Potential
Transmembrane93 – 11321 Potential
Topological domain114 – 15037Extracellular Potential
Transmembrane151 – 17121 Potential
Topological domain172 – 356185Cytoplasmic Potential
Transmembrane357 – 37620 Potential
Topological domain377 – 40933Extracellular Potential
Transmembrane410 – 42718 Potential
Topological domain428 – 840413Cytoplasmic Potential
Transmembrane841 – 86020 Potential
Topological domain861 – 87010Extracellular Potential
Transmembrane871 – 89121 Potential
Topological domain892 – 91120Cytoplasmic Potential
Transmembrane912 – 93423 Potential
Topological domain935 – 95218Extracellular Potential
Transmembrane953 – 97422 Potential
Topological domain975 – 99319Cytoplasmic Potential
Transmembrane994 – 101522 Potential
Topological domain1016 – 102510Extracellular Potential
Transmembrane1026 – 104722 Potential
Topological domain1048 – 1241194Cytoplasmic Potential
Region1086 – 110318Calmodulin-binding subdomain A
Region1104 – 111310Calmodulin-binding subdomain B By similarity
Compositional bias297 – 3037Poly-Lys
Compositional bias1186 – 11905Poly-Glu

Sites

Active site46514-aspartylphosphate intermediate By similarity
Metal binding7851Magnesium By similarity
Metal binding7891Magnesium By similarity

Amino acid modifications

Modified residue11021Phosphothreonine; by PKC By similarity

Natural variations

Alternative sequence301 – 31212Missing in isoform ZA, isoform ZK, isoform ZB and isoform ZD.
VSP_000402
Alternative sequence1009 – 104436Missing in isoform XK and isoform ZK.
VSP_000403
Alternative sequence1104 – 113936Missing in isoform XB and isoform ZB.
VSP_000404
Alternative sequence1140 – 1241102IKVVK…LETSV → VAVAPVKSSPTTSVPAVSSP PMGNQSGQSVP in isoform XA, isoform XK, isoform ZA and isoform ZK.
VSP_000405

Experimental info

Sequence conflict11441K → N AA sequence Ref.6
Sequence conflict11471H → S AA sequence Ref.6
Sequence conflict11531S → F AA sequence Ref.6
Sequence conflict11781L → Q AA sequence Ref.7
Sequence conflict11871E → Q AA sequence Ref.7

Secondary structure

.... 1241
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform XD (AIICIV) [UniParc].

Last modified June 1, 2001. Version 2.
Checksum: 568544103CD5F494

FASTA1,241137,920
        10         20         30         40         50         60 
MTNPSDRVLP ANSMAESREG DFGCTVMELR KLMELRSRDA LTQINVHYGG VQNLCSRLKT 

        70         80         90        100        110        120 
SPVEGLSGNP ADLEKRRQVF GHNVIPPKKP KTFLELVWEA LQDVTLIILE IAAIISLVLS 

       130        140        150        160        170        180 
FYRPAGEENE LCGQVATTPE DENEAQAGWI EGAAILFSVI IVVLVTAFND WSKEKQFRGL 

       190        200        210        220        230        240 
QCRIEQEQKF SIIRNGQLIQ LPVAEIVVGD IAQVKYGDLL PADGILIQGN DLKIDESSLT 

       250        260        270        280        290        300 
GESDHVKKSL DKDPMLLSGT HVMEGSGRMV VTAVGVNSQT GIILTLLGVN EDDEGEKKKK 

       310        320        330        340        350        360 
GKKQGVPENR NKAKTQDGVA LEIQPLNSQE GIDNEEKDKK AVKVPKKEKS VLQGKLTRLA 

       370        380        390        400        410        420 
VQIGKAGLLM SALTVFILIL YFVIDNFVIN RRPWLPECTP IYIQYFVKFF IIGITVLVVA 

       430        440        450        460        470        480 
VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL TMNRMTVVQA 

       490        500        510        520        530        540 
YIGGIHYRQI PSPDVFLPKV LDLIVNGISI NSAYTSKILP PEKEGGLPRQ VGNKTECALL 

       550        560        570        580        590        600 
GFVTDLKQDY QAVRNEVPEE KLYKVYTFNS VRKSMSTVIR NPNGGFRMYS KGASEIILRK 

       610        620        630        640        650        660 
CNRILDRKGE AVPFKNKDRD DMVRTVIEPM ACDGLRTICI AYRDFDDTEP SWDNENEILT 

       670        680        690        700        710        720 
ELTCIAVVGI EDPVRPEVPD AIAKCKQAGI TVRMVTGDNI NTARAIATKC GILTPGDDFL 

       730        740        750        760        770        780 
CLEGKEFNRL IRNEKGEVEQ EKLDKIWPKL RVLARSSPTD KHTLVKGIID STVGEHRQVV 

       790        800        810        820        830        840 
AVTGDGTNDG PALKKADVGF AMGIAGTDVA KEASDIILTD DNFTSIVKAV MWGRNVYDSI 

       850        860        870        880        890        900 
SKFLQFQLTV NVVAVIVAFT GACITQDSPL KAVQMLWVNL IMDTFASLAL ATEPPTESLL 

       910        920        930        940        950        960 
KRRPYGRNKP LISRTMMKNI LGHAFYQLIV IFILVFAGEK FFDIDSGRKA PLHSPPSQHY 

       970        980        990       1000       1010       1020 
TIVFNTFVLM QLFNEINSRK IHGEKNVFSG IYRNIIFCSV VLGTFICQIF IVEFGGKPFS 

      1030       1040       1050       1060       1070       1080 
CTSLSLSQWL WCLFIGIGEL LWGQFISAIP TRSLKFLKEA GHGTTKEEIT KDAEGLDEID 

      1090       1100       1110       1120       1130       1140 
HAEMELRRGQ ILWFRGLNRI QTQIDVINTF QTGASFKGVL RRQNMGQHLD VKLVPSSSYI 

      1150       1160       1170       1180       1190       1200 
KVVKAFHSSL HESIQKPYNQ KSIHSFMTHP EFAIEEELPR TPLLDEEEEE NPDKASKFGT 

      1210       1220       1230       1240 
RVLLLDGEVT PYANTNNNAV DCNQVQLPQS DSSLQSLETS V 

« Hide

Isoform XA (AIICII).

Checksum: C4ED2E2EFE1BB043
Show »

FASTA1,170129,403
Isoform ZA (AICII).

Checksum: E7AA8CC9C25E0727
Show »

FASTA1,158128,066
Isoform XK (XG).

Checksum: 088F8CB994D46238
Show »

FASTA1,134125,344
Isoform ZK (ZG).

Checksum: 4AD4378ED226853B
Show »

FASTA1,122124,007
Isoform XB (AIICI).

Checksum: 76CE806974035974
Show »

FASTA1,205133,931
Isoform ZB (AICI).

Checksum: 6AA34BD1850CADB7
Show »

FASTA1,193132,594
Isoform ZD (AICIV).

Checksum: 5E9E48B86464E926
Show »

FASTA1,229136,584

References

« Hide 'large scale' references
[1]"Peptide sequence analysis and molecular cloning reveal two calcium pump isoforms in the human erythrocyte membrane."
Strehler E.E., James P., Fischer R., Heim R., Vorherr T.E., Filoteo A.G., Penniston J.T., Carafoli E.
J. Biol. Chem. 265:2835-2842(1990) [PubMed: 2137451] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM XB), PARTIAL PROTEIN SEQUENCE.
Tissue: Erythrocyte.
[2]"Analysis of the tissue-specific distribution of mRNAs encoding the plasma membrane calcium-pumping ATPases and characterization of an alternately spliced form of PMCA4 at the cDNA and genomic levels."
Brandt P., Neve R.L., Kammesheidt A., Rhoads R.E., Vanaman T.C.
J. Biol. Chem. 267:4376-4385(1992) [PubMed: 1531651] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM XA).
Tissue: Fetal brain.
[3]"Analysis of mRNA expression and cloning of a novel plasma membrane Ca(2+)-ATPase splice variant in human heart."
Santiago-Garcia J., Mas-Oliva J., Saavedra D., Zarain-Herzberg A.
Mol. Cell. Biochem. 155:173-182(1996) [PubMed: 8700162] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS XA; XB; XK; ZA; ZB AND ZK).
Tissue: Heart muscle.
[4]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. expand/collapse author list , 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].
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Identification and primary structure of a calmodulin binding domain of the Ca2+ pump of human erythrocytes."
James P., Maeda M., Fischer R., Verma A.K., Krebs J., Penniston J.T., Carafoli E.
J. Biol. Chem. 263:2905-2910(1988) [PubMed: 2963820] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1085-1153 (ISOFORMS XB/ZB), CALMODULIN-BINDING SUBDOMAIN A.
[7]"A C-terminal, calmodulin-like regulatory domain from the plasma membrane Ca2+-pumping ATPase."
Brandt P., Zurini M., Neve R.L., Rhoads R.E., Vanaman T.C.
Proc. Natl. Acad. Sci. U.S.A. 85:2914-2918(1988) [PubMed: 2966397] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1177-1190.
[8]"Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes."
Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.
J. Biol. Chem. 268:25993-26003(1993) [PubMed: 8245032] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS X AND Z).
Tissue: Heart.
[9]Erratum
Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.
J. Biol. Chem. 269:32022-32022(1994) [PubMed: 7989379] [Abstract]
[10]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]"NMR solution structure of a complex of calmodulin with a binding peptide of the Ca(2+) pump."
Elshorst B., Hennig M., Foersterling H., Diener A., Maurer M., Schulte P., Schwalbe H., Griesinger C., Krebs J., Schmid H., Vorherr T.E., Carafoli E.
Biochemistry 38:12320-12332(1999) [PubMed: 10493800] [Abstract]
Cited for: STRUCTURE BY NMR OF 1086-1104 IN COMPLEX WITH CALMODULIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M25874 mRNA. Translation: AAA50819.1.
M83363 mRNA. Translation: AAA36455.1.
U42026 mRNA. Translation: AAB17577.1.
U42061 mRNA. Translation: AAB17578.1.
U42062 mRNA. Translation: AAB17579.1.
U42378 mRNA. Translation: AAB17580.1.
AL513343, AC114402 Genomic DNA. Translation: CAI17026.1.
CH471067 Genomic DNA. Translation: EAW91486.1.
IPIIPI00012490.
IPI00217164.
IPI00217165.
IPI00217166.
IPI00217168.
IPI00217169.
IPI00217170.
IPI00217171.
PIRA35547.
RefSeqNP_001001396.1.
NP_001675.3.
UniGeneHs.343522

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CFFNMR-B1086-1104[»]
2KNENMR-B1086-1104[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-6128N.
IntActP23634. 4 interactions.
STRINGP23634.

Protein family/group databases

TCDB3.A.3.2.1. P-type ATPase (P-ATPase) superfamily.

PTM databases

PhosphoSiteP23634.

Proteomic databases

PRIDEP23634.

Genome annotation databases

EnsemblENST00000341360; ENSP00000340930; ENSG00000058668; Homo sapiens. [Genome view]
ENST00000367218; ENSP00000356187; ENSG00000058668; Homo sapiens. [Genome view]
GeneID493.
KEGGhsa:493.
UCSCuc001gzv.1. human.
uc001gzw.1. human.

Organism-specific databases

CTD493.
GeneCardsGC01P201862.
H-InvDBHIX0023651.
HGNCHGNC:817. ATP2B4.
HPACAB016118.
MIM108732. gene.
PharmGKBPA25110.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP23634.
InParanoidP23634.
OMALKTNPVE.
OrthoDBEOG9KM1NM.
PhylomeDBP23634.

Enzyme and pathway databases

BRENDA3.6.3.8. 247.

Gene expression databases

ArrayExpressP23634.
BgeeP23634.
CleanExHS_ATP2B2.
HS_ATP2B4.
GenevestigatorP23634.
GermOnlineENSG00000058668. Homo sapiens.

Family and domain databases

InterProIPR008250. ATPase_P-typ_ATPase-assoc-dom.
IPR006408. ATPase_P-typ_Ca-transp_PMCA.
IPR006068. ATPase_P-typ_cation-transptr_C.
IPR004014. ATPase_P-typ_cation-transptr_N.
IPR001757. ATPase_P-typ_ion-transptr.
IPR018303. ATPase_P-typ_P_site.
IPR005834. Dehalogen-like_hydro.
[Graphical view]
PANTHERPTHR11939. ATPase_P. 1 hit.
PfamPF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
PF00702. Hydrolase. 1 hit.
[Graphical view]
PRINTSPR00119. CATATPASE.
SMARTSM00831. Cation_ATPase_N. 1 hit.
[Graphical view]
TIGRFAMsTIGR01517. ATPase-IIB_Ca. 1 hit.
TIGR01494. ATPase_P-type. 4 hits.
PROSITEPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

SOURCESearch...

Entry information

Entry nameAT2B4_HUMAN
AccessionPrimary (citable) accession number: P23634
Secondary accession number(s): B1APW6 expand/collapse secondary AC list , Q13450, Q13452, Q13455, Q16817
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: June 1, 2001
Last modified: February 9, 2010
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents