P26927 (HGFL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hepatocyte growth factor-like protein

Alternative name(s):
Macrophage stimulatory protein
Macrophage-stimulating protein
Short name=MSP

Cleaved into the following 2 chains:

1. Hepatocyte growth factor-like protein alpha chain
2. Hepatocyte growth factor-like protein beta chain

Gene names

Name:	MST1
Synonyms:	D3F15S2, DNF15S2, HGFL

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	711 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)

Subunit structure	Dimer of an alpha chain and a beta chain linked by a disulfide bond. Ref.5
Subcellular location	Secreted.
Post-translational modification	Cleaved after Arg-483, probably by HPN/Hepsin, to yield the active form consisting of two disulfide-linked chains.
Sequence similarities	Belongs to the peptidase S1 family. Plasminogen subfamily. Contains 4 kringle domains. Contains 1 PAN domain. Contains 1 peptidase S1 domain.
Caution	Although related to peptidase S1 family, the active site residues characteristic of serine proteases appear to be absent from this protein, which may therefore lack protease activity.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Kringle Repeat Signal
Molecular function	Serine protease homolog
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 711

693

Hepatocyte growth factor-like protein

PRO_0000028085

Chain

19 – 483

465

Hepatocyte growth factor-like protein alpha chain Probable

PRO_0000028086

Chain

484 – 711

228

Hepatocyte growth factor-like protein beta chain Probable

PRO_0000028087

Regions

Domain

21 – 105

85

PAN

Domain

110 – 186

77

Kringle 1

Domain

191 – 268

78

Kringle 2

Domain

283 – 361

79

Kringle 3

Domain

370 – 448

79

Kringle 4

Domain

484 – 709

226

Peptidase S1

Amino acid modifications

Glycosylation

72

1

N-linked (GlcNAc...) Potential

Glycosylation

296

1

N-linked (GlcNAc...) Ref.6

Glycosylation

615

1

N-linked (GlcNAc...) Ref.7

Disulfide bond

56 ↔ 78

By similarity

Disulfide bond

60 ↔ 66

By similarity

Disulfide bond

110 ↔ 186

By similarity

Disulfide bond

131 ↔ 169

By similarity

Disulfide bond

157 ↔ 181

By similarity

Disulfide bond

191 ↔ 268

By similarity

Disulfide bond

194 ↔ 324

By similarity

Disulfide bond

212 ↔ 251

By similarity

Disulfide bond

240 ↔ 263

By similarity

Disulfide bond

283 ↔ 361

By similarity

Disulfide bond

304 ↔ 343

By similarity

Disulfide bond

332 ↔ 355

By similarity

Disulfide bond

370 ↔ 448

By similarity

Disulfide bond

391 ↔ 431

By similarity

Disulfide bond

419 ↔ 443

By similarity

Disulfide bond

468 ↔ 588

Interchain (between alpha and beta chains) Ref.9

Disulfide bond

507 ↔ 523

By similarity

Disulfide bond

602 ↔ 667

By similarity

Disulfide bond

632 ↔ 646

By similarity

Disulfide bond

657 ↔ 685

By similarity

Natural variations

Natural variant

13

1

C → Y. Ref.1

VAR_006631

Natural variant

212

1

C → F.

VAR_006632

Natural variant

551

1

S → G.
Corresponds to variant rs6791037 [ dbSNP | Ensembl ].

VAR_059787

Natural variant

676

1

E → K.
Corresponds to variant rs7798 [ dbSNP | Ensembl ].

VAR_014569

Experimental info

Sequence conflict

292

1

R → G AA sequence Ref.5

Sequence conflict

304

1

C → E AA sequence Ref.5

Sequence conflict

306

1

R → E AA sequence Ref.5

Sequence conflict

550

1

Missing AA sequence Ref.5

Sequence conflict

593

1

W → E AA sequence Ref.5

Sequence conflict

623

1

L → F in AAA59872. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

711

Helix Strand Turn

Details...

Beta strand

495 – 499

5

Beta strand

505 – 513

9

Beta strand

516 – 520

5

Helix

521 – 523

3

Beta strand

535 – 539

5

Beta strand

541 – 544

4

Beta strand

553 – 562

10

Beta strand

569 – 576

8

Beta strand

581 – 584

4

Beta strand

601 – 608

8

Beta strand

620 – 627

8

Helix

629 – 635

7

Turn

636 – 638

3

Beta strand

644 – 647

4

Beta strand

664 – 669

6

Beta strand

672 – 679

8

Beta strand

683 – 686

4

Beta strand

692 – 696

5

Helix

697 – 699

3

Helix

701 – 707

7

Sequences

	Sequence		Length	Mass (Da)
	P26927 [UniParc]. Last modified May 15, 2007. Version 2. Checksum: 2E4B3C7D4AA9B566	FASTA	711	80,320
	10 20 30 40 50 60 MGWLPLLLLL TQCLGVPGQR SPLNDFQVLR GTELQHLLHA VVPGPWQEDV ADAEECAGRC 70 80 90 100 110 120 GPLMDCRAFH YNVSSHGCQL LPWTQHSPHT RLRRSGRCDL FQKKDYVRTC IMNNGVGYRG 130 140 150 160 170 180 TMATTVGGLP CQAWSHKFPN DHKYTPTLRN GLEENFCRNP DGDPGGPWCY TTDPAVRFQS 190 200 210 220 230 240 CGIKSCREAA CVWCNGEEYR GAVDRTESGR ECQRWDLQHP HQHPFEPGKF LDQGLDDNYC 250 260 270 280 290 300 RNPDGSERPW CYTTDPQIER EFCDLPRCGS EAQPRQEATT VSCFRGKGEG YRGTANTTTA 310 320 330 340 350 360 GVPCQRWDAQ IPHQHRFTPE KYACKDLREN FCRNPDGSEA PWCFTLRPGM RAAFCYQIRR 370 380 390 400 410 420 CTDDVRPQDC YHGAGEQYRG TVSKTRKGVQ CQRWSAETPH KPQFTFTSEP HAQLEENFCR 430 440 450 460 470 480 NPDGDSHGPW CYTMDPRTPF DYCALRRCAD DQPPSILDPP DQVQFEKCGK RVDRLDQRRS 490 500 510 520 530 540 KLRVVGGHPG NSPWTVSLRN RQGQHFCGGS LVKEQWILTA RQCFSSCHMP LTGYEVWLGT 550 560 570 580 590 600 LFQNPQHGEP SLQRVPVAKM VCGPSGSQLV LLKLERSVTL NQRVALICLP PEWYVVPPGT 610 620 630 640 650 660 KCEIAGWGET KGTGNDTVLN VALLNVISNQ ECNIKHRGRV RESEMCTEGL LAPVGACEGD 670 680 690 700 710 YGGPLACFTH NCWVLEGIII PNRVCARSRW PAVFTRVSVF VDWIHKVMRL G

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor." Han S., Stuart L.A., Friezner Degen S.J. Biochemistry 30:9768-9780(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TYR-13. Tissue: Liver.
[2]	"Cloning, sequencing, and expression of human macrophage stimulating protein (MSP, MST1) confirms MSP as a member of the family of kringle proteins and locates the MSP gene on chromosome 3." Yoshimura T., Yuhki N., Wang M.H., Skeel A., Leonard E.J. J. Biol. Chem. 268:15461-15468(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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].
[5]	"Macrophage stimulating protein: purification, partial amino acid sequence, and cellular activity." Skeel A., Yoshimura T., Showalter S.D., Tanaka S., Appella E., Leonard E.J. J. Exp. Med. 173:1227-1234(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 230-247; 288-310; 326-341; 484-501; 530-552; 574-596 AND 602-611, SUBUNIT. Tissue: Plasma.
[6]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-296, MASS SPECTROMETRY. Tissue: Plasma.
[7]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-615, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Proteolytic activation of pro-macrophage-stimulating protein by hepsin." Ganesan R., Kolumam G.A., Lin S.J., Xie M.H., Santell L., Wu T.D., Lazarus R.A., Chaudhuri A., Kirchhofer D. Mol. Cancer Res. 9:1175-1186(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC CLEAVAGE.
[9]	"Crystal structure of the beta-chain of human hepatocyte growth factor-like/macrophage stimulating protein." Carafoli F., Chirgadze D.Y., Blundell T.L., Gherardi E. FEBS J. 272:5799-5807(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 465-711, INTERCHAIN DISULFIDE BOND.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M74178 mRNA. Translation: AAA50165.1.
U37055 Genomic DNA. Translation: AAC50471.1.
L11924 mRNA. Translation: AAA59872.1.
AC099668 Genomic DNA. No translation available.
BC048330 mRNA. Translation: AAH48330.1.

IPI

IPI00925540.

PIR

A47136. A40331.

RefSeq

NP_066278.3. NM_020998.3.

UniGene

Hs.349110.
Hs.512587.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ASU	X-ray	1.85	A	465-483	[»]
			B	484-711	[»]

ProteinModelPortal

P26927.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6028N.

MINT

MINT-4787531.

STRING

9606.ENSP00000308226.

Protein family/group databases

MEROPS

S01.975.

PTM databases

PhosphoSite

P26927.

Polymorphism databases

DMDM

147744563.

Proteomic databases

PaxDb

P26927.

PRIDE

P26927.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000383728; ENSP00000373234; ENSG00000173531.

GeneID

4485.

KEGG

hsa:4485.

UCSC

uc003cxg.3. human.

Organism-specific databases

CTD

4485.

GeneCards

GC03M049696.

H-InvDB

HIX0024339.

HGNC

HGNC:7380. MST1.

HPA

HPA024036.

MIM

142408. gene.

neXtProt

NX_P26927.

PharmGKB

PA31185.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000112892.

HOVERGEN

HBG004381.

InParanoid

P26927.

Enzyme and pathway databases

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
amb2_neutrophils_pathway. amb2 Integrin signaling.
foxopathway. FoxO family signaling.

Gene expression databases

ArrayExpress

P26927.

Bgee

P26927.

CleanEx

HS_MST1.

Genevestigator

P26927.

GermOnline

ENSG00000173531. Homo sapiens.

Family and domain databases

Gene3D

2.40.20.10. 4 hits.

InterPro

IPR024174. HGF_MST1.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR003014. PAN-1_domain.
IPR003609. Pan_app.
IPR001254. Peptidase_S1.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00051. Kringle. 4 hits.
PF00024. PAN_1. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]

PIRSF

PIRSF001152. HGF_MST1. 1 hit.

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00130. KR. 4 hits.
SM00473. PAN_AP. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF57440. Kringle-like. 4 hits.
SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS00021. KRINGLE_1. 4 hits.
PS50070. KRINGLE_2. 4 hits.
PS50948. PAN. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL6042.

EvolutionaryTrace

P26927.

GenomeRNAi

4485.

NextBio

17351.

PMAP-CutDB

P26927.

SOURCE

Search...

Entry information

Entry name

HGFL_HUMAN

Accession

Primary (citable) accession number: P26927
Secondary accession number(s): A6NLA3 , A8MSX3, Q13350, Q14870, Q6GTN4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	May 15, 2007
Last modified:	May 1, 2013
This is version 139 of the entry and version 2 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.