ID F111A_HUMAN Reviewed; 611 AA. AC Q96PZ2; A8K5Y8; Q5RKS9; Q5XKM2; Q68DK9; Q6IPR7; Q9H5Y1; DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 2. DT 13-SEP-2023, entry version 144. DE RecName: Full=Serine protease FAM111A {ECO:0000305}; DE EC=3.4.21.- {ECO:0000269|PubMed:32165630}; GN Name=FAM111A {ECO:0000303|PubMed:23093934, ECO:0000312|HGNC:HGNC:24725}; GN Synonyms=KIAA1895 {ECO:0000303|PubMed:11572484}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=11572484; DOI=10.1093/dnares/8.4.179; RA Nagase T., Kikuno R., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XXI. The RT complete sequences of 60 new cDNA clones from brain which code for large RT proteins."; RL DNA Res. 8:179-187(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Ileal mucosa; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterine endothelium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH SV40 VIRUS RP LARGE T ANTIGEN (MICROBIAL INFECTION). RX PubMed=23093934; DOI=10.1371/journal.ppat.1002949; RA Fine D.A., Rozenblatt-Rosen O., Padi M., Korkhin A., James R.L., RA Adelmant G., Yoon R., Guo L., Berrios C., Zhang Y., Calderwood M.A., RA Velmurgan S., Cheng J., Marto J.A., Hill D.E., Cusick M.E., Vidal M., RA Florens L., Washburn M.P., Litovchick L., DeCaprio J.A.; RT "Identification of FAM111A as an SV40 host range restriction and adenovirus RT helper factor."; RL PLoS Pathog. 8:E1002949-E1002949(2012). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PCNA, AND MUTAGENESIS OF RP 24-TYR-PHE-25. RX PubMed=24561620; DOI=10.1038/ncb2918; RA Alabert C., Bukowski-Wills J.C., Lee S.B., Kustatscher G., Nakamura K., RA de Lima Alves F., Menard P., Mejlvang J., Rappsilber J., Groth A.; RT "Nascent chromatin capture proteomics determines chromatin dynamics during RT DNA replication and identifies unknown fork components."; RL Nat. Cell Biol. 16:281-293(2014). RN [8] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-20; LYS-30 AND LYS-65, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, PROTEOLYTIC CLEAVAGE, MUTAGENESIS OF RP 24-TYR-PHE-25; PHE-231; PHE-334 AND SER-541, CHARACTERIZATION OF VARIANTS RP GCLEB SER-342 DEL AND GLY-528, AND CHARACTERIZATION OF VARIANTS KCS2 RP HIS-511 AND HIS-569. RX PubMed=32165630; DOI=10.1038/s41467-020-15170-7; RA Kojima Y., Machida Y., Palani S., Caulfield T.R., Radisky E.S., RA Kaufmann S.H., Machida Y.J.; RT "FAM111A protects replication forks from protein obstacles via its trypsin- RT like domain."; RL Nat. Commun. 11:1318-1318(2020). RN [10] RP VARIANTS KCS2 HIS-511 AND HIS-569, AND VARIANTS GCLEB ALA-338; SER-342 DEL; RP THR-527 AND GLY-528. RX PubMed=23684011; DOI=10.1016/j.ajhg.2013.04.020; RA Unger S., Gorna M.W., Le Bechec A., Do Vale-Pereira S., Bedeschi M.F., RA Geiberger S., Grigelioniene G., Horemuzova E., Lalatta F., Lausch E., RA Magnani C., Nampoothiri S., Nishimura G., Petrella D., Rojas-Ringeling F., RA Utsunomiya A., Zabel B., Pradervand S., Harshman K., Campos-Xavier B., RA Bonafe L., Superti-Furga G., Stevenson B., Superti-Furga A.; RT "FAM111A mutations result in hypoparathyroidism and impaired skeletal RT development."; RL Am. J. Hum. Genet. 92:990-995(2013). RN [11] RP VARIANT KCS2 HIS-569. RX PubMed=24635597; DOI=10.1111/cge.12290; RA Nikkel S., Ahmed A., Smith A., Marcadier J., Bulman D., Boycott K.; RT "Mother-to-daughter transmission of Kenny-Caffey syndrome associated with RT the recurrent, dominant FAM111A mutation p.Arg569His."; RL Clin. Genet. 86:394-395(2014). RN [12] RP VARIANT KCS2 HIS-569. RX PubMed=23996431; DOI=10.1002/jbmr.2091; RA Isojima T., Doi K., Mitsui J., Oda Y., Tokuhiro E., Yasoda A., Yorifuji T., RA Horikawa R., Yoshimura J., Ishiura H., Morishita S., Tsuji S., Kitanaka S.; RT "A recurrent de novo FAM111A mutation causes kenny-caffey syndrome type RT 2."; RL J. Bone Miner. Res. 29:992-998(2014). CC -!- FUNCTION: Single-stranded DNA-binding serine protease that mediates the CC proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during CC DNA synthesis, thereby playing a key role in maintaining genomic CC integrity (PubMed:32165630). DPCs are highly toxic DNA lesions that CC interfere with essential chromatin transactions, such as replication CC and transcription, and which are induced by reactive agents, such as UV CC light or formaldehyde (PubMed:32165630). Protects replication fork from CC stalling by removing DPCs, such as covalently trapped topoisomerase 1 CC (TOP1) adducts on DNA lesion, or poly(ADP-ribose) polymerase 1 (PARP1)- CC DNA complexes trapped by PARP inhibitors (PubMed:32165630). Required CC for PCNA loading on replication sites (PubMed:24561620). Promotes S- CC phase entry and DNA synthesis (PubMed:24561620). CC {ECO:0000269|PubMed:24561620, ECO:0000269|PubMed:32165630}. CC -!- FUNCTION: (Microbial infection) May directly function at replication CC forks, explaining why Simian virus 40 (SV40) interacts with FAM111A to CC overcome host range restriction. {ECO:0000269|PubMed:23093934}. CC -!- SUBUNIT: Interacts (via PIP-box) with PCNA; then interaction is direct. CC {ECO:0000269|PubMed:24561620}. CC -!- SUBUNIT: (Microbial infection) Interacts with SV40 virus large T CC antigen and this interaction is required for efficient viral CC replication and sustained viral gene expression in restrictive cell CC types. {ECO:0000269|PubMed:23093934}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23093934, CC ECO:0000269|PubMed:24561620}. Chromosome {ECO:0000269|PubMed:24561620}. CC Cytoplasm {ECO:0000269|PubMed:23093934}. Note=Mainly localizes to CC nucleus: colocalizes with PCNA on replication sites. CC {ECO:0000269|PubMed:24561620}. CC -!- INDUCTION: Regulated in a cell cycle dependent manner with the lowest CC expression during G0 or the quiescent phase and with peak expression CC during G2/M phase (at protein level). {ECO:0000269|PubMed:23093934}. CC -!- DOMAIN: The PIP-box mediates the interaction with PCNA. CC {ECO:0000269|PubMed:24561620}. CC -!- PTM: Autocatalytically cleaved; activating the protein CC (PubMed:32165630). Autocatalytic cleavage takes place in trans CC (PubMed:32165630). {ECO:0000269|PubMed:32165630}. CC -!- DISEASE: Kenny-Caffey syndrome 2 (KCS2) [MIM:127000]: A disorder CC characterized by impaired skeletal development with small and dense CC bones, short stature, and primary hypoparathyroidism with hypocalcemia. CC Clinical features include cortical thickening and medullary stenosis of CC the tubular bones, delayed closure of fontanels, defective dentition, CC small eyes with hypermetropia, and frontal bossing with a triangular CC face. {ECO:0000269|PubMed:23684011, ECO:0000269|PubMed:23996431, CC ECO:0000269|PubMed:24635597, ECO:0000269|PubMed:32165630}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Gracile bone dysplasia (GCLEB) [MIM:602361]: A perinatally CC lethal condition characterized by narrowing of the medullary cavity of CC the long bones and of the skull, gracile bones with thin diaphyses, CC premature closure of basal cranial sutures, and microphthalmia. Most CC affected individuals who survive beyond the perinatal period develop CC hypocalcemia with low parathyroid hormone levels. CC {ECO:0000269|PubMed:23684011, ECO:0000269|PubMed:32165630}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the FAM111 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB15486.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB67788.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB067482; BAB67788.1; ALT_INIT; mRNA. DR EMBL; AK026447; BAB15486.1; ALT_INIT; mRNA. DR EMBL; AK291453; BAF84142.1; -; mRNA. DR EMBL; CR749358; CAH18211.1; -; mRNA. DR EMBL; BC013137; AAH13137.1; -; mRNA. DR EMBL; BC054515; AAH54515.1; -; mRNA. DR EMBL; BC071759; AAH71759.1; -; mRNA. DR CCDS; CCDS7973.1; -. DR RefSeq; NP_001135991.1; NM_001142519.2. DR RefSeq; NP_001135992.1; NM_001142520.2. DR RefSeq; NP_001135993.1; NM_001142521.2. DR RefSeq; NP_001299838.1; NM_001312909.1. DR RefSeq; NP_001299839.1; NM_001312910.1. DR RefSeq; NP_001299840.1; NM_001312911.1. DR RefSeq; NP_071357.2; NM_022074.3. DR RefSeq; NP_942144.1; NM_198847.2. DR AlphaFoldDB; Q96PZ2; -. DR BioGRID; 121979; 95. DR IntAct; Q96PZ2; 8. DR STRING; 9606.ENSP00000434435; -. DR MEROPS; S01.530; -. DR GlyGen; Q96PZ2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96PZ2; -. DR MetOSite; Q96PZ2; -. DR PhosphoSitePlus; Q96PZ2; -. DR SwissPalm; Q96PZ2; -. DR BioMuta; FAM111A; -. DR DMDM; 125991848; -. DR EPD; Q96PZ2; -. DR jPOST; Q96PZ2; -. DR MassIVE; Q96PZ2; -. DR MaxQB; Q96PZ2; -. DR PaxDb; Q96PZ2; -. DR PeptideAtlas; Q96PZ2; -. DR ProteomicsDB; 77794; -. DR Antibodypedia; 27720; 53 antibodies from 14 providers. DR DNASU; 63901; -. DR Ensembl; ENST00000361723.7; ENSP00000355264.3; ENSG00000166801.17. DR Ensembl; ENST00000420244.6; ENSP00000406683.1; ENSG00000166801.17. DR Ensembl; ENST00000527629.6; ENSP00000436128.2; ENSG00000166801.17. DR Ensembl; ENST00000528737.5; ENSP00000434435.1; ENSG00000166801.17. DR Ensembl; ENST00000529985.3; ENSP00000502754.2; ENSG00000166801.17. DR Ensembl; ENST00000531147.1; ENSP00000431631.1; ENSG00000166801.17. DR Ensembl; ENST00000531408.6; ENSP00000432821.2; ENSG00000166801.17. DR Ensembl; ENST00000533703.1; ENSP00000433154.1; ENSG00000166801.17. DR Ensembl; ENST00000674617.1; ENSP00000501786.1; ENSG00000166801.17. DR Ensembl; ENST00000675163.1; ENSP00000501952.1; ENSG00000166801.17. DR Ensembl; ENST00000675806.2; ENSP00000501617.2; ENSG00000166801.17. DR Ensembl; ENST00000676340.1; ENSP00000501909.1; ENSG00000166801.17. DR Ensembl; ENST00000676459.1; ENSP00000501771.1; ENSG00000166801.17. DR Ensembl; ENST00000682018.1; ENSP00000507215.1; ENSG00000166801.17. DR GeneID; 63901; -. DR KEGG; hsa:63901; -. DR MANE-Select; ENST00000675163.1; ENSP00000501952.1; NM_001312909.2; NP_001299838.1. DR UCSC; uc001nno.4; human. DR AGR; HGNC:24725; -. DR CTD; 63901; -. DR DisGeNET; 63901; -. DR GeneCards; FAM111A; -. DR GeneReviews; FAM111A; -. DR HGNC; HGNC:24725; FAM111A. DR HPA; ENSG00000166801; Low tissue specificity. DR MalaCards; FAM111A; -. DR MIM; 127000; phenotype. DR MIM; 602361; phenotype. DR MIM; 615292; gene. DR neXtProt; NX_Q96PZ2; -. DR OpenTargets; ENSG00000166801; -. DR Orphanet; 93325; Autosomal dominant Kenny-Caffey syndrome. DR Orphanet; 2763; Osteocraniostenosis. DR PharmGKB; PA143485468; -. DR VEuPathDB; HostDB:ENSG00000166801; -. DR eggNOG; KOG0866; Eukaryota. DR GeneTree; ENSGT00390000005182; -. DR HOGENOM; CLU_022719_0_0_1; -. DR InParanoid; Q96PZ2; -. DR OMA; YIHAIGK; -. DR OrthoDB; 3849333at2759; -. DR PhylomeDB; Q96PZ2; -. DR TreeFam; TF332538; -. DR PathwayCommons; Q96PZ2; -. DR SignaLink; Q96PZ2; -. DR BioGRID-ORCS; 63901; 10 hits in 1161 CRISPR screens. DR ChiTaRS; FAM111A; human. DR GenomeRNAi; 63901; -. DR Pharos; Q96PZ2; Tbio. DR PRO; PR:Q96PZ2; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q96PZ2; Protein. DR Bgee; ENSG00000166801; Expressed in monocyte and 188 other tissues. DR ExpressionAtlas; Q96PZ2; baseline and differential. DR Genevisible; Q96PZ2; HS. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0006260; P:DNA replication; IMP:UniProtKB. DR GO; GO:0045071; P:negative regulation of viral genome replication; IMP:UniProtKB. DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB. DR GO; GO:0106300; P:protein-DNA covalent cross-linking repair; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0031297; P:replication fork processing; IDA:UniProtKB. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR PANTHER; PTHR14389:SF14; SERINE PROTEASE FAM111A; 1. DR PANTHER; PTHR14389; SI:CH1073-475A24.1; 1. DR Pfam; PF13365; Trypsin_2; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. PE 1: Evidence at protein level; KW Autocatalytic cleavage; Chromosome; Cytoplasm; Disease variant; DNA damage; KW DNA repair; DNA replication; DNA-binding; Dwarfism; Host-virus interaction; KW Hydrolase; Isopeptide bond; Nucleus; Phosphoprotein; Protease; KW Reference proteome; Ubl conjugation. FT CHAIN 1..611 FT /note="Serine protease FAM111A" FT /id="PRO_0000274407" FT REGION 44..73 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 336..611 FT /note="Interaction with SV40 large T antigen" FT /evidence="ECO:0000269|PubMed:23093934" FT MOTIF 16..28 FT /note="PIP-box" FT /evidence="ECO:0000269|PubMed:24561620" FT ACT_SITE 385 FT /note="Charge relay system" FT /evidence="ECO:0000250|UniProtKB:P06681" FT ACT_SITE 439 FT /note="Charge relay system" FT /evidence="ECO:0000250|UniProtKB:P06681" FT ACT_SITE 541 FT /note="Charge relay system" FT /evidence="ECO:0000305|PubMed:32165630" FT SITE 334..335 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000305|PubMed:32165630" FT MOD_RES 26 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 20 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 30 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 65 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VARIANT 338 FT /note="T -> A (in GCLEB; dbSNP:rs587777014)" FT /evidence="ECO:0000269|PubMed:23684011" FT /id="VAR_069513" FT VARIANT 342 FT /note="Missing (in GCLEB; enhanced autocatalytic cleavage)" FT /evidence="ECO:0000269|PubMed:23684011, FT ECO:0000269|PubMed:32165630" FT /id="VAR_069514" FT VARIANT 511 FT /note="Y -> H (in KCS2; enhanced autocatalytic cleavage; FT dbSNP:rs587777012)" FT /evidence="ECO:0000269|PubMed:23684011, FT ECO:0000269|PubMed:32165630" FT /id="VAR_069515" FT VARIANT 527 FT /note="P -> T (in GCLEB; dbSNP:rs587777015)" FT /evidence="ECO:0000269|PubMed:23684011" FT /id="VAR_069516" FT VARIANT 528 FT /note="D -> G (in GCLEB; enhanced autocatalytic cleavage; FT dbSNP:rs587777013)" FT /evidence="ECO:0000269|PubMed:23684011, FT ECO:0000269|PubMed:32165630" FT /id="VAR_069517" FT VARIANT 569 FT /note="R -> H (in KCS2; enhanced autocatalytic cleavage; FT dbSNP:rs587777011)" FT /evidence="ECO:0000269|PubMed:23684011, FT ECO:0000269|PubMed:23996431, ECO:0000269|PubMed:24635597, FT ECO:0000269|PubMed:32165630" FT /id="VAR_069518" FT MUTAGEN 24..25 FT /note="YF->AA: In PIPmt; affects subcellular localization. FT Impaired PCNA stability and chromatin binding. Does not FT affect protease activity." FT /evidence="ECO:0000269|PubMed:24561620, FT ECO:0000269|PubMed:32165630" FT MUTAGEN 231 FT /note="F->A: Strongly decreased single-stranded DNA- FT binding." FT /evidence="ECO:0000269|PubMed:32165630" FT MUTAGEN 334 FT /note="F->R,G: Abolished autocatalytic cleavage." FT /evidence="ECO:0000269|PubMed:32165630" FT MUTAGEN 541 FT /note="S->A: Abolished protease activity." FT /evidence="ECO:0000269|PubMed:32165630" FT CONFLICT 97 FT /note="T -> S (in Ref. 4; AAH71759)" FT /evidence="ECO:0000305" SQ SEQUENCE 611 AA; 70196 MW; 97425E4198B809EA CRC64; MSCKKQRSRK HSVNEKCNMK IEHYFSPVSK EQQNNCSTSL MRMESRGDPR ATTNTQAQRF HSPKKNPEDQ TMPQNRTIYV TLKVNHRRNQ DMKLKLTHSE NSSLYMALNT LQAVRKEIET HQGQEMLVRG TEGIKEYINL GMPLSCFPEG GQVVITFSQS KSKQKEDNHI FGRQDKASTE CVKFYIHAIG IGKCKRRIVK CGKLHKKGRK LCVYAFKGET IKDALCKDGR FLSFLENDDW KLIENNDTIL ESTQPVDELE GRYFQVEVEK RMVPSAAASQ NPESEKRNTC VLREQIVAQY PSLKRESEKI IENFKKKMKV KNGETLFELH RTTFGKVTKN SSSIKVVKLL VRLSDSVGYL FWDSATTGYA TCFVFKGLFI LTCRHVIDSI VGDGIEPSKW ATIIGQCVRV TFGYEELKDK ETNYFFVEPW FEIHNEELDY AVLKLKENGQ QVPMELYNGI TPVPLSGLIH IIGHPYGEKK QIDACAVIPQ GQRAKKCQER VQSKKAESPE YVHMYTQRSF QKIVHNPDVI TYDTEFFFGA SGSPVFDSKG SLVAMHAAGF AYTYQNETRS IIEFGSTMES ILLDIKQRHK PWYEEVFVNQ QDVEMMSDED L //