Q8NHW4 (CC4L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-C motif chemokine 4-like

Alternative name(s):
Lymphocyte activation gene 1 protein
Short name=LAG-1
Macrophage inflammatory protein 1-beta
Short name=MIP-1-beta
Monocyte adherence-induced protein 5-alpha
Small-inducible cytokine A4-like

Gene names

Name:	CCL4L1
Synonyms:	CCL4L, LAG1, SCYA4L1
AND
Name:	CCL4L2
Synonyms:	CCL4L, SCYA4L2

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	92 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Chemokine that induces chemotaxis of cells expressing CCR5 or CCR1. Inhibits HIV replication in peripheral blood monocytes that express CCR5. Ref.5
Subunit structure	Interacts with CCR5. Ref.5
Subcellular location	Secreted By similarity.
Tissue specificity	Detected in B-cells. Ref.7
Polymorphism	The copy number of the CC4L1 gene varies among individuals; most individuals have 1 to 6 copies in the diploid genome.
Sequence similarities	Belongs to the intercrine beta (chemokine CC) family.

Ontologies

Keywords
Biological process	Chemotaxis Inflammatory response
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chemotaxis Inferred from electronic annotation. Source: UniProtKB-KW immune response Inferred from electronic annotation. Source: InterPro inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 10 isoforms produced by alternative splicing. [Align] [Select]

Note: CCL4L1 and CCL4L2 genes differ in their non-coding regions. Thus, alternative splicing events differ between the two genes.

Isoform 1 (identifier: Q8NHW4-1)

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: Q8NHW4-2)

Also known as: CCL4L2;

The sequence of this isoform differs from the canonical sequence as follows:
     65-69: Missing.

Isoform 3 (identifier: Q8NHW4-3)

Also known as: CC4L2d;

The sequence of this isoform differs from the canonical sequence as follows:
     65-92: FQTKRGKQVCADPSESWVQEYVYDLELN → AAPGRIPSTRAAPHGPWSGRGRCLPQARDKAR

Isoform 4 (identifier: Q8NHW4-4)

Also known as: CC4L2f;

The sequence of this isoform differs from the canonical sequence as follows:
     65-92: FQTKRGKQVCADPSESWVQEYVYDLELN → EWKLQGVCFQCCSGKDPIHQSCPTWTMVRQRKMPTTGKG

Isoform 5 (identifier: Q8NHW4-5)

Also known as: CC4L2b1; CC4L2b2;

The sequence of this isoform differs from the canonical sequence as follows:
     65-92: Missing.

Isoform 6 (identifier: Q8NHW4-6)

Also known as: CC4L2e;

The sequence of this isoform differs from the canonical sequence as follows:
     65-92: FQTKRGKQVCADPSESWVQEYVYDLELN → AAPHGPWSGRGRCLPQARDKAR

Isoform 7 (identifier: Q8NHW4-7)

Also known as: CC4L2d2;

The sequence of this isoform differs from the canonical sequence as follows:
     26-92: MGSDPPTACC...QEYVYDLELN → KASKSALTPVSPGSRSTCMTWN

Isoform 8 (identifier: Q8NHW4-8)

Also known as: CC4L1d2;

The sequence of this isoform differs from the canonical sequence as follows:
     26-92: MGSDPPTACC...QEYVYDLELN → NSKPKEASKSALTPVSPGSRSTCMTWN

Isoform 9 (identifier: Q8NHW4-9)

Also known as: CC4L2bd2;

The sequence of this isoform differs from the canonical sequence as follows:
     26-92: MGSDPPTACC...QEYVYDLELN → TKSSEWKLQG...QRKMPTTGKG

Isoform 10 (identifier: Q8NHW4-10)

Also known as: CC44L2c;

The sequence of this isoform differs from the canonical sequence as follows:
     65-92: FQTKRGKQVCADPSESWVQEYVYDLELN → YRESASSAAPGRIPSTRAAPHGPWSGRGRCLPQARDKAR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	By similarity
	Chain	24 – 92	69	C-C motif chemokine 4-like		PRO_0000326234
Amino acid modifications
	Disulfide bond	34 ↔ 58		By similarity
	Disulfide bond	35 ↔ 74		By similarity
Natural variations
	Alternative sequence	26 – 92	67	MGSDP…DLELN → KASKSALTPVSPGSRSTCMT WN in isoform 7.		VSP_032625
	Alternative sequence	26 – 92	67	MGSDP…DLELN → NSKPKEASKSALTPVSPGSR STCMTWN in isoform 8.		VSP_032626
	Alternative sequence	26 – 92	67	MGSDP…DLELN → TKSSEWKLQGVCFQCCSGKD PIHQSCPTWTMVRQRKMPTT GKG in isoform 9.		VSP_032627
	Alternative sequence	65 – 92	28	FQTKR…DLELN → YRESASSAAPGRIPSTRAAP HGPWSGRGRCLPQARDKAR in isoform 10.		VSP_032628
	Alternative sequence	65 – 92	28	FQTKR…DLELN → AAPGRIPSTRAAPHGPWSGR GRCLPQARDKAR in isoform 3.		VSP_032629
	Alternative sequence	65 – 92	28	FQTKR…DLELN → EWKLQGVCFQCCSGKDPIHQ SCPTWTMVRQRKMPTTGKG in isoform 4.		VSP_032630
	Alternative sequence	65 – 92	28	Missing in isoform 5.		VSP_032631
	Alternative sequence	65 – 92	28	FQTKR…DLELN → AAPHGPWSGRGRCLPQARDK AR in isoform 6.		VSP_032632
	Alternative sequence	65 – 69	5	Missing in isoform 2.		VSP_032633
Experimental info
	Sequence conflict	45	1	R → H in AAH70310. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 4C8D01E926CDE882	FASTA	92	10,166
	10 20 30 40 50 60 MKLCVTVLSL LVLVAAFCSL ALSAPMGSDP PTACCFSYTA RKLPRNFVVD YYETSSLCSQ 70 80 90 PAVVFQTKRG KQVCADPSES WVQEYVYDLE LN
	Isoform 2 (CCL4L2) [UniParc]. Checksum: 8140E8AA4D95C05C	FASTA	87	9,505
	10 20 30 40 50 60 MKLCVTVLSL LVLVAAFCSL ALSAPMGSDP PTACCFSYTA RKLPRNFVVD YYETSSLCSQ 70 80 PAVVGKQVCA DPSESWVQEY VYDLELN
	Isoform 3 (CC4L2d) [UniParc]. Checksum: CA14E1C6FC2D1745	FASTA	96	10,227
	10 20 30 40 50 60 MKLCVTVLSL LVLVAAFCSL ALSAPMGSDP PTACCFSYTA RKLPRNFVVD YYETSSLCSQ 70 80 90 PAVVAAPGRI PSTRAAPHGP WSGRGRCLPQ ARDKAR
	Isoform 4 (CC4L2f) [UniParc]. Checksum: 5603FE25DE1B08E9	FASTA	103	11,286
	10 20 30 40 50 60 MKLCVTVLSL LVLVAAFCSL ALSAPMGSDP PTACCFSYTA RKLPRNFVVD YYETSSLCSQ 70 80 90 100 PAVVEWKLQG VCFQCCSGKD PIHQSCPTWT MVRQRKMPTT GKG
	Isoform 5 (CC4L2b1) (CC4L2b2) [UniParc]. Checksum: 60EA92F22897BEDF	FASTA	64	6,850
	10 20 30 40 50 60 MKLCVTVLSL LVLVAAFCSL ALSAPMGSDP PTACCFSYTA RKLPRNFVVD YYETSSLCSQ PAVV
	Isoform 6 (CC4L2e) [UniParc]. Checksum: BE0C616BBA0CBDC8	FASTA	86	9,220
	10 20 30 40 50 60 MKLCVTVLSL LVLVAAFCSL ALSAPMGSDP PTACCFSYTA RKLPRNFVVD YYETSSLCSQ 70 80 PAVVAAPHGP WSGRGRCLPQ ARDKAR
	Isoform 7 (CC4L2d2) [UniParc]. Checksum: E0D5FB87C91506C9	FASTA	47	4,855
	10 20 30 40 MKLCVTVLSL LVLVAAFCSL ALSAPKASKS ALTPVSPGSR STCMTWN
	Isoform 8 (CC4L1d2) [UniParc]. Checksum: C066A711CE38A507	FASTA	52	5,410
	10 20 30 40 50 MKLCVTVLSL LVLVAAFCSL ALSAPNSKPK EASKSALTPV SPGSRSTCMT WN
	Isoform 9 (CC4L2bd2) [UniParc]. Checksum: 384D8E62C63366CA	FASTA	68	7,403
	10 20 30 40 50 60 MKLCVTVLSL LVLVAAFCSL ALSAPTKSSE WKLQGVCFQC CSGKDPIHQS CPTWTMVRQR KMPTTGKG
	Isoform 10 (CC44L2c) [UniParc]. Checksum: DB0F566E66B545F7	FASTA	103	11,008
	10 20 30 40 50 60 MKLCVTVLSL LVLVAAFCSL ALSAPMGSDP PTACCFSYTA RKLPRNFVVD YYETSSLCSQ 70 80 90 100 PAVVYRESAS SAAPGRIPST RAAPHGPWSG RGRCLPQARD KAR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Variation in gene copy number of the human chemokines macrophage inflammatory protein-1a/CCL3 and macrophage inflammatory protein-1b/CCL4." Nibbs R.J., Barcellos L.F., Townson J.R. Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[2]	"Multiple products derived from two CCL4 loci: high incidence of a new polymorphism in HIV+ patients." Colobran R., Adreani P., Ashhab Y., Llano A., Este J.A., Dominguez O., Pujol-Borrell R., Juan M. J. Immunol. 174:5655-5664(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8; 9 AND 10).
[3]	"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] (ISOFORMS 1 AND 5). Tissue: Blood and Brain.
[4]	"The human MIP-1beta chemokine is encoded by two paralogous genes, ACT-2 and LAG-1." Modi W.S., Bergeron J., Sanford M. Immunogenetics 53:543-549(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
[5]	"Functional redundancy of the human CCL4 and CCL4L1 chemokine genes." Howard O.M.Z., Turpin J.A., Goldman R., Modi W.S. Biochem. Biophys. Res. Commun. 320:927-931(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CCR5, GENOMIC DUPLICATION.
[6]	"CCL3L1 and CCL4L1 chemokine genes are located in a segmental duplication at chromosome 17q12." Modi W.S. Genomics 83:735-738(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, GENOMIC DUPLICATION.
[7]	"Independent expression of the two paralogous CCL4 genes in monocytes and B lymphocytes." Lu J., Honczarenko M., Sloan S.R. Immunogenetics 55:706-711(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"CCL3L1 and CCL4L1: variable gene copy number in adolescents with and without human immunodeficiency virus type 1 (HIV-1) infection." Shao W., Tang J., Song W., Wang C., Li Y., Wilson C.M., Kaslow R.A. Genes Immun. 8:224-231(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, POLYMORPHISM OF GENE COPY NUMBER.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY079147 Genomic DNA. Translation: AAL87008.1. AY766460 Genomic DNA. Translation: AAX07294.1. AY766460 Genomic DNA. Translation: AAX07295.1. AY766461 Genomic DNA. Translation: AAX07296.1. AY766461 Genomic DNA. Translation: AAX07297.1. AY766461 Genomic DNA. Translation: AAX07298.1. AY766461 Genomic DNA. Translation: AAX07299.1. AY766461 Genomic DNA. Translation: AAX07300.1. AY766461 Genomic DNA. Translation: AAX07301.1. AY766461 Genomic DNA. Translation: AAX07302.1. AY766461 Genomic DNA. Translation: AAX07303.1. AY766461 Genomic DNA. Translation: AAX07304.1. AY766447 mRNA. Translation: AAX07306.1. AY766449 mRNA. Translation: AAX07308.1. AY766450 mRNA. Translation: AAX07309.1. AY766451 mRNA. Translation: AAX07310.1. AY766452 mRNA. Translation: AAX07311.1. AY766453 mRNA. Translation: AAX07312.1. AY766454 mRNA. Translation: AAX07313.1. AY766455 mRNA. Translation: AAX07314.1. AY766456 mRNA. Translation: AAX07315.1. AY766457 mRNA. Translation: AAX07316.1. AY766458 mRNA. Translation: AAX07317.1. BC070310 mRNA. Translation: AAH70310.1. BC092445 mRNA. Translation: AAH92445.1. BC130456 mRNA. Translation: AAI30457.1. BC130458 mRNA. Translation: AAI30459.1. BC144393 mRNA. Translation: AAI44394.1. BC144394 mRNA. Translation: AAI44395.1. BC171864 mRNA. Translation: AAI71864.1. BC146944 mRNA. Translation: AAI46945.1. BC146958 mRNA. Translation: AAI46959.1.
IPI	IPI00377046. IPI00604479. IPI00604648. IPI00604668. IPI00604771. IPI00745043. IPI00791533. IPI00792183. IPI00877019. IPI00887535.
PIR	C60407.
RefSeq	NP_001001435.1. NM_001001435.2. NP_996890.1. NM_207007.2.
UniGene	Hs.655293. Hs.661942.
3D structure databases
HSSP	HSSP built from PDB template 1HUM based on UniProtKB P13236.
ProteinModelPortal	Q8NHW4.
ModBase	Search...
Proteomic databases
PaxDb	Q8NHW4.
PRIDE	Q8NHW4.
Protocols and materials databases
DNASU	388372. 9560.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000339270; ENSP00000345572; ENSG00000197262. ENST00000378350; ENSP00000367601; ENSG00000205020. ENST00000389068; ENSP00000373720; ENSG00000205020. ENST00000394463; ENSP00000377976; ENSG00000197262. ENST00000394465; ENSP00000377978; ENSG00000197262. ENST00000400702; ENSP00000383538; ENSG00000205020. ENST00000444414; ENSP00000405533; ENSG00000205020. ENST00000482104; ENSP00000466965; ENSG00000197262. ENST00000562236; ENSP00000456735; ENSG00000260717. ENST00000563132; ENSP00000458095; ENSG00000260717. ENST00000563802; ENSP00000455820; ENSG00000260717. ENST00000564234; ENSP00000456123; ENSG00000260717. ENST00000567608; ENSP00000455148; ENSG00000260717. ENST00000567807; ENSP00000456156; ENSG00000260717. ENST00000567858; ENSP00000454525; ENSG00000260717. ENST00000569856; ENSP00000456951; ENSG00000260717. ENST00000586598; ENSP00000467658; ENSG00000205020. ENST00000588929; ENSP00000465568; ENSG00000205020. ENST00000589079; ENSP00000466720; ENSG00000205020. ENST00000589336; ENSP00000467722; ENSG00000205020. ENST00000591167; ENSP00000467085; ENSG00000205020. ENST00000591637; ENSP00000468405; ENSG00000205020.
GeneID	388372. 9560.
KEGG	hsa:388372. hsa:9560.
UCSC	uc002hlj.1. human. uc002hlw.3. human.
Organism-specific databases
CTD	388372. 9560.
GeneCards	GC17P034538. GC17P034639.
HGNC	HGNC:10631. CCL4L1. HGNC:24066. CCL4L2.
MIM	603782. gene. 610757. gene.
neXtProt	NX_Q8NHW4.
PharmGKB	PA35563.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG124416.
HOVERGEN	HBG017871.
KO	K12964.
OMA	LMAAFCS.
OrthoDB	EOG42Z4RR.
PhylomeDB	Q8NHW4.
Gene expression databases
ArrayExpress	Q8NHW4.
Bgee	Q8NHW4.
CleanEx	HS_CCL4L1.
Genevestigator	Q8NHW4.
Family and domain databases
InterPro	IPR000827. Chemokine_CC_CS. IPR001811. Chemokine_IL8-like_dom. [Graphical view]
Pfam	PF00048. IL8. 1 hit. [Graphical view]
SMART	SM00199. SCY. 1 hit. [Graphical view]
SUPFAM	SSF54117. Chemokine_IL8. 1 hit.
PROSITE	PS00472. SMALL_CYTOKINES_CC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	102005.
SOURCE	Search...

Entry information

Entry name

CC4L_HUMAN

Accession

Primary (citable) accession number: Q8NHW4
Secondary accession number(s): B2RUZ3 , B7ZMA8, Q50EM1, Q50EM2, Q50EM3, Q50EM4, Q50EM5, Q50EM6, Q50EM7, Q50EM8, Q569J2, Q6NSB0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 86 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.