Q96L12 (CALR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calreticulin-3

Alternative name(s):
Calreticulin-2
Calsperin

Gene names

Name:	CALR3
Synonyms:	CRT2

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	384 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	During spermatogenesis, may act as a lectin-independent chaperone for specific client proteins such as ADAM3. Required for sperm fertility By similarity. CALR3 capacity for calcium-binding may be absent or much lower than that of CALR. Ref.1
Subunit structure	Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 By similarity.
Subcellular location	Endoplasmic reticulum lumen Ref.1.
Tissue specificity	Testis specific. Ref.6
Domain	Can be divided into a N-terminal globular domain, a proline-rich P-domain forming an elongated arm-like structure and a C-terminal acidic domain. The P-domain binds one molecule of calcium with high affinity, whereas the acidic C-domain binds multiple calcium ions with low affinity By similarity. The interaction with glycans occurs through a binding site in the globular lectin domain By similarity. The zinc binding sites are localized to the N-domain By similarity.
Involvement in disease	Cardiomyopathy, familial hypertrophic 19 (CMH19) [MIM:613875]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the calreticulin family.

Ontologies

Keywords
Biological process	Differentiation Spermatogenesis
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Polymorphism
Disease	Cardiomyopathy Disease mutation
Domain	Repeat Signal
Ligand	Lectin Metal-binding Zinc
Molecular function	Chaperone
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW protein folding Inferred from electronic annotation. Source: InterPro spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 384	365	Calreticulin-3		PRO_0000004178
Regions
	Repeat	191 – 202	12	1-1
	Repeat	208 – 219	12	1-2
	Repeat	221 – 230	10	1-3
	Repeat	234 – 245	12	1-4
	Repeat	249 – 259	11	2-1
	Repeat	263 – 271	9	2-2
	Repeat	273 – 283	11	2-3
	Region	20 – 197	178	N-domain
	Region	191 – 245	55	4 X approximate repeats
	Region	198 – 294	97	P-domain
	Region	249 – 283	35	3 X approximate repeats
	Region	295 – 384	90	C-domain
	Motif	381 – 384	4	Prevents secretion from ER Potential
	Compositional bias	337 – 362	26	Glu/Lys-rich
Sites
	Binding site	109	1	Carbohydrate By similarity
	Binding site	111	1	Carbohydrate By similarity
	Binding site	128	1	Carbohydrate By similarity
	Binding site	135	1	Carbohydrate By similarity
	Binding site	303	1	Carbohydrate By similarity
Amino acid modifications
	Glycosylation	42	1	N-linked (GlcNAc...) Potential
	Glycosylation	201	1	N-linked (GlcNAc...) Potential
	Disulfide bond	105 ↔ 137		By similarity
Natural variations
	Natural variant	8	1	L → F. Ref.5 Corresponds to variants rs17851207 [ dbSNP | Ensembl ] and rs11544148 [ dbSNP | Ensembl ].		VAR_027944
	Natural variant	82	1	K → R in CMH19. Ref.7		VAR_065476
	Natural variant	248	1	D → G. Corresponds to variant rs10411092 [ dbSNP | Ensembl ].		VAR_027945
	Natural variant	274	1	V → I. Corresponds to variant rs12459238 [ dbSNP | Ensembl ].		VAR_027946
	Natural variant	284	1	D → N. Corresponds to variant rs10404156 [ dbSNP | Ensembl ].		VAR_048589

Sequences

	Sequence		Length	Mass (Da)
	Q96L12 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 32D8AFB23D1DF7C5	FASTA	384	44,996
	10 20 30 40 50 60 MARALVQLWA ICMLRVALAT VYFQEEFLDG EHWRNRWLQS TNDSRFGHFR LSSGKFYGHK 70 80 90 100 110 120 EKDKGLQTTQ NGRFYAISAR FKPFSNKGKT LVIQYTVKHE QKMDCGGGYI KVFPADIDQK 130 140 150 160 170 180 NLNGKSQYYI MFGPDICGFD IKKVHVILHF KNKYHENKKL IRCKVDGFTH LYTLILRPDL 190 200 210 220 230 240 SYDVKIDGQS IESGSIEYDW NLTSLKKETS PAESKDWEQT KDNKAQDWEK HFLDASTSKQ 250 260 270 280 290 300 SDWNGDLDGD WPAPMLQKPP YQDGLKPEGI HKDVWLHRKM KNTDYLTQYD LSEFENIGAI 310 320 330 340 350 360 GLELWQVRSG TIFDNFLITD DEEYADNFGK ATWGETKGPE REMDAIQAKE EMKKAREEEE 370 380 EELLSGKINR HEHYFNQFHR RNEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Calreticulin-2 is localized in the lumen of the endoplasmic reticulum but is not a Ca2+ -binding protein." Nomura R., Orii M., Senda T. Histochem. Cell Biol. 135:531-538(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, LACK OF CALCIUM-BINDING.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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. , 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 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], VARIANT PHE-8. Tissue: Testis.
[6]	"Identification of a novel calreticulin isoform (Crt2) in human and mouse." Persson S., Rosenquist M., Sommarin M. Gene 297:151-158(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, TISSUE SPECIFICITY.
[7]	"Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy." Chiu C., Tebo M., Ingles J., Yeates L., Arthur J.W., Lind J.M., Semsarian C. J. Mol. Cell. Cardiol. 43:337-343(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMH19 ARG-82.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB576176 mRNA. Translation: BAJ14705.1. AK058084 mRNA. Translation: BAB71655.1. AC008764 Genomic DNA. No translation available. CH471106 Genomic DNA. Translation: EAW84546.1. BC014595 mRNA. Translation: AAH14595.1.
IPI	IPI00153053.
RefSeq	NP_659483.2. NM_145046.4.
UniGene	Hs.304020.
3D structure databases
ProteinModelPortal	Q96L12.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000269881.
PTM databases
PhosphoSite	Q96L12.
Polymorphism databases
DMDM	116241279.
Proteomic databases
PaxDb	Q96L12.
PRIDE	Q96L12.
Protocols and materials databases
DNASU	125972.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000269881; ENSP00000269881; ENSG00000269058.
GeneID	125972.
KEGG	hsa:125972.
UCSC	uc002ned.2. human.
Organism-specific databases
CTD	125972.
GeneCards	GC19M016589.
H-InvDB	HIX0080124.
HGNC	HGNC:20407. CALR3.
HPA	CAB025749.
MIM	611414. gene. 613875. phenotype.
neXtProt	NX_Q96L12.
Orphanet	155. Familial isolated hypertrophic cardiomyopathy.
PharmGKB	PA134922944.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG268919.
HOGENOM	HOG000192435.
HOVERGEN	HBG005407.
InParanoid	Q96L12.
KO	K10098.
OMA	QDWEKHF.
PhylomeDB	Q96L12.
Gene expression databases
ArrayExpress	Q96L12.
Bgee	Q96L12.
CleanEx	HS_CALR3.
Genevestigator	Q96L12.
GermOnline	ENSG00000141979. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.200. 1 hit.
InterPro	IPR001580. Calret/calnex. IPR018124. Calret/calnex_CS. IPR009169. Calreticulin. IPR009033. Calreticulin/calnexin_P_dom. IPR008985. ConA-like_lec_gl_sf. IPR013320. ConA-like_subgrp. [Graphical view]
PANTHER	PTHR11073. PTHR11073. 1 hit.
Pfam	PF00262. Calreticulin. 1 hit. [Graphical view]
PIRSF	PIRSF002356. Calreticulin. 1 hit.
PRINTS	PR00626. CALRETICULIN.
SUPFAM	SSF63887. Calret_calnex_P. 1 hit. SSF49899. ConA_like_lec_gl. 1 hit.
PROSITE	PS00803. CALRETICULIN_1. 1 hit. PS00804. CALRETICULIN_2. 1 hit. PS00014. ER_TARGET. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	125972.
NextBio	81602.
SOURCE	Search...

Entry information

Entry name

CALR3_HUMAN

Accession

Primary (citable) accession number: Q96L12
Secondary accession number(s): D9N574, Q96LN3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 22, 2003
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 118 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.