P48061 (SDF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Stromal cell-derived factor 1
Short name=SDF-1
Short name=hSDF-1

Alternative name(s):
C-X-C motif chemokine 12
Intercrine reduced in hepatomas
Short name=IRH
Short name=hIRH
Pre-B cell growth-stimulating factor
Short name=PBSF

Cleaved into the following 2 chains:

1. SDF-1-beta(3-72)
2. SDF-1-alpha(3-67)

Gene names

Name:	CXCL12
Synonyms:	SDF1, SDF1A, SDF1B

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	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. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to another C-X-C chemokine receptor CXCR7, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. 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. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and CXCR7, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of CXCR7 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Ref.13 Ref.16 Ref.17 Ref.19 Ref.22 Ref.23
Subunit structure	Monomer or homodimer; in equilibrium. Dimer formation is induced by non acidic pH and the presence of multivalent anions, and by binding to CXCR4 or heparin. Monomeric form is required for full chemotactic activity and resistance to ischemia/reperfusion injury, whereas the dimeric form acts as a partial agonist of CXCR4, stimulating Ca2+ mobilization but with no chemotactic activity and instead acts as a selective antagonist that blocks chemotaxis induced by the monomeric form. Interacts with the N-terminus of CXCR7. Ref.14 Ref.15 Ref.19 Ref.20 Ref.21 Ref.23 Ref.30 Ref.31 Ref.33
Subcellular location	Secreted.
Tissue specificity	Isoform Alpha and isoform Beta are ubiquitously expressed, with highest levels detected in liver, pancreas and spleen. Isoform Gamma is mainly expressed in heart, with weak expression detected in several other tissues. Isoform Delta, isoform Epsilon and isoform Theta have highest expression levels in pancreas, with lower levels detected in heart, kidney, liver and spleen. Ref.2
Developmental stage	Isoform Alpha is ubiquitously expressed in fetal tissues. Isoform Beta and isoform Delta have more limited expression patterns, with highest levels detected in fetal spleen and fetal liver, respectively. Isoform Gamma and isoform Theta are weakly detected in fetal kidney. Ref.2
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 processed at the N-terminus. The C-terminal processing of isoform Alpha is reduced by binding to heparin and, probably, cell surface proteoglycans. Ref.18
Sequence similarities	Belongs to the intercrine alpha (chemokine CxC) family.
Mass spectrometry	Isoform Alpha: Molecular mass is 7959 Da from positions 22 - 89. Determined by ESI. Ref.18 Isoform Alpha: Molecular mass is 7606 Da from positions 24 - 88. Determined by ESI. Ref.18 Isoform Beta: Molecular mass is 8522 Da from positions 22 - 93. Determined by ESI. Ref.18 Isoform Beta: Molecular mass is 8297 Da from positions 24 - 93. Determined by ESI. Ref.18
Sequence caution	The sequence CAC10202.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Chemotaxis
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Traceable author statement PubMed 8752280. Source: ProtInc T cell proliferation Inferred from electronic annotation. Source: Compara ameboidal cell migration Inferred from electronic annotation. Source: Compara blood circulation Traceable author statement PubMed 10772939. Source: ProtInc brain development Inferred from electronic annotation. Source: Compara cell adhesion Traceable author statement PubMed 10198043. Source: ProtInc cellular calcium ion homeostasis Traceable author statement PubMed 10772939. Source: ProtInc chemokine-mediated signaling pathway Inferred from direct assay PubMed 20388803. Source: BHF-UCL chemotaxis Traceable author statement PubMed 10620615. Source: ProtInc germ cell development Inferred from electronic annotation. Source: Compara germ cell migration Inferred from electronic annotation. Source: Compara immune response Traceable author statement PubMed 10802710. Source: ProtInc induction of positive chemotaxis Inferred from electronic annotation. Source: Compara motor neuron axon guidance Inferred from electronic annotation. Source: Compara negative regulation of leukocyte apoptotic process Inferred from direct assay PubMed 15059845. Source: BHF-UCL patterning of blood vessels Inferred from electronic annotation. Source: Compara positive regulation of monocyte chemotaxis Inferred from direct assay Ref.22. Source: UniProtKB regulation of actin polymerization or depolymerization Traceable author statement PubMed 10570282. Source: ProtInc response to virus Traceable author statement PubMed 10772939. Source: ProtInc
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	CXCR chemokine receptor binding Inferred from direct assay PubMed 20388803. Source: BHF-UCL chemokine activity Traceable author statement PubMed 10772939. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform Beta (identifier: P48061-1)

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

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); hSDF-1alpha;

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

Isoform Gamma (identifier: P48061-3)

Also known as: hSDF-1gamma; SDF-1g;

The sequence of this isoform differs from the canonical sequence as follows:
     90-93: RFKM → GRREEKVGKKEKIGKKKRQKKRKAAQKRKN

Isoform Delta (identifier: P48061-4)

Also known as: hSDF-1delta;

The sequence of this isoform differs from the canonical sequence as follows:
     89-93: KRFKM → NLISAAPAGKRVIAGARALHPSPPRACPTARALCEIRLWPPPEWSWPSPGDV

Isoform Epsilon (identifier: P48061-5)

Also known as: hSDFepsilon;

The sequence of this isoform differs from the canonical sequence as follows:
     89-93: KRFKM → NC

Isoform Theta (identifier: P48061-6)

Also known as: hSDFphi; hSDFtheta; Phi;

The sequence of this isoform differs from the canonical sequence as follows:
     90-93: RFKM → IWLYGNAETSR

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 93

72

Stromal cell-derived factor 1

PRO_0000005109

Chain

24 – 93

70

SDF-1-beta(3-72)

PRO_0000005110

Chain

24 – 88

65

SDF-1-alpha(3-67)

PRO_0000005111

Regions

Region

29 – 33

5

Receptor and heparin binding Probable

Region

39 – 41

3

Receptor binding

Region

41 – 51

11

Heparin binding

Region

48 – 50

3

Receptor binding

Region

60 – 70

11

Receptor binding

Motif

22 – 23

2

Receptor activation motif

Sites

Binding site

62

1

Heparin

Binding site

69

1

Heparin

Binding site

85

1

Heparin

Site

46

1

Important for dimer formation

Amino acid modifications

Disulfide bond

30 ↔ 55

Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32

Disulfide bond

32 ↔ 71

Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32

Natural variations

Alternative sequence

89 – 93

5

KRFKM → NLISAAPAGKRVIAGARALH PSPPRACPTARALCEIRLWP PPEWSWPSPGDV in isoform Delta.

VSP_042118

Alternative sequence

89 – 93

5

KRFKM → NC in isoform Epsilon.

VSP_042119

Alternative sequence

90 – 93

4

Missing in isoform Alpha.

VSP_001056

Alternative sequence

90 – 93

4

RFKM → GRREEKVGKKEKIGKKKRQK KRKAAQKRKN in isoform Gamma.

VSP_041209

Alternative sequence

90 – 93

4

RFKM → IWLYGNAETSR in isoform Theta.

VSP_042120

Experimental info

Mutagenesis

22 – 23

2

Missing: Abolished CXCR4 activation ability, but only slightly impaired binding to the receptor. Ref.24 Ref.29

Mutagenesis

22

1

K → A: Loss of chemotactic activity. Ref.24 Ref.29

Mutagenesis

22

1

K → R: Abolished CXCR4 activation ability, but only slightly impaired binding to the receptor. Ref.24 Ref.29

Mutagenesis

22

1

Missing: Abolished CXCR4 activation ability, but only slightly impaired binding to the receptor. Ref.24 Ref.29

Mutagenesis

23

1

P → G: Abolished CXCR4 activation ability, but only slightly impaired binding to the receptor. Ref.24

Mutagenesis

25 – 27

3

SLS → AQA: Significantly impaired CXCR4 activation ability, but only slightly impaired binding to the receptor. Ref.24

Mutagenesis

28

1

Y → A: Impaired CXCR4 activation ability, but only slightly impaired binding to the receptor. Ref.24

Mutagenesis

28

1

Y → H: No significant effect on CXCR4 binding or activation. Ref.24

Mutagenesis

29

1

R → K: Slightly impaired binding and activation of CXCR4. Ref.24 Ref.28

Mutagenesis

29

1

R → Q: Greatly impaired chemotactic activity and enhanced inhibition by heparin. Ref.24 Ref.28

Mutagenesis

33 – 38

6

RFFESH → AAAAAA: Significantly decreased chemotactic activity. Ref.26 Ref.28

Mutagenesis

33

1

R → A: Significantly decreased anti-HIV-1 and chemotactic activities. Ref.26 Ref.28

Mutagenesis

33

1

R → Q: Slightly impaired chemotactic activity and enhanced inhibition by heparin. Greatly impaired chemotactic activity; when associated with Q-29. Ref.26 Ref.28

Mutagenesis

34

1

F → A: No effect on anti-HIV-1 and chemotactic activities. Slightly impaired chemotactic activity and no effect on inhibition by heparin; when associated with A-35. Ref.26

Mutagenesis

35

1

F → A: No effect on anti-HIV-1 and chemotactic activities. Slightly impaired chemotactic activity and no effect on inhibition by heparin; when associated with A-34. Ref.26

Mutagenesis

36 – 38

3

ESH → QSN: Slightly impaired chemotactic activity, no effect on inhibition by heparin. Ref.26 Ref.28

Mutagenesis

36

1

E → A: No effect on anti-HIV-1 and chemotactic activities. Ref.26

Mutagenesis

37

1

S → A: No effect on anti-HIV-1 and chemotactic activities. Ref.26

Mutagenesis

38

1

H → A: No effect on anti-HIV-1 and chemotactic activities. Ref.26

Mutagenesis

41

1

R → A: No effect on CXCR4 activation. Ref.30

Mutagenesis

45 – 48

4

KHLK → SSLS: Loss of heparin-binding capacity. Ref.15 Ref.28 Ref.30

Mutagenesis

46

1

H → A: Reduced dimerization in neutral pH. Eliminates the pH dependence of dimerization. Ref.20 Ref.28 Ref.30

Mutagenesis

46

1

H → L: No significant effect on dimerization in neutral pH. Eliminates the pH dependence of dimerization. Ref.20 Ref.28 Ref.30

Mutagenesis

46

1

H → N: Slightly impaired CXCR4 activation and clear resistance to inhibition by heparin; when associated with Q-48; Q-62; Q-68 and N-69. Ref.20 Ref.28 Ref.30

Mutagenesis

46

1

H → R: No effect on CXCR4 activation. Impaired dimer formation, leading to increased chemotactic activity. Eliminates the pH dependence of dimerization. Ref.20 Ref.28 Ref.30

Mutagenesis

48

1

K → A: Impaired CXCR4 activation. Ref.28 Ref.30

Mutagenesis

48

1

K → E: Impaired CXCR4 activation. Ref.28 Ref.30

Mutagenesis

48

1

K → Q: Slightly impaired CXCR4 activation and clear resistance to inhibition by heparin; when associated with N-46; Q-62; Q-68 and N-69. Ref.28 Ref.30

Mutagenesis

52 – 56

5

TPNCA → GPGCG: Slightly impaired chemotactic activity, no effect on inhibition by heparin. Ref.28

Mutagenesis

57

1

L → C: Formation of an intermolecular disulfide bond, leading to a locked dimer; when associated with C-86. No effect on CXCR4 activation, but loss of chemotactic activity; when associated with C-86.

Mutagenesis

60

1

V → A: Impaired CXCR4 activation. Ref.30

Mutagenesis

62

1

R → A: No effect on CXCR4 activation. Ref.28 Ref.30

Mutagenesis

62

1

R → Q: Slightly impaired CXCR4 activation and clear resistance to inhibition by heparin; when associated with N-46; Q-48; Q-68 and N-69. Ref.28 Ref.30

Mutagenesis

68

1

R → A: Impaired CXCR4 activation. Ref.28 Ref.30

Mutagenesis

68

1

R → E: Greatly impaired CXCR4 activation. Ref.28 Ref.30

Mutagenesis

68

1

R → Q: Slightly impaired CXCR4 activation and clear resistance to inhibition by heparin; when associated with N-46; Q-48; Q-62 and N-69. Ref.28 Ref.30

Mutagenesis

69

1

Q → N: Slightly impaired CXCR4 activation and clear resistance to inhibition by heparin; when associated with N-46; Q-48; Q-62 and Q-68. Ref.28

Mutagenesis

70

1

V → A: Impaired CXCR4 activation. Ref.30

Mutagenesis

81

1

E → A: No effect on CXCR4 activation. Ref.30

Mutagenesis

84

1

E → A: No effect on CXCR4 activation. Ref.30

Mutagenesis

85

1

K → A: No effect on CXCR4 activation. Ref.30

Mutagenesis

86

1

A → C: Formation of an intermolecular disulfide bond, leading to a locked dimer; when associated with C-57. No effect on CXCR4 activation, but loss of chemotactic activity; when associated with C-57.

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

93

Helix Strand Turn

Details...

Turn

24 – 26

3

Beta strand

27 – 29

3

Beta strand

31 – 34

4

Beta strand

36 – 38

3

Helix

41 – 43

3

Beta strand

44 – 49

6

Turn

53 – 55

3

Beta strand

59 – 63

5

Turn

64 – 66

3

Beta strand

69 – 72

4

Helix

79 – 86

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform Beta (SDF-1-beta(1-72)) (hSDF-1beta) [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)) (hSDF-1alpha) [UniParc]. Checksum: 62B44E8D209C3A14	FASTA	89	10,103
	10 20 30 40 50 60 MNAKVVVVLV LVLTALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV 70 80 ARLKNNNRQV CIDPKLKWIQ EYLEKALNK
	Isoform Gamma (hSDF-1gamma) (SDF-1g) [UniParc]. Checksum: C36297D68341B824	FASTA	119	13,705
	10 20 30 40 50 60 MNAKVVVVLV LVLTALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV 70 80 90 100 110 ARLKNNNRQV CIDPKLKWIQ EYLEKALNKG RREEKVGKKE KIGKKKRQKK RKAAQKRKN
	Isoform Delta (hSDF-1delta) [UniParc]. Checksum: 602BFEB309014ED2	FASTA	140	15,495
	10 20 30 40 50 60 MNAKVVVVLV LVLTALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV 70 80 90 100 110 120 ARLKNNNRQV CIDPKLKWIQ EYLEKALNNL ISAAPAGKRV IAGARALHPS PPRACPTARA 130 140 LCEIRLWPPP EWSWPSPGDV
	Isoform Epsilon (hSDFepsilon) [UniParc]. Checksum: 7375C44E8D209C3A	FASTA	90	10,192
	10 20 30 40 50 60 MNAKVVVVLV LVLTALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV 70 80 90 ARLKNNNRQV CIDPKLKWIQ EYLEKALNNC
	Isoform Theta (hSDFphi) (hSDFtheta) (Phi) [UniParc]. Checksum: BEF2739B8E70BAAD	FASTA	100	11,395
	10 20 30 40 50 60 MNAKVVVVLV LVLTALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV 70 80 90 100 ARLKNNNRQV CIDPKLKWIQ EYLEKALNKI WLYGNAETSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
[2]	"Identification and expression of novel isoforms of human stromal cell-derived factor 1." Yu L., Cecil J., Peng S.B., Schrementi J., Kovacevic S., Paul D., Su E.W., Wang J. Gene 374:174-179(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GAMMA; DELTA; EPSILON AND THETA), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, ALTERNATIVE SPLICING. Tissue: Fetal brain, Fetal heart and Heart.
[3]	Spotila L.D. Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA). Tissue: Fibroblast.
[4]	"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.
[5]	"Inhibition of X4 and R5 HIV-1 by human SDF-1g, a novel chemokine that interferes with HIV transcription." Callebaut C., Verdin E. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GAMMA).
[6]	"Polymorphism study of cell-derived factor 1 (SDF1) gene and their correlation with HIV infection in a Chinese cohort." Zhao X., Zhang H., Lee S., Wong K., Zheng B. Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
[7]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA AND BETA). Tissue: Thymus and Uterus.
[9]	SeattleSNPs variation discovery resource Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"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] (ISOFORM ALPHA). Tissue: Brain.
[13]	"The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1." Oberlin E., Amara A., Bachelerie F., Bessia C., Virelizier J.-L., Arenzana-Seisdedos F., Schwartz O., Heard J.-M., Clark-Lewis I., Legler D.F., Loetscher M., Baggiolini M., Moser B. Nature 382:833-835(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor." Donzella G.A., Schols D., Lin S.W., Este J.A., Nagashima K.A., Maddon P.J., Allaway G.P., Sakmar T.P., Henson G., De Clercq E., Moore J.P. Nat. Med. 4:72-77(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CXCR4.
[15]	"Stromal cell-derived factor-1alpha associates with heparan sulfates through the first beta-strand of the chemokine." Amara A., Lorthioir O., Valenzuela A., Magerus A., Thelen M., Montes M., Virelizier J.L., Delepierre M., Baleux F., Lortat-Jacob H., Arenzana-Seisdedos F. J. Biol. Chem. 274:23916-23925(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HEPARAN SULFATE, MUTAGENESIS OF 45-LYS--LYS-48.
[16]	"Characterization of a Xenopus laevis CXC chemokine receptor 4: implications for hematopoietic cell development in the vertebrate embryo." Moepps B., Braun M., Knoepfle K., Dillinger K., Knoechel W., Gierschik P. Eur. J. Immunol. 30:2924-2934(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[17]	"Xenopus laevis stromal cell-derived factor 1: conservation of structure and function during vertebrate development." Braun M., Wunderlin M., Spieth K., Knoechel W., Gierschik P., Moepps B. J. Immunol. 168:2340-2347(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[18]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF SDF-1ALPHA(3-67) AND SDF-1BETA(3-72) BY MASS SPECTROMETRY, PROTEOLYTIC PROCESSING OF N-TERMINUS AND C-TERMINUS.
[19]	"The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes." Balabanian K., Lagane B., Infantino S., Chow K.Y., Harriague J., Moepps B., Arenzana-Seisdedos F., Thelen M., Bachelerie F. J. Biol. Chem. 280:35760-35766(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CXCR7.
[20]	"The monomer-dimer equilibrium of stromal cell-derived factor-1 (CXCL 12) is altered by pH, phosphate, sulfate, and heparin." Veldkamp C.T., Peterson F.C., Pelzek A.J., Volkman B.F. Protein Sci. 14:1071-1081(2005) [PubMed] [Europe PMC] [Abstract] Cited for: DIMERIZATION, MUTAGENESIS OF HIS-46.
[21]	"Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12)." Veldkamp C.T., Seibert C., Peterson F.C., Sakmar T.P., Volkman B.F. J. Mol. Biol. 359:1400-1409(2006) [PubMed] [Europe PMC] [Abstract] Cited for: DIMERIZATION, INTERACTION WITH CXCR4.
[22]	"Monocyte migration and LFA-1-mediated attachment to brain microvascular endothelia is regulated by SDF-1 alpha through Lyn kinase." Malik M., Chen Y.-Y., Kienzle M.F., Tomkowicz B.E., Collman R.G., Ptasznik A. J. Immunol. 181:4632-4637(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[23]	"AMD3100 is a CXCR7 ligand with allosteric agonist properties." Kalatskaya I., Berchiche Y.A., Gravel S., Limberg B.J., Rosenbaum J.S., Heveker N. Mol. Pharmacol. 75:1240-1247(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CXCR7.
[24]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 22-88, DISULFIDE BONDS, MUTAGENESIS OF LYS-22; PRO-23; 22-LYS-PRO-23; 25-SER--SER-27; TYR-28 AND ARG-29.
[25]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 22-88 OF MUTANT ALA-54, DISULFIDE BONDS.
[26]	"Crystal structure of recombinant native SDF-1alpha with additional mutagenesis studies: an attempt at a more comprehensive interpretation of accumulated structure-activity relationship data." Ohnishi Y., Senda T., Nandhagopal N., Sugimoto K., Shioda T., Nagal Y., Mitsui Y. J. Interferon Cytokine Res. 20:691-700(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 22-88, DISULFIDE BONDS, MUTAGENESIS OF ARG-33; PHE-34; PHE-35; GLU-36; SER-37; HIS-38 AND 33-ARG--HIS-38.
[27]	"Mapping the binding of the N-terminal extracellular tail of the CXCR4 receptor to stromal cell-derived factor-1alpha." Gozansky E.K., Louis J.M., Caffrey M., Clore G.M. J. Mol. Biol. 345:651-658(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 22-89, DISULFIDE BONDS.
[28]	"Structural and functional basis of CXCL12 (stromal cell-derived factor-1 alpha) binding to heparin." Murphy J.W., Cho Y., Sachpatzidis A., Fan C., Hodsdon M.E., Lolis E. J. Biol. Chem. 282:10018-10027(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 22-88 IN COMPLEX WITH HEPARIN DISACCHARIDE I-S, DISULFIDE BONDS, MUTAGENESIS OF ARG-29; ARG-33; 34-PHE-PHE-35; 36-GLU--HIS-38; HIS-46; LYS-48; 52-THR--ALA-56; ARG-62; ARG-68 AND GLN-69.
[29]	"Crystal structure of recombinant human stromal cell-derived factor-1alpha." Ryu E.K., Kim T.G., Kwon T.H., Jung I.D., Ryu D., Park Y.M., Kim J., Ahn K.H., Ban C. Proteins 67:1193-1197(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 22-89, DISULFIDE BONDS, MUTAGENESIS OF LYS-22.
[30]	"Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12." Veldkamp C.T., Seibert C., Peterson F.C., De la Cruz N.B., Haugner J.C. III, Basnet H., Sakmar T.P., Volkman B.F. Sci. Signal. 1:RA4-RA4(2008) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 22-89 OF MUTANT CYS-57 AND CYS-86 IN COMPLEX WITH CXCR4 FRAGMENT, SUBUNIT, DIMERIZATION, DISULFIDE BONDS, MUTAGENESIS OF ARG-41; HIS-46; LYS-48; VAL-60; ARG-62; ARG-68; VAL-70; GLU-81; GLU-84 AND LYS-85.
[31]	"Monomeric structure of the cardioprotective chemokine SDF-1/CXCL12." Veldkamp C.T., Ziarek J.J., Su J., Basnet H., Lennertz R., Weiner J.J., Peterson F.C., Baker J.E., Volkman B.F. Protein Sci. 18:1359-1369(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 22-89, ASSAY ON RAT ISCHEMIA/REPERFUSION MODEL, DIMERIZATION, DISULFIDE BONDS.
[32]	"Solution structure of human SDF1-alpha H25R." Ziarek J.J., Veldkamp C.T., Peterson F.C., Volkman B.F. Submitted (SEP-2009) to the PDB data bank Cited for: STRUCTURE BY NMR OF 22-89, DISULFIDE BONDS.
[33]	"Heterologous quaternary structure of CXCL12 and its relationship to the CC chemokine family." Murphy J.W., Yuan H., Kong Y., Xiong Y., Lolis E.J. Proteins 78:1331-1337(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 22-88, DIMERIZATION.
+	Additional computationally mapped references.

Web resources

Wikipedia

SDF-1 entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L36033 mRNA. Translation: AAB39332.1.
L36034 mRNA. Translation: AAB39333.1.
DQ345517 mRNA. Translation: ABC69270.1.
DQ345518 mRNA. Translation: ABC69271.1.
DQ345519 mRNA. Translation: ABC69272.1.
DQ345520 mRNA. Translation: ABC69273.1.
U16752 mRNA. Translation: AAA97434.1.
U19495 mRNA. Translation: AAB40516.1.
AY644456 mRNA. Translation: AAT76437.1.
AY874118 mRNA. Translation: AAW82036.1.
CR450283 mRNA. Translation: CAG29279.1.
AK292628 mRNA. Translation: BAF85317.1.
AK311814 mRNA. Translation: BAG34757.1.
AY802782 Genomic DNA. Translation: AAV49999.1.
AL137026 Genomic DNA. Translation: CAC10202.1. Sequence problems.
AL137026 Genomic DNA. Translation: CAC10203.1.
CH471160 Genomic DNA. Translation: EAW86619.1.
BC039893 mRNA. Translation: AAH39893.1.

IPI

IPI00413781.
IPI00651692.
IPI00719836.
IPI00848299.
IPI01011188.

PIR

G01540.

RefSeq

NP_000600.1. NM_000609.5.
NP_001029058.1. NM_001033886.2.
NP_001171605.1. NM_001178134.1.
NP_954637.1. NM_199168.3.

UniGene

Hs.522891.

3D structure databases

PDBe
RCSB PDB
PDBj

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	22-89	[»]
2J7Z	X-ray	1.95	A/B	22-89	[»]
2K01	NMR	-	A/C	22-89	[»]
2K03	NMR	-	A/C	22-89	[»]
2K04	NMR	-	A/C	22-89	[»]
2K05	NMR	-	A/C	22-89	[»]
2KEC	NMR	-	A	22-89	[»]
2KED	NMR	-	A	22-89	[»]
2KEE	NMR	-	A	22-89	[»]
2KOL	NMR	-	A	22-89	[»]
2NWG	X-ray	2.07	A/B	22-88	[»]
2SDF	NMR	-	A	22-88	[»]
3GV3	X-ray	1.60	A	26-88	[»]
3HP3	X-ray	2.20	A/B/C/D/E/F/G/H/I/J	22-88	[»]

ProteinModelPortal

P48061.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-391N.
DIP-5894N.
DIP-5895N.

IntAct

P48061. 1 interaction.

MINT

MINT-6491347.

STRING

9606.ENSP00000363548.

PTM databases

PhosphoSite

P48061.

Polymorphism databases

DMDM

1352728.

Proteomic databases

PaxDb

P48061.

PRIDE

P48061.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000343575; ENSP00000339913; ENSG00000107562.
ENST00000374426; ENSP00000363548; ENSG00000107562.
ENST00000374429; ENSP00000363551; ENSG00000107562.
ENST00000395794; ENSP00000379140; ENSG00000107562.
ENST00000395795; ENSP00000379141; ENSG00000107562.

GeneID

6387.

KEGG

hsa:6387.

UCSC

uc001jbf.3. human.
uc001jbh.3. human.
uc021ppm.1. human.

Organism-specific databases

CTD

6387.

GeneCards

GC10M044865.

H-InvDB

HIX0008784.

HGNC

HGNC:10672. CXCL12.

HPA

CAB017564.

MIM

600835. gene.

neXtProt

NX_P48061.

PharmGKB

PA35602.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG26489.

HOGENOM

HOG000220915.

HOVERGEN

HBG107437.

KO

K10031.

OMA

HVARVNI.

OrthoDB

EOG4H72D7.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.
syndecan_4_pathway. Syndecan-4-mediated signaling events.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P48061.

Bgee

P48061.

CleanEx

HS_CXCL12.

Genevestigator

P48061.

GermOnline

ENSG00000107562. Homo sapiens.

Family and domain databases

InterPro

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

PS00471. SMALL_CYTOKINES_CXC. False negative.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01234. Dexamethasone.

EvolutionaryTrace

P48061.

GenomeRNAi

6387.

NextBio

24808.

PMAP-CutDB

Q5IT36.

SOURCE

Search...

Entry information

Entry name

SDF1_HUMAN

Accession

Primary (citable) accession number: P48061
Secondary accession number(s): B2R4G0 , E7EVL0, Q2L985, Q2L986, Q2L988, Q5IT36, Q6ICW0, Q9H554

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	May 29, 2013
This is version 141 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.