CPLM-008204

Genbank Nucleotide ID

Histidine triad nucleotide-binding protein 1

Protein Synonyms/Alias

Adenosine 5'-monophosphoramidase; Protein kinase C inhibitor 1; Protein kinase C-interacting protein 1; PKCI-1

HINT; PKCI1; PRKCNH1

Homo sapiens (Human)

Position	Peptide	Type	References
7	*MADEIAKAQVARPG	ubiquitination	[1, 2, 3]
21	GGDTIFGKIIRKEIP	acetylation	[4, 5]
21	GGDTIFGKIIRKEIP	ubiquitination	[1, 2, 3, 6]
30	IRKEIPAKIIFEDDR	acetylation	[4]
30	IRKEIPAKIIFEDDR	ubiquitination	[1, 2, 3, 6, 7, 8]
83	HLMIVGKKCAADLGL	ubiquitination	[2]
92	AADLGLNKGYRMVVN	ubiquitination	[2, 9]

[1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[5] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
[6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[7] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[8] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[9] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]

Functional Description

Hydrolyzes purine nucleotide phosphoramidates with a single phosphate group, including adenosine 5'monophosphoramidate (AMP-NH2), adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase, as well as Met-AMP, His- AMP and Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) and AMP-N-alanine methyl ester. Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O- phosphorothioate to the corresponding nucleoside 5'-O-phosphates with concomitant release of hydrogen sulfide. In addition, functions as scaffolding protein that modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed with MITF and CTNNB1. Modulates p53/TP53 levels and p53/TP53-mediated apoptosis. Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin- protein ligase complex.

DOMAIN 18 126 HIT.
NP_BIND 43 44 Purine nucleotide phosphoramidate.
NP_BIND 105 107 Purine nucleotide phosphoramidate.
NP_BIND 112 114 Purine nucleotide phosphoramidate.
MOTIF 110 114 Histidine triad motif.
ACT_SITE 112 112 Tele-AMP-histidine intermediate.
BINDING 99 99 Purine nucleotide phosphoramidate.
MOD_RES 2 2 N-acetylalanine (By similarity).
MOD_RES 21 21 N6-acetyllysine.
MOD_RES 30 30 N6-acetyllysine.

3D-structure; Acetylation; Apoptosis; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Hydrolase; Neuropathy; Nucleotide-binding; Nucleus; Reference proteome; Transcription; Transcription regulation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IDA:HPA.
GO:0005856; C:cytoskeleton; TAS:ProtInc.
GO:0000118; C:histone deacetylase complex; IDA:UniProtKB.
GO:0005886; C:plasma membrane; IDA:HPA.
GO:0016787; F:hydrolase activity; IDA:UniProtKB.
GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
GO:0005080; F:protein kinase C binding; TAS:ProtInc.
GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:UniProtKB.
GO:0009154; P:purine ribonucleotide catabolic process; IDA:UniProtKB.
GO:0006355; P:regulation of transcription, DNA-dependent; IMP:UniProtKB.
GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.

IPR019808; Histidine_triad_CS.
IPR001310; Histidine_triad_HIT.
IPR011146; HIT-like.

PS00892; HIT_1
PS51084; HIT_2