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P80303 (NUCB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nucleobindin-2
Alternative name(s):
DNA-binding protein NEFA
Gastric cancer antigen Zg4
Prepronesfatin

Cleaved into the following chain:

  1. Nesfatin-1
Gene names
Name:NUCB2
Synonyms:NEFA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length420 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-binding protein. May have a role in calcium homeostasis.

Nesfatin-1: Anorexigenic peptide, seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis, acting in a leptin-independent manner. May also exert hypertensive roles and modulate blood pressure through directly acting on peripheral arterial resistance By similarity.

Subcellular location

Golgi apparatus. Membrane; Peripheral membrane protein. Cytoplasm. Secreted Ref.8. Endoplasmic reticulum By similarity. Nucleus envelope By similarity. Note: Golgi retention is mediated by its N-terminal region. Ref.8

Nesfatin-1: Secreted Ref.8.

Tissue specificity

Predominantly expressed in spleen, testis and normal stomach. Ref.3

Polymorphism

Deletion of Gln-402 is frequent.

Miscellaneous

NEFA stands for N=DNA-binding; EF=EF-hand; A=Acidic region.

Sequence similarities

Belongs to the nucleobindin family.

Contains 2 EF-hand domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GADD45AP245222EBI-2296670,EBI-448167

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P80303-1)

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: P80303-2)

The sequence of this isoform differs from the canonical sequence as follows:
     419-420: HI → RV
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 420396Nucleobindin-2
PRO_0000004165
Chain25 – 10682Nesfatin-1
PRO_0000419819

Regions

Domain241 – 27636EF-hand 1
Domain293 – 32836EF-hand 2
DNA binding171 – 22353 By similarity
Calcium binding254 – 265121
Calcium binding306 – 317122
Region213 – 420208Binds to necdin By similarity
Compositional bias282 – 29312Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue2571Phosphoserine Ref.9
Modified residue3321Phosphoserine Ref.10

Natural variations

Alternative sequence419 – 4202HI → RV in isoform 2.
VSP_036450
Natural variant3031S → N. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.11
Corresponds to variant rs2521998 [ dbSNP | Ensembl ].
VAR_068746
Natural variant3381Q → E.
Corresponds to variant rs757081 [ dbSNP | Ensembl ].
VAR_024399
Natural variant4021Missing. Ref.3 Ref.5
VAR_020923

Experimental info

Sequence conflict1501F → L in BAF84196. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 3, 2009. Version 2.
Checksum: 5BA7459AB725A1A3

FASTA42050,196
        10         20         30         40         50         60 
MRWRTILLQY CFLLITCLLT ALEAVPIDID KTKVQNIHPV ESAKIEPPDT GLYYDEYLKQ 

        70         80         90        100        110        120 
VIDVLETDKH FREKLQKADI EEIKSGRLSK ELDLVSHHVR TKLDELKRQE VGRLRMLIKA 

       130        140        150        160        170        180 
KLDSLQDIGM DHQALLKQFD HLNHLNPDKF ESTDLDMLIK AATSDLEHYD KTRHEEFKKY 

       190        200        210        220        230        240 
EMMKEHERRE YLKTLNEEKR KEEESKFEEM KKKHENHPKV NHPGSKDQLK EVWEETDGLD 

       250        260        270        280        290        300 
PNDFDPKTFF KLHDVNSDGF LDEQELEALF TKELEKVYDP KNEEDDMVEM EEERLRMREH 

       310        320        330        340        350        360 
VMSEVDTNKD RLVTLEEFLK ATEKKEFLEP DSWETLDQQQ FFTEEELKEY ENIIALQENE 

       370        380        390        400        410        420 
LKKKADELQK QKEELQRQHD QLEAQKLEYH QVIQQMEQKK LQQGIPPSGP AGELKFEPHI 

« Hide

Isoform 2 [UniParc].

Checksum: 4922A59AB725A1A3
Show »

FASTA42050,201

References

« Hide 'large scale' references
[1]"Human protein NEFA, a novel DNA binding/EF-hand/leucine zipper protein. Molecular cloning and sequence analysis of the cDNA, isolation and characterization of the protein."
Barnikol-Watanabe S., Gross N.A., Goetz H., Henkel T., Karabinos A., Kratzin H., Barnikol H.U., Hilschmann N.
Biol. Chem. Hoppe-Seyler 375:497-512(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANT ASN-303.
Tissue: Blood.
[2]"Assembly of a high-resolution map of the Acadian Usher syndrome region and localization of the nuclear EF-hand acidic gene."
Deangelis M.M., Doucet J.P., Drury S., Sherry S.T., Robichaux M.B., Den Z., Pelias M.Z., Ditta G.M., Keats B.J., Deininger P.L., Batzer M.A.
Biochim. Biophys. Acta 1407:84-91(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASN-303.
[3]"Serological identification and expression analysis of gastric cancer-associated genes."
Line A., Stengrevics A., Slucka Z., Li G., Jankevics E., Rees R.C.
Br. J. Cancer 86:1824-1830(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS ASN-303 AND GLN-402 DEL.
[4]"Troglitazone, a ligand of peroxisome proliferator-activated receptor-gamma, stabilizes NUCB2 (Nesfatin) mRNA by activating the ERK1/2 pathway: isolation and characterization of the human NUCB2 gene."
Yamada M., Horiguchi K., Umezawa R., Hashimoto K., Satoh T., Ozawa A., Shibusawa N., Monden T., Okada S., Shimizu H., Mori M.
Endocrinology 151:2494-2503(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-303.
[5]"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. expand/collapse author list , 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 2), VARIANTS ASN-303 AND GLN-402 DEL.
[6]"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. expand/collapse author list , 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].
[7]Mural R.J., Istrail S., Sutton 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. expand/collapse author list , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASN-303.
[8]"Golgi retention of human protein NEFA is mediated by its N-terminal Leu/Ile-rich region."
Nesselhut J., Jurgan U., Onken E., Gotz H., Barnikol H.U., Hirschfeld G., Barnikol-Watanabe S., Hilschmann N.
FEBS Lett. 509:469-475(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"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-332, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"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: VARIANT [LARGE SCALE ANALYSIS] ASN-303, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X76732 mRNA. Translation: CAA54148.1.
AF052642 mRNA. Translation: AAC06300.1.
AF052643 mRNA. Translation: AAC06301.1.
AF052644 mRNA. Translation: AAC06302.1.
AF450266 mRNA. Translation: AAM73810.1.
AB478625 Genomic DNA. Translation: BAJ09615.1.
AK291507 mRNA. Translation: BAF84196.1.
AC107956 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68439.1.
CH471064 Genomic DNA. Translation: EAW68440.1.
PIRS55272.
RefSeqNP_005004.1. NM_005013.2.
XP_005252998.2. XM_005252941.2.
XP_005252999.2. XM_005252942.2.
XP_005253000.2. XM_005252943.2.
XP_005253001.2. XM_005252944.2.
XP_005253002.2. XM_005252945.2.
XP_005253004.2. XM_005252947.2.
XP_005253005.2. XM_005252948.2.
UniGeneHs.654599.

3D structure databases

ProteinModelPortalP80303.
SMRP80303. Positions 229-327.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110979. 15 interactions.
IntActP80303. 11 interactions.
MINTMINT-2804938.
STRING9606.ENSP00000320168.

PTM databases

PhosphoSiteP80303.

Polymorphism databases

DMDM224471846.

Proteomic databases

PaxDbP80303.
PRIDEP80303.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000323688; ENSP00000320168; ENSG00000070081. [P80303-2]
ENST00000529010; ENSP00000436455; ENSG00000070081. [P80303-1]
GeneID4925.
KEGGhsa:4925.
UCSCuc001mms.1. human. [P80303-1]

Organism-specific databases

CTD4925.
GeneCardsGC11P017229.
HGNCHGNC:8044. NUCB2.
HPACAB015931.
HPA008395.
MIM608020. gene.
neXtProtNX_P80303.
PharmGKBPA31826.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG262100.
HOGENOMHOG000007216.
HOVERGENHBG052685.
InParanoidP80303.
OMADHPKVNH.
PhylomeDBP80303.
TreeFamTF323218.

Gene expression databases

ArrayExpressP80303.
BgeeP80303.
CleanExHS_NUCB2.
GenevestigatorP80303.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR028813. NUCB2.
[Graphical view]
PANTHERPTHR19237:SF3. PTHR19237:SF3. 1 hit.
PfamPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTSM00054. EFh. 2 hits.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNUCB2. human.
GeneWikiNUCB2.
GenomeRNAi4925.
NextBio18967.
PMAP-CutDBP80303.
PROP80303.
SOURCESearch...

Entry information

Entry nameNUCB2_HUMAN
AccessionPrimary (citable) accession number: P80303
Secondary accession number(s): A8K642, D3DQX5, Q8NFT5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: March 3, 2009
Last modified: April 16, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM