P80303 (NUCB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	420 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	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.

Ontologies

Keywords
Cellular component	Cytoplasm Endoplasmic reticulum Golgi apparatus Membrane Nucleus Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
Ligand	Calcium DNA-binding Metal-binding
PTM	Cleavage on pair of basic residues Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA cytosol Traceable author statement Ref.1. Source: ProtInc endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum-Golgi intermediate compartment Inferred from direct assay PubMed 15308636. Source: UniProtKB extracellular space Traceable author statement Ref.1. Source: ProtInc nuclear outer membrane Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	DNA binding Traceable author statement Ref.1. Source: ProtInc calcium ion binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GADD45A	P24522	2	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 420	396	Nucleobindin-2		PRO_0000004165
	Chain	25 – 106	82	Nesfatin-1		PRO_0000419819
Regions
	Domain	241 – 276	36	EF-hand 1
	Domain	293 – 328	36	EF-hand 2
	DNA binding	171 – 223	53	By similarity
	Calcium binding	254 – 265	12	1
	Calcium binding	306 – 317	12	2
	Region	213 – 420	208	Binds to necdin By similarity
	Compositional bias	282 – 293	12	Asp/Glu-rich (acidic)
Amino acid modifications
	Modified residue	257	1	Phosphoserine Ref.9
	Modified residue	332	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	419 – 420	2	HI → RV in isoform 2.		VSP_036450
	Natural variant	303	1	S → N. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.11 Corresponds to variant rs2521998 [ dbSNP | Ensembl ].		VAR_068746
	Natural variant	338	1	Q → E. Corresponds to variant rs757081 [ dbSNP | Ensembl ].		VAR_024399
	Natural variant	402	1	Missing. Ref.3 Ref.5		VAR_020923
Experimental info
	Sequence conflict	150	1	F → L in BAF84196. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 3, 2009. Version 2. Checksum: 5BA7459AB725A1A3	FASTA	420	50,196
	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
	Isoform 2 [UniParc]. Checksum: 4922A59AB725A1A3	FASTA	420	50,201
	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 AGELKFEPRV

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
+	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.
IPI	IPI00009123. IPI00922708.
PIR	S55272.
RefSeq	NP_005004.1. NM_005013.2.
UniGene	Hs.654599.
3D structure databases
ProteinModelPortal	P80303.
ModBase	Search...
Protein-protein interaction databases
IntAct	P80303. 6 interactions.
MINT	MINT-2804938.
STRING	9606.ENSP00000320168.
PTM databases
PhosphoSite	P80303.
Polymorphism databases
DMDM	224471846.
Proteomic databases
PaxDb	P80303.
PRIDE	P80303.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000323688; ENSP00000320168; ENSG00000070081. ENST00000529010; ENSP00000436455; ENSG00000070081.
GeneID	4925.
KEGG	hsa:4925.
UCSC	uc001mms.1. human.
Organism-specific databases
CTD	4925.
GeneCards	GC11P017229.
HGNC	HGNC:8044. NUCB2.
HPA	CAB015931. HPA008395.
MIM	608020. gene.
neXtProt	NX_P80303.
PharmGKB	PA31826.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG262100.
HOGENOM	HOG000007216.
HOVERGEN	HBG052685.
InParanoid	P80303.
OMA	DHPKVNH.
Gene expression databases
ArrayExpress	P80303.
Bgee	P80303.
CleanEx	HS_NUCB2.
Genevestigator	P80303.
GermOnline	ENSG00000070081. Homo sapiens.
Family and domain databases
Gene3D	1.10.238.10. 1 hit.
InterPro	IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. IPR002048. EF_hand_dom. [Graphical view]
Pfam	PF13499. EF_hand_5. 1 hit. [Graphical view]
SMART	SM00054. EFh. 2 hits. [Graphical view]
PROSITE	PS00018. EF_HAND_1. 2 hits. PS50222. EF_HAND_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NUCB2. human.
GenomeRNAi	4925.
NextBio	18967.
PMAP-CutDB	P80303.
SOURCE	Search...

Entry information

Entry name

NUCB2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 120 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.