CL3L1_HUMAN
ID CL3L1_HUMAN Reviewed; 93 AA.
AC P16619; A6NGK6; B2RUX4; Q3B7A8; Q53YA5; Q96I68;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=C-C motif chemokine 3-like 1;
DE AltName: Full=G0/G1 switch regulatory protein 19-2;
DE AltName: Full=LD78-beta(1-70);
DE AltName: Full=PAT 464.2;
DE AltName: Full=Small-inducible cytokine A3-like 1;
DE AltName: Full=Tonsillar lymphocyte LD78 beta protein;
DE Contains:
DE RecName: Full=LD78-beta(3-70);
DE Contains:
DE RecName: Full=LD78-beta(5-70);
DE Flags: Precursor;
GN Name=CCL3L1; Synonyms=D17S1718, G0S19-2, SCYA3L1;
GN and
GN Name=CCL3L3;
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 [MRNA].
RC TISSUE=T-cell;
RX PubMed=1972563; DOI=10.1093/nar/18.11.3261;
RA Irving S.G., Zipfel P.F., Balke J., McBride O.W., Morton C.C., Burd P.R.,
RA Siebenlist U., Kelly K.;
RT "Two inflammatory mediator cytokine genes are closely linked and variably
RT amplified on chromosome 17q.";
RL Nucleic Acids Res. 18:3261-3270(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2271120; DOI=10.1089/dna.1990.9.589;
RA Blum S., Forsdyke R.E., Forsdyke D.R.;
RT "Three human homologs of a murine gene encoding an inhibitor of stem cell
RT proliferation.";
RL DNA Cell Biol. 9:589-602(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1694014; DOI=10.1128/mcb.10.7.3646-3658.1990;
RA Nakao M., Nomiyama H., Shimada K.;
RT "Structures of human genes coding for cytokine LD78 and their expression.";
RL Mol. Cell. Biol. 10:3646-3658(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell, Brain, Pancreas, and Spleen;
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 [6]
RP PROTEIN SEQUENCE OF 24-38.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP IDENTIFICATION OF LD78-BETA(3-70) AND LD78-BETA(5-70), PROTEOLYTIC
RP PROCESSING OF N-TERMINAL, AND FUNCTION.
RX PubMed=10961862;
RA Proost P., Menten P., Struyf S., Schutyser E., De Meester I., Van Damme J.;
RT "Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78beta
RT into a most efficient monocyte attractant and CCR1 agonist.";
RL Blood 96:1674-1680(2000).
RN [8]
RP FUNCTION.
RX PubMed=11449371;
RX DOI=10.1002/1521-4141(200107)31:7<2170::aid-immu2170>3.0.co;2-d;
RA Struyf S., Menten P., Lenaerts J.-P., Put W., D'Haese A., De Clercq E.,
RA Schols D., Proost P., Van Damme J.;
RT "Diverging binding capacities of natural LD78beta isoforms of macrophage
RT inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect
RT their anti-HIV-1 activity and chemotactic potencies for neutrophils and
RT eosinophils.";
RL Eur. J. Immunol. 31:2170-2178(2001).
RN [9]
RP POLYMORPHISM OF GENE COPY NUMBER.
RX PubMed=17330138; DOI=10.1038/sj.gene.6364378;
RA Shao W., Tang J., Song W., Wang C., Li Y., Wilson C.M., Kaslow R.A.;
RT "CCL3L1 and CCL4L1: variable gene copy number in adolescents with and
RT without human immunodeficiency virus type 1 (HIV-1) infection.";
RL Genes Immun. 8:224-231(2007).
CC -!- FUNCTION: Chemotactic for lymphocytes and monocytes. Is a ligand for
CC CCR1, CCR3 and CCR5. Is an inhibitor of HIV-1-infection. The processed
CC form LD78-beta(3-70) shows a 20-fold to 30-fold higher chemotactic
CC activity and is a very potent inhibitor of HIV-1-infection. LD78-
CC beta(3-70) is also a ligand for CCR1, CCR3 and CCR5.
CC {ECO:0000269|PubMed:10961862, ECO:0000269|PubMed:11449371}.
CC -!- INTERACTION:
CC P16619; Q99735: MGST2; NbExp=3; IntAct=EBI-12934095, EBI-11324706;
CC P16619; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-12934095, EBI-744081;
CC P16619; Q96GZ6: SLC41A3; NbExp=3; IntAct=EBI-12934095, EBI-7225508;
CC P16619; Q7Z7N9: TMEM179B; NbExp=3; IntAct=EBI-12934095, EBI-11724423;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: The N-terminal processed forms LD78-beta(3-70) and LD78-beta(5-70)
CC are produced by proteolytic cleavage after secretion from peripheral
CC blood monocytes. The cleavage to yield LD78-beta(3-70) is probably
CC achieved by DPP4. {ECO:0000269|PubMed:10961862}.
CC -!- POLYMORPHISM: The copy number of the CCL3L1 gene varies among
CC individuals; most individuals have 1-6 copies in the diploid genome,
CC although rare individuals have zero or more than 6 copies.
CC {ECO:0000269|PubMed:17330138}.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
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DR EMBL; X52149; CAA36397.1; -; mRNA.
DR EMBL; M24110; AAA35859.1; -; Genomic_DNA.
DR EMBL; D90145; BAA14173.1; -; Genomic_DNA.
DR EMBL; BT006783; AAP35429.1; -; mRNA.
DR EMBL; BC007783; AAH07783.1; -; mRNA.
DR EMBL; BC027888; AAH27888.1; -; mRNA.
DR EMBL; BC107710; AAI07711.1; -; mRNA.
DR EMBL; BC146914; AAI46915.1; -; mRNA.
DR EMBL; BC146919; AAI46920.1; -; mRNA.
DR EMBL; BC147008; AAI47009.1; -; mRNA.
DR EMBL; BC147013; AAI47014.1; -; mRNA.
DR CCDS; CCDS32626.1; -.
DR PIR; B35673; B35673.
DR RefSeq; NP_001001437.2; NM_001001437.3.
DR RefSeq; NP_066286.1; NM_021006.5.
DR AlphaFoldDB; P16619; -.
DR SMR; P16619; -.
DR BioGRID; 112253; 75.
DR BioGRID; 135929; 4.
DR IntAct; P16619; 4.
DR STRING; 9606.ENSP00000480558; -.
DR BioMuta; CCL3L1; -.
DR DMDM; 127077; -.
DR MassIVE; P16619; -.
DR PaxDb; P16619; -.
DR PeptideAtlas; P16619; -.
DR PRIDE; P16619; -.
DR ProteomicsDB; 53390; -.
DR Antibodypedia; 72761; 203 antibodies from 20 providers.
DR DNASU; 6349; -.
DR Ensembl; ENST00000612067.2; ENSP00000484704.1; ENSG00000277796.2.
DR Ensembl; ENST00000615140.2; ENSP00000480051.1; ENSG00000277768.2.
DR Ensembl; ENST00000619989.1; ENSP00000480558.1; ENSG00000276085.1.
DR Ensembl; ENST00000621940.2; ENSP00000482487.1; ENSG00000277336.2.
DR GeneID; 414062; -.
DR GeneID; 6349; -.
DR KEGG; hsa:414062; -.
DR KEGG; hsa:6349; -.
DR MANE-Select; ENST00000619989.1; ENSP00000480558.1; NM_001001437.4; NP_001001437.2.
DR UCSC; uc002hlf.4; human.
DR CTD; 414062; -.
DR CTD; 6349; -.
DR DisGeNET; 414062; -.
DR DisGeNET; 6349; -.
DR GeneCards; CCL3L1; -.
DR GeneCards; CCL3L3; -.
DR HGNC; HGNC:10628; CCL3L1.
DR HGNC; HGNC:30554; CCL3L3.
DR HPA; ENSG00000276085; Group enriched (bone marrow, lung, lymphoid tissue).
DR MalaCards; CCL3L1; -.
DR MIM; 601395; gene.
DR MIM; 609468; gene.
DR neXtProt; NX_P16619; -.
DR OpenTargets; ENSG00000276085; -.
DR PharmGKB; PA35560; -.
DR VEuPathDB; HostDB:ENSG00000276085; -.
DR eggNOG; ENOG502SAF0; Eukaryota.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_4_0_1; -.
DR InParanoid; P16619; -.
DR OMA; MKTSQRC; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; P16619; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; P16619; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR SignaLink; P16619; -.
DR BioGRID-ORCS; 414062; 6 hits in 581 CRISPR screens.
DR BioGRID-ORCS; 6349; 6 hits in 183 CRISPR screens.
DR GeneWiki; CCL3L1; -.
DR Pharos; P16619; Tbio.
DR PRO; PR:P16619; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P16619; protein.
DR Bgee; ENSG00000276085; Expressed in bone marrow and 100 other tissues.
DR Genevisible; P16619; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR GO; GO:0008009; F:chemokine activity; IBA:GO_Central.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IBA:GO_Central.
DR GO; GO:0071347; P:cellular response to interleukin-1; IBA:GO_Central.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0048247; P:lymphocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0002548; P:monocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR InterPro; IPR039809; Chemokine_b/g/d.
DR InterPro; IPR000827; Chemokine_CC_CS.
DR InterPro; IPR001811; Chemokine_IL8-like_dom.
DR InterPro; IPR036048; Interleukin_8-like_sf.
DR PANTHER; PTHR12015; PTHR12015; 1.
DR Pfam; PF00048; IL8; 1.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; SSF54117; 1.
DR PROSITE; PS00472; SMALL_CYTOKINES_CC; 1.
PE 1: Evidence at protein level;
KW Chemotaxis; Cytokine; Direct protein sequencing; Disulfide bond;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 24..93
FT /note="C-C motif chemokine 3-like 1"
FT /id="PRO_0000005161"
FT CHAIN 26..93
FT /note="LD78-beta(3-70)"
FT /id="PRO_0000005162"
FT CHAIN 28..93
FT /note="LD78-beta(5-70)"
FT /id="PRO_0000005163"
FT SITE 25..26
FT /note="Cleavage; by DPP4"
FT /evidence="ECO:0000305"
FT DISULFID 34..58
FT /evidence="ECO:0000250"
FT DISULFID 35..74
FT /evidence="ECO:0000250"
FT CONFLICT 91
FT /note="L -> P (in Ref. 4; AAP35429 and 5; AAH07783)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 93 AA; 10161 MW; A7A79E774006D61E CRC64;
MQVSTAALAV LLCTMALCNQ VLSAPLAADT PTACCFSYTS RQIPQNFIAD YFETSSQCSK
PSVIFLTKRG RQVCADPSEE WVQKYVSDLE LSA
