Q6UXS9 (CASPC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inactive caspase-12
Short name=CASP-12

Gene names

Name:	CASP12
ORF Names:	UNQ9415/PRO34398

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

General annotation (Comments)

Function	Has no protease activity. May reduce cytokine release in response to bacterial lipopolysaccharide during infections. Reduces activation of NF-kappa-B in response to TNF. Ref.1 Ref.4
Tissue specificity	Detected in heart, kidney, liver, lung, pancreas, small intestine, spleen, stomach, thymus and testis. Ref.1
Polymorphism	The most frequent variant has a stop codon instead of Arg-125, giving rise to truncated forms of isoform 1 (named delta, epsilon, eta, gamma) and isoform 3 (iota, teta). The variant Arg-125 (Csp12-L) is rare, except in some populations from sub-Saharan Africa. Csp12-L may increase the susceptibility to severe sepsis, and may also increase the mortality rate in sepsis patients.
Sequence similarities	Belongs to the peptidase C14A family. Contains 1 CARD domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endoplasmic reticulum unfolded protein response Inferred from electronic annotation. Source: Compara intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Inferred from electronic annotation. Source: Compara proteolysis Inferred from electronic annotation. Source: InterPro virus-infected cell apoptotic process Inferred from electronic annotation. Source: Compara
Cellular_component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular_function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6UXS9-1)

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: Q6UXS9-2)

Also known as: Alpha; Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     87-168: DISSDGEREA...HQSSDSTFLV → AFLEIQGAQP...YLKTLDTQWL
     169-341: Missing.

Isoform 3 (identifier: Q6UXS9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     3-86: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 341	341	Inactive caspase-12		PRO_0000317441
Regions
	Domain	1 – 92	92	CARD
Sites
	Active site	172	1	Potential
	Active site	220	1	Potential
Natural variations
	Alternative sequence	3 – 86	84	Missing in isoform 3.		VSP_030953
	Alternative sequence	87 – 168	82	DISSD…STFLV → AFLEIQGAQPSGKLKLCPHA HFHELKTKRADEIYPVMEKE RRTCLASTSATKNSTIFIIE MVLNLTFWGCEIYLKTLDTQ WL in isoform 2.		VSP_030954
	Alternative sequence	169 – 341	173	Missing in isoform 2.		VSP_030955
Experimental info
	Sequence conflict	68	1	T → I in AF464191. Ref.1
	Sequence conflict	68	1	T → I in AF464192. Ref.1
	Sequence conflict	68	1	T → I in AF464193. Ref.1
	Sequence conflict	68	1	T → I in AF464194. Ref.1
	Sequence conflict	68	1	T → I in AF486844. Ref.1
	Sequence conflict	68	1	T → I in AF486845. Ref.1
	Sequence conflict	68	1	T → I in AF486846. Ref.1
	Sequence conflict	68	1	T → I in AAQ88589. Ref.2
	Sequence conflict	238	1	G → S in AAQ88589. Ref.2
Isoform 2:
	Sequence conflict	88	1	F → L in AF486844. Ref.1
	Sequence conflict	88	1	F → L in AF486845. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 11, 2012. Version 2. Checksum: 5C6C9FDFE9D9BE6B	FASTA	341	38,865
	10 20 30 40 50 60 MADEKPSNGV LVHMVKLLIK TFLDGIFDDL MENNVLNTDE IHLIGKCLKF VVSNAENLVD 70 80 90 100 110 120 DITETAQTAG KIFREHLWNS KKQLSSDISS DGEREANMPG LNIRNKEFNY LHNRNGSELD 130 140 150 160 170 180 LLGMRDLLEN LGYSVVIKEN LTAQEMETAL RQFAAHPEHQ SSDSTFLVFM SHSILNGICG 190 200 210 220 230 240 TKHWDQEPDV LHDDTIFEIF NNRNCQSLKD KPKVIIMQAC RGNGAGIVWF TTDSGKAGAD 250 260 270 280 290 300 THGRLLQGNI CNDAVTKAHV EKDFIAFKSS TPHNVSWRHE TNGSVFISQI IYYFREYSWS 310 320 330 340 HHLEEIFQKV QHSFETPNIL TQLPTIERLS MTRYFYLFPG N
	Isoform 2 (Alpha) (Beta) [UniParc]. Checksum: 9F3EBC2D48479556	FASTA	168	19,124
	10 20 30 40 50 60 MADEKPSNGV LVHMVKLLIK TFLDGIFDDL MENNVLNTDE IHLIGKCLKF VVSNAENLVD 70 80 90 100 110 120 DITETAQTAG KIFREHLWNS KKQLSSAFLE IQGAQPSGKL KLCPHAHFHE LKTKRADEIY 130 140 150 160 PVMEKERRTC LASTSATKNS TIFIIEMVLN LTFWGCEIYL KTLDTQWL
	Isoform 3 [UniParc]. Checksum: B0417E43C6041199	FASTA	257	29,399
	10 20 30 40 50 60 MADISSDGER EANMPGLNIR NKEFNYLHNR NGSELDLLGM RDLLENLGYS VVIKENLTAQ 70 80 90 100 110 120 EMETALRQFA AHPEHQSSDS TFLVFMSHSI LNGICGTKHW DQEPDVLHDD TIFEIFNNRN 130 140 150 160 170 180 CQSLKDKPKV IIMQACRGNG AGIVWFTTDS GKAGADTHGR LLQGNICNDA VTKAHVEKDF 190 200 210 220 230 240 IAFKSSTPHN VSWRHETNGS VFISQIIYYF REYSWSHHLE EIFQKVQHSF ETPNILTQLP 250 TIERLSMTRY FYLFPGN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human caspase 12 has acquired deleterious mutations." Fischer H., Koenig U., Eckhart L., Tschachler E. Biochem. Biophys. Res. Commun. 293:722-726(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, POLYMORPHISM, TISSUE SPECIFICITY. Tissue: Lung.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms." Saleh M., Vaillancourt J.P., Graham R.K., Huyck M., Srinivasula S.M., Alnemri E.S., Steinberg M.H., Nolan V., Baldwin C.T., Hotchkiss R.S., Buchman T.G., Zehnbauer B.A., Hayden M.R., Farrer L.A., Roy S., Nicholson D.W. Nature 429:75-79(2004) [PubMed] [Europe PMC] [Abstract] Cited for: POLYMORPHISM, FUNCTION.
[5]	"Population distribution of the functional caspase-12 allele." Kachapati K., O'Brien T.R., Bergeron J., Zhang M., Dean M. Hum. Mutat. 27:975-975(2006) [PubMed] [Europe PMC] [Abstract] Cited for: POLYMORPHISM.
[6]	"Spread of an inactive form of caspase-12 in humans is due to recent positive selection." Xue Y., Daly A., Yngvadottir B., Liu M., Coop G., Kim Y., Sabeti P., Chen Y., Stalker J., Huckle E., Burton J., Leonard S., Rogers J., Tyler-Smith C. Am. J. Hum. Genet. 78:659-670(2006) [PubMed] [Europe PMC] [Abstract] Cited for: POLYMORPHISM.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF464191 mRNA. No translation available. AF464192 mRNA. No translation available. AF464193 mRNA. No translation available. AF464194 mRNA. No translation available. AF464195 mRNA. No translation available. AF486844 mRNA. No translation available. AF486845 mRNA. No translation available. AF486846 mRNA. No translation available. AF486847 mRNA. No translation available. AY358222 mRNA. Translation: AAQ88589.1.
IPI	IPI00432707. IPI00885043. IPI00885062.
RefSeq	NP_001177945.1. NM_001191016.1.
UniGene	Hs.476989.
3D structure databases
ProteinModelPortal	Q6UXS9.
SMR	Q6UXS9. Positions 75-341.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6UXS9. 1 interaction.
Protein family/group databases
MEROPS	C14.P01.
Polymorphism databases
DMDM	74749429.
Proteomic databases
PRIDE	Q6UXS9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375726; ENSP00000424038; ENSG00000204403. ENST00000417998; ENSP00000424963; ENSG00000204403. ENST00000422698; ENSP00000427128; ENSG00000204403. ENST00000458137; ENSP00000421408; ENSG00000204403. ENST00000508062; ENSP00000426566; ENSG00000204403.
GeneID	100506742.
KEGG	hsa:100506742.
UCSC	uc001pht.2. human.
Organism-specific databases
CTD	100506742.
GeneCards	GC11M104757.
H-InvDB	HIX0035901.
HGNC	HGNC:19004. CASP12.
HPA	HPA046232.
MIM	608633. gene.
neXtProt	NX_Q6UXS9.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HOG000234399.
HOVERGEN	HBG076981.
InParanoid	Q6UXS9.
KO	K04741.
OMA	SWSHHLE.
Gene expression databases
ArrayExpress	Q6UXS9.
Bgee	Q6UXS9.
Genevestigator	Q6UXS9.
Family and domain databases
Gene3D	1.10.533.10. 1 hit.
InterPro	IPR001315. CARD. IPR017350. Caspase_IL-1_beta. IPR011029. DEATH-like_dom. IPR011600. Pept_C14_cat. IPR001309. Pept_C14_ICE_p20. IPR016129. Pept_C14_ICE_p20_AS. IPR002138. Pept_C14_p10. IPR002398. Pept_C14_p45. IPR015917. Pept_C14_p45_core. [Graphical view]
PANTHER	PTHR10454. PTHR10454. 1 hit.
Pfam	PF00619. CARD. 1 hit. PF00656. Peptidase_C14. 1 hit. [Graphical view]
PIRSF	PIRSF038001. Caspase_ICE. 1 hit.
PRINTS	PR00376. IL1BCENZYME.
SMART	SM00115. CASc. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	PS50209. CARD. 1 hit. PS01122. CASPASE_CYS. 1 hit. PS50207. CASPASE_P10. 1 hit. PS50208. CASPASE_P20. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	34054392.
SOURCE	Search...

Entry information

Entry name

CASPC_HUMAN

Accession

Primary (citable) accession number: Q6UXS9
Secondary accession number(s): D6RBN7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	July 11, 2012
Last modified:	May 29, 2013
This is version 75 of the entry and version 2 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.