A6NHC0 (CAN8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calpain-8
EC=3.4.22.53

Alternative name(s):
New calpain 2
Short name=nCL-2
Stomach-specific M-type calpain

Gene names

Name:	CAPN8
Synonyms:	NCL2

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	703 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Calcium-regulated non-lysosomal thiol-protease. Involved in membrane trafficking in the gastric surface mucus cells (pit cells) and may involve the membrane trafficking of mucus cells via interactions with coat protein. Proteolytically cleaves the beta-subunit of coatomer complex By similarity.
Catalytic activity	Broad endopeptidase specificity.
Cofactor	Binds 2 calcium ions Potential.
Subunit structure	Monomer and homooligomer. Interacts with COPS1/GPS1, COPB1, EYA2, NME2, NME4 and TOMM70A By similarity.
Subcellular location	Cytoplasm By similarity. Golgi apparatus By similarity.
Tissue specificity	Stomach.
Domain	The domain III mediates oligomerization By similarity.
Post-translational modification	Undergoes autolytic cleavage between Ala-5 and Ala-6 which gives rise to fragments extending from Ala-6 to the C-terminus, Ala-6 to the EF-hand 2 domain and from Ala-6 to the beginning of domain III By similarity.
Sequence similarities	Belongs to the peptidase C2 family. Contains 1 calpain catalytic domain. Contains 3 EF-hand domains.

Ontologies

Keywords
Cellular component	Cytoplasm Golgi apparatus
Domain	Repeat
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Protease Thiol protease
PTM	Autocatalytic cleavage
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro calcium-dependent cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 703	703	Calpain-8		PRO_0000349280
Regions
	Domain	45 – 344	300	Calpain catalytic
	Domain	575 – 610	36	EF-hand 1
	Domain	605 – 640	36	EF-hand 2
	Domain	670 – 703	34	EF-hand 3
	Calcium binding	588 – 599	12	1 Potential
	Calcium binding	618 – 629	12	2 Potential
	Region	356 – 379	24	Domain III
Sites
	Active site	105	1	By similarity
	Active site	262	1	By similarity
	Active site	286	1	By similarity
Experimental info
	Sequence conflict	245	1	S → Y in AAI57894. Ref.3
	Sequence conflict	592	1	T → M in AAI57894. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	A6NHC0 [UniParc]. Last modified August 10, 2010. Version 3. Checksum: 2A6DFFC0814894A8	FASTA	703	79,144
	10 20 30 40 50 60 MAAQAAGVSR QRAATQGLGS NQNALKYLGQ DFKTLRQQCL DSGVLFKDPE FPACPSALGY 70 80 90 100 110 120 KDLGPGSPQT QGIIWKRPTE LCPSPQFIVG GATRTDICQG GLGDCWLLAA IASLTLNEEL 130 140 150 160 170 180 LYRVVPRDQD FQENYAGIFH FQFWQYGEWV EVVIDDRLPT KNGQLLFLHS EQGNEFWSAL 190 200 210 220 230 240 LEKAYAKLNG CYEALAGGST VEGFEDFTGG ISEFYDLKKP PANLYQIIRK ALCAGSLLGC 250 260 270 280 290 300 SIDVSSAAEA EAITSQKLVK SHAYSVTGVE EVNFQGHPEK LIRLRNPWGE VEWSGAWSDD 310 320 330 340 350 360 APEWNHIDPR RKEELDKKVE DGEFWMSLSD FVRQFSRLEI CNLSPDSLSS EEVHKWNLVL 370 380 390 400 410 420 FNGHWTRGST AGGCQNYPAT YWTNPQFKIR LDEVDEDQEE SIGEPCCTVL LGLMQKNRRW 430 440 450 460 470 480 RKRIGQGMLS IGYAVYQVPK ELESHTDAHL GRDFFLAYQP SARTSTYVNL REVSGRARLP 490 500 510 520 530 540 PGEYLVVPST FEPFKDGEFC LRVFSEKKAQ ALEIGDVVAG NPYEPHPSEV DQEDDQFRRL 550 560 570 580 590 600 FEKLAGKDSE ITANALKILL NEAFSKRTDI KFDGFNINTC REMISLLDSN GTGTLGAVEF 610 620 630 640 650 660 KTLWLKIQKY LEIYWETDYN HSGTIDAHEM RTALRKAGFT LNSQVQQTIA LRYACSKLGI 670 680 690 700 NFDSFVACMI RLETLFKLFS LLDEDKDGMV QLSLAEWLCC VLV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Both the conserved and the unique gene structure of stomach-specific calpains reveal processes of calpain gene evolution." Hata S., Nishi K., Kawamoto T., Lee H.-J., Kawahara H., Maeda T., Shintani Y., Sorimachi H., Suzuki K. J. Mol. Evol. 53:191-203(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Leukocyte.
[2]	"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. , 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC099065 Genomic DNA. No translation available. CR628412 Genomic DNA. No translation available. CR848842 Genomic DNA. No translation available. BC157893 mRNA. Translation: AAI57894.1.
IPI	IPI00874238.
RefSeq	NP_001137434.1. NM_001143962.1.
UniGene	Hs.291487.
3D structure databases
ProteinModelPortal	A6NHC0.
SMR	A6NHC0. Positions 2-699.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000397140.
Protein family/group databases
MEROPS	C02.007.
PTM databases
PhosphoSite	A6NHC0.
Proteomic databases
PaxDb	A6NHC0.
PRIDE	A6NHC0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000366872; ENSP00000355837; ENSG00000203697.
GeneID	388743.
KEGG	hsa:388743.
UCSC	uc009xee.2. human.
Organism-specific databases
CTD	388743.
GeneCards	GC01M223711.
HGNC	HGNC:1485. CAPN8.
HPA	HPA021480.
neXtProt	NX_A6NHC0.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG327523.
HOGENOM	HOG000232035.
HOVERGEN	HBG012645.
InParanoid	A6NHC0.
KO	K08577.
OrthoDB	EOG4HX50K.
Gene expression databases
ArrayExpress	A6NHC0.
Bgee	A6NHC0.
CleanEx	HS_CAPN8.
Genevestigator	A6NHC0.
Family and domain databases
Gene3D	1.10.238.10. 1 hit.
InterPro	IPR022684. Calpain_cysteine_protease. IPR022682. Calpain_domain_III. IPR022683. Calpain_III. IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. IPR002048. EF_hand_dom. IPR000169. Pept_cys_AS. IPR001300. Peptidase_C2_calpain_cat. [Graphical view]
Pfam	PF01067. Calpain_III. 1 hit. PF00648. Peptidase_C2. 1 hit. [Graphical view]
PRINTS	PR00704. CALPAIN.
SMART	SM00720. calpain_III. 1 hit. SM00230. CysPc. 1 hit. SM00054. EFh. 2 hits. [Graphical view]
SUPFAM	SSF49758. Peptidase_C2. 1 hit.
PROSITE	PS50203. CALPAIN_CAT. 1 hit. PS00018. EF_HAND_1. 2 hits. PS50222. EF_HAND_2. 3 hits. PS00640. THIOL_PROTEASE_ASN. False negative. PS00139. THIOL_PROTEASE_CYS. 1 hit. PS00639. THIOL_PROTEASE_HIS. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	388743.
NextBio	102335.

Entry information

Entry name

CAN8_HUMAN

Accession

Primary (citable) accession number: A6NHC0
Secondary accession number(s): B2RXL2

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 2, 2008
Last sequence update:	August 10, 2010
Last modified:	May 1, 2013
This is version 56 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.