P20810 (ICAL_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 127.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Calpastatin Alternative name(s): Calpain inhibitor Sperm BS-17 component | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Reference proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 708 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue. |
| Domain | Each of the four flexible inhibitory domains can inhibit one calcium-bound calpain molecule by occupying both sides of the active site By similarity. |
| Post-translational modification | The N-terminus is blocked. |
| Sequence similarities | Belongs to the protease inhibitor I27 (calpastatin) family. [View classification] |
| Sequence caution | The sequence AAH16066.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence. |
Ontologies
| Keywords | |
|---|---|
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Repeat |
| Molecular function | Protease inhibitor Thiol protease inhibitor |
| PTM | Phosphoprotein |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Molecular_function | cysteine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW endopeptidase inhibitor activityTraceable author statement PubMed 7638179. Source: ProtInc |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| NCK1 | P16333 | 2 | EBI-1268770,EBI-389883 |
Alternative products
| This entry describes 8 isoforms produced by alternative splicing. [Align] [Select] Note: Additional isoforms seem to exist. | ||||||
| Isoform 1 (identifier: P20810-1) 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. | ||||||
| Isoform 2 (identifier: P20810-2) The sequence of this isoform differs from the canonical sequence as follows: 212-224: Missing. | ||||||
| Isoform 3 (identifier: P20810-3) The sequence of this isoform differs from the canonical sequence as follows: 1-105: Missing. 212-224: Missing. | ||||||
| Isoform 4 (identifier: P20810-4) The sequence of this isoform differs from the canonical sequence as follows: 9-30: Missing. 44-62: Missing. | ||||||
| Isoform 5 (identifier: P20810-5) The sequence of this isoform differs from the canonical sequence as follows: 1-29: MNPTETKAIPVSQQMEGPHLPNKKKHKKQ → MSQPGQKPAA...SSSMNPTETK 212-224: Missing. | ||||||
| Note: Contains a phosphoserine at position 11. | ||||||
| Isoform 6 (identifier: P20810-6) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MSQPGQKPAA...SGATSKSSSM | ||||||
| Note: Contains a phosphoserine at position 11. | ||||||
| Isoform 7 (identifier: P20810-7) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MSQPGQKPAA...SGATSKSSSM 44-62: Missing. | ||||||
| Note: Contains a phosphoserine at position 11. | ||||||
| Isoform 8 (identifier: P20810-8) The sequence of this isoform differs from the canonical sequence as follows: 9-30: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 708 | 708 | Calpastatin | PRO_0000147632 | |||||
Regions | |||||||||
| Repeat | 170 – 222 | 53 | Inhibitory domain 1 | ||||||
| Repeat | 304 – 356 | 53 | Inhibitory domain 2 | ||||||
| Repeat | 446 – 499 | 54 | Inhibitory domain 3 | ||||||
| Repeat | 583 – 636 | 54 | Inhibitory domain 4 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 87 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 133 | 1 | Phosphoserine Ref.19 | ||||||
| Modified residue | 222 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 243 | 1 | Phosphoserine Ref.18 | ||||||
| Modified residue | 364 | 1 | Phosphoserine Ref.18 | ||||||
| Modified residue | 366 | 1 | Phosphoserine Ref.18 | ||||||
| Modified residue | 373 | 1 | Phosphoserine Ref.18 | ||||||
| Modified residue | 575 | 1 | Phosphoserine Ref.19 | ||||||
| Modified residue | 577 | 1 | Phosphoserine Ref.19 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 105 | 105 | Missing in isoform 3. | VSP_000741 | |||||
| Alternative sequence | 1 – 29 | 29 | MNPTE…KHKKQ → MSQPGQKPAASPRPRRAAAA RRTHEHVSEKTSESPSKPGE KKGSDEKKAASLGSSQSSRT YAGGTASATKVSASSGATSK SSSMNPTETK in isoform 5. | VSP_038037 | |||||
| Alternative sequence | 1 | 1 | M → MSQPGQKPAASPRPRRAAAA RRTHEHVSEKTSESPSKPGE KKGSDEKKAASLGSSQSSRT YAGGTASATKVSASSGATSK SSSM in isoform 6 and isoform 7. | VSP_038038 | |||||
| Alternative sequence | 9 – 30 | 22 | Missing in isoform 4 and isoform 8. | VSP_000742 | |||||
| Alternative sequence | 44 – 62 | 19 | Missing in isoform 4 and isoform 7. | VSP_000743 | |||||
| Alternative sequence | 212 – 224 | 13 | Missing in isoform 2, isoform 3 and isoform 5. | VSP_000744 | |||||
| Natural variant | 380 | 1 | E → K. Corresponds to variant rs1643702 [ dbSNP | Ensembl ]. | VAR_030741 | |||||
| Natural variant | 408 | 1 | C → S. Ref.1 Ref.7 Ref.11 Ref.14 Corresponds to variant rs754615 [ dbSNP | Ensembl ]. | VAR_022686 | |||||
| Natural variant | 537 | 1 | A → V. Corresponds to variant rs4948 [ dbSNP | Ensembl ]. | VAR_030742 | |||||
| Natural variant | 592 | 1 | E → G. Ref.1 | VAR_005298 | |||||
Experimental info | |||||||||
| Sequence conflict | 467 | 1 | R → L in AAC50136. Ref.11 | ||||||
| Sequence conflict | 486 – 488 | 3 | VKD → GKE in AAC50136. Ref.11 | ||||||
| Sequence conflict | 543 | 1 | V → L in AAC50136. Ref.11 | ||||||
| Sequence conflict | 562 | 1 | Missing in AAB60371. Ref.14 | ||||||
| Sequence conflict | 651 | 1 | I → V in AAD09102. Ref.15 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "cDNA cloning of human calpastatin: sequence homology among human, pig, and rabbit calpastatins." Asada K., Ishino Y., Shimada M., Shimojo T., Endo M., Kimizuka F., Kato I., Maki M., Hatanaka M., Murachi T. J. Enzym. Inhib. 3:49-56(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS SER-408 AND GLY-592. |
| [2] | "Cloning and characterization of a novel isoform of calpastatin in human adult testis." Zhu H., Zhou Z.-M., Li J.-M., Zhu H., Cheng L.-J., Shan Y.-X., Yin L.-L., Sha J.H. Acta Pharmacol. Sin. 23:450-454(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Testis. |
| [3] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). |
| [4] | "The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. Rubin E.M.Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 6 AND 7). |
| [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. 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 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-319 (ISOFORM 5). Tissue: Lung and Skin. |
| [7] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-479 (ISOFORM 8), VARIANT SER-408. |
| [8] | "Molecular diversity in amino-terminal domains of human calpastatin by exon skipping." Lee W.J., Ma H., Takano E., Yang H.Q., Hatanaka M., Maki M. J. Biol. Chem. 267:8437-8442(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-283 (ISOFORM 1), ALTERNATIVE SPLICING. Tissue: Lung. |
| [9] | "Inhibition of calpain by a synthetic oligopeptide corresponding to an exon of the human calpastatin gene." Maki M., Bagci H., Hamaguchi K., Ueda M., Murachi T., Hatanaka M. J. Biol. Chem. 264:18866-18869(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 101-317. |
| [10] | "Characterization of a functional domain of human calpastatin." Uemori T., Shimojo T., Asada K., Asano T., Kimizuka F., Kato I., Maki M., Hatanaka M., Murachi T., Hanzawa H., Arata Y. Biochem. Biophys. Res. Commun. 166:1485-1493(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 125-283 (ISOFORMS 2/3). |
| [11] | Wang L.F. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 153-708 (ISOFORMS 2/3), SEQUENCE REVISION, VARIANT SER-408. |
| [12] | "Calpastatin gene in human testis." Wang L.F., Wei S.G., Miao S.Y., Liu Q.Y., Koide S.S. Biochem. Mol. Biol. Int. 33:245-252(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 523-708 (ISOFORMS 1/2/3/4). Tissue: Testis. |
| [13] | "Detection and expression of a cDNA clone that encodes a polypeptide containing two inhibitory domains of human calpastatin and its recognition by rheumatoid arthritis sera." Despres N., Talbot G., Plouffe B., Boire G., Menard H.A. J. Clin. Invest. 95:1891-1896(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 425-708 (ISOFORMS 1/2/3/4). Tissue: Placenta. |
| [14] | El-Amine M., Talbot G., Despres N., Asselin C., Boire G., Menard H.A. Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 244-708 (ISOFORMS 1/2/3/4), VARIANT SER-408. Tissue: Placenta. |
| [15] | "New calpastatin 3' UTR." Rochdi M.D., El-Amine M., Menard H.A. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 636-708 (ISOFORMS 1/2/3/4). |
| [16] | "Phosphorylation and subcellular distribution of calpastatin in human hematopoietic system cells." Adachi Y., Ishida-Takahashi A., Takahashi C., Takano E., Murachi T., Hatanaka M. J. Biol. Chem. 266:3968-3972(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION. |
| [17] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma. |
| [18] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-243; SER-364; SER-366 AND SER-373, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [19] | "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133; SER-575 AND SER-577, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 (ISOFORMS 5; 6 AND 7), MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [20] | "Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | D16217 mRNA. Translation: BAA03747.1. D50827 mRNA. Translation: BAA09438.1. AF327443 mRNA. Translation: AAG48151.1. BT009783 mRNA. Translation: AAP88785.1. AC008906 Genomic DNA. No translation available. AC020900 Genomic DNA. No translation available. AC104125 Genomic DNA. No translation available. CH471084 Genomic DNA. Translation: EAW96068.1. CH471084 Genomic DNA. Translation: EAW96075.1. BC013579 mRNA. Translation: AAH13579.1. BC016066 mRNA. Translation: AAH16066.1. Sequence problems. AL832349 mRNA. No translation available. M86258 mRNA. Translation: AAB59398.1. M28230 M28229 Genomic DNA. Translation: AAA52066.1.M33328 mRNA. Translation: AAA52296.1. U26724 mRNA. Translation: AAC50136.2. S73329 mRNA. Translation: AAB32311.1. U38525 mRNA. Translation: AAA80684.1. U31345 mRNA. Translation: AAB60371.1. U31346 mRNA. Translation: AAB60372.1. AF095891 mRNA. Translation: AAD09102.1. |
| IPI | IPI00220857. IPI00305750. IPI00413492. IPI00760715. IPI00761035. IPI00761160. IPI00979393. |
| PIR | A38091. |
| RefSeq | NP_001035905.1. NM_001042440.2. NP_001177371.1. NM_001190442.1. NP_775083.1. NM_173060.3. |
| UniGene | Hs.436186. |
3D structure databases | |
| DisProt | DP00196. |
| ProteinModelPortal | P20810. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P20810. 8 interactions. |
| STRING | 9606.ENSP00000379158. |
Protein family/group databases | |
| MEROPS | I27.001. |
PTM databases | |
| PhosphoSite | P20810. |
Polymorphism databases | |
| DMDM | 126302556. |
Proteomic databases | |
| PaxDb | P20810. |
| PRIDE | P20810. |
Protocols and materials databases | |
| DNASU | 831. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000309190; ENSP00000312523; ENSG00000153113. ENST00000325674; ENSP00000320319; ENSG00000153113. ENST00000338252; ENSP00000343421; ENSG00000153113. ENST00000341926; ENSP00000339914; ENSG00000153113. ENST00000359176; ENSP00000352098; ENSG00000153113. ENST00000395813; ENSP00000379158; ENSG00000153113. ENST00000508830; ENSP00000425721; ENSG00000153113. ENST00000510098; ENSP00000427195; ENSG00000153113. |
| GeneID | 831. |
| KEGG | hsa:831. |
| UCSC | uc003klt.3. human. uc003klz.1. human. uc003kma.2. human. |
Organism-specific databases | |
| CTD | 831. |
| GeneCards | GC05P095865. |
| HGNC | HGNC:1515. CAST. |
| HPA | CAB009491. |
| MIM | 114090. gene. |
| neXtProt | NX_P20810. |
| PharmGKB | PA26098. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG25116. |
| HOGENOM | HOG000082405. |
| HOVERGEN | HBG000183. |
| InParanoid | P20810. |
| KO | K04281. |
| OMA | GPDDAID. |
Gene expression databases | |
| ArrayExpress | P20810. |
| Bgee | P20810. |
| CleanEx | HS_CAST. |
| Genevestigator | P20810. |
| GermOnline | ENSG00000153113. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR026998. Calpastatin. IPR001259. Prot_inh_calpain. [Graphical view] |
| PANTHER | PTHR10077. PTHR10077. 1 hit. |
| Pfam | PF00748. Calpain_inhib. 4 hits. [Graphical view] |
| ProtoNet | Search... |
Other | |
| ChiTaRS | CAST. human. |
| GenomeRNAi | 831. |
| NextBio | 3422. |
| SOURCE | Search... |
Entry information
| Entry name | ICAL_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P20810 Secondary accession number(s): G5E946 Q9H1Z5 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human chromosome 5 Human chromosome 5: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
