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Protein

Nucleobindin-2

Gene

NUCB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi171 – 22353By similarityAdd
BLAST
Calcium bindingi254 – 265121Add
BLAST
Calcium bindingi306 – 317122Add
BLAST

GO - Molecular functioni

  1. calcium ion binding Source: ProtInc
  2. DNA binding Source: ProtInc
Complete GO annotation...

Keywords - Ligandi

Calcium, DNA-binding, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleobindin-2
Alternative name(s):
DNA-binding protein NEFA
Gastric cancer antigen Zg4
Prepronesfatin
Cleaved into the following chain:
Gene namesi
Name:NUCB2
Synonyms:NEFA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Unplaced

Organism-specific databases

HGNCiHGNC:8044. NUCB2.

Subcellular locationi

Golgi apparatus 1 Publication. Membrane 1 Publication; Peripheral membrane protein 1 Publication. Cytoplasm 1 Publication. Secreted 1 Publication. Endoplasmic reticulum By similarity. Nucleus envelope By similarity
Note: Golgi retention is mediated by its N-terminal region.

GO - Cellular componenti

  1. cytosol Source: ProtInc
  2. endoplasmic reticulum Source: UniProtKB-SubCell
  3. endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB
  4. extracellular space Source: UniProtKB
  5. extracellular vesicular exosome Source: UniProtKB
  6. Golgi apparatus Source: HPA
  7. nuclear envelope Source: UniProtKB-SubCell
  8. plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane, Nucleus, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31826.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 420396Nucleobindin-2PRO_0000004165Add
BLAST
Chaini25 – 10682Nesfatin-1PRO_0000419819Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei257 – 2571Phosphoserine1 Publication
Modified residuei332 – 3321Phosphoserine1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Phosphoprotein

Proteomic databases

MaxQBiP80303.
PaxDbiP80303.
PRIDEiP80303.

PTM databases

PhosphoSiteiP80303.

Miscellaneous databases

PMAP-CutDBP80303.

Expressioni

Tissue specificityi

Predominantly expressed in spleen, testis and normal stomach.1 Publication

Gene expression databases

BgeeiP80303.
CleanExiHS_NUCB2.
GenevestigatoriP80303.

Organism-specific databases

HPAiCAB015931.
HPA008395.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
GADD45AP245222EBI-2296670,EBI-448167

Protein-protein interaction databases

BioGridi110979. 17 interactions.
IntActiP80303. 11 interactions.
MINTiMINT-2804938.
STRINGi9606.ENSP00000320168.

Structurei

3D structure databases

ProteinModelPortaliP80303.
SMRiP80303. Positions 229-327.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini241 – 27636EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini293 – 32836EF-hand 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni213 – 420208Binds to necdinBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi282 – 29312Asp/Glu-rich (acidic)Add
BLAST

Sequence similaritiesi

Belongs to the nucleobindin family.Curated
Contains 2 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG262100.
HOGENOMiHOG000007216.
HOVERGENiHBG052685.
InParanoidiP80303.
OMAiMNEVDIN.
PhylomeDBiP80303.
TreeFamiTF323218.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR028813. NUCB2.
[Graphical view]
PANTHERiPTHR19237:SF22. PTHR19237:SF22. 1 hit.
PfamiPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P80303-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MRWRTILLQY CFLLITCLLT ALEAVPIDID KTKVQNIHPV ESAKIEPPDT
60 70 80 90 100
GLYYDEYLKQ VIDVLETDKH FREKLQKADI EEIKSGRLSK ELDLVSHHVR
110 120 130 140 150
TKLDELKRQE VGRLRMLIKA KLDSLQDIGM DHQALLKQFD HLNHLNPDKF
160 170 180 190 200
ESTDLDMLIK AATSDLEHYD KTRHEEFKKY EMMKEHERRE YLKTLNEEKR
210 220 230 240 250
KEEESKFEEM KKKHENHPKV NHPGSKDQLK EVWEETDGLD PNDFDPKTFF
260 270 280 290 300
KLHDVNSDGF LDEQELEALF TKELEKVYDP KNEEDDMVEM EEERLRMREH
310 320 330 340 350
VMSEVDTNKD RLVTLEEFLK ATEKKEFLEP DSWETLDQQQ FFTEEELKEY
360 370 380 390 400
ENIIALQENE LKKKADELQK QKEELQRQHD QLEAQKLEYH QVIQQMEQKK
410 420
LQQGIPPSGP AGELKFEPHI
Length:420
Mass (Da):50,196
Last modified:March 3, 2009 - v2
Checksum:i5BA7459AB725A1A3
GO
Isoform 2 (identifier: P80303-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     419-420: HI → RV

Note: No experimental confirmation available.

Show »
Length:420
Mass (Da):50,201
Checksum:i4922A59AB725A1A3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti150 – 1501F → L in BAF84196 (PubMed:14702039).Curated

Polymorphismi

Deletion of Gln-402 is frequent.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti303 – 3031S → N.7 Publications
Corresponds to variant rs2521998 [ dbSNP | Ensembl ].
VAR_068746
Natural varianti338 – 3381Q → E.
Corresponds to variant rs757081 [ dbSNP | Ensembl ].
VAR_024399
Natural varianti402 – 4021Missing .2 Publications
VAR_020923

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei419 – 4202HI → RV in isoform 2. 1 PublicationVSP_036450

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41623.1. [P80303-1]
PIRiS55272.
RefSeqiNP_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.
UniGeneiHs.654599.

Genome annotation databases

GeneIDi4925.
KEGGihsa:4925.
UCSCiuc001mms.1. human. [P80303-1]

Polymorphism databases

DMDMi224471846.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41623.1. [P80303-1]
PIRiS55272.
RefSeqiNP_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.
UniGeneiHs.654599.

3D structure databases

ProteinModelPortaliP80303.
SMRiP80303. Positions 229-327.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110979. 17 interactions.
IntActiP80303. 11 interactions.
MINTiMINT-2804938.
STRINGi9606.ENSP00000320168.

PTM databases

PhosphoSiteiP80303.

Polymorphism databases

DMDMi224471846.

Proteomic databases

MaxQBiP80303.
PaxDbiP80303.
PRIDEiP80303.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi4925.
KEGGihsa:4925.
UCSCiuc001mms.1. human. [P80303-1]

Organism-specific databases

CTDi4925.
GeneCardsiGC11P017229.
HGNCiHGNC:8044. NUCB2.
HPAiCAB015931.
HPA008395.
MIMi608020. gene.
neXtProtiNX_P80303.
PharmGKBiPA31826.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG262100.
HOGENOMiHOG000007216.
HOVERGENiHBG052685.
InParanoidiP80303.
OMAiMNEVDIN.
PhylomeDBiP80303.
TreeFamiTF323218.

Miscellaneous databases

ChiTaRSiNUCB2. human.
GeneWikiiNUCB2.
GenomeRNAii4925.
NextBioi18967.
PMAP-CutDBP80303.
PROiP80303.
SOURCEiSearch...

Gene expression databases

BgeeiP80303.
CleanExiHS_NUCB2.
GenevestigatoriP80303.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR028813. NUCB2.
[Graphical view]
PANTHERiPTHR19237:SF22. PTHR19237:SF22. 1 hit.
PfamiPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. 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. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  12. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-303, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiNUCB2_HUMAN
AccessioniPrimary (citable) accession number: P80303
Secondary accession number(s): A8K642, D3DQX5, Q8NFT5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: March 3, 2009
Last modified: March 4, 2015
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.