Reviewed, UniProtKB/Swiss-Prot P48061 (SDF1_HUMAN)

Names and origin

Protein names

Recommended name:
    Stromal cell-derived factor 1
      Short name=SDF-1
Alternative name(s):
    C-X-C motif chemokine 12
    Pre-B cell growth-stimulating factor
      Short name=PBSF
      Short name=hIRH
Cleaved into the following 2 chains:
    1- Recommended name:
            SDF-1-beta(3-72)
    2- Recommended name:
            SDF-1-alpha(3-67)

Gene names

Name:	CXCL12
Synonyms:	SDF1, SDF1A, SDF1B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	93 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	Chemoattractant active on T-lymphocytes, monocytes, but not neutrophils. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites.
Subcellular location	Secreted.
Post-translational modification	Processed forms SDF-1-beta(3-72) and SDF-1-alpha(3-67) are produced after secretion by proteolytic cleavage of isoforms Beta and Alpha, respectively. The N-terminal processing is probably achieved by DPP4. Isoform Alpha is first cleaved at the C-terminus to yield a SDF-1-alpha(1-67) intermediate before being processsed at the N-terminus. The C-terminal processing of isoform Alpha is reduced by binding to heparin and, probably, cell surface proteoglycans.
Sequence similarities	Belongs to the intercrine alpha (chemokine CxC) family.

Ontologies

Keywords
Biological process	Chemotaxis
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Cytokine Growth factor
Technical term	3D-structure
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Traceable author statement. Source: ProtInc blood circulation Traceable author statement. Source: ProtInc cell adhesion Traceable author statement. Source: ProtInc cellular calcium ion homeostasis Traceable author statement. Source: ProtInc chemotaxis Traceable author statement. Source: ProtInc immune response Traceable author statement. Source: ProtInc regulation of actin polymerization and/or depolymerization Traceable author statement. Source: ProtInc response to virus Traceable author statement. Source: ProtInc
Molecular function	chemokine activity Traceable author statement. Source: ProtInc signal transducer activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Beta (identifier: P48061-1)

Also known as: SDF-1-beta(1-72);

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 Alpha (identifier: P48061-2)

Also known as: SDF-1-alpha(1-68);

The sequence of this isoform differs from the canonical sequence as follows:
     90-93: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 93

72

Stromal cell-derived factor 1

Chain

24 – 93

70

SDF-1-beta(3-72)

Chain

24 – 88

65

SDF-1-alpha(3-67)

Amino acid modifications

Disulfide bond

30 ↔ 55

Disulfide bond

32 ↔ 71

Natural variations

Alternative sequence

90 – 93

4

Missing in isoform Alpha.

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

93

Helix Strand Turn

Details...

Beta strand

25 – 28

4

Helix

41 – 43

3

Beta strand

44 – 52

9

Turn

53 – 55

3

Beta strand

56 – 63

8

Turn

64 – 66

3

Beta strand

69 – 72

4

Helix

77 – 85

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform Beta (SDF-1-beta(1-72)) [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 505B5A29C2B44E8D	FASTA	93	10,666
	10 20 30 40 50 60 MNAKVVVVLV LVLTALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV 70 80 90 ARLKNNNRQV CIDPKLKWIQ EYLEKALNKR FKM
	Isoform Alpha (SDF-1-alpha(1-68)) [UniParc]. Checksum: 62B44E8D209C3A14		89	10,103
	10 20 30 40 50 60 MNAKVVVVLV LVLTALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV 70 80 ARLKNNNRQV CIDPKLKWIQ EYLEKALNK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Spotila L.D. Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene." Shirozu M., Nakano T., Inazawa J., Tashiro K., Tada H., Shinohara T., Honjo T. Genomics 28:495-500(1995) [PubMed: 7490086] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Nucleotide sequence of hIRH, human intercrine reduced in hepatomas." Begum N.A., Barnard G.F. Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA). Tissue: Liver.
[4]	SeattleSNPs program for genomic applications Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). Tissue: Brain.
[7]	"Differential processing of stromal-derived factor-1alpha and beta explains functional diversity." De La Luz Sierra M., Yang F., Narazaki M., Salvucci O., Davis D., Yarchoan R., Zhang H.H., Fales H., Tosato G. Blood 103:2452-2459(2004) [PubMed: 14525775] [Abstract] Cited for: IDENTIFICATION OF SDF-1ALPHA(3-67) AND SDF-1BETA(3-72) BY MASS SPECTROMETRY, PROTEOLYTIC PROCESSING OF N-TERMINAL AND C-TERMINAL.
[8]	"Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1." Crump M.P., Gong J.H., Loetscher P., Rajarathnam K., Amara A., Arenzana-Seisdedos F., Virelizier J.-L., Baggiolini M., Sykes B.D., Clark-Lewis I. EMBO J. 16:6996-7007(1997) [PubMed: 9384579] [Abstract] Cited for: STRUCTURE BY NMR OF 22-88.
[9]	"Crystal structure of chemically synthesized [N33A] stromal cell-derived factor 1alpha, a potent ligand for the HIV-1 'fusin' coreceptor." Dealwis C., Fernandez E.J., Thompson D.A., Simon R.J., Siani M.A., Lolis E. Proc. Natl. Acad. Sci. U.S.A. 95:6941-6946(1998) [PubMed: 9618518] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 22-88.
+	Additional computationally mapped references.

Web resources

Wikipedia

SDF-1 entry

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

U16752 mRNA. Translation: AAA97434.1.
L36033 mRNA. Translation: AAB39332.1.
L36034 mRNA. Translation: AAB39333.1.
U19495 mRNA. Translation: AAB40516.1.
AY802782 Genomic DNA. Translation: AAV49999.1.
AL137026 Genomic DNA. Translation: CAC10203.1.
BC039893 mRNA. Translation: AAH39893.1.

PIR

G01540.

RefSeq

NP_000600.1.
NP_954637.1.

UniGene

Hs.522891

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A15	X-ray	2.20	A/B	22-88	[»]
1QG7	X-ray	2.00	A/B	22-88	[»]
1SDF	NMR	-	A	22-88	[»]
1VMC	NMR	-	A	19-89	[»]
2J7Z	X-ray	1.95	A/B	22-89	[»]
2NWG	X-ray	2.07	A/B	22-88	[»]
2SDF	NMR	-	A	22-88	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:391N.
DIP:5895N.

Genome annotation databases

Ensembl

ENSG00000107562. Homo sapiens. [Contig view]

GeneID

6387.

KEGG

hsa:6387.

Organism-specific databases

H-InvDB

HIX0008784.

HGNC

HGNC:10672. CXCL12.

HPA

CAB017564.

MIM

600835. gene.

PharmGKB

PA35602.

GenAtlas

Search...

GeneCards

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Phylogenomic databases

HOVERGEN

P48061.

Gene expression databases

ArrayExpress

P48061.

CleanEx

HS_CXCL12.

GermOnline

ENSG00000107562. Homo sapiens.

Family and domain databases

InterPro

IPR002473. C-X-C/Interlkn_8.
IPR001811. Chemokine_IL8.
IPR001089. CXC_chmkine_smll.
[Graphical view]

Pfam

PF00048. IL8. 1 hit.
[Graphical view]

PRINTS

PR00436. INTERLEUKIN8.

SMART

SM00199. SCY. 1 hit.
[Graphical view]

PROSITE

PS00471. SMALL_CYTOKINES_CXC. False negative.
[Graphical view]

ProDom

P48061.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

DrugBank

DB01234. Dexamethasone.

LinkHub

P48061.

SOURCE

Search...

ProtoNet

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Entry information

Entry name

SDF1_HUMAN

Accession

Primary (citable) accession number: P48061

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	July 22, 2008
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)