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Overview

Uniprot IDQ9Y657
Protein NameSpindlin-1
Gene NameSPIN1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
28 GVSANMMKKRTSHKK
29 VSANMMKKRTSHKKH
44 RSSVGPSKPVSQPRR
7 *MKTPFGKTPGQRSR

Function

Chromatin reader that specifically recognizes and binds histone H3 both trimethylated at 'Lys-4' and 'Lys-9' (H3K4me3K9me3) and is involved in piRNA-mediated retrotransposon silencing during spermatogenesis (PubMed:33574238). Plays a key role in the initiation of the PIWIL4-piRNA pathway, a pathway that directs transposon DNA methylation and silencing in the male embryonic germ cells, by promoting recruitment of DNA methylation machinery to transposons: binds young, but not old, LINE1 transposons, which are specifically marked with H3K4me3K9me3, and promotes the recruitment of PIWIL4 and SPOCD1 to transposons, leading to piRNA-directed DNA methylation (By similarity). Also recognizes and binds histone H3 both trimethylated at 'Lys-4' and asymmetrically dimethylated at 'Arg-8' (H3K4me3 and H3R8me2a) and acts as an activator of Wnt signaling pathway downstream of PRMT2 (PubMed:22258766, PubMed:29061846). In case of cancer, promotes cell cancer proliferation via activation of the Wnt signaling pathway (PubMed:24589551). Overexpression induces metaphase arrest and chromosomal instability. Localizes to active rDNA loci and promotes the expression of rRNA genes (PubMed:21960006). May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity). Involved in oocyte meiotic resumption, a process that takes place before ovulation to resume meiosis of oocytes blocked in prophase I: may act by regulating maternal transcripts to control meiotic resumption (By similarity)

Protein Sequence

10 MKTPFGKTPG 20 QRSRADAGHA 30 GVSANMMKKR 40 TSHKKHRSSV 50 GPSKPVSQPR 60 RNIVGCRIQH 70 GWKEGNGPVT 80 QWKGTVLDQV 90 PVNPSLYLIK 100 YDGFDCVYGL 110 ELNKDERVSA 120 LEVLPDRVAT 130 SRISDAHLAD 140 TMIGKAVEHM 150 FETEDGSKDE 160 WRGMVLARAP 170 VMNTWFYITY 180 EKDPVLYMYQ 190 LLDDYKEGDL 200 RIMPDSNDSP 210 PAEREPGEVV 220 DSLVGKQVEY 230 AKEDGSKRTG 240 MVIHQVEAKP 250 SVYFIKFDDD 260 FHIYVYDLVK TS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005819 spindle
Molecular Function GO:0140002 histone H3K4me3 reader activity
Molecular Function GO:0140566 histone reader activity
Biological Process GO:0007276 gamete generation
Biological Process GO:0051321 meiotic cell cycle
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0030177 positive regulation of Wnt signaling pathway
Biological Process GO:0071168 protein localization to chromatin
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:0009303 rRNA transcription
Biological Process GO:0141196 transposable element silencing by piRNA-mediated DNA methylation
Biological Process GO:0016055 Wnt signaling pathway

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[3] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.