Q99727 (TIMP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metalloproteinase inhibitor 4

Alternative name(s):
Tissue inhibitor of metalloproteinases 4
Short name=TIMP-4

Gene names

Name:

TIMP4

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	224 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	Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9.
Subcellular location	Secreted.
Tissue specificity	Abundant in heart and present at low levels in many other tissues.
Sequence similarities	Belongs to the protease inhibitor I35 (TIMP) family. [View classification] Contains 1 NTR domain.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Metalloenzyme inhibitor Metalloprotease inhibitor
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase inhibitor activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Chain	30 – 224	195	Metalloproteinase inhibitor 4		PRO_0000034349
Regions
	Domain	30 – 156	127	NTR
	Region	30 – 34	5	Involved in metalloproteinase-binding By similarity
	Region	99 – 100	2	Involved in metalloproteinase-binding By similarity
Sites
	Metal binding	30	1	Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner By similarity
Amino acid modifications
	Disulfide bond	30 ↔ 102		By similarity
	Disulfide bond	32 ↔ 131		By similarity
	Disulfide bond	42 ↔ 156		By similarity
	Disulfide bond	158 ↔ 205		By similarity
	Disulfide bond	163 ↔ 168		By similarity
	Disulfide bond	176 ↔ 197		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q99727 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 39C7187D78D99442	FASTA	224	25,503
	10 20 30 40 50 60 MPGSPRPAPS WVLLLRLLAL LRPPGLGEAC SCAPAHPQQH ICHSALVIRA KISSEKVVPA 70 80 90 100 110 120 SADPADTEKM LRYEIKQIKM FKGFEKVKDV QYIYTPFDSS LCGVKLEANS QKQYLLTGQV 130 140 150 160 170 180 LSDGKVFIHL CNYIEPWEDL SLVQRESLNH HYHLNCGCQI TTCYTVPCTI SAPNECLWTD 190 200 210 220 WLLERKLYGY QAQHYVCMKH VDGTCSWYRG HLPLRKEFVD IVQP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4." Greene J., Wang M., Liu Y.E., Raymond L.A., Rosen C., Shi Y.E. J. Biol. Chem. 271:30375-30380(1996) [PubMed: 8939999] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[2]	"Cloning of the human tissue inhibitor of metalloproteinase-4 gene (TIMP4) and localization of the TIMP4 and timp4 genes to human chromosome 3p25 and mouse chromosome 6, respectively." Olson T.M., Hirohata S., Ye J., Leco K., Seldin M.F., Apte S.S. Genomics 51:148-151(1998) [PubMed: 9693046] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[5]	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].
[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]. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U76456 mRNA. Translation: AAB40391.1. AF057532 , AF057528, AF057529, AF057530, AF057531 Genomic DNA. Translation: AAC34422.1. BT019627 mRNA. Translation: AAV38433.1. AK313018 mRNA. Translation: BAG35853.1. CH471055 Genomic DNA. Translation: EAW64122.1. BC010553 mRNA. Translation: AAH10553.1.
IPI	IPI00017745.
RefSeq	NP_003247.1. NM_003256.3.
UniGene	Hs.591665.
3D structure databases
ProteinModelPortal	Q99727.
SMR	Q99727. Positions 30-222.
ModBase	Search...
Protein-protein interaction databases
STRING	Q99727.
Protein family/group databases
MEROPS	I35.004.
Polymorphism databases
DMDM	3915135.
Proteomic databases
PRIDE	Q99727.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000287814; ENSP00000287814; ENSG00000157150.
GeneID	7079.
KEGG	hsa:7079.
UCSC	uc003bwo.1. human.
Organism-specific databases
CTD	7079.
GeneCards	GC03M012169.
H-InvDB	HIX0003063.
HGNC	HGNC:11823. TIMP4.
HPA	CAB002771.
MIM	601915. gene.
neXtProt	NX_Q99727.
PharmGKB	PA36529.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06335.
GeneTree	ENSGT00390000004555.
HOGENOM	HBG713231.
HOVERGEN	HBG068749.
InParanoid	Q99727.
OMA	PNECLWT.
OrthoDB	EOG4DV5N7.
PhylomeDB	Q99727.
Gene expression databases
ArrayExpress	Q99727.
Bgee	Q99727.
CleanEx	HS_TIMP4.
Genevestigator	Q99727.
GermOnline	ENSG00000157150. Homo sapiens.
Family and domain databases
InterPro	IPR001134. Netrin_domain. IPR001820. Prot_inh_TIMP. IPR008993. TIMP-like_OB-fold. IPR015614. TIMP4. [Graphical view]
PANTHER	PTHR11844. Prot_inh_TIMP. 1 hit. PTHR11844:SF8. TIMP4. 1 hit.
Pfam	PF00965. TIMP. 1 hit. [Graphical view]
SMART	SM00206. NTR. 1 hit. [Graphical view]
SUPFAM	SSF50242. TIMP_like. 1 hit.
PROSITE	PS50189. NTR. 1 hit. PS00288. TIMP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	27689.
SOURCE	Search...

Entry information

Entry name

TIMP4_HUMAN

Accession

Primary (citable) accession number: Q99727
Secondary accession number(s): B2R7K6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	May 1, 1997
Last modified:	December 14, 2011
This is version 95 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.