P16333 (NCK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytoplasmic protein NCK1

Alternative name(s):
NCK adaptor protein 1
Short name=Nck-1
SH2/SH3 adaptor protein NCK-alpha

Gene names

Name:	NCK1
Synonyms:	NCK

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

General annotation (Comments)

Function	Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Ref.13 Ref.19 Ref.21
Subunit structure	Interacts (via SH2 domain and SH3 domain 2) with EGFR. Interacts with PAK1 and SOS1. Interacts (via SH3 domains) with PKN2. Associates with BLNK, PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with SOCS7. This interaction is required for nuclear import. Part of a complex containing PPP1R15B, PP1 and NCK1. Interacts with RALGPS1. Interacts with CAV2 (tyrosine phosphorylated form). Interacts with ADAM15. Interacts with FASLG. Directly interacts with RASA1. Interacts with isoform 4 of MINK1. Interacts with FLT1 (tyrosine. phosphorylated). Interacts with KDR (tyrosine phosphorylated). Interacts (via SH2 domain) with EPHB1; activates the JUN cascade to regulate cell adhesion. Interacts (via SH2 domain) with PDGFRB (tyrosine phosphorylated). Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20 Ref.21 Ref.23 Ref.25 Ref.29 Ref.31
Subcellular location	Cytoplasm. Endoplasmic reticulum. Nucleus. Note: Mostly cytoplasmic, but shuttles between the cytoplasm and the nucleus. Import into the nucleus requires the interaction with SOCS7. Predominantly nuclear following genotoxic stresses, such as UV irradiation, hydroxyurea or mitomycin C treatments. Ref.19 Ref.21
Domain	Only the first and third SH3 domains seem to be involved in RASA1-binding; the second SH3 domain and the SH2 domains do not seeem to be involved.
Post-translational modification	Phosphorylated on Ser and Tyr residues. Phosphorylated in response to activation of EGFR and FcERI. Phosphorylated by activated PDGFRB. Ref.6 Ref.7 Ref.8 Ref.13
Sequence similarities	Contains 1 SH2 domain. Contains 3 SH3 domains.

Ontologies

Keywords
Biological process	Translation regulation
Cellular component	Cytoplasm Endoplasmic reticulum Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat SH2 domain SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell activation Inferred from mutant phenotype PubMed 12110186. Source: UniProtKB T cell receptor signaling pathway Traceable author statement. Source: Reactome actin filament organization Inferred from electronic annotation. Source: Compara axon guidance Traceable author statement. Source: Reactome cell migration Inferred from electronic annotation. Source: Compara lamellipodium assembly Inferred from electronic annotation. Source: Compara positive regulation of T cell proliferation Inferred from mutant phenotype PubMed 12110186. Source: UniProtKB positive regulation of actin filament polymerization Inferred from mutant phenotype PubMed 12110186. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.13. Source: UniProtKB regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW signal complex assembly Non-traceable author statement PubMed 12110186. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Traceable author statement. Source: Reactome vesicle membrane Inferred from electronic annotation. Source: Compara
Molecular_function	cytoskeletal adaptor activity Non-traceable author statement PubMed 12110186. Source: UniProtKB receptor signaling complex scaffold activity Non-traceable author statement PubMed 12110186. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABCG5	Q9H222	2	EBI-389883,EBI-1761423
ABL1	P00519	2	EBI-389883,EBI-375543
ABL2	P42684	3	EBI-389883,EBI-1102694
AGER	Q15109	2	EBI-389883,EBI-1646426
AIRE	O43918	2	EBI-389883,EBI-1753081
ARHGEF11	O15085	3	EBI-389883,EBI-311099
ASAP1	Q9ULH1	5	EBI-389883,EBI-346622
ASB16	Q96NS5	2	EBI-389883,EBI-1751918
BAZ2A	Q9UIF9	2	EBI-389883,EBI-934890
BRD4	O60885	2	EBI-389883,EBI-723869
BRPF3	Q9ULD4	3	EBI-389883,EBI-1753470
C6	P13671	2	EBI-389883,EBI-1753221
CAST	P20810	2	EBI-389883,EBI-1268770
CDC27	P30260	3	EBI-389883,EBI-994813
CELSR3	Q9NYQ7	2	EBI-389883,EBI-308417
CHAF1A	Q13111	2	EBI-389883,EBI-1020839
CKAP5	Q14008	3	EBI-389883,EBI-310585
CNTNAP1	P78357	2	EBI-389883,EBI-1751903
COBRA1	Q8WX92	6	EBI-389883,EBI-347721
CYP4F2	P78329	2	EBI-389883,EBI-1752413
DAB2	P98082	2	EBI-389883,EBI-1171238
DAG1	Q14118	2	EBI-389883,EBI-1755945
DLGAP1	O14490	4	EBI-389883,EBI-1753207
DLGAP2	Q9P1A6	4	EBI-389883,EBI-1753397
DLGAP3	O95886	2	EBI-389883,EBI-1752541
DLGAP4	Q9Y2H0	5	EBI-389883,EBI-722139
DLX4	Q92988	3	EBI-389883,EBI-1752755
DNM1	Q05193	2	EBI-389883,EBI-713135
DOCK3	Q8IZD9	3	EBI-389883,EBI-1752361
DUSP15	Q9H1R2	2	EBI-389883,EBI-1752795
ECT2	Q9H8V3	3	EBI-389883,EBI-1054039
ELK3	P41970	3	EBI-389883,EBI-1758534
EPS15	P42566	2	EBI-389883,EBI-396684
F2RL2	O00254	2	EBI-389883,EBI-1751853
FAM110A	Q9BQ89	2	EBI-389883,EBI-1752811
FCGR2B	P31994	2	EBI-389883,EBI-724784
FCGR2C	P31995	2	EBI-389883,EBI-1396036
FLNB	O75369	3	EBI-389883,EBI-352089
FOXH1	O75593	2	EBI-389883,EBI-1759806
FYB	O15117	3	EBI-389883,EBI-1753267
GABBR1	Q9UBS5	3	EBI-389883,EBI-724156
GAD1	Q99259	2	EBI-389883,EBI-743184
GHR	P10912	2	EBI-389883,EBI-286316
GLTSCR1	Q9NZM4	3	EBI-389883,EBI-1754943
GNS	P15586	2	EBI-389883,EBI-1752200
GSTZ1	O43708	2	EBI-389883,EBI-748043
HIST1H1E	P10412	2	EBI-389883,EBI-358163
HNRNPR	O43390	2	EBI-389883,EBI-713419
ID4	P47928	3	EBI-389883,EBI-1754719
ISG20L2	Q9H9L3	2	EBI-389883,EBI-751335
JAK2	O60674	2	EBI-389883,EBI-518647
LRRC3	Q9BY71	2	EBI-389883,EBI-1761329
MAP4	P27816	2	EBI-389883,EBI-715255
MAP4K1	Q92918	2	EBI-389883,EBI-881
MAP4K5	Q9Y4K4	2	EBI-389883,EBI-1279
MEPE	Q9NQ76	3	EBI-389883,EBI-1753293
MYLK	Q15746	2	EBI-389883,EBI-968482
NKX2-1	P43699	2	EBI-389883,EBI-1391923
NPHS1	O60500	3	EBI-389883,EBI-996920
PDIA2	Q13087	3	EBI-389883,EBI-1752525
PHACTR2	O75167	2	EBI-389883,EBI-1754409
PIK3C2B	O00750	3	EBI-389883,EBI-641107
PNMA2	Q9UL42	2	EBI-389883,EBI-302355
PRX	Q9BXM0	2	EBI-389883,EBI-1753064
PTPN4	P29074	3	EBI-389883,EBI-710431
RAG1	P15918	2	EBI-389883,EBI-1755109
RAPGEF1	Q13905	2	EBI-389883,EBI-976876
RASA1	P20936	6	EBI-389883,EBI-1026476
RIMS2	Q9UQ26	2	EBI-389883,EBI-1756749
RIN3	Q8TB24	2	EBI-389883,EBI-1570523
RPL13	P26373	2	EBI-389883,EBI-356849
RPP38	P78345	2	EBI-389883,EBI-366493
RRAS	P10301	3	EBI-389883,EBI-968703
SCARF2	Q96GP6	2	EBI-389883,EBI-1752088
SEMA7A	O75326	2	EBI-389883,EBI-1753538
SEPN1	Q9NZV5	2	EBI-389883,EBI-1751965
SHANK2	Q9UPX8	6	EBI-389883,EBI-1570571
SHANK3	Q9BYB0	4	EBI-389883,EBI-1752330
SHROOM2	Q13796	2	EBI-389883,EBI-1644065
SLC23A1	Q9UHI7	2	EBI-389883,EBI-1759386
SLC24A1	O60721	3	EBI-389883,EBI-1753504
SNX12	Q9UMY4	3	EBI-389883,EBI-1752602
SNX17	Q15036	3	EBI-389883,EBI-1752620
SNX8	Q9Y5X2	2	EBI-389883,EBI-1752557
SOS1	Q07889	5	EBI-389883,EBI-297487
SOS2	Q07890	3	EBI-389883,EBI-298181
SP1	P08047	2	EBI-389883,EBI-298336
SPEN	Q96T58	3	EBI-389883,EBI-765739
SUV39H2	Q9H5I1	2	EBI-389883,EBI-723127
SYNJ2	O15056	3	EBI-389883,EBI-310513
TGOLN2	O43493	3	EBI-389883,EBI-1752146
TMPO	P42167	2	EBI-389883,EBI-455283
TPSAB1	Q15661	2	EBI-389883,EBI-1761369
TPX2	Q9ULW0	4	EBI-389883,EBI-1037322
TRAIP	Q9BWF2	3	EBI-389883,EBI-1756205
TRIM39	Q9HCM9	2	EBI-389883,EBI-739510
TULP1	O00294	2	EBI-389883,EBI-1756778
VPS13A	Q96RL7	3	EBI-389883,EBI-1752583
WBP7	Q9UMN6	2	EBI-389883,EBI-765774
WIPF1	O43516	2	EBI-389883,EBI-346356

Alternative products

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

Isoform 1 (identifier: P16333-1)

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: P16333-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: MAEEVVVVAK...IVKNLKDTLG → MDWLNVFKDFFS

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 377

377

Cytoplasmic protein NCK1

PRO_0000096766

Regions

Domain

2 – 61

60

SH3 1

Domain

115 – 165

51

SH3 2

Domain

190 – 252

63

SH3 3

Domain

282 – 376

95

SH2

Amino acid modifications

Modified residue

85

1

Phosphoserine Ref.24 Ref.26

Modified residue

91

1

Phosphoserine Ref.24

Modified residue

96

1

Phosphoserine Ref.24

Modified residue

105

1

Phosphotyrosine Ref.22 Ref.26 Ref.27

Natural variations

Alternative sequence

1 – 76

76

MAEEV…KDTLG → MDWLNVFKDFFS in isoform 2.

VSP_043122

Natural variant

180

1

A → V.
Corresponds to variant rs13320485 [ dbSNP | Ensembl ].

VAR_051228

Experimental info

Mutagenesis

38

1

W → K: Small decrease in RASA1-binding. Almost complete loss of RASA1-binding; when associated with K-143 and K-229. Ref.29

Mutagenesis

143

1

W → K: No effect on RASA1-binding. Almost complete loss of RASA1-binding; when associated with K-38 and K-229. Ref.29

Mutagenesis

229

1

W → K: Small decrease in RASA1-binding. Almost complete loss of RASA1-binding; when associated with K-38 and K-229. Ref.29

Mutagenesis

308

1

R → K: No effect on RASA1-binding. Ref.29

Secondary structure

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377

Helix Strand Turn

Details...

Beta strand

5 – 11

7

Beta strand

28 – 33

6

Beta strand

35 – 42

8

Beta strand

48 – 51

4

Turn

53 – 55

3

Beta strand

56 – 58

3

Beta strand

99 – 101

3

Beta strand

109 – 115

7

Beta strand

131 – 138

8

Beta strand

142 – 148

7

Beta strand

151 – 156

6

Helix

157 – 159

3

Beta strand

160 – 162

3

Beta strand

168 – 170

3

Helix

289 – 299

11

Beta strand

304 – 309

6

Beta strand

311 – 313

3

Beta strand

316 – 321

6

Beta strand

324 – 326

3

Beta strand

328 – 335

8

Beta strand

338 – 341

4

Beta strand

344 – 348

5

Helix

349 – 358

10

Beta strand

361 – 363

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 554E9B1A936AEF30	FASTA	377	42,864
	10 20 30 40 50 60 MAEEVVVVAK FDYVAQQEQE LDIKKNERLW LLDDSKSWWR VRNSMNKTGF VPSNYVERKN 70 80 90 100 110 120 SARKASIVKN LKDTLGIGKV KRKPSVPDSA SPADDSFVDP GERLYDLNMP AYVKFNYMAE 130 140 150 160 170 180 REDELSLIKG TKVIVMEKCS DGWWRGSYNG QVGWFPSNYV TEEGDSPLGD HVGSLSEKLA 190 200 210 220 230 240 AVVNNLNTGQ VLHVVQALYP FSSSNDEELN FEKGDVMDVI EKPENDPEWW KCRKINGMVG 250 260 270 280 290 300 LVPKNYVTVM QNNPLTSGLE PSPPQCDYIR PSLTGKFAGN PWYYGKVTRH QAEMALNERG 310 320 330 340 350 360 HEGDFLIRDS ESSPNDFSVS LKAQGKNKHF KVQLKETVYC IGQRKFSTME ELVEHYKKAP 370 IFTSEQGEKL YLVKHLS
	Isoform 2 [UniParc]. Checksum: D10F0F2DEF1D72F7	FASTA	313	35,511
	10 20 30 40 50 60 MDWLNVFKDF FSIGKVKRKP SVPDSASPAD DSFVDPGERL YDLNMPAYVK FNYMAEREDE 70 80 90 100 110 120 LSLIKGTKVI VMEKCSDGWW RGSYNGQVGW FPSNYVTEEG DSPLGDHVGS LSEKLAAVVN 130 140 150 160 170 180 NLNTGQVLHV VQALYPFSSS NDEELNFEKG DVMDVIEKPE NDPEWWKCRK INGMVGLVPK 190 200 210 220 230 240 NYVTVMQNNP LTSGLEPSPP QCDYIRPSLT GKFAGNPWYY GKVTRHQAEM ALNERGHEGD 250 260 270 280 290 300 FLIRDSESSP NDFSVSLKAQ GKNKHFKVQL KETVYCIGQR KFSTMEELVE HYKKAPIFTS 310 EQGEKLYLVK HLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nck, a melanoma cDNA encoding a cytoplasmic protein consisting of the src homology units SH2 and SH3." Lehmann J.M., Riethmueller G., Johnson J.P. Nucleic Acids Res. 18:1048-1048(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] (ISOFORM 2). Tissue: Synovium.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [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 (SEP-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] (ISOFORM 1). Tissue: Uterus.
[6]	"Phosphorylation of Nck in response to a variety of receptors, phorbol myristate acetate, and cyclic AMP." Park D., Rhee S.G. Mol. Cell. Biol. 12:5816-5823(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, PARTIAL PROTEIN SEQUENCE.
[7]	"The SH2/SH3 domain-containing protein Nck is recognized by certain anti-phospholipase C-gamma 1 monoclonal antibodies, and its phosphorylation on tyrosine is stimulated by platelet-derived growth factor and epidermal growth factor treatment." Meisenhelder J., Hunter T. Mol. Cell. Biol. 12:5843-5856(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[8]	"Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor." Nishimura R., Li W., Kashishian A., Mondino A., Zhou M., Cooper J., Schlessinger J. Mol. Cell. Biol. 13:6889-6896(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDGFRB, PHOSPHORYLATION.
[9]	"A novel ligand for an SH3 domain of the adaptor protein Nck bears an SH2 domain and nuclear signaling motifs." Matuoka K., Miki H., Takahashi K., Takenawa T. Biochem. Biophys. Res. Commun. 239:488-492(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SOCS7.
[10]	"Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2." Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I. Biochem. Biophys. Res. Commun. 246:95-99(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FLT1.
[11]	"BLNK: a central linker protein in B cell activation." Fu C., Turck C.W., Kurosaki T., Chan A.C. Immunity 9:93-103(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BLNK; GRB2; PLCG1 AND VAV.
[12]	"Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun kinase." Stein E., Huynh-Do U., Lane A.A., Cerretti D.P., Daniel T.O. J. Biol. Chem. 273:1303-1308(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EPHB1. Tissue: Kidney.
[13]	"Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck." Braverman L.E., Quilliam L.A. J. Biol. Chem. 274:5542-5549(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EGFR; PAK1; PKN2 AND SOS1, PHOSPHORYLATION.
[14]	"Identification and characterization of a new family of guanine nucleotide exchange factors for the ras-related GTPase Ral." Rebhun J.F., Chen H., Quilliam L.A. J. Biol. Chem. 275:13406-13410(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RALGPS1.
[15]	"Src-induced phosphorylation of caveolin-2 on tyrosine 19. Phospho-caveolin-2 (Tyr(P)19) is localized near focal adhesions, remains associated with lipid rafts/caveolae, but no longer forms a high molecular mass hetero-oligomer with caveolin-1." Lee H., Park D.S., Wang X.B., Scherer P.E., Schwartz P.E., Lisanti M.P. J. Biol. Chem. 277:34556-34567(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CAV2.
[16]	"Tyrosine phosphorylation of caveolin-2 at residue 27: differences in the spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27)." Wang X.B., Lee H., Capozza F., Marmon S., Sotgia F., Brooks J.W., Campos-Gonzalez R., Lisanti M.P. Biochemistry 43:13694-13706(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CAV2.
[17]	"Identification and functional characterization of a novel human misshapen/Nck interacting kinase-related kinase, hMINK beta." Hu Y., Leo C., Yu S., Huang B.C., Wang H., Shen M., Luo Y., Daniel-Issakani S., Payan D.G., Xu X. J. Biol. Chem. 279:54387-54397(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MINK1.
[18]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[19]	"Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress." Latreille M., Larose L. J. Biol. Chem. 281:26633-26644(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH PP1 AND PPP1R15B, FUNCTION, SUBCELLULAR LOCATION.
[20]	"Phosphorylation of Tyr1214 within VEGFR-2 triggers the recruitment of Nck and activation of Fyn leading to SAPK2/p38 activation and endothelial cell migration in response to VEGF." Lamalice L., Houle F., Huot J. J. Biol. Chem. 281:34009-34020(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KDR.
[21]	"Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7." Kremer B.E., Adang L.A., Macara I.G. Cell 130:837-850(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SOCS7.
[22]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, MASS SPECTROMETRY. Tissue: Platelet.
[23]	"Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma." Zhong J.L., Poghosyan Z., Pennington C.J., Scott X., Handsley M.M., Warn A., Gavrilovic J., Honert K., Kruger A., Span P.N., Sweep F.C., Edwards D.R. Mol. Cancer Res. 6:383-394(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ADAM15.
[24]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-91 AND SER-96, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening." Voss M., Lettau M., Janssen O. BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FASLG.
[26]	"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-85 AND TYR-105, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[27]	"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 TYR-105, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[28]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]	"Adaptor protein Nck1 interacts with p120 Ras GTPase-activating protein and regulates its activity." Ger M., Zitkus Z., Valius M. Cell. Signal. 23:1651-1658(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RASA1, MUTAGENESIS OF TRP-38; TRP-143; TRP-229 AND ARG-308.
[30]	"Solution structure of the SH3 domain of the human cytoplasmic protein NCK1." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 99-174.
[31]	"Specificity determinants of a novel Nck interaction with the juxtamembrane domain of the epidermal growth factor receptor." Hake M.J., Choowongkomon K., Kostenko O., Carlin C.R., Sonnichsen F.D. Biochemistry 47:3096-3108(2008) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-61 AND 107-165, INTERACTION WITH EGFR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X17576 mRNA. Translation: CAA35599.1.
AK301460 mRNA. Translation: BAH13487.1.
AC011597 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79105.1.
CH471052 Genomic DNA. Translation: EAW79108.1.
CH471052 Genomic DNA. Translation: EAW79109.1.
BC006403 mRNA. Translation: AAH06403.1.

IPI

IPI00028065.
IPI00793968.

PIR

S08636.

RefSeq

NP_001177725.1. NM_001190796.1.
NP_006144.1. NM_006153.4.

UniGene

Hs.477693.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CI8	X-ray	1.80	A	281-377	[»]
2CI9	X-ray	1.50	A/B	281-377	[»]
2CUB	NMR	-	A	99-173	[»]
2JS0	NMR	-	A	107-165	[»]
2JS2	NMR	-	A	1-61	[»]
2JW4	NMR	-	A	1-63	[»]

ProteinModelPortal

P16333.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-639N.

IntAct

P16333. 170 interactions.

MINT

MINT-92747.

STRING

9606.ENSP00000288986.

PTM databases

PhosphoSite

P16333.

Polymorphism databases

DMDM

127962.

Proteomic databases

PaxDb

P16333.

PeptideAtlas

P16333.

PRIDE

P16333.

Protocols and materials databases

DNASU

4690.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000288986; ENSP00000288986; ENSG00000158092.
ENST00000469404; ENSP00000419631; ENSG00000158092.
ENST00000481752; ENSP00000417273; ENSG00000158092.

GeneID

4690.

KEGG

hsa:4690.

UCSC

uc003erh.3. human.

Organism-specific databases

CTD

4690.

GeneCards

GC03P136581.

HGNC

HGNC:7664. NCK1.

HPA

CAB005063.

MIM

600508. gene.

neXtProt

NX_P16333.

PharmGKB

PA31466.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG261435.

HOGENOM

HOG000290684.

HOVERGEN

HBG000719.

InParanoid

P16333.

KO

K07365.

OMA

AIVKYNY.

OrthoDB

EOG40ZQXR.

PhylomeDB

P16333.

Enzyme and pathway databases

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
ephbfwdpathway. EPHB forward signaling.
insulin_pathway. Insulin Pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
tcrpathway. TCR signaling in naive CD4+ T cells.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P16333.

Bgee

P16333.

CleanEx

HS_NCK1.

Genevestigator

P16333.

GermOnline

ENSG00000158092. Homo sapiens.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR017304. Cytoplasmic_NCK.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00017. SH2. 1 hit.
PF00018. SH3_1. 3 hits.
[Graphical view]

PIRSF

PIRSF037874. Cytoplasmic_NCK. 1 hit.

PRINTS

PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 3 hits.
[Graphical view]

SUPFAM

SSF50044. SH3. 3 hits.

PROSITE

PS50001. SH2. 1 hit.
PS50002. SH3. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P16333.

ChEMBL

CHEMBL4846.

EvolutionaryTrace

P16333.

GenomeRNAi

4690.

NextBio

18086.

PMAP-CutDB

P16333.

SOURCE

Search...

Entry information

Entry name

NCK1_HUMAN

Accession

Primary (citable) accession number: P16333
Secondary accession number(s): B7Z751, D3DNE3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	May 1, 2013
This is version 148 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.