Q15493 (RGN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Regucalcin
Short name=RC

Alternative name(s):
Gluconolactonase
Short name=GNL
EC=3.1.1.17
Senescence marker protein 30
Short name=SMP-30

Gene names

Name:	RGN
Synonyms:	SMP30

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	299 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Gluconolactonase with low activity towards other sugar lactones, including gulonolactone and galactonolactone. Can also hydrolyze diisopropyl phosphorofluoridate and phenylacetate (in vitro). Calcium-binding protein. Modulates Ca2+ signaling, and Ca2+-dependent cellular processes and enzyme activities By similarity.
Catalytic activity	D-glucono-1,5-lactone + H2O = D-gluconate. Ref.7
Cofactor	Binds 1 divalent metal cation per subunit. Most active with zinc and manganese ions. The physiological cofactor is most likely calcium or magnesium. Ref.7
Subcellular location	Cytoplasm By similarity.
Sequence similarities	Belongs to the SMP-30/CGR1 family.
Caution	Gluconolactonase catalyzes a key step in ascorbic acid (vitamin C) biosynthesis, but primates lack the last enzyme in the pathway and are unable to synthesize vitamin C.
Biophysicochemical properties	Kinetic parameters: KM=2.7 mM for gluconolactone (with Zn2+ as cofactor) Ref.7 KM=0.6 mM for gluconolactone (with Mn2+ as cofactor) KM=1.3 mM for gluconolactone (with Mg2+ as cofactor) KM=3.7 mM for gluconolactone (with Ca2+ as cofactor)

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular calcium ion homeostasis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of ATPase activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of calcium-mediated signaling Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from direct assay Ref.7. Source: UniProtKB enzyme regulator activity Inferred from electronic annotation. Source: InterPro gluconolactonase activity Inferred from direct assay Ref.7. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q15493-1)

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: Q15493-2)

The sequence of this isoform differs from the canonical sequence as follows:
     116-187: Missing.
     188-188: S → A

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 299

299

Regucalcin

PRO_0000173046

Sites

Metal binding

18

1

Divalent metal cation

Metal binding

154

1

Divalent metal cation

Metal binding

204

1

Divalent metal cation

Amino acid modifications

Modified residue

3

1

Phosphoserine By similarity

Natural variations

Alternative sequence

116 – 187

72

Missing in isoform 2.

VSP_025456

Alternative sequence

188

1

S → A in isoform 2.

VSP_025457

Experimental info

Mutagenesis

18

1

E → A: Reduces enzyme activity by about 90%. Ref.7

Mutagenesis

103

1

N → A: Reduces enzyme activity by about 95%. Ref.7

Mutagenesis

154

1

N → A: Reduces enzyme activity by about 95%. Ref.7

Mutagenesis

204

1

D → A: Reduces enzyme activity by over 98%. Ref.7

Sequence conflict

292 – 293

2

IA → TS in BAD97080. Ref.4

Secondary structure

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299

Helix Strand Turn

Details...

Beta strand

5 – 10

6

Beta strand

15 – 23

9

Turn

24 – 27

4

Beta strand

28 – 33

6

Turn

34 – 37

4

Beta strand

38 – 43

6

Turn

44 – 46

3

Beta strand

49 – 53

5

Beta strand

58 – 64

7

Beta strand

67 – 73

7

Beta strand

76 – 81

6

Turn

82 – 85

4

Beta strand

86 – 92

7

Beta strand

98 – 107

10

Beta strand

113 – 119

7

Beta strand

132 – 137

6

Beta strand

143 – 158

16

Beta strand

164 – 169

6

Helix

170 – 172

3

Beta strand

174 – 180

7

Turn

182 – 184

3

Beta strand

187 – 195

9

Helix

198 – 200

3

Beta strand

202 – 209

8

Beta strand

214 – 219

6

Turn

220 – 222

3

Beta strand

223 – 227

5

Turn

229 – 231

3

Beta strand

234 – 239

6

Beta strand

241 – 243

3

Beta strand

245 – 252

8

Helix

253 – 255

3

Beta strand

257 – 263

7

Helix

269 – 274

6

Turn

276 – 279

4

Beta strand

281 – 285

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 95BA1C73B7B77635	FASTA	299	33,253
	10 20 30 40 50 60 MSSIKIECVL PENCRCGESP VWEEVSNSLL FVDIPAKKVC RWDSFTKQVQ RVTMDAPVSS 70 80 90 100 110 120 VALRQSGGYV ATIGTKFCAL NWKEQSAVVL ATVDNDKKNN RFNDGKVDPA GRYFAGTMAE 130 140 150 160 170 180 ETAPAVLERH QGALYSLFPD HHVKKYFDQV DISNGLDWSL DHKIFYYIDS LSYSVDAFDY 190 200 210 220 230 240 DLQTGQISNR RSVYKLEKEE QIPDGMCIDA EGKLWVACYN GGRVIRLDPV TGKRLQTVKL 250 260 270 280 290 PVDKTTSCCF GGKNYSEMYV TCARDGMDPE GLLRQPEAGG IFKITGLGVK GIAPYSYAG
	Isoform 2 [UniParc]. Checksum: 19BC938A52DA72D4	FASTA	227	24,968
	10 20 30 40 50 60 MSSIKIECVL PENCRCGESP VWEEVSNSLL FVDIPAKKVC RWDSFTKQVQ RVTMDAPVSS 70 80 90 100 110 120 VALRQSGGYV ATIGTKFCAL NWKEQSAVVL ATVDNDKKNN RFNDGKVDPA GRYFAANRRS 130 140 150 160 170 180 VYKLEKEEQI PDGMCIDAEG KLWVACYNGG RVIRLDPVTG KRLQTVKLPV DKTTSCCFGG 190 200 210 220 KNYSEMYVTC ARDGMDPEGL LRQPEAGGIF KITGLGVKGI APYSYAG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of cDNA clone encoding human homologue of senescence marker protein-30 (SMP30) and its location on the X chromosome." Fujita T., Mandel J.-L., Shirasawa T., Hino O., Shirai T., Maruyama N. Biochim. Biophys. Acta 1263:249-252(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"Transcript heterogeneity of the human gene for Ca2+-binding protein regucalcin." Misawa H., Yamaguchi M. Int. J. Mol. Med. 5:283-287(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[3]	"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] (ISOFORM 1). Tissue: Thalamus.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[5]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] 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] (ISOFORMS 1 AND 2). Tissue: Colon and PNS.
[7]	"Crystal structure of human senescence marker protein 30: insights linking structural, enzymatic, and physiological functions." Chakraborti S., Bahnson B.J. Biochemistry 49:3436-3444(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.42 ANGSTROMS) IN COMPLEXES WITH CALCIUM AND ZINC IONS, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, MUTAGENESIS OF GLU-18; ASN-103; ASN-154 AND ASP-204.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D31815 mRNA. Translation: BAA06602.1.
AB028125 mRNA. Translation: BAA78693.1.
AB032064 mRNA. Translation: BAA84082.1.
AK290136 mRNA. Translation: BAF82825.1.
AK223360 mRNA. Translation: BAD97080.1.
AL513366 Genomic DNA. Translation: CAI41697.1.
BC050371 mRNA. Translation: AAH50371.1.
BC073173 mRNA. Translation: AAH73173.1.

IPI

IPI00017551.
IPI00845361.

PIR

S60035.

RefSeq

NP_004674.1. NM_004683.4.
NP_690608.1. NM_152869.2.

UniGene

Hs.77854.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3G4E	X-ray	1.42	A/B	3-299	[»]
3G4H	X-ray	1.92	A/B	3-299	[»]

ProteinModelPortal

Q15493.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000253303.

PTM databases

PhosphoSite

Q15493.

Polymorphism databases

DMDM

3334328.

Proteomic databases

PaxDb

Q15493.

PeptideAtlas

Q15493.

PRIDE

Q15493.

Protocols and materials databases

DNASU

9104.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000336169; ENSP00000338400; ENSG00000130988.
ENST00000352078; ENSP00000253303; ENSG00000130988.
ENST00000397180; ENSP00000380365; ENSG00000130988.
ENST00000457380; ENSP00000406568; ENSG00000130988.

GeneID

9104.

KEGG

hsa:9104.

UCSC

uc004dgz.1. human.
uc010nhp.1. human.

Organism-specific databases

CTD

9104.

GeneCards

GC0XP046937.

HGNC

HGNC:9989. RGN.

HPA

HPA029102.
HPA029103.

MIM

300212. gene.

neXtProt

NX_Q15493.

PharmGKB

PA34359.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3386.

HOGENOM

HOG000220627.

HOVERGEN

HBG004347.

InParanoid

Q15493.

KO

K01053.

OMA

CVLRENC.

OrthoDB

EOG4255TD.

PhylomeDB

Q15493.

Gene expression databases

Bgee

Q15493.

CleanEx

HS_RGN.

Genevestigator

Q15493.

GermOnline

ENSG00000130988. Homo sapiens.

Family and domain databases

Gene3D

2.120.10.30. 1 hit.

InterPro

IPR011042. 6-blade_b-propeller_TolB-like.
IPR008367. Regucalcin.
IPR013658. SGL.
IPR005511. SMP-30.
[Graphical view]

Pfam

PF08450. SGL. 1 hit.
[Graphical view]

PRINTS

PR01791. REGUCALCIN.
PR01790. SMP30FAMILY.

ProtoNet

Search...

Other

EvolutionaryTrace

Q15493.

GenomeRNAi

9104.

NextBio

34129.

SOURCE

Search...

Entry information

Entry name

RGN_HUMAN

Accession

Primary (citable) accession number: Q15493
Secondary accession number(s): A4FTW1 , A8K271, Q53FC9, Q5JRR5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 106 of the entry and version 1 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.